@article {pmid36737487, year = {2023}, author = {Poto, R and Laniro, G and de Paulis, A and Spadaro, G and Marone, G and Gasbarrini, A and Varricchi, G}, title = {Is there a role for microbiome-based approach in common variable immunodeficiency?.}, journal = {Clinical and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10238-023-01006-3}, pmid = {36737487}, issn = {1591-9528}, abstract = {Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.}, }
@article {pmid36736919, year = {2023}, author = {Krishaa, L and Ng, TKS and Wee, HN and Ching, J}, title = {Gut-brain axis through the lens of gut microbiota and their relationships with Alzheimer's disease pathology: review and recommendations.}, journal = {Mechanisms of ageing and development}, volume = {}, number = {}, pages = {111787}, doi = {10.1016/j.mad.2023.111787}, pmid = {36736919}, issn = {1872-6216}, abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Growing evidence suggests that the gut microbiome (GM) plays a pivotal role in the pathogenesis of AD through the microbiota-gut-brain axis (MGB). Alterations in GM composition and diversity have been observed in both animal models and in human patients with AD. GM dysbiosis has been implicated in increased intestinal permeability, blood-brain barrier (BBB) impairment, neuroinflammation and the development of hallmarks of AD. Further elucidation of the role of GM in AD could pave way for the development of holistic predictive methods for determining AD risk and progression of disease. Furthermore, accumulating evidence suggests that GM modulation could alleviate adverse symptoms of AD or serve as a preventive measure. In addition, increasing evidence shows that Type 2 Diabetes Mellitus (T2DM) is often comorbid with AD, with common GM alterations and inflammatory response, which could chart the development of GM-related treatment interventions for both diseases. We conclude by exploring the therapeutic potential of GM in alleviating symptoms of AD and in reducing risk. Furthermore, we also propose future directions in AD research, namely fecal microbiota transplantation (FMT) and precision medicine.}, }
@article {pmid36735734, year = {2023}, author = {Lee, C and Kim, S and Kim, B and Holzapfel, WH and Hyun, CK}, title = {Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0280850}, doi = {10.1371/journal.pone.0280850}, pmid = {36735734}, issn = {1932-6203}, abstract = {Hepatobiliary abnormality and metabolic disorders are frequently observed complications in patients with inflammatory bowel diseases (IBD). Given that microbiota dysbiosis is a common pathophysiological feature of both IBD and metabolic diseases, we examined how the IBD-induced dysbiosis affects the host metabolism and contributes to the development of associated metabolic diseases using germ-free (GF) mice transplanted with fecal microbiota of DSS-induced colitis mice. There was no significant change in inflammation or barrier integrity in the gut of GF mice that received microbiota from colitis mice compared to their counterparts that were transplanted with microbiota from non-colitis healthy mice. Interestingly, it was observed that the GF recipients of colitis-induced altered microbiota showed a significant decrease in the weight of adipose tissues including mesenteric, epididymal, subcutaneous, and brown fat without any change in body weight, which was accompanied by abnormalities in adipose tissue functions such as fat storage and adiponectin production. Transplantation of colitis-induced altered microbiota also disrupted hepatic lipid metabolism in the GF recipient mice, which was observed by increases in synthesis and accumulation of cholesterol and bile acids in hepatocytes and a decrease in plasma HDL-cholesterol. Additional observations including elevated plasma levels of insulin, decreased hepatic production of FGF21, and decreased levels of fecal short chain fatty acids (SCFAs) and hepatic expression of SCFA receptors led to a conclusion that the transplantation of the colitis-associated dysbiotic microbiota was causally associated with impairments of insulin action and FGF21-adiponectin axis, possibly due to the low SCFA-producing capacity of the colonized microbiota, leading to metabolic abnormalities including adipose tissue dysfunction and dysregulated hepatic lipid metabolism. Our findings suggest potential mechanisms that explain how colitis-associated gut dysbiosis may contribute to the development of metabolic dysfunctions, which could be applied to clinical practice to improve the efficacy of treatment of IBD patients with comorbid metabolic disorders or vice versa.}, }
@article {pmid36735599, year = {2023}, author = {Kahn, SA and Bousvaros, A}, title = {Topic of the month: How to write an effective letter of medical necessity.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000003724}, pmid = {36735599}, issn = {1536-4801}, abstract = {Insurance companies and pharmacy benefit managers frequently deny prescriptions that are medically necessary but expensive. Physicians may appeal denials by providing insurers with additional clinical information and supporting medical evidence. One component of the appeal process is a well-written letter of medical necessity. The review article below provides guidance for the clinician to write a compelling and powerful letter. Among other components, the letter should include a clear description of the patient's specific case, the medical literature that supports the prescribing physician's choice of therapy, and the adverse consequences (e.g., hospitalization) if the patient does not get the needed medication.}, }
@article {pmid36732497, year = {2023}, author = {Xu, Y and Wang, J and Wu, X and Jing, H and Zhang, S and Hu, Z and Rao, L and Chang, Q and Wang, L and Zhang, Z}, title = {Gut microbiota alteration after cholecystectomy contributes to post-cholecystectomy diarrhea via bile acids stimulating colonic serotonin.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2168101}, doi = {10.1080/19490976.2023.2168101}, pmid = {36732497}, issn = {1949-0984}, abstract = {Post-cholecystectomy diarrhea (PCD) is highly prevalent among outpatients with cholecystectomy, and gut microbiota alteration is correlated with it. However, how and to what extent changed fecal bacteria contributes to diarrhea are still unrevealed. Humanized gut microbiome mice model by fecal microbiota transplantation was established to explore the diarrhea-inducible effects of gut microbiota. The role of microbial bile acids (BAs) metabolites was identified by UPLC/MS and the underlying mechanisms were investigated with selective inhibitors and antagonists as probes. These mice transplanted with fecal microbiome of PCD patients (PCD mice) exhibited significantly enhanced gastrointestinal motility and elevated fecal water content, compared with these mice with fecal microbiome of NonPCD patients and HC. In analyzing gut microbiota, tryptophan metabolism was enriched in PCD microbiome. In addition, overabundant serotonin in serum and colon, along with elevated biosynthesis gene and reduced reuptake gene, and highly expressed 5-HT receptors (5-HTRs) in colon of PCD mice were found, but not in small intestine. Notably, diarrheal phenotypes in PCD mice were depleted by tryptophan hydroxylase 1 inhibitor (LX1606) and 5-HTRs selective antagonists (alosetron and GR113808). Furthermore, increased microbial secondary BAs metabolites of DCA, HDCA and LCA were revealed in feces of PCD mice and they were found responsible for stimulating 5-HT level in vitro and in vivo. Intriguingly, blocking BAs-conjugated TGR5/TRPA1 signaling pathway could significantly alleviate PCD. In conclusion, altered gut microbiota after cholecystectomy contributes to PCD by promoting secondary BAs in colon, which stimulates colonic 5-HT and increases colon motility.}, }
@article {pmid36732495, year = {2023}, author = {Dong, TS and Katzka, W and Yang, JC and Chang, C and Arias-Jayo, N and Lagishetty, V and Balioukova, A and Chen, Y and Dutson, E and Li, Z and Mayer, EA and Pisegna, JR and Sanmiguel, C and Jacobs, JP}, title = {Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2167170}, doi = {10.1080/19490976.2023.2167170}, pmid = {36732495}, issn = {1949-0984}, abstract = {Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes.}, }
@article {pmid36728562, year = {2023}, author = {Yang, W and Ren, D and Shao, H and Zhang, X and Li, T and Zhang, L and Liu, L and Zhao, Y and Niu, P and Yang, X}, title = {Theabrownin from Fu Brick Tea Improves Ulcerative Colitis by Shaping the Gut Microbiota and Modulating the Tryptophan Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c06821}, pmid = {36728562}, issn = {1520-5118}, abstract = {Fu brick tea theabrownin (FBTB) is a kind of biomacromolecule produced by oxidative polymerization of tea polyphenols. Although a variety of diseases can be alleviated by TB, its ability to treat ulcerative colitis (UC) is still worth exploring. A dextran sulfate sodium (DSS)-induced chronic UC mouse model was designed to first explore the alleviatory effect of FBTB on UC and its underlying mechanism by the sequencing of fecal 16S rRNA genes, metabolomics, and fecal microbiota transplantation (FMT). Administration of FBTB at 400 mg/kg bw in DSS-damaged mice could effectively reduce colonic damage and inflammation and improve colonic antioxidant capacity to relieve the UC-caused symptoms. FBTB could correct the disrupted gut microbiota caused by UC and contribute to the proliferation of Lactobacillus and Parasutterella. FMT in combination with antibiotic treatment showed that FBTB could elevate the levels of microbial tryptophan metabolites, including indole-3-acetaldehyde (IAld) and indole-3-acetic acid (IAA), by selectively promoting the growth of Lactobacillus. Importantly, FBTB-elevated IAld and IAA could activate aromatic hydrocarbon receptors (AhRs) and enhance interleukin-22 production to repair the intestinal barrier. These findings demonstrated that FBTB alleviated UC mainly by targeting the gut microbiota involved in the AhR pathway for prophylactic and therapeutic treatment of UC.}, }
@article {pmid36726574, year = {2022}, author = {Han, TR and Yang, WJ and Tan, QH and Bai, S and Zhong, H and Tai, Y and Tong, H}, title = {Gut microbiota therapy for nonalcoholic fatty liver disease: Evidence from randomized clinical trials.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1004911}, pmid = {36726574}, issn = {1664-302X}, abstract = {Nonalcoholic fatty liver disease (NAFLD) has a high prevalence worldwide, but there are no medications approved for treatment. Gut microbiota would be a novel and promising therapeutic target based on the concept of the gut-liver axis in liver disease. We reviewed randomized controlled trials on gut microbiota therapy in NAFLD in this study to evaluate its efficacy and plausibility in NAFLD.}, }
@article {pmid36725289, year = {2023}, author = {Zhao, Q and Hao, Y and Yang, XQ and Yan, XY and Qiu, YL}, title = {[Preliminary study on the effect of fecal microbiota transplantation on neurobehavior and gut microbiota of offspring rats exposed to arsenic].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {41}, number = {1}, pages = {14-20}, doi = {10.3760/cma.j.cn121094-20220311-00125}, pmid = {36725289}, issn = {1001-9391}, abstract = {Objective: To explore the effects of fecal microbiota transplantation (FMT) on neurobehavior and gut microbiota of arsenic-exposed offspring rats. Methods: In April 2021, Thirty-six SPF SD rats aged 8 weeks were seleted, rats were ranked by weight and divided into four groups according to randomized block design, namely control group, arsenic exposure group (As group) , arsenic+normal saline group (As+NaCl group) and As+FMT group, 6 females and 3 males in each group. Fecal microbiota fluid were provided by feces of rats in control group. Rats drank tap water containing 75 mg/L sodium arsenite for one week and then were caged together. The arsenic exposure was terminated until the pups were born. Female rats with vaginal plug were treated with fecal microbiota fluid via gavage during neurodevelopmental teratogenic window period. The volume of gavage was 1 ml/100 g with once every two days, for a total of three times. Weight alterations of offspring rats were recorded every week after weaning, and when offspring rats grew up for 6 weeks, Morris test and open field experiment was used to observe learning and memory abilities, as well as neurobehavioral performance of autonomous exploration and tension, respectively. 16S rDNA sequencing technology was used to detect microbiota diversities in fecal samples of rats in As group and As+FMT group. Results: Compared with the control group, the ratio of swimming distance and staying time in the target quadrant and the times of crossing the platform of rats in As group decreased significantly, and the motor distance, times entering central zone and the number of grid crossing of rats decreased significantly (P<0.05) . Compared with As group, the ratio of swimming distance in target quadrant, the motor distance in central zone and times entering central zone of rats in As+FMT group were evidently increased (P<0.05) . The analysis of fecal microbiota diversities showed that, at the phyla level, the relative abundance of Bacteroidetes in feces of rats in As+FMT group was higher than that in As group (68.34% vs 60.55%) , while the relative abundance of Firmicutes was lower than that in As group (28.02% vs 33.48%) . At the genus level, the relative abundance of Prevotella in As+FMT group was significantly higher than that in As group, becoming the dominant genus (42.08% vs 21.78%) . Additionally, compared with As group, a total of 22 genus were increased with 21 decreased genus in As+FMT group (P<0.05) . LEfSe analysis showed that dominant genuses in As+FMT group were Prevotella and UCG_005, and their relative abundance was significantly higher than that of As group (P<0.05) . Conclusion: FMT may alleviate the impaired learning and memory ability and anxiety like behavior of the offspring rats exposed to arsenic, and improve the disrupted gut microbiota.}, }
@article {pmid36725206, year = {2023}, author = {Peng, Y and Dong, W and Chen, G and Mi, J and Lu, L and Xie, Z and Xu, W and Zhou, W and Sun, Y and Zeng, X and Cao, Y and Yan, Y}, title = {Anthocyanins from Lycium ruthenicum Murray Ameliorated High-Fructose Diet-Induced Neuroinflammation through the Promotion of the Integrity of the Intestinal Barrier and the Proliferation of Lactobacillus.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c06713}, pmid = {36725206}, issn = {1520-5118}, abstract = {In the present study, we found that anthocyanins from Lycium ruthenicum Murray (ACN) potently ameliorated a high-fructose diet (HFrD)-induced neuroinflammation in mice. ACN improved the integrity of the intestinal barrier and suppressed the toll-like receptor 4 (TLR4) signaling pathway to ameliorate the neuroinflammation, which was verified by Tlr4[-/-] mice. Furthermore, ACN could modulate the HFrD-induced dysbiosis of gut microbiota. The fecal microbiota transplantation from ACN-induced mice was sufficient to attenuate the neuroinflammation, while the amelioration of neuroinflammation by ACN was blocked upon gut microbiota depletion. In addition, ACN-induced increment of the relative abundance of Lactobacillus might be responsible for the alleviation of the neuroinflammation, which was further confirmed in the promoting effect of ACN on the growth of Lactobacillus in vitro. Overall, these results provided the evidence of a comprehensive cross-talk mechanism between ACN and neuroinflammation in HFrD-fed mice, which was mediated by reducing gut microbiota dysbiosis and maintaining the intestinal barrier integrity.}, }
@article {pmid36722516, year = {2023}, author = {Kwa, WT and Sundarajoo, S and Toh, KY and Lee, J}, title = {Application of emerging technologies for gut microbiome research.}, journal = {Singapore medical journal}, volume = {64}, number = {1}, pages = {45-52}, doi = {10.4103/singaporemedj.SMJ-2021-432}, pmid = {36722516}, issn = {0037-5675}, abstract = {Microbiome is associated with a wide range of diseases. The gut microbiome is also a dynamic reflection of health status, which can be modified, thus representing great potential to exploit the mechanisms that influence human physiology. Recent years have seen a dramatic rise in gut microbiome studies, which has been enabled by the rapidly evolving high-throughput sequencing methods (i.e. 16S rRNA sequencing and shotgun sequencing). As the emerging technologies for microbiome research continue to evolve (i.e. metatranscriptomics, metabolomics, culturomics, synthetic biology), microbiome research has moved beyond phylogenetic descriptions and towards mechanistic analyses. In this review, we highlight different approaches to study the microbiome, in particular, the current limitations and future promise of these techniques. This review aims to provide clinicians with a framework for studying the microbiome, as well as to accelerate the adoption of these techniques in clinical practice.}, }
@article {pmid36721210, year = {2023}, author = {Pi, Y and Wu, Y and Zhang, X and Lu, D and Han, D and Zhao, J and Zheng, X and Zhang, S and Ye, H and Lian, S and Bai, Y and Wang, Z and Tao, S and Ni, D and Zou, X and Jia, W and Zhang, G and Li, D and Wang, J}, title = {Gut microbiota-derived ursodeoxycholic acid alleviates low birth weight-induced colonic inflammation by enhancing M2 macrophage polarization.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {19}, doi = {10.1186/s40168-022-01458-x}, pmid = {36721210}, issn = {2049-2618}, abstract = {BACKGROUND: Low birth weight (LBW) is associated with intestinal inflammation and dysbiosis after birth. However, the underlying mechanism remains largely unknown.<br><br>OBJECTIVE: In the present study, we aimed to investigate the metabolism, therapeutic potential, and mechanisms of action of bile acids (BAs) in LBW-induced intestinal inflammation in a piglet model.<br><br>METHODS: The fecal microbiome and BA profile between LBW and normal birth weight (NBW) neonatal piglets were compared. Fecal microbiota transplantation (FMT) was employed to further confirm the linkage between microbial BA metabolism and intestinal inflammation. The therapeutic potential of ursodeoxycholic acid (UDCA), a highly differentially abundant BA between LBW and NBW piglets, in alleviating colonic inflammation was evaluated in both LBW piglets, an LBW-FMT mice model, and a DSS-induced colitis mouse model. The underlying cellular and molecular mechanisms by which UDCA suppresses intestinal inflammation were also investigated in both DSS-treated mice and a macrophage cell line. Microbiomes were analyzed by using 16S ribosomal RNA sequencing. Fecal and intestinal BA profiles were measured by using targeted BA metabolomics. Levels of farnesoid X receptor (FXR) were knocked down in J774A.1 cells with small interfering RNAs.<br><br>RESULTS: We show a significant difference in both the fecal microbiome and BA profiles between LBW and normal birth weight animals in a piglet model. Transplantation of the microbiota of LBW piglets to antibiotic-treated mice leads to intestinal inflammation. Importantly, oral administration of UDCA, a major BA diminished in the intestinal tract of LBW piglets, markedly alleviates intestinal inflammation in LBW piglets, an LBW-FMT mice model, and a mouse model of colitis by inducing M2 macrophage polarization. Mechanistically, UDCA reduces inflammatory cytokine production by engaging BA receptor FXR while suppressing NF-&#x3ba;B activation in macrophages.<br><br>CONCLUSIONS: These findings establish a causal relationship between LBW-associated intestinal abnormalities and dysbiosis, suggesting that restoring intestinal health and postnatal maldevelopment of LBW infants may be achieved by targeting intestinal microbiota and BA metabolism. Video Abstract.}, }
@article {pmid36721179, year = {2023}, author = {Wang, X and Wang, Z and Cao, J and Dong, Y and Chen, Y}, title = {Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {17}, doi = {10.1186/s40168-022-01452-3}, pmid = {36721179}, issn = {2049-2618}, abstract = {Sleep loss is a serious global health concern. Consequences include memory deficits and gastrointestinal dysfunction. Our previous research showed that melatonin can effectively improve cognitive impairment and intestinal microbiota disturbances caused by sleep deprivation (SD). The present study further explored the mechanism by which exogenous melatonin prevents SD-induced cognitive impairments. Here, we established fecal microbiota transplantation, Aeromonas colonization and LPS or butyrate supplementation tests to evaluate the role of the intestinal microbiota and its metabolites in melatonin in alleviating SD-induced memory impairment. RESULTS: Transplantation of the SD-gut microbiota into normal mice induced microglia overactivation and neuronal apoptosis in the hippocampus, cognitive decline, and colonic microbiota disorder, manifesting as increased levels of Aeromonas and LPS and decreased levels of Lachnospiraceae_NK4A136 and butyrate. All these events were reversed with the transplantation of SD + melatonin-gut microbiota. Colonization with Aeromonas and the addition of LPS produced an inflammatory response in the hippocampus and spatial memory impairment in mice. These changes were reversed by supplementation with melatonin, accompanied by decreased levels of Aeromonas and LPS. Butyrate administration to sleep-deprived mice restored inflammatory responses and memory impairment. In vitro, LPS supplementation caused an inflammatory response in BV2 cells, which was improved by butyrate supplementation. This ameliorative effect of butyrate was blocked by pretreatment with MCT1 inhibitor and HDAC3 agonist but was mimicked by TLR4 and p-P65 antagonists. CONCLUSIONS: Gut microbes and their metabolites mediate the ameliorative effects of melatonin on SD-induced cognitive impairment. A feasible mechanism is that melatonin downregulates the levels of Aeromonas and constituent LPS and upregulates the levels of Lachnospiraceae_NK4A136 and butyrate in the colon. These changes lessen the inflammatory response and neuronal apoptosis in the hippocampus through crosstalk between the TLR4/NF-κB and MCT1/ HDAC3 signaling pathways. Video Abstract.}, }
@article {pmid36720452, year = {2023}, author = {Yang, JZ and Zhang, KK and He, JT and Chen, LJ and Ding, JF and Liu, JL and Li, JH and Liu, Y and Li, XW and Zhao, D and Xie, XL and Wang, Q}, title = {Obeticholic acid protects against methamphetamine-induced anxiety-like behavior by ameliorating microbiota-mediated intestinal barrier impairment.}, journal = {Toxicology}, volume = {486}, number = {}, pages = {153447}, doi = {10.1016/j.tox.2023.153447}, pmid = {36720452}, issn = {1879-3185}, abstract = {Methamphetamine (Meth) abuse can cause severe anxiety disorder and interfere with gut homeostasis. Obeticholic acid (OCA) has emerged as a protective agent against diet-related anxiety that improves gut homeostasis. The potential for OCA to ameliorate Meth-induced anxiety, and the microbial mechanisms involved, remain obscure. Here, C57/BL6 mice were intraperitoneally injected with Meth (15 mg/kg) to induce anxiety-like behavior. 16 S rRNA sequence analysis and fecal microbiome transplantation (FMT) were used to profile the gut microbiome and evaluate its effects, respectively. Orally administered OCA was investigated for protection against Meth-induced anxiety. Results indicated that Meth mediated anxiety-like behavior, aroused hippocampal neuroinflammation through activation of the TLR4/MyD88/NF-κB pathway, weakened intestinal barrier and disturbed the gut microbiome. Specifically, abundance of anxiety-related Rikenella was increased. FMT from Meth-administrated mice also weakened intestinal barrier and elevated serum LPS, inducing hippocampal neuroinflammation and anxiety-like behavior in recipient mice. Finally, OCA pretreatment ameliorated Meth-induced impairment of gut homeostasis by reshaping the microbial composition and improving the intestinal barrier. Meth-induced anxiety-like behavior and hippocampal neuroinflammation were also ameliorated by OCA pretreatment. These preliminary findings reveal the crucial role of gut microbiota in Meth-induced anxiety-like behavior and neuroinflammation, highlighting OCA as a potential candidate for the prevention of Meth-induced anxiety.}, }
@article {pmid36720105, year = {2023}, author = {Conover, KR and Absah, I and Ballal, S and Brumbaugh, D and Cho, S and Cardenas, MC and Knackstedt, ED and Goyal, A and Jensen, MK and Kaplan, JL and Kellermayer, R and Kociolek, LK and Michail, S and Oliva-Hemker, M and Reed, AW and Weatherly, M and Kahn, SA and Nicholson, MR}, title = {FECAL MICROBIOTA TRANSPLANTATION FOR CLOSTRIDIOIDES DIFFICILE INFECTION IN IMMUNOCOMPROMISED PEDIATRIC PATIENTS.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000003714}, pmid = {36720105}, issn = {1536-4801}, abstract = {OBJECTIVES: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients.<br><br>METHODS: This is a multi-center retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition.<br><br>RESULTS: Of 59 pediatric patients identified at nine centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after one or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; four (9.5%) of which were likely treatment-related. There were no deaths or infections with multi-drug resistant organisms during follow-up and all patients with a serious adverse event fully recovered.<br><br>CONCLUSIONS: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.}, }
@article {pmid36719820, year = {2023}, author = {Rokkas, T and Hold, GL}, title = {A systematic review, pairwise meta-analysis and network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in irritable bowel syndrome.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MEG.0000000000002519}, pmid = {36719820}, issn = {1473-5687}, abstract = {BACKGROUND: Treatment is a challenge in Irritable Bowel Syndrome (IBS) and fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials (RCTs) comparing therapeutic intervention competing for similar therapeutic results. No NWM exists concerning the comparative effectiveness and safety of various FMT modalities for IBS.<br><br>AIM: We updated pairwise meta-analyses published in the past and assessed the comparative effectiveness and safety of various FMT delivery modalities for IBS.<br><br>METHODS: Pairwise meta-analyses and Bayesian NWM were performed. Heterogeneity, consistency of results and publication bias were explored.<br><br>RESULTS: Of 510 titles raised by initial search, seven RCTs were entered into meta-analyses and NWM. They included 470 patients and controls, in whom four FMT delivery modalities were used, that is via colonoscopy, nasojejunal tube, duodenoscope and capsules per os. In the pairwise meta-analysis, the pooled results showed that overall FMT was not superior to placebo, whereas the subgroup analyses showed that FMT via duodenoscope and nasojejunal tube was superior. The NWM showed that 60-g FMT via duodenoscope had the highest efficacy (OR, 26.38; 95% CI, 9.22-75.51) and was by far the highest in the efficacy ranking (SUCRA, 98.8%).<br><br>CONCLUSION: The pooled results showed no overall advantage of FMT over placebo in IBS. However, upper GI delivery (via duodenoscopy or nasojejunal tube) proved to be effective. Consequently, well-designed RCTs are needed to ensure the efficacy and safety profile before FMT can be applied in everyday clinical practice for IBS patients.}, }
@article {pmid36717922, year = {2023}, author = {Xu, QQ and Su, ZR and Yang, W and Zhong, M and Xian, YF and Lin, ZX}, title = {Patchouli alcohol attenuates the cognitive deficits in a transgenic mouse model of Alzheimer's disease via modulating neuropathology and gut microbiota through suppressing C/EBPβ/AEP pathway.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {19}, pmid = {36717922}, issn = {1742-2094}, abstract = {BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive cognitive dysfunctions and behavioral impairments. Patchouli alcohol (PA), isolated from Pogostemonis Herba, exhibits multiple pharmacological properties, including neuroprotective effects. This study aimed to investigate the therapeutic effects of PA against AD using the TgCRND8 transgenic AD mouse model, and to explore the underlying mechanisms targeting CCAAT/enhancer-binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling pathway.<br><br>METHODS: After genotyping to confirm the transgenicity, drug treatments were administered intragastrically once daily to 3-month-old TgCRND8 mice for 4 consecutive months. Several behavioral tests were applied to assess different aspects of neurological functions. Then the brain and colon tissues were harvested for in-depth mechanistic studies. To further verify whether PA exerts anti-AD effects via modulating C/EBP&#x3b2;/AEP signaling pathway in TgCRND8 mice, adeno-associated virus (AAV) vectors encoding CEBP/&#x3b2; were bilaterally injected into the hippocampal CA1 region in TgCRND8 mice to overexpress C/EBP&#x3b2;. Additionally, the fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of gut microbiota on the anti-AD effects of PA.<br><br>RESULTS: Our results showed that PA treatment significantly improved activities of daily living (ADL), ameliorated the anxiety-related behavioral deficits and cognitive impairments in TgCRND8 mice. PA modulated the amyloid precursor protein (APP) processing. PA also markedly reduced the levels of beta-amyloid (A&#x3b2;) 40 and A&#x3b2;42, suppressed A&#x3b2; plaque burdens, inhibited tau protein hyperphosphorylation at several sites and relieved neuroinflammation in the brains of TgCRND8 mice. Moreover, PA restored gut dysbiosis and inhibited the activation of the C/EBP&#x3b2;/AEP signaling pathway in the brain and colon tissues of TgCRND8 mice. Interestingly, PA strikingly alleviated the AD-like pathologies induced by the overexpression of C/EBP&#x3b2; in TgCRND8 mice. Additionally, the FMT of fecal microbiota from the PA-treated TgCRND8 mice significantly alleviated the cognitive impairments and AD-like pathologies in the germ-free TgCRND8 mice.<br><br>CONCLUSION: All these findings amply demonstrated that PA could ameliorate the cognitive deficits in TgCRND8 mice via suppressing A&#x3b2; plaques deposition, hyperphosphorylation of tau protein, neuroinflammation and gut dysbiosis through inhibiting the activation of C/EBP&#x3b2;/AEP pathway, suggesting that PA is a promising naturally occurring chemical worthy of further development into the pharmaceutical treatment of AD.}, }
@article {pmid36717576, year = {2023}, author = {Sun, WL and Hua, S and Li, XY and Shen, L and Wu, H and Ji, HF}, title = {Microbially produced vitamin B12 contributes to the lipid-lowering effect of silymarin.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {477}, doi = {10.1038/s41467-023-36079-x}, pmid = {36717576}, issn = {2041-1723}, abstract = {Silymarin has been used for improving hepatic damage and lipid disorders, but its action mechanism remains to be clarified. Here, we investigate the contributions of the gut microbiota to the improvement of liver lipid metabolism by silymarin. We find i) strong and significant microbial shifts upon silymarin but not silibinin treatment; ii) over 60% variations of liver fat are explained by silymarin-induced bacterial B12 production in male rats but not in male germ-free mice; iii) fecal microbiota transplantation confirms their protective roles against liver fat accumulation; iv) upregulation of one-carbon metabolism and fatty acid degradation pathways are observed based on the liver transcriptome analyses; and v) in humans the delta changes of serum B12 associate negatively with the fluctuations of serum triglycerides. Overall, we reveal a mechanism of action underpinning the lipid-lowering effect of silymarin via the gut microbiota and its vitamin B12 producing capabilities.}, }
@article {pmid36717202, year = {2023}, author = {}, title = {Early use of faecal microbiota transplantation for C. difficile infection.}, journal = {Drug and therapeutics bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1136/dtb.2023.000003}, pmid = {36717202}, issn = {1755-5248}, abstract = {Overview of: Baunwall SMD, Andreasen SE, Hansen MM, et al Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol 2022;7:1083-91.}, }
@article {pmid36714122, year = {2022}, author = {Hocking, L and Wilcox, M and Petrosillo, N and Griffin, P and Steiner, T and Attara, G and Doré, J and Cabling, M and Stockwell, S and Romanelli, RJ and Marjanovic, S}, title = {Improving care for patients with Clostridioides difficile infection: A clinical practice and healthcare systems perspective.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1033417}, pmid = {36714122}, issn = {2296-858X}, abstract = {INTRODUCTION: Arriving at a C. difficile infection (CDI) diagnosis, treating patients and dealing with recurrences is not straightforward, but a comprehensive and well-rounded understanding of what is needed to improve patient care is lacking. This manuscript addresses the paucity of multidisciplinary perspectives that consider clinical practice related and healthcare system-related challenges to optimizing care delivery.<br><br>METHODS: We draw on narrative review, consultations with clinical experts and patient representatives, and a survey of 95 clinical and microbiology experts from the UK, France, Italy, Australia and Canada, adding novel multi-method evidence to the knowledge base.<br><br>RESULTS AND DISCUSSION: We examine the patient pathway and variations in clinical practice and identify, synthesize insights on and discuss associated challenges. Examples of key challenges include the need to conduct multiple tests for a conclusive diagnosis, treatment side-effects, the cost of some antibiotics and barriers to access of fecal microbiota transplantation, difficulties in distinguishing recurrence from new infection, workforce capacity constraints to effective monitoring of patients on treatment and of recurrence, and ascertaining whether a patient has been cured. We also identify key opportunities and priorities for improving patient care that target both clinical practice and the wider healthcare system. While there is some variety across surveyed countries' healthcare systems, there is also strong agreement on some priorities. Key improvement actions seen as priorities by at least half of survey respondents in at least three of the five surveyed countries include: developing innovative products for both preventing (Canada, Australia, UK, Italy, and France) and treating (Canada, Australia, and Italy) recurrences; facilitating more multidisciplinary patient care (UK, Australia, and France); updating diagnosis and treatment guidelines (Australia, Canada, and UK); and educating and supporting professionals in primary care (Italy, UK, Canada, and Australia) and those in secondary care who are not CDI experts (Italy, Australia, and France) on identifying symptoms and managing patients. Finally, we discuss key evidence gaps for a future research agenda.}, }
@article {pmid36714101, year = {2022}, author = {Tkach, S and Dorofeyev, A and Kuzenko, I and Falalyeyeva, T and Tsyryuk, O and Kovalchuk, O and Kobyliak, N and Abenavoli, L and Boccuto, L}, title = {Efficacy and safety of fecal microbiota transplantation via colonoscopy as add-on therapy in patients with mild-to-moderate ulcerative colitis: A randomized clinical trial.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1049849}, pmid = {36714101}, issn = {2296-858X}, abstract = {INTRODUCTION: Growing evidence supports the effectiveness of fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), although its effects seem to depend on the method of introduction, the number of procedures, the donor material, and the severity of UC.<br><br>AIM: This study aimed to assess FMT's clinical and microbiological efficacy, tolerability, and safety in patients with mild-to-moderate UC.<br><br>MATERIAL AND METHODS: Patients with mild-to-moderate UC were randomized into two groups. The first group (standard-care, n = 27) was treated with basic therapy-mesalazine-at a daily dose of 3 g (2 g orally + 1 g rectally). In the second group (FMT group, n = 26), while taking mesalazine at the indicated dose, each patient with UC as add-on therapy underwent a single FMT procedure with fresh material delivered by colonoscopy from a healthy donor. The clinical efficacy of treatment in both groups was evaluated after 4 and 8 weeks. The primary outcome was remission of UC, defined as a partial Mayo score &#x2264;2, and decreased fecal calprotectin. All patients underwent bacteriological examination of feces for quantitative microbiota composition changes.<br><br>RESULTS: Clinical response in the form of a significant decrease in stool frequency and a tendency to normalize its consistency after 4 weeks was detected in 14 (51.9%) patients of the standard care group and 16 patients (61.5%) of the FMT group (p = 0.583). The Mayo score in the standard care group was 3.59 &#xb1; 1.21 and in the FMT group-3.15&#xb1;1.04 (p=0.166). After 8 weeks, the main primary endpoint was achieved in 70.4% of the standard-care group patients as compared to 84.6% of participants who received FMT as add-on therapy (p = 0.215). A more pronounced decrease in Mayo score was observed in the FMT group compared to the standard-care group (1.34 &#xb1; 1.44 vs. 2.14 &#xb1; 1.4; p = 0.045). All patients also showed a significant decrease in fecal calprotectin levels, which correlated with clinical data, stool frequency, and clinical remission. An improvement in gut microbiota composition was noted in both groups, albeit it was significantly more pronounced in the FMT group.<br><br>CONCLUSIONS: FTM in patients with mild-to-moderate UC is a well-tolerated, effective, and safe method of treatment in comparison to basic therapy.<br><br>CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT05538026?term=kobyliak&amp;draw=2&amp;rank=4, identifier: NCT05538026.}, }
@article {pmid36713461, year = {2022}, author = {Lou, X and Xue, J and Shao, R and Yang, Y and Ning, D and Mo, C and Wang, F and Chen, G}, title = {Fecal microbiota transplantation and short-chain fatty acids reduce sepsis mortality by remodeling antibiotic-induced gut microbiota disturbances.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1063543}, pmid = {36713461}, issn = {1664-3224}, abstract = {OBJECTIVE: Sepsis is the leading cause of death in critically ill patients. The gastrointestinal tract has long been thought to play an important role in the pathophysiology of sepsis. Antibiotic therapy can reduce a patient's commensal bacterial population and raise their risk of developing subsequent illnesses, where gut microbiota dysbiosis may be a key factor.<br><br>METHODS: In this study, we analyzed the 16S rRNA of fecal samples from both healthy people and patients with sepsis to determine if alterations in gut bacteria are associated with sepsis. Then, we developed a mouse model of sepsis using cecal ligation and puncture (CLP) in order to examine the effects of fecal microbiota transplantation (FMT) and short-chain fatty acids (SCFAs) on survival rate, systemic inflammatory response, gut microbiota, and mucosal barrier function.<br><br>RESULTS: Sepsis patients' gut microbiota composition significantly differed from that of healthy people. At the phylum level, the amount of Proteobacteria in the intestinal flora of sepsis patients was much larger than that of the control group, whereas the number of Firmicutes was significantly lower. Mice with gut microbiota disorders (ANC group) were found to have an elevated risk of death, inflammation, and organ failure as compared to CLP mice. However, all of these could be reversed by FMT and SCFAs. FMT and SCFAs could regulate the abundance of bacteria such as Firmicutes, Proteobacteria, Escherichia Shigella, and Lactobacillus, restoring them to levels comparable to those of healthy mice. In addition, they increased the expression of the Occludin protein in the colon of mice with sepsis, downregulated the expression of the NLRP3 and GSDMD-N proteins, and reduced the release of the inflammatory factors IL-1&#x3b2; and IL-18 to inhibit cell pyroptosis, ultimately playing a protective role in sepsis.<br><br>DISCCUSION: FMT and SCFAs provide a microbe-related survival benefit in a mouse model of sepsis, suggesting that they may be a viable treatment for sepsis.}, }
@article {pmid36713428, year = {2022}, author = {Li, N and Xu, S and Zhang, S and Zhu, Q and Meng, X and An, W and Fu, B and Zhong, M and Yang, Y and Lin, Z and Liu, X and Xia, J and Wang, J and You, T and Yan, C and Tang, H and Zhuang, G and Peng, Z}, title = {MSI2 deficiency in ILC3s attenuates DSS-induced colitis by affecting the intestinal microbiota.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {963379}, pmid = {36713428}, issn = {1664-3224}, abstract = {BACKGROUND: The etiology and pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are generally believed to be related to immune dysfunction and intestinal microbiota disorder. However, the exact mechanism is not yet fully understood. The pathological changes associated with dextran sodium sulfate (DSS)-induced colitis are similar to those in human UC. As a subgroup of the innate immune system, group 3 innate lymphoid cells (ILC3s) are widely distributed in the lamina propria of the intestinal mucosa, and their function can be regulated by a variety of molecules. Musashi2 (MSI2) is a type of evolutionarily conserved RNA-binding protein that maintains the function of various tissue stem cells and is essential for postintestinal epithelial regeneration. The effect of MSI2 deficiency in ILC3s on IBD has not been reported. Thus, mice with conditional MSI2 knockout in ILC3s were used to construct a DSS-induced colitis model and explore its effects on the pathogenesis of IBD and the species, quantity and function of the intestinal microbiota.<br><br>METHODS: Msi2[flox/flox] mice (Msi2[fl/fl]) and Msi2[flox/flox]Rorc[Cre] mice (Msi2[&#x394;Rorc]) were induced by DSS to establish the IBD model. The severity of colitis was evaluated by five measurements: body weight percentage, disease activity index, colon shortening degree, histopathological score and routine blood examination. The species, quantity and function of the intestinal microbiota were characterized by high-throughput 16S rRNA gene sequencing of DNA extracted from fecal samples.<br><br>RESULTS: MSI2 was knocked out in the ILC3s of Msi2[&#x394;Rorc] mice. The Msi2[&#x394;Rorc] mice exhibited reductions in body weight loss, the disease activity index, degree of colon shortening, tissue histopathological score and immune cells in the peripheral blood compared to those of Msi2[fl/fl] mice after DSS administration. The 16S rRNA sequencing results showed that the diversity of the intestinal microbiota in DSS-treated Msi2[&#x394;Rorc] mice changed, with the abundance of Firmicutes increasing and that of Bacteroidetes decreasing. The linear discriminant analysis effect size (LEfSe) approach revealed that Lactobacillaceae could be the key bacteria in the Msi2[&#x394;Rorc] mouse during the improvement of colitis. Using PICRUST2 to predict the function of the intestinal microbiota, it was found that the functions of differential bacteria inferred by modeling were mainly enriched in infectious diseases, immune system and metabolic functions.<br><br>CONCLUSIONS: MSI2 deficiency in ILC3s attenuated DSS-induced colonic inflammation in mice and affected intestinal microbiota diversity, composition, and function, with Lactobacillaceae belonging to the phylum Firmicutes possibly representing the key bacteria. This finding could contribute to our understanding of the pathogenesis of IBD and provide new insights for its clinical diagnosis and treatment.}, }
@article {pmid36713373, year = {2022}, author = {Jiang, L and Yuan, C and Ye, W and Huang, Q and Chen, Z and Wu, W and Qian, L}, title = {Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1061627}, pmid = {36713373}, issn = {1664-3224}, abstract = {INTRODUCTION: Campylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host's innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a central role in resistance to C. jejuni infection have not been explored.<br><br>METHODS: We treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques.<br><br>RESULTS: We first investigated the therapeutic effect of FMT on C. jejuni infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of C.jejuni into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that C.jejuni induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of C. jejuni and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by C. jejuni, with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by C. jejuni.<br><br>DISCUSSION: This is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by C. jejuni and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens.}, }
@article {pmid36713364, year = {2022}, author = {Alam, MZ and Maslanka, JR and Abt, MC}, title = {Immunological consequences of microbiome-based therapeutics.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1046472}, pmid = {36713364}, issn = {1664-3224}, abstract = {The complex network of microscopic organisms living on and within humans, collectively referred to as the microbiome, produce wide array of biologically active molecules that shape our health. Disruption of the microbiome is associated with susceptibility to a range of diseases such as cancer, diabetes, allergy, obesity, and infection. A new series of next-generation microbiome-based therapies are being developed to treat these diseases by transplanting bacteria or bacterial-derived byproducts into a diseased individual to reset the recipient's microbiome and restore health. Microbiome transplantation therapy is still in its early stages of being a routine treatment option and, with a few notable exceptions, has had limited success in clinical trials. In this review, we highlight the successes and challenges of implementing these therapies to treat disease with a focus on interactions between the immune system and microbiome-based therapeutics. The immune activation status of the microbiome transplant recipient prior to transplantation has an important role in supporting bacterial engraftment. Following engraftment, microbiome transplant derived signals can modulate immune function to ameliorate disease. As novel microbiome-based therapeutics are developed, consideration of how the transplants will interact with the immune system will be a key factor in determining whether the microbiome-based transplant elicits its intended therapeutic effect.}, }
@article {pmid36713166, year = {2022}, author = {Singh, V and Lee, G and Son, H and Koh, H and Kim, ES and Unno, T and Shin, JH}, title = {Butyrate producers, "The Sentinel of Gut": Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1103836}, pmid = {36713166}, issn = {1664-302X}, abstract = {Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most butyrate producers belong to the Clostridium cluster of the phylum Firmicutes, such as Faecalibacterium, Roseburia, Eubacterium, Anaerostipes, Coprococcus, Subdoligranulum, and Anaerobutyricum. They metabolize carbohydrates via the butyryl-CoA: acetate CoA-transferase pathway and butyrate kinase terminal enzymes to produce most of butyrate. Although, in minor fractions, amino acids can also be utilized to generate butyrate via glutamate and lysine pathways. Butyrogenic microbes play a vital role in various gut-associated metabolisms. Butyrate is used by colonocytes to generate energy, stabilizes hypoxia-inducible factor to maintain the anaerobic environment in the gut, maintains gut barrier integrity by regulating Claudin-1 and synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), and inhibits oncogenic pathways (Akt/ERK, Wnt, and TGF-β signaling). Colonic butyrate producers shape the gut microbial community by secreting various anti-microbial substances, such as cathelicidins, reuterin, and β-defensin-1, and maintain gut homeostasis by releasing anti-inflammatory molecules, such as IgA, vitamin B, and microbial anti-inflammatory molecules. Additionally, butyrate producers, such as Roseburia, produce anti-carcinogenic metabolites, such as shikimic acid and a precursor of conjugated linoleic acid. In this review, we summarized the significance of butyrate, critically examined the role and relevance of butyrate producers, and contextualized their importance as microbial therapeutics.}, }
@article {pmid36713033, year = {2023}, author = {Li, R and Liu, R and Chen, L and Wang, G and Qin, L and Yu, Z and Wan, Z}, title = {Microbiota from Exercise Mice Counteracts High-Fat High-Cholesterol Diet-Induced Cognitive Impairment in C57BL/6 Mice.}, journal = {Oxidative medicine and cellular longevity}, volume = {2023}, number = {}, pages = {2766250}, pmid = {36713033}, issn = {1942-0994}, abstract = {Gut microbes may be the critical mediators for the cognitive enhancing effects of exercise. Via fecal microbiota transplantation (FMT), this study is aimed at determining the mechanism of how voluntary exercise improved learning and memory ability impairment post a high-fat, high-cholesterol (HFHC) diet. The learning and memory abilities assessed via the Morris water maze in the FMT recipient group of voluntary exercising mice were improved compared to sedentary group. 16S rRNA gene sequencing results indicated that exercise-induced changes in gut microbiota distribution were transmissible, mainly in terms of elevated Lactobacillus, Lactobacillus, and Eubacterium nodatum, as well as decreased Clostrida_UCG-014 and Akkermansia after FMT. The neuroprotective effects of FMT were mainly related to the improved insulin signaling pathway (IRS2/PI3K/AKT) and mitochondrial function; inhibition of AQP4; decreased p-Tau at serine 396 and 404; increased BDNF, PSD95, and synaptophysin in the hippocampus; and also decreased HDAC2 and HDAC3 protein expressions in the nuclear and cytoplasmic fractions of the hippocampus. The findings of qRT-PCR suggested that exercise-induced gut microbes, on the one hand, elevated GPR109A and decreased GPR43 and TNF-α in the hippocampus. On the other hand, it increased GPR109A and GPR41 expressions in the proximal colon tissue. In addition, total short-chain fatty acid (SCFA), acetic acid, propionic acid, isobutyric acid, valeric acid, and isovaleric acid contents were also elevated in the cecum. In conclusion, exercise-induced alterations in gut microbiota play a decisive role in ameliorating HFHC diet-induced cognitive deficits. FMT treatment may be a new considerable direction in ameliorating cognitive impairment induced by exposure to HFHC diet.}, }
@article {pmid36710337, year = {2023}, author = {Tian, F and Li, Y and Wang, Y and Yu, B and Song, J and Ning, Q and Jian, C and Ni, M}, title = {Risk factors and molecular epidemiology of fecal carriage of carbapenem resistant Enterobacteriaceae in patients with liver disease.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {22}, number = {1}, pages = {10}, pmid = {36710337}, issn = {1476-0711}, abstract = {BACKGROUND: Carbapenem resistant Enterobacteriaceae (CRE) colonization is a risk factor for CRE infection. CRE infection results in an increase in mortality in patients with cirrhosis. However, minimal data regarding the prevalence and the risk factors of CRE colonization in patients with liver disease yet without liver transplantation are available. The present study aimed to investigate the prevalence, risk factors and molecular epidemiology characteristics of CRE fecal carriage among patients with liver disease.<br><br>METHODS: Stool specimens from 574 adult inpatients with liver disease were collected from December 2020 to April 2021. CRE were screened using selective chromogenic agar medium and identified by the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the broth microdilution method. Carbapenemase genes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Multilocus sequence typing (MLST) was performed for Carbapenem Resistant Klebsiella pneumoniae (CR-KPN) isolates and Carbapenem Resistant Escherichia Coli (CR-ECO) isolates.<br><br>RESULTS: The total number of stool specimens (732) were collected from 574 patients with liver disease. 43 non-duplicated CRE strains were isolated from 39 patients with a carriage rate of 6.79% (39/574). The carriage rate was 15.60% (17/109) in patients with acute-on-chronic liver failure (ACLF). Multivariate analysis indicated that ACLF (P&#x2009;=&#x2009;0.018), the history of pulmonary infection within past 3&#xa0;months (P&#x2009;=&#x2009;0.001) and the use of third generation cephalosporin/&#x3b2;-lactamases inhibitor within past 3&#xa0;months (P&#x2009;=&#x2009;0.000) were independent risk factors of CRE colonization in patients with liver disease. Klebsiella Pnuemoniae (KPN) (51.28%) and Escherichia coli (ECO) (30.77%) were main strains in these patients. All CRE strains showed high resistance to most antimicrobials except for polymyxin B and tigecycline. Most (83.72%, 36/43) of the CRE carried carbapenemase genes. blaKPC-2 was the major carbapenemase gene. The molecular epidemiology of KPN were dominated by ST11, while the STs of ECO were scattered.<br><br>CONCLUSIONS: The present study revealed that CRE fecal carriage rates were higher in patients with ACLF than in patients without liver failure. ACLF, the history of pulmonary infection within past 3&#xa0;months and the use of third generation cephalosporin/&#x3b2;-lactamases inhibitor within past 3&#xa0;months were independent risk factors of CRE colonization in patients with liver disease. Regular CRE screening for hospitalized patients with liver disease should be conducted to limit the spread of CRE strain.}, }
@article {pmid36710269, year = {2023}, author = {Zhao, Q and Yu, J and Zhou, H and Wang, X and Zhang, C and Hu, J and Hu, Y and Zheng, H and Zeng, F and Yue, C and Gu, L and Wang, Z and Zhao, F and Zhou, P and Zhang, H and Huang, N and Wu, W and Zhou, Y and Li, J}, title = {Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {40}, pmid = {36710269}, issn = {2059-3635}, abstract = {The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis. We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota. We performed co-housing and fecal microbial transplantation (FMT) experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms, including increasing the infiltration and differentiation of Th17, and increased the abundance of Prevotella, while decreasing that of Parabacteroides distasonis, in the colon. These alterations affected fatty acid metabolism, increasing the abundance of oleic and stearic acids. Meanwhile, gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod (IMQ)-induced psoriasis-like mice. Indeed, administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo, as well as increased the secretion of IL-23 by stimulating DCs in vitro. At last, we found that, treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota, including the decrease of Prevotella and increase of Parabacteroides distasonis. Overall, our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice, suggesting a new target for the clinical diagnosis and treatment of psoriasis.}, }
@article {pmid36706918, year = {2023}, author = {Lu, T and Li, Q and Lin, W and Zhao, X and Li, F and Ji, J and Zhang, Y and Xu, N}, title = {Gut microbiota-derived glutamine attenuates liver ischemia/reperfusion injury via macrophage metabolic reprogramming.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcmgh.2023.01.004}, pmid = {36706918}, issn = {2352-345X}, abstract = {OBJECTIVE &amp; AIMS: Many studies have revealed crucial roles of the gut microbiota and its metabolites in liver disease progression. However, the mechanism underlying their effects on liver ischemia/reperfusion (I/R) injury remain largely unknown. Here, we investigate the function of gut microbiota and its metabolites in liver I/R injury.<br><br>METHODS: C57BL/6 mice was pretreated with an antibiotic cocktail. Then, we used multi-omics detection methods including 16s rRNA sequencing, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) to explore the changes of gut microbiota and metabolites both in feces and portal blood in order to reveal the mechanism of their protective effect in liver I/R injury.<br><br>RESULTS: We found that antibiotic pretreatment (ABX) could significantly reduce the severity of I/R-induced hepatic injury, and this effect could be transferred to germ-free (GF) mice by fecal microbiota transplantation (FMT), suggesting a protective role of the gut microbiota depletion. During I/R, the rates of serum &#x3b1;-ketoglutarate (aKG) production and glutamate reduction, downstream products of gut microbiota-derived glutamine were more significant in the ABX mice. Then, we showed that aKG could promote alternative (M2) macrophage activation through oxidative phosphorylation (OXPHOS) and Oligomycin A could inhibit M2 macrophage polarization and reversed this protective effect.<br><br>CONCLUSIONS: These findings show that the gut microbiota and its metabolites play critical roles in hepatic I/R injury by modulating macrophage metabolic reprogramming. Potential therapies that target macrophage metabolism, including antibiotic therapies and novel immunometabolism modulators can be exploited for the treatment of liver I/R injury.}, }
@article {pmid36704100, year = {2022}, author = {Wu, Z and Zhang, B and Chen, F and Xia, R and Zhu, D and Chen, B and Lin, A and Zheng, C and Hou, D and Li, X and Zhang, S and Chen, Y and Hou, K}, title = {Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: A randomized, controlled, prospective study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1089991}, pmid = {36704100}, issn = {2235-2988}, abstract = {OBJECTIVES: Recent studies have shown that fecal microbiota transplantation (FMT) improved the metabolic profiles of patients with type 2 diabetes mellitus (T2DM), yet the effectiveness in reversing insulin resistance and increasing metformin sensitivity in T2DM patients have not been reported. In this study, we evaluated the improvements of T2DM patients and their gut microbiota by FMT alone and FMT plus metformin.<br><br>METHODS: A total of 31 patients with newly diagnosed T2DM were randomized to intervention by metformin, FMT, or FMT plus metformin in the study. Patients were followed up at baseline and week 4 after treatment. Blood and stool samples were collected and subject to analyze clinical parameters and microbial communities by metagenomic sequencing, respectively.<br><br>RESULTS: FMT alone and FMT plus metformin significantly improved the clinical indicators HOMA-IR and BMI in T2DM, besides fasting blood glucose, postprandial blood glucose, and hemoglobin A1c that were also controlled by metformin. Donor microbiota effectively colonized in T2DM with slightly higher colonization ration in FMT than FMT plus metformin within 4 weeks, resulting in increased microbial diversity and community changes from baseline after treatment. A total of 227 species and 441 species were significantly alerted after FMT and FMT plus metformin, respectively. FMT were significantly associated with the clinical parameters. Among them, Chlorobium phaeovibrioides, Bifidibacterium adolescentis and Synechococcus sp.WH8103 were potential due to their significantly negative correlations with HOMA-IR.<br><br>CONCLUSIONS: FMT with or without metformin significantly improve insulin resistance and body mass index and gut microbial communities of T2DM patients by colonization of donor-derived microbiota.}, }
@article {pmid36701104, year = {2023}, author = {Fan, L and Zeng, X and Xu, G}, title = {Metformin Regulates Gut Microbiota Abundance to Suppress M2 Skewing of Macrophages and Colorectal Tumorigenesis in Mice.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {}, number = {}, pages = {}, pmid = {36701104}, issn = {1976-3794}, abstract = {The correlation of imbalanced gut microbiota with the onset and progression of colorectal cancer (CRC) has become clear. This work investigates the effect of metformin on gut microbiota and genesis of CRC in mice. Human fecal samples were collected from healthy control (HC) donors and CRC patients. Compared to HC donors, CRC patients had reduced abundance of gut microbiota; however, they had increased abundance of detrimental Bacteroidetes. Mice were injected with azomethane (AOM) to induce colorectal tumorigenesis models. Treatment of CRC patients-sourced fecal microbiota promoted tumorigenesis, and it increased the expression of Ki67, β-catenin, COX-2, and Cyclin D1 in mouse colon tissues. Further treatment of metformin blocked the colorectal tumorigenesis in mice. Fecal microbiota from the metformin-treated mice was collected, which showed decreased Bacteroidetes abundance and suppressed AOM-induced colorectal tumorigenesis in mice as well. Moreover, the metformin- modified microbiota promoted the M1 macrophage-related markers IL-6 and iNOS but suppressed the M2 macrophage-related markers IL-4R and Arg1 in mouse colon tissues. In conclusion, this study suggests that metformin-mediated gut microbiota alteration suppresses macrophage M2 polarization to block colorectal tumorigenesis.}, }
@article {pmid36700221, year = {2022}, author = {Chen, L and Ruan, G and Cheng, Y and Yi, A and Chen, D and Wei, Y}, title = {The role of Th17 cells in inflammatory bowel disease and the research progress.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1055914}, pmid = {36700221}, issn = {1664-3224}, abstract = {Th17 cells play an important role in the abnormal immune response in inflammatory bowel disease (IBD) and are involved in the development and progression of inflammation and fibrosis. An increasing amount of data has shown that gut microbes are important parts of intestinal immunity and regulators of Th17 cellular immunity. Th17 cell differentiation is regulated by intestinal bacteria and cytokines, and Th17 cells regulate the intestinal mucosal immune microenvironment by secreting cytokines, such as IL-17, IL-21, and IL-26. Solid evidence showed that, regarding the treatment of IBD by targeting Th17 cells, the therapeutic effect of different biological agents varies greatly. Fecal bacteria transplantation (FMT) in the treatment of IBD has been a popular research topic in recent years and is safe and effective with few side effects. To further understand the role of Th17 cells in the progression of IBD and associated therapeutic prospects, this review will discuss the progress of related research on Th17 cells in IBD by focusing on the interaction and immune regulation between Th17 cells and gut microbiota.}, }
@article {pmid36698844, year = {2022}, author = {Chopra, T and Hecht, G and Tillotson, G}, title = {Gut microbiota and microbiota-based therapies for Clostridioides difficile infection.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1093329}, pmid = {36698844}, issn = {2296-858X}, abstract = {Clostridioides difficile infection poses significant clinical challenges due to its recurrent nature. Current antibiotic management does not address the underlying issue, that of a disturbed gastrointestinal microbiome, called dysbiosis. This provides a supportive environment for the germination of C. difficile spores which lead to infection and toxin production as well as an array of other health conditions. The use of microbiome restoration therapies such as live biotherapeutics can reverse dysbiosis and lead to good clinical outcomes. Several such therapies are under clinical investigation.}, }
@article {pmid36693853, year = {2023}, author = {Chadchan, SB and Naik, SK and Popli, P and Talwar, C and Putluri, S and Ambati, CR and Lint, MA and Kau, AL and Stallings, CL and Kommagani, R}, title = {Gut microbiota and microbiota-derived metabolites promotes endometriosis.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {28}, pmid = {36693853}, issn = {2058-7716}, abstract = {Endometriosis is a pathological condition of the female reproductive tract characterized by the existence of endometrium-like tissue at ectopic sites, affecting 10% of women between the age 15 and 49 in the USA. However, currently there is no reliable non-invasive method to detect the presence of endometriosis without surgery and many women find hormonal therapy and surgery as ineffective in avoiding the recurrences. There is a lack of knowledge on the etiology and the factors that contribute to the development of endometriosis. A growing body of recent evidence suggests an association between gut microbiota and endometriosis pathophysiology. However, the direct impact of microbiota and microbiota-derived metabolites on the endometriosis disease progression is largely unknown. To understand the causal role of gut microbiota and endometriosis, we have implemented a novel model using antibiotic-induced microbiota-depleted (MD) mice to investigate the endometriosis disease progression. Interestingly, we found that MD mice showed reduced endometriotic lesion growth and, the transplantation of gut microbiota by oral gavage of feces from mice with endometriosis rescued the endometriotic lesion growth. Additionally, using germ-free donor mice, we indicated that the uterine microbiota is dispensable for endometriotic lesion growth in mice. Furthermore, we showed that gut microbiota modulates immune cell populations in the peritoneum of lesions-bearing mice. Finally, we found a novel signature of microbiota-derived metabolites that were significantly altered in feces of mice with endometriosis. Finally, we found one the altered metabolite, quinic acid promoted the survival of endometriotic epithelial cells in vitro and lesion growth in vivo, suggesting the disease-promoting potential of microbiota-derived metabolites. In summary, these data suggest that gut microbiota and microbiota-derived metabolome contribute to lesion growth in mice, possibly through immune cell adaptations. Of translational significance, these findings will aid in designing non-invasive diagnostics using stool metabolites for endometriosis.}, }
@article {pmid36693599, year = {2023}, author = {Hou, Q and Huang, J and Zhao, L and Pan, X and Liao, C and Jiang, Q and Lei, J and Guo, F and Cui, J and Guo, Y and Zhang, B}, title = {Dietary genistein increases microbiota-derived short chain fatty acid levels, modulates homeostasis of the aging gut, and extends healthspan and lifespan.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106676}, doi = {10.1016/j.phrs.2023.106676}, pmid = {36693599}, issn = {1096-1186}, abstract = {Age-related gastrointestinal decline contributes to whole-organism frailty and mortality. Genistein is known to have beneficial effects on age-related diseases, but its precise role in homeostasis of the aging gut remains to be elucidated. Here, wild-type aging mice and Zmpste24[-/-] progeroid mice were used to investigate the role of genistein in lifespan and homeostasis of the aging gut in mammals. A series of longitudinal, clinically relevant measurements were performed to evaluate the effect of genistein on healthspan. It was found that dietary genistein promoted a healthier and longer life and was associated with a decrease in the levels of systemic inflammatory cytokines in aging mice. Furthermore, dietary genistein ameliorated gut dysfunctions, such as intestinal inflammation, leaky gut, and impaired epithelial regeneration. A distinct genistein-mediated alteration in gut microbiota was observed by increasing Lachnospira abundance and short-chain fatty acid (SCFA) production. Further fecal microbiota transplantation and dirty cage sharing experiments indicated that the gut microbiota from genistein-fed mice rejuvenated the aging gut and extended the lifespan of progeroid mice. It was demonstrated that genistein-associated SCFAs alleviated tumor necrosis factor alpha-induced intestinal organoid damage. Moreover, genistein-associated propionate promoted regulatory T cell-derived interleukin 10 production, which alleviated macrophage-derived inflammation. This study provided the first data, to the authors' knowledge, indicating that dietary genistein modulates homeostasis in the aging gut and extends the healthspan and lifespan of aging mammals. Moreover, the existence of a link between genistein and the gut microbiota provides a rationale for dietary interventions against age-associated frailty.}, }
@article {pmid36692308, year = {2023}, author = {Pensinger, DA and Fisher, AT and Dobrila, HA and Van Treuren, W and Gardner, JO and Higginbottom, SK and Carter, MM and Schumann, B and Bertozzi, CR and Anikst, V and Martin, C and Robilotti, EV and Chow, JM and Buck, RH and Tompkins, LS and Sonnenburg, JL and Hryckowian, AJ}, title = {Butyrate Differentiates Permissiveness to Clostridioides difficile Infection and Influences Growth of Diverse C. difficile Isolates.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0057022}, doi = {10.1128/iai.00570-22}, pmid = {36692308}, issn = {1098-5522}, abstract = {A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome is short-chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known to decrease the fitness of C. difficile in vitro, and high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI than in those from healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. IMPORTANCE Clostridioides difficile is a leading cause of infectious diarrhea in humans, and it imposes a tremendous burden on the health care system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI, but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.}, }
@article {pmid36678325, year = {2023}, author = {Daskova, N and Heczkova, M and Modos, I and Hradecky, J and Hudcovic, T and Kuzma, M and Pelantova, H and Buskova, I and Sticova, E and Funda, D and Golias, J and Drabonova, B and Jarkovska, J and Kralova, M and Cibulkova, I and Gojda, J and Cahova, M}, title = {Protective Effect of Vegan Microbiota on Liver Steatosis Is Conveyed by Dietary Fiber: Implications for Fecal Microbiota Transfer Therapy.}, journal = {Nutrients}, volume = {15}, number = {2}, pages = {}, pmid = {36678325}, issn = {2072-6643}, mesh = {Mice ; Animals ; Humans ; Fecal Microbiota Transplantation ; Vegans ; Inulin/pharmacology ; Dietary Fiber/pharmacology ; *Fatty Liver/prevention &amp; control/drug therapy ; *Gastrointestinal Microbiome ; Diet, Western ; Glucose/pharmacology ; }, abstract = {Fecal microbiota transfer may serve as a therapeutic tool for treating obesity and related disorders but currently, there is no consensus regarding the optimal donor characteristics. We studied how microbiota from vegan donors, who exhibit a low incidence of non-communicable diseases, impact on metabolic effects of an obesogenic diet and the potential role of dietary inulin in mediating these effects. Ex-germ-free animals were colonized with human vegan microbiota and fed a standard or Western-type diet (WD) with or without inulin supplementation. Despite the colonization with vegan microbiota, WD induced excessive weight gain, impaired glucose metabolism, insulin resistance, and liver steatosis. However, supplementation with inulin reversed steatosis and improved glucose homeostasis. In contrast, inulin did not affect WD-induced metabolic changes in non-humanized conventional mice. In vegan microbiota-colonized mice, inulin supplementation resulted in a significant change in gut microbiota composition and its metabolic performance, inducing the shift from proteolytic towards saccharolytic fermentation (decrease of sulfur-containing compounds, increase of SCFA). We found that (i) vegan microbiota alone does not protect against adverse effects of WD; and (ii) supplementation with inulin reversed steatosis and normalized glucose metabolism. This phenomenon is associated with the shift in microbiota composition and accentuation of saccharolytic fermentation at the expense of proteolytic fermentation.}, }
@article {pmid36689162, year = {2023}, author = {Lin, MC and Peng, ZY and Chou, HC and Tsai, YT and Wei, YS and Wang, YS and Wang, YL and Chang, SJ and Chan, HL}, title = {Fecal Protein Analysis of Dusp6 Knockout C57BL/6J Mice by Metaproteomics.}, journal = {Applied biochemistry and biotechnology}, volume = {}, number = {}, pages = {}, pmid = {36689162}, issn = {1559-0291}, abstract = {The research of obesity and gut microbiota has been carried out for years, yet the study process was in a slow pace for several challenges to conquer. As a complex status of disorder, the contributing factors refer to gut microbiota about obesity were controversial in a wide range. In terms of proteomics, 2D-DIGE technology is a powerful method for this study to identify fecal proteins from lean microbiota in Dusp6 knockout C57BL/6J mice, exploring the protein markers of the ability resisting to diet-induced obesity (DIO) transferred to the host mice after fecal microbiota transplantation. The results showed that the fecal microbiota expressed 289 proteins differentially with 23 proteins identified, which were considered to be the reasons to assist the microbiota exhibiting distinct behavior. By means of proteomics technology, we had found that differentially expressed proteins of lean microbiota determined the lean microbial behavior might be able to resist leaky gut. To sum up our study, the proteomics strategies offered as a tool to demonstrate and analyze the features of lean microbiota, providing new speculations in the behavior about the gut microbiota reacting to DIO.}, }
@article {pmid36689003, year = {2023}, author = {Rajindrajith, S and Devanarayana, NM and Thapar, N and Benninga, MA}, title = {Myths and misconceptions about childhood constipation.}, journal = {European journal of pediatrics}, volume = {}, number = {}, pages = {}, pmid = {36689003}, issn = {1432-1076}, abstract = {Many widely held beliefs and assumptions concerning childhood constipation continue to interfere with rational management of childhood constipation. Although many still believe that constipation is not a common disease, about 9.5% of the world's children suffer from chronic constipation. Most of these children live in non-Western countries. There are major misconceptions about the etiology of constipation as a significant proportion of clinicians still believe that constipation is caused by some form an organic pathology, whereas in reality, the majority have functional constipation. Contrary to a commonly held belief that children outgrow constipation without long-term problems, there is evidence that constipation leads to significant bowel and psychological consequences and has a major impact on the quality of life which detrimentally affects future health and education. Finally, ineffective management strategies such as increasing fiber and water in the diet, and short duration of treatment owing to the fear that long-term laxative treatment leads to colonic dysfunction, interfere with effective therapeutic strategies. Conclusions: It is apparent that myths and misconception often lead to wrong assumptions regarding the distribution of the disease, its etiology, pathophysiology, and management leading to ordering incorrect investigations and ineffective therapeutic strategies while spending large sums of public funds unnecessarily. Poorly treated constipation leads to deleterious psychological consequences predisposing children to develop significant psychological damage and bowel dysfunctions. This review aims to challenge these myths about various elements of constipation by exploring the existing literature and encouraging clinicians to have a fresh look at old concepts that could interfere with the well-being of children with constipation. What is Known: • Childhood constipation is a growing problem in the world leading to significant suffering and high healthcare expenditure • Myths and misconceptions lead to poor management strategies causing psychological and bowel damage What is New: • Organic, systemic, and bowel disorders leading to constipation are uncommon, and in the majority, it arises due to deliberate fecal withholding and most investigations ordered by clinicians are not very helpful in the management • Most non-pharmacological interventions are not effective in the day-to-day management of childhood constipation. The use of laxatives is considered to be the first-line management strategy.}, }
@article {pmid36688695, year = {2023}, author = {Pan, J and Chui, L and Liu, T and Zheng, Q and Liu, X and Liu, L and Zhao, Y and Zhang, L and Song, M and Han, J and Huang, J and Tang, C and Tao, C and Zhao, J and Wang, Y}, title = {Fecal Microbiota Was Reshaped in UCP1 Knock-In Pigs via the Adipose-Liver-Gut Axis and Contributed to Less Fat Deposition.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0354022}, doi = {10.1128/spectrum.03540-22}, pmid = {36688695}, issn = {2165-0497}, abstract = {The relationship between the host gut microbiota and obesity has been well documented in humans and mice; however, few studies reported the association between the gut microbiota and fat deposition in pigs. In a previous study, we generated uncoupling protein 1 (UCP1) knock-in pigs (UCP1 pigs), which exhibited a lower fat deposition phenotype. Whether the gut microbiota was reshaped in these pigs and whether the reshaped gut microbiota contributes to the lower fat content remain unknown. Here, we revealed that the fecal microbiota composition and metabolites were significantly altered under both chow diet (CD) and high-fat/high-cholesterol (HFHC) diet conditions in UCP1 pigs compared to those in wild-type (WT) pigs. The abundance of Oscillospira and Coprococcus and the level of metabolite hyodeoxycholic acid (HDCA) from feces were observed to be significantly increased in UCP1 pigs. An association analysis revealed that Oscillospira and Coprococcus were significantly negatively related to backfat thickness. In addition, after fecal microbiota transplantation (FMT), the mice that were orally gavaged with feces from UCP1 pigs exhibited less fat deposition under both CD and high-fat diet (HFD) conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Consistently, HDCA-treated mice also exhibited reduced fat content. Mechanistically, we found that UCP1 expression in white adipose tissue alters the gut microbiota via the adipose-liver-gut axis in pigs. Our study provides new data concerning the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolites in the regulation of fat deposition in pigs. IMPORTANCE This article investigated the effect of the ectopic expression of UCP1 on the regulation of fecal microbiota composition and metabolites and which alters the fat deposition phenotype. Bacteria, including Oscillospira and Coprococcus, and the metabolite HDCA were found to be significantly increased in feces of UCP1 pigs and had a negative relationship with backfat thickness. Mice with fecal microbiota transplantation phenocopied the UCP1 pigs under both CD and HFD conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Our study provides new data regarding the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolic production in the regulation of fat deposition in pigs.}, }
@article {pmid36688692, year = {2023}, author = {Strahm, N and Didriksen, H and Fretheim, H and Molberg, &#xd8; and Midtvedt, &#xd8; and Farstad, IN and Midtvedt, T and Lundin, KEA and Aabakken, L and Błyszczuk, P and Distler, O and Kania, G and Hoffmann-Vold, AM}, title = {Effects of faecal microbiota transplantation on small intestinal mucosa in systemic sclerosis.}, journal = {Rheumatology (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/rheumatology/kead014}, pmid = {36688692}, issn = {1462-0332}, abstract = {OBJECTIVES: In systemic sclerosis (SSc), gastrointestinal tract (GIT) involvement is a major concern, with no disease-modifying and limited symptomatic therapies available. Faecal microbiota transplantation (FMT) represents a new therapeutic option for GIT-affliction in SSc, showing clinical promise in a recent controlled pilot trial. Here, we aim to investigate effects of FMT on duodenal biopsies collected from SSc patients by immunohistochemistry and transcriptome profiling.<br><br>METHODS: We analysed duodenal biopsies obtained pre- (week 0) and post-intervention (weeks 2 and 16) from nine SSc patients receiving intestinal infusion of FMT (n&#x2009;=&#x2009;5) or placebo (n&#x2009;=&#x2009;4). The analysis included immunohistochemistry (IHC) with a selected immune function and fibrosis markers, and whole biopsy transcriptome profiling.<br><br>RESULTS: In patients receiving FMT, the number of podoplanin and CD64-expressing cells in the mucosa were lower at week 2 compared to baseline. This decline in podoplanin- (r&#x2009;=&#x2009;0.94) and CD64-positive (r&#x2009;=&#x2009;0.89) cells correlated with improved patient-reported lower GIT symptoms. Whole biopsy transcriptome profiling from week 2 showed significant enrichment of pathways critical for cellular and endoplasmic reticulum stress responses, microvillus and secretory vesicles, vascular and sodium-dependent transport, and circadian rhythm. At week 16, we found enrichment of pathways mandatory for binding activity of immunoglobulin receptors, T-cell receptor complex, and chemokine receptor, as well as response to zinc-ions. We found that 25 genes, including Matrix metalloproteinase-1 were upregulated at both week 2 and week 16.<br><br>CONCLUSION: Combining selective IHC and unbiased gene expression analyses, this exploratory study highlights the potential for disease-relevant organ effects of FMT in SSc patients with GIT involvement.}, }
@article {pmid36687192, year = {2023}, author = {Aydin, OC and Aydın, S and Barun, S}, title = {Role of natural products and intestinal flora on type 2 diabetes mellitus treatment.}, journal = {World journal of clinical cases}, volume = {11}, number = {1}, pages = {65-72}, pmid = {36687192}, issn = {2307-8960}, abstract = {Diabetes mellitus (DM) is a complicated, globally expanding disease that is influenced by hereditary and environmental variables. Changes in modern society's food choices, physical inactivity, and obesity are significant factors in the development of type 2 DM (T2DM). The association between changes in intestinal flora and numerous disorders, including obesity, diabetes, and cardiovascular diseases, has been studied in recent years. The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients' intestinal flora, as well as their therapeutic choices. Also included is a summary of the anti-diabetic benefits of natural compounds demonstrated by studies. The short-chain fatty acids theory, the bile acid theory, and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM. Due to an intestinal flora imbalance, abnormalities in short-chain fatty acids and secondary bile acids have been found in diabetic patients. Additionally, metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation. The agenda for diabetes treatment includes the use of short-chain fatty acids, probiotics, prebiotics in the diet, fecal bacteria transplantation, and antibiotics. Animal studies have proven the antidiabetic benefits of numerous bioactive substances, including Flavonoids, Alkaloids, Saponin, and Allicin. However, further research is required to contribute to the treatment of diabetes.}, }
@article {pmid36687179, year = {2023}, author = {Yan, XX and Wu, D}, title = {Intestinal microecology-based treatment for inflammatory bowel disease: Progress and prospects.}, journal = {World journal of clinical cases}, volume = {11}, number = {1}, pages = {47-56}, pmid = {36687179}, issn = {2307-8960}, abstract = {Inflammatory bowel disease (IBD) is a chronic, recurrent, and debilitating disorder, and includes Crohn's disease and ulcerative colitis. The pathogenesis of IBD is closely associated with intestinal dysbiosis, but has not yet been fully clarified. Genetic and environmental factors can influence IBD patients' gut microbiota and metabolism, disrupt intestinal barriers, and trigger abnormal immune responses. Studies have reported the alteration of gut microbiota and metabolites in IBD, providing the basis for potential therapeutic options. Intestinal microbiota-based treatments such as pre/probiotics, metabolite supplementation, and fecal microbiota transplantation have been extensively studied, but their clinical efficacy remains controversial. Repairing the intestinal barrier and promoting mucosal healing have also been proposed. We here review the current clinical trials on intestinal microecology and discuss the prospect of research and practice in this field.}, }
@article {pmid36686492, year = {2022}, author = {Wang, G and Wang, Y and Bai, J and Li, G and Liu, Y and Deng, S and Zhou, R and Tao, K and Xia, Z}, title = {Increased plasma genistein after bariatric surgery could promote remission of NAFLD in patients with obesity.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1024769}, pmid = {36686492}, issn = {1664-2392}, abstract = {BACKGROUND: Bariatric surgery is associated with a positive effect on the progress of non-alcoholic associated fatty liver disease (NAFLD). Although weight loss is the obvious mechanism, there are also weight-independent mechanisms.<br><br>METHODS: We collected blood samples from 5 patients with obesity before and 3 months after surgery and performed an LC-MS-based untargeted metabolomics test to detect potential systemic changes. We also constructed sleeve gastrectomy (SG) mice models. The plasma, liver and intestine samples were collected and analyzed by qPCR, ELISA and HPLC. Cohousing experiments and feces transplantation experiments were performed on mice to study the effect of gut microbiota. Genistein administration experiments were used to study the in vivo function of the metabolites.<br><br>RESULTS: Plasma genistein (GE) was identified to be elevated after surgery. Both clinical data and rodent models suggested that plasma GE is negatively related to the degree of NAFLD. We fed diet-induced obese (DIO) mice with GE, and we found that there was significant remission of NAFLD. Both in vivo and in vitro experiments showed that GE could restrict the inflammation state in the liver and thus relieve NAFLD. Finally, we used co-housing experiments to alter the gut microbiota in mice, and it was identified that sleeve gastrectomy (SG) mice had a special gut microbiota phenotype, which could result in higher plasma GE levels. By feces transplantation experiment (FMT), we found that only feces from the SG mice (and not from other lean mice) could induce higher plasma GE levels.<br><br>CONCLUSION: Our studies showed that SG but not calorie restriction could induce higher plasma GE levels by altering the gut microbiota. This change could promote NAFLD remission. Our study provides new insights into the systemic effects of bariatric surgery. Bariatric surgery could affect remote organs via altered metabolites from the gut microbiota. Our study also identified that additional supplement of GE after surgery could be a therapy for NAFLD.}, }
@article {pmid36685764, year = {2022}, author = {Minuti, A and Brufani, F and Menculini, G and Moretti, P and Tortorella, A}, title = {The complex relationship between gut microbiota dysregulation and mood disorders: A narrative review.}, journal = {Current research in neurobiology}, volume = {3}, number = {}, pages = {100044}, pmid = {36685764}, issn = {2665-945X}, abstract = {Gut microbiota regulates neurotransmission, neurogenesis, neuroinflammation, and neuroendocrine signaling. The aim of the present review is to analyze the literature concerning gut microbiota dysregulation and mood symptoms, with the specific hypothesis that such alterations play a role in the onset of mood disorders. Here, in fact, we review recent research focusing on how gut microbiota dysregulation influences the onset of mood disorders and on possible pathophysiological mechanisms involved in this interaction. We pay specific attention to the relationship between gut microbiota dysregulation and inflammatory state, Th17 differentiation, neuroactive factors, and TRP metabolism. The association between gut microbiota dysregulation and mood disorders is critically analyzed under a clinical point of view, also focusing on the emergence of mood symptoms in the context of medical conditions. These latter correlations may enable an interdisciplinary perspective in the clinical approach to such symptoms, as well as new treatment strategies, such as nutritional interventions, psychobiotics, antibiotics, as well as fecal microbiota transplantation.}, }
@article {pmid36683718, year = {2023}, author = {Senchukova, MA}, title = {Microbiota of the gastrointestinal tract: Friend or foe?.}, journal = {World journal of gastroenterology}, volume = {29}, number = {1}, pages = {19-42}, pmid = {36683718}, issn = {2219-2840}, abstract = {The gut microbiota is currently considered an external organ of the human body that provides important mechanisms of metabolic regulation and protection. The gut microbiota encodes over 3 million genes, which is approximately 150 times more than the total number of genes present in the human genome. Changes in the qualitative and quantitative composition of the microbiome lead to disruption in the synthesis of key bacterial metabolites, changes in intestinal barrier function, and inflammation and can cause the development of a wide variety of diseases, such as diabetes, obesity, gastrointestinal disorders, cardiovascular issues, neurological disorders and oncological concerns. In this review, I consider issues related to the role of the microbiome in the regulation of intestinal barrier function, its influence on physiological and pathological processes occurring in the body, and potential new therapeutic strategies aimed at restoring the gut microbiome. Herewith, it is important to understand that the gut microbiota and human body should be considered as a single biological system, where change of one element will inevitably affect its other components. Thus, the study of the impact of the intestinal microbiota on health should be considered only taking into account numerous factors, the role of which has not yet been fully elucidated.}, }
@article {pmid36683714, year = {2023}, author = {Luo, M and Xin, RJ and Hu, FR and Yao, L and Hu, SJ and Bai, FH}, title = {Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis.}, journal = {World journal of gastroenterology}, volume = {29}, number = {1}, pages = {144-156}, pmid = {36683714}, issn = {2219-2840}, abstract = {Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.}, }
@article {pmid36683707, year = {2022}, author = {Chen, Q and Fan, Y and Zhang, B and Yan, C and Chen, Z and Wang, L and Hu, Y and Huang, Q and Su, J and Ren, J and Xu, H}, title = {Specific fungi associated with response to capsulized fecal microbiota transplantation in patients with active ulcerative colitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1086885}, pmid = {36683707}, issn = {2235-2988}, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is a novel microbial treatment for patients with ulcerative colitis (UC). In this study, we performed a clinical trial of capsulized FMT in UC patients to determine the association between the gut fungal community and capsulized FMT outcomes.<br><br>DESIGN: This study recruited patients with active UC (N = 22) and healthy individuals (donor, N = 9) according to the criteria. The patients received capsulized FMT three times a week. Patient stool samples were collected before (week 0) and after FMT follow-up visits at weeks 1, 4, and 12. Fungal communities were analysed using shotgun metagenomic sequencing.<br><br>RESULTS: According to metagenomic analysis, fungal community evenness index was greater in samples collected from patients, and the overall fungal community was clustered among the samples collected from donors. The dominant fungi in fecal samples collected from donors and patients were Ascomycota and Basidiomycota. However, capsulized FMT ameliorated microbial fungal diversity and altered fungal composition, based on metagenomic analysis of fecal samples collected before and during follow-up visits after capsulized FMT. Fungal diversity decreased in samples collected from patients who achieved remission after capsulized FMT, similar to samples collected from donors. Patients achieving remission after capsulized FMT had specific enrichment of Kazachstania naganishii, Pyricularia grisea, Lachancea thermotolerans, and Schizosaccharomyces pombe compared with patients who did not achieve remission. In addition, the relative abundance of P. grisea was higher in remission fecal samples during the follow-up visit. Meanwhile, decreased levels of pathobionts, such as Candida and Debaryomyces hansenii, were associated with remission in patients receiving capsulized FMT.<br><br>CONCLUSION: In the metagenomic analysis of fecal samples from donors and patients with UC receiving capsulized FMT, shifts in gut fungal diversity and composition were associated with capsulized FMT and validated in patients with active UC. We also identified the specific fungi associated with the induction of remission. ClinicalTrails.gov (NCT03426683).}, }
@article {pmid36683147, year = {2023}, author = {Jin, J and Xu, Z and Zhang, L and Zhang, C and Zhao, X and Mao, Y and Zhang, H and Liang, X and Wu, J and Yang, Y and Zhang, J}, title = {Gut-derived β-amyloid: Likely a centerpiece of the gut-brain axis contributing to Alzheimer's pathogenesis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2167172}, doi = {10.1080/19490976.2023.2167172}, pmid = {36683147}, issn = {1949-0984}, abstract = {Peripheral β-amyloid (Aβ), including those contained in the gut, may contribute to the formation of Aβ plaques in the brain, and gut microbiota appears to exert an impact on Alzheimer's disease (AD) via the gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused on uncovering the potential interactions among gut-derived Aβ in aging, gut microbiota, and AD pathogenesis. To achieve this goal, the expression levels of Aβ and several key proteins involved in Aβ metabolism were initially assessed in mouse gut, with key results confirmed in human tissue. The results demonstrated that a high level of Aβ was detected throughout the gut in both mice and human, and gut Aβ42 increased with age in wild type and mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, the gut microbiome of mice was characterized by 16S rRNA sequencing, and we found the gut microbiome altered significantly in aged APP/PS1 mice and fecal microbiota transplantation (FMT) of aged APP/PS1 mice increased gut BACE1 and Aβ42 levels. Intra-intestinal injection of isotope or fluorescence labeled Aβ combined with vagotomy was also performed to investigate the transmission of Aβ from gut to brain. The data showed that, in aged mice, the gut Aβ42 was transported to the brain mainly via blood rather than the vagal nerve. Furthermore, FMT of APP/PS1 mice induced neuroinflammation, a phenotype that mimics early AD pathology. Taken together, this study suggests that the gut is likely a critical source of Aβ in the brain, and gut microbiota can further upregulate gut Aβ production, thereby potentially contributing to AD pathogenesis.}, }
@article {pmid36682132, year = {2022}, author = {Cao, S and Guo, D and Yin, H and Ding, X and Bai, S and Zeng, Q and Liu, J and Zhang, K and Mao, X and Wang, J}, title = {Improvement in ovarian function following fecal microbiota transplantation from high-laying rate breeders.}, journal = {Poultry science}, volume = {102}, number = {3}, pages = {102467}, doi = {10.1016/j.psj.2022.102467}, pmid = {36682132}, issn = {1525-3171}, abstract = {The underlying mechanism between the gut microbiota and reproductive function is not yet well-known. This study was conducted to investigate the effect of the administration of fecal microbiota transplantation (FMT) from highly laying rate donors on the cecal microbiota, intestinal health and ovarian function in broiler breeders. A total of 60 broiler breeders (53 wk of age) were selected by their laying rate [high (HP, 90.67 ± 0.69%; n = 10) and low (LP, 70.23 ± 0.87%; n = 20)]. The LP breeders were then be transplanted with fecal microbiota from HP hens (FMTHP; n = 10) or the same dosage of PBS (FMTCON; n = 10) for 28 d. The results revealed that FMT from HP donors increased egg-laying rate and serum hormone levels [17β-estradiol (E2), anti-Müller hormone], also decreased proinflammatory cytokine levels (interleukin-6, interleukin-8, tumor necrosis factor-α) of LP breeders (P < 0.05). The FMTHP group breeders had higher villus height, villus height/crypt depth ratio, and upregulated mRNA expression of jejunum barrier-related gene (ZO-2 and mucin-2) and estrogen, follicle-stimulating hormone (FSH) and anti-Müller hormone (AMH) receptor genes (ESR1, ESR2, FSHR, AMHR) (P < 0.05) than FMTCON group. FMT from HP donors led to higher mRNA expression of Bcl2 and sirtuin1 (SIRT1), while it downregulated the proapoptotic genes (Bax, caspase-3, caspase-8, and caspase-9) mRNA expressions in ovary compared with the FMTCON breeders (P < 0.05), and this pattern was also observed in HP donors. Also, HP breeder had higher observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group, while FMTHP can increase observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group (P < 0.05). The bacteria enrichment of Firmicutes (phylum), Bacteroidetes (phylum), Lactobacillus (genus), Enterococcus (genus), and Bacteroides (genus) were increased by FMTHP treatment. The genera Butyricicoccus, Enterococcus, and Lactobacillus were positively correlated with egg-laying rate. Therefore, cecal microbiomes of breeders with high egg-laying performance have more diverse activities, which may be related to the metabolism and health of the host; and FMT from high-yield donors can increase the hormone secretion, intestinal health, and ovarian function to improve egg-laying performance and the SIRT1-related apoptosis and cytokine signaling pathway were involved in this process.}, }
@article {pmid36681571, year = {2023}, author = {Ferre-Aracil, C and El Hajra Martínez, I and Vera Mendoza, MI and Ramos Martínez, A and Muñez Rubio, E and Fernández-Cruz, A and Matallana Royo, V and García-Maseda, S and Sánchez Romero, I and Martínez Ruiz, R and Calleja Panero, JL}, title = {[Faecal microbiota transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice].}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eimce.2022.01.004}, pmid = {36681571}, issn = {2529-993X}, abstract = {INTRODUCTION: Faecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile (CD) infection. The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting.<br><br>METHODS: Retrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the fecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhea in the first 72 h after the procedure with no relapse within the following 8 weeks after the therapy was started.<br><br>RESULTS: 15 FMT were performed in 13 patients. The mean age of the patients was 73 &#xb1; 19,4 years (range: 40-98 years); being 60% women. The indication for FMT was relapsing colitis due to CD in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the TMF was effective in 11 of 13 patients (84.61%; 95% CI; 54.55-98.07). Time until resolution of symptoms was less than 48h in all cases. Post-transplant follow-up was 25.66 &#xb1; 17.5 months. No significant short or long-term complications were recorded at follow-up.<br><br>CONCLUSION: TMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.}, }
@article {pmid36680756, year = {2023}, author = {Liu, Z and Wang, T and Zhu, Y and Zhao, H and Zhou, Z and Wu, Q}, title = {Improvements in gut microbiota dysbiosis in aged mice transplanted with adipose-derived stem cells.}, journal = {Stem cells and development}, volume = {}, number = {}, pages = {}, doi = {10.1089/scd.2022.0257}, pmid = {36680756}, issn = {1557-8534}, abstract = {Adipose-derived stem cells (ASCs), as a cell therapy with considerable therapeutic potential, have received increasing attention in tissue repair, endocrine regulation, immune regulation, and aging and obesity research. Gut microbiota are present in all organisms and play important roles in the development of aging and obesity. Dysbiosis activates inflammatory pathways that may contribute to the development of aging and obesity. We used C57BL/6J mice of different ages to carry out the experiment. Young mice were used as donors for ASC. Feces from the three groups were collected for 16sRNA sequencing to analyze the species composition of intestinal microorganisms. Then, predicted metabolic pathways by PICRUSt2 using 16s rRNA gene sequences. Immune cell levels in abdominal adipose tissue was assessed by flow cytometry. The content of IL-6、TNF-α and LPS in serum was measured by ELISA kit. Our 16sRNA sequencing data showed restoration of gut microbiota diversity and an increase in beneficial flora (Akkermansia, Lactobacillus, Prevotella) 7 days after ASC transplantation. In addition, the inflammatory environment improved in older transplanted mice.}, }
@article {pmid36680641, year = {2023}, author = {Campos-Madueno, EI and Moradi, M and Eddoubaji, Y and Shahi, F and Moradi, S and Bernasconi, OJ and Moser, AI and Endimiani, A}, title = {Intestinal colonization with multidrug-resistant Enterobacterales: screening, epidemiology, clinical impact, and strategies to decolonize carriers.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {36680641}, issn = {1435-4373}, abstract = {The clinical impact of infections due to extended-spectrum β-lactamase (ESBL)- and/or carbapenemase-producing Enterobacterales (Ent) has reached dramatic levels worldwide. Infections due to these multidrug-resistant (MDR) pathogens-especially Escherichia coli and Klebsiella pneumoniae-may originate from a prior asymptomatic intestinal colonization that could also favor transmission to other subjects. It is therefore desirable that gut carriers are rapidly identified to try preventing both the occurrence of serious endogenous infections and potential transmission. Together with the infection prevention and control countermeasures, any strategy capable of effectively eradicating the MDR-Ent from the intestinal tract would be desirable. In this narrative review, we present a summary of the different aspects linked to the intestinal colonization due to MDR-Ent. In particular, culture- and molecular-based screening techniques to identify carriers, data on prevalence and risk factors in different populations, clinical impact, length of colonization, and contribution to transmission in various settings will be overviewed. We will also discuss the standard strategies (selective digestive decontamination, fecal microbiota transplant) and those still in development (bacteriophages, probiotics, microcins, and CRISPR-Cas-based) that might be used to decolonize MDR-Ent carriers.}, }
@article {pmid36678326, year = {2023}, author = {Ma, X and Yan, H and Hong, S and Yu, S and Gong, Y and Wu, D and Li, Y and Xiao, H}, title = {Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice.}, journal = {Nutrients}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/nu15020456}, pmid = {36678326}, issn = {2072-6643}, abstract = {Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman's correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis.}, }
@article {pmid36677385, year = {2022}, author = {DuPont, HL and Jiang, ZD and Alexander, AS and DuPont, AW and Brown, EL}, title = {Intestinal IgA-Coated Bacteria in Healthy- and Altered-Microbiomes (Dysbiosis) and Predictive Value in Successful Fecal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {11}, number = {1}, pages = {}, doi = {10.3390/microorganisms11010093}, pmid = {36677385}, issn = {2076-2607}, abstract = {IgA-coated bacteria in the gut (IgA-biome) provide a homeostatic function in healthy people through inhibition of microbial invaders and by protecting the epithelial monolayer of the gut. The laboratory methods used to detect this group of bacteria require flow cytometry and DNA sequencing (IgA-Seq). With dysbiosis (reduced diversity of the microbiome), the IgA-biome also is impaired. In the presence of enteric infection, oral vaccines, or an intestinal inflammatory disorder, the IgA-biome focuses on the pathogenic bacteria or foreign antigens, while in other chronic diseases associated with dysbiosis, the IgA-biome is reduced in capacity. Fecal microbiota transplantation (FMT), the use of fecal product from well-screened, healthy donors administered to patients with dysbiosis, has been successful in engrafting the intestine with healthy microbiota and metabolites leading to improve health. Through FMT, IgA-coated bacteria have been transferred to recipients retaining their immune coating. The IgA-biome should be evaluated in FMT studies as these mucosal-associated bacteria are more likely to be associated with successful transplantation than free luminal organisms. Studies of the microbiome pre- and post-FMT should employ metagenomic methods that identify bacteria at least at the species level to better identify organisms of interest while allowing comparisons of microbiota data between studies.}, }
@article {pmid36674775, year = {2023}, author = {Przybyciński, J and Drożdżal, S and Wilk, A and Dziedziejko, V and Szumilas, K and Pawlik, A}, title = {The Effect of the Gut Microbiota on Transplanted Kidney Function.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, doi = {10.3390/ijms24021260}, pmid = {36674775}, issn = {1422-0067}, abstract = {The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.}, }
@article {pmid36674517, year = {2023}, author = {Matheson, JT and Holsinger, RMD}, title = {The Role of Fecal Microbiota Transplantation in the Treatment of Neurodegenerative Diseases: A Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, doi = {10.3390/ijms24021001}, pmid = {36674517}, issn = {1422-0067}, abstract = {Neurodegenerative diseases are highly prevalent but poorly understood, and with few treatment options despite decades of intense research, attention has recently shifted toward other mediators of neurological disease that may present future targets for therapeutic research. One such mediator is the gut microbiome, which communicates with the brain through the gut-brain axis and has been implicated in various neurological disorders. Alterations in the gut microbiome have been associated with numerous neurological and other diseases, and restoration of the dysbiotic gut has been shown to improve disease conditions. One method of restoring a dysbiotic gut is via fecal microbiota transplantation (FMT), recolonizing the "diseased" gut with normal microbiome. Fecal microbiota transplantation is a treatment method traditionally used for Clostridium difficile infections, but it has recently been used in neurodegenerative disease research as a potential treatment method. This review aims to present a summary of neurodegenerative research that has used FMT, whether as a treatment or to investigate how the microbiome influences pathogenesis.}, }
@article {pmid36672796, year = {2022}, author = {Conti, G and D'Amico, F and Fabbrini, M and Brigidi, P and Barone, M and Turroni, S}, title = {Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out.}, journal = {Genes}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/genes14010055}, pmid = {36672796}, issn = {2073-4425}, abstract = {Anticancer treatments have shown a variable therapeutic outcome that may be partly attributable to the activity of the gut microbiota on the pathology and/or therapies. In recent years, microbiota-drug interactions have been extensively investigated, but most of the underlying molecular mechanisms still remain unclear. In this review, we discuss the relationship between the gut microbiota and some of the most commonly used drugs in oncological diseases. Different strategies for manipulating the gut microbiota layout (i.e., prebiotics, probiotics, antibiotics, and fecal microbiota transplantation) are then explored in order to optimize clinical outcomes in cancer patients. Anticancer technologies that exploit tumor-associated bacteria to target tumors and biotransform drugs are also briefly discussed. In the field of pharmacomicrobiomics, multi-omics strategies coupled with machine and deep learning are urgently needed to bring to light the interaction among gut microbiota, drugs, and host for the development of truly personalized precision therapies.}, }
@article {pmid36672518, year = {2022}, author = {Boicean, A and Neamtu, B and Birsan, S and Batar, F and Tanasescu, C and Dura, H and Roman, MD and Hașegan, A and Bratu, D and Mihetiu, A and Mohor, CI and Mohor, C and Bacila, C and Negrea, MO and Fleaca, SR}, title = {Fecal Microbiota Transplantation in Patients Co-Infected with SARS-CoV2 and Clostridioides difficile.}, journal = {Biomedicines}, volume = {11}, number = {1}, pages = {}, doi = {10.3390/biomedicines11010007}, pmid = {36672518}, issn = {2227-9059}, abstract = {BACKGROUND: The COVID-19 pandemic has challenged the treatment of Clostridioides&amp;nbsp;Difficile (CD)-infected patients given the increasing number of co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, fecal microbiota transplantation (FMT) shows promise in modulating the immune system's function and alleviating the burdens associated with this condition.<br><br>METHODS: To achieve this goal, we performed a comparative, retrospective, single-center study on 86 patients (admitted between January 2020 and March 2022). We based our approach on specific inclusion criteria: 1. The study group included 46 co-infected patients (COVID-19 and CD) receiving antibiotics and FMT; 2. In the control group, 40 co-infected patients received antibiotics only. Our results showed no significant group differences in terms of gender, age, risk factors such as cardiovascular and neurological diseases, type 2 diabetes, and obesity (p > 0.05), or in pre-treatment inflammatory status, evaluated by white blood cell (WBC) count and C-reactive protein (CRP) levels. We report a significant decrease in inflammatory syndrome (CRP, WBC) in coinfected patients receiving FMT in addition to antibiotics (p < 0.05), with a lower relapse rate and mitigation of cramping and abdominal pain (91.3%). In addition, a higher level of fibrinogen, persistent moderate abdominal pain (82.5%), and a significantly higher CD infection relapse rate (42.5%) were recorded in co-infected patients treated only with antibiotics (p < 0.05).<br><br>CONCLUSION: Our study provides new data to support the multiple benefits of FMT in the case of COVID-19 and CD co-infection by improving patients' quality of life and inflammatory syndrome.}, }
@article {pmid36670104, year = {2023}, author = {Wang, J and Cao, Y and Hou, W and Bi, D and Yin, F and Gao, Y and Huang, D and Li, Y and Cao, Z and Yan, Y and Zhao, J and Kong, D and Lv, X and Huang, L and Zhong, H and Wu, C and Chen, Q and Yang, R and Wei, Q and Qin, H}, title = {Fecal microbiota transplantation improves VPA-induced ASD mice by modulating the serotonergic and glutamatergic synapse signaling pathways.}, journal = {Translational psychiatry}, volume = {13}, number = {1}, pages = {17}, pmid = {36670104}, issn = {2158-3188}, abstract = {Autism spectrum disorder (ASD) is a complex behavioral disorder diagnosed by social interaction difficulties, restricted verbal communication, and repetitive behaviors. Fecal microbiota transplantation (FMT) is a safe and efficient strategy to adjust gut microbiota dysbiosis and improve ASD-related behavioral symptoms, but its regulatory mechanism is unknown. The impact of the microbiota and its functions on ASD development is urgently being investigated to develop new therapeutic strategies for ASD. We reconstituted the gut microbiota of a valproic acid (VPA)-induced autism mouse model through FMT and found that ASD is in part driven by specific gut dysbiosis and metabolite changes that are involved in the signaling of serotonergic synapse and glutamatergic synapse pathways, which might be associated with behavioral changes. Further analysis of the microbiota showed a profound decrease in the genera Bacteroides and Odoribacter, both of which likely contributed to the regulation of serotonergic and glutamatergic synapse metabolism in mice. The engraftment of Turicibacter and Alistipes was also positively correlated with the improvement in behavior after FMT. Our results suggested that successful transfer of the gut microbiota from healthy donors to ASD mice was sufficient to improve ASD-related behaviors. Modulation of gut dysbiosis by FMT could be an effective approach to improve ASD-related behaviors in patients.}, }
@article {pmid36656870, year = {2023}, author = {Zhao, C and Bao, L and Zhao, Y and Wu, K and Qiu, M and Feng, L and Zhang, N and Hu, X and Fu, Y}, title = {A fiber-enriched diet alleviates Staphylococcus aureus-induced mastitis by activating the HDAC3-mediated antimicrobial program in macrophages via butyrate production in mice.}, journal = {PLoS pathogens}, volume = {19}, number = {1}, pages = {e1011108}, doi = {10.1371/journal.ppat.1011108}, pmid = {36656870}, issn = {1553-7374}, abstract = {Mounting evidence suggests that the gut microbiota plays an important role in the pathogenesis of mastitis, an important disease affecting the health of lactating women and the development of the dairy industry. However, the effect of the regulation of the gut microbiota by dietary components on mastitis development remains unknown. In this study, we found that a fiber-enriched diet alleviated Staphylococcus aureus (S. au)-induced mastitis in mice, which was dependent on the gut microbiota as depletion of the gut microbiota by antibiotics abolished this protective effect. Likewise, fecal microbiota transplantation (FMT) from high-inulin (HI)-treated mice (HIF) to recipient mice improved S. au-induced mastitis in mice. Consumption of an HI diet and HIF increased fecal short-chain fatty acid (SCFA) levels compared with the control group. Moreover, treatment with SCFAs, especially butyrate, alleviated S. au-induced mastitis in mice. Mechanistically, consumption of an HI diet enhanced the host antimicrobial program in macrophages through inhibiting histone deacetylase 3 by the production of butyrate. Collectively, our results suggest that modulation of the gut microbiota and its metabolism by dietary components is a potential strategy for mastitis intervention and serve as a basis for other infectious diseases.}, }
@article {pmid36656270, year = {2022}, author = {Gangwani, MK and Aziz, M and Aziz, A and Priyanka, F and Weissman, S and Phan, K and Dahiya, DS and Ahmed, Z and Sohail, AH and Lee-Smith, W and Kamal, F and Javaid, T and Nawras, A and Hart, B}, title = {Fresh Versus Frozen Versus Lyophilized Fecal Microbiota Transplant for Recurrent Clostridium Difficile Infection: A Systematic Review and Network Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001777}, pmid = {36656270}, issn = {1539-2031}, abstract = {INTRODUCTION: Clostridium difficile Infection is a significant source of morbidity and mortality, which is on the rise. Fecal Microbiota Transplantation (FMT) is an alternative therapy to antibiotics with a high success rate and low relapse rate. Current data regarding the efficacy of the types of FMT used, namely fresh, frozen, and lyophilized is conflicting. Our review attempts to consolidate this data and highlight the most efficacious treatment currently available.<br><br>METHODOLOGY: MEDLINE, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, SciELO, the Korean Citation Index, and Global Index Medicus were systematically searched from inception through May 3, 2022. Studies in which patients are undergoing any form of FMT who had failed antibiotic treatment previously were included. Both pairwise (direct) and network (direct + indirect) meta-analysis were performed using a random effects model and DerSimonian-Laird approach. A frequentist approach was used for network meta-analysis. Risk differences with (RD) with 95% confidence interval (CI) were calculated.<br><br>RESULTS: A total of 8 studies, including 4 RCTs and 4 cohort studies, were included with a total of 616 patients. Fresh FMT was determined to be most successful with 93% efficacy 95% CI (0.913 to 0.999) followed by frozen with 88% efficacy 95% CI (0.857 to 0.947) and lyophilized with 83% efficacy 95% CI (0.745 to 0.910). The direct meta-analysis showed no statistically significant difference between fresh and frozen group. (RD -0.051 95% CI -0.116 to 0.014 P=0.178). No significant differences were noted in frozen versus lyophilized groups with an overall trend towards Fresh FM (RD -0.061 95% CI -0.038 to 0.160 P=0.617). On network meta-analysis, when compared with fresh group, a lower recovery rate was noted with both frozen group (RD -0.06 95% CI -0.11 to 0.00 P=0.05) and lyophilized group (RD -0.16 95% CI -0.27 to -0.05 P=0.01).<br><br>CONCLUSION: We conclude the efficacy of Frozen and Lyophilized preparations is high with no difference in direct comparison, and the relative efficacy reduction based on network analysis is outweighed by the safety, accessibility, and practicality of Frozen or Lyophilized preparations.}, }
@article {pmid36654766, year = {2023}, author = {Hao, S and Yang, S and Zhang, N and Cheng, H}, title = {Fecal Microbiota Transplantation Research over the Past Decade: Current Status and Trends.}, journal = {The Canadian journal of infectious diseases &amp; medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale}, volume = {2023}, number = {}, pages = {6981721}, pmid = {36654766}, issn = {1712-9532}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a current research hotspot, with a surge in the output of publications over the past decade. This study dedicates to the exploration of the research status and highlights significant themes and future trends in FMT research with the aid of bibliometric analysis.<br><br>METHODS: FMT publications from 2012 to 2021 were retrieved on August 12, 2022, using the SCI-Expanded of Web of Science (WoS). The Bibliometrix in R program, Microsoft Office Excel, VOSviewer, and CiteSpace were utilized for bibliometrics and visual analysis, revealing the main publications, journals, countries, agencies, authors, and keywords distribution in FMT research.<br><br>RESULTS: There were 2,931 papers included. FMT research presented a growing trend from 2012 to 2021. The countries with the most publications and contributions in FMT area were China and the United States. The high-yield institutions were Harvard University, Udice French Research Universities, and the University of California System. The primary authors were Nieuwdorp Max, Allegretti Jessica R, and Kassam Zain. Frontiers in Microbiology and Science were the top-ranked journals in publications and total citations, respectively. The important topics primarily included FMT-related mechanisms and the usage of FMT in Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), metabolic disease, neurological disorders, and psychiatric disorders. Future research would primarily concentrate on neurological disorders, chemotherapy and immunotherapy for malignant tumors, and FMT-related consensus and guidelines.<br><br>CONCLUSION: With the help of bibliometric analysis, we were able to obtain the understanding of the status and trends of global FMT-related research. The field of FMT is undergoing tremendous progress, and our findings can guide clinical researchers' and practitioners' future work in the rapidly evolving field of FMT.}, }
@article {pmid36654598, year = {2022}, author = {Ferreira, A and Neves, MT and Baleiras, A and Malheiro, M and Martins, A}, title = {Fecal Microbiota Transplant in Immunotherapy-Resistant Melanoma: What Can We Expect in the Near Future?.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32586}, pmid = {36654598}, issn = {2168-8184}, abstract = {Melanoma is a malignancy of melanocytes, melanin-producing cells in the basal layer of the epidermis. Despite representing only 1% of skin cancers, melanoma is responsible for over 80% of skin cancer deaths. Treatment with immune checkpoint inhibitors (ICIs) that target the programmed death 1 (PD-1) protein and the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways drastically transformed the management of patients with advanced melanoma. Before the introduction of ICIs, the average life expectancy for a patient with advanced melanoma ranged from six to 12 months, and now, this average survival has increased to over six years. However, despite this outstanding clinical success, most patients with advanced melanoma treated with ICIs will experience disease progression, immediately or after an initial response to treatment. Nowadays, some studies have looked at the mechanism behind the resistance to immunotherapy, with the aim of developing new treatments to overcome it. Emerging data suggest that gut microbiota (GM) influences response to immunotherapy. Importantly, unlike tumor genomics, the GM is changeable; thus, modulation of the GM is an attractive approach to overcome immunotherapy resistance. One of these approaches is the fecal microbiota transplant (FMT), which consists of the exchange of manipulated feces from a donor to a recipient who has a disorder related to intestinal dysbiosis to directly change the recipient's gut microbial composition and confer a health benefit. This review pretends to discuss the clinical benefit of FMT in the treatment of immunotherapy-resistant melanoma and potential adverse effects, including recent and ongoing clinical trials.}, }
@article {pmid36648505, year = {2023}, author = {Märtson, AG and da Silva Ferreira, AR and Veringa, A and Liu, L and Wardill, HR and Junier, LAT and van der Werf, TS and Harmsen, HJM and Sturkenboom, MGG and Span, LF and Tissing, WJE and Alffenaar, JC}, title = {Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study.}, journal = {Annals of hematology}, volume = {}, number = {}, pages = {}, pmid = {36648505}, issn = {1432-0584}, abstract = {Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.}, }
@article {pmid36647403, year = {2023}, author = {Wakil, A and Niazi, M and Meybodi, MA and Pyrsopoulos, NT}, title = {Emerging Pharmacotherapies in Alcohol-Associated Hepatitis.}, journal = {Journal of clinical and experimental hepatology}, volume = {13}, number = {1}, pages = {116-126}, pmid = {36647403}, issn = {0973-6883}, abstract = {UNLABELLED: The incidence of alcoholic-associated hepatitis (AH) is increasing. The treatment options for severe AH (sAH) are scarce and limited to corticosteroid therapy which showed limited mortality benefit in short-term use only. Therefore, there is a dire need for developing safe and effective therapies for patients with sAH and to improve their high mortality rates.This review article focuses on the current novel therapeutics targeting various mechanisms in the pathogenesis of alcohol-related hepatitis. Anti-inflammatory agents such as IL-1 inhibitor, Pan-caspase inhibitor, Apoptosis signal-regulating kinase-1, and CCL2 inhibitors are under investigation. Other group of agents include gut-liver axis modulators, hepatic regeneration, antioxidants, and Epigenic modulators. We describe the ongoing clinical trials of some of the new agents for alcohol-related hepatitis.<br><br>CONCLUSION: A combination of therapies was investigated, possibly providing a synergistic effect of drugs with different mechanisms. Multiple clinical trials of novel therapies in AH remain ongoing. Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample.}, }
@article {pmid36641624, year = {2023}, author = {Uribe-Herranz, M and Beghi, S and Ruella, M and Parvathaneni, K and Salaris, S and Kostopoulos, N and George, SS and Pierini, S and Krimitza, E and Costabile, F and Ghirardi, G and Amelsberg, KV and Lee, YG and Pajarillo, R and Markmann, C and McGettigan-Croce, B and Agarwal, D and Frey, N and Lacey, SF and Scholler, J and Gabunia, K and Wu, G and Chong, E and Porter, DL and June, CH and Schuster, SJ and Bhoj, V and Facciabene, A}, title = {Modulation of the gut microbiota engages antigen cross-presentation to enhance antitumor effects of CAR T cell immunotherapy.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2023.01.012}, pmid = {36641624}, issn = {1525-0024}, abstract = {Several studies have shown the influence of commensal microbes on T cell function, specifically in the setting of checkpoint immunotherapy for cancer. In this study, we investigated how vancomycin-induced gut microbiota dysbiosis affects CAR T immunotherapy using multiple preclinical models as well as clinical correlates. In two murine tumor models, the hematopoietic CD19[+]-A20 lymphoma and the CD19[+]-B16 melanoma, mice receiving vancomycin in combination with CD19-directed CAR T cell (CART-19) therapy displayed increased tumor control and tumor associated antigens (TAAs) cross-presentation compared to CART-19 alone. Fecal microbiota transplant from human healthy donors to pre-conditioned mice recapitulated the results obtained in naïve gut microbiota mice. Lastly, B-cell acute lymphoblastic leukemia patients treated with CART-19 and exposed to oral vancomycin showed higher CART-19 peak expansion compared to unexposed patients. These results substantiate the role of the gut microbiota on CAR T cell therapy and suggest that modulation of the gut microbiota using vancomycin may improve outcomes after CAR T cell therapy across tumor types.}, }
@article {pmid36641024, year = {2023}, author = {Zhao, H and Li, M and Liu, L and Li, D and Zhao, L and Wu, Z and Zhou, M and Jia, L and Yang, F}, title = {Cordyceps militaris polysaccharide alleviates diabetic symptoms by regulating gut microbiota against TLR4/NF-κB pathway.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {123241}, doi = {10.1016/j.ijbiomac.2023.123241}, pmid = {36641024}, issn = {1879-0003}, abstract = {The relationship between gut microbiota and type 2 diabetes mellitus (T2DM) has attracted increasing attention. In our work, one purified fraction a (AEPSa) was obtained from Cordyceps militaris polysaccharides, and its hypoglycemic activity and underlying mechanisms were investigated in high-fat diet (HFD)- and streptozotocin (STZ)-induced T2DM mice. The results revealed that AEPSa reshaped gut microbiota by increasing Allobaculum, Alistipes, Lachnospiraceae_NK4A136_group and norank_f_Muribaculaceae and decreasing Enterococcus and Ruminococcus_torques_group to inhibit the colonic toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and upregulate intestinal tight junction protein expression, thereby improving glucose and serum lipid metabolism, hormone secretion and complications. Fecal microbiota transplantation (FMT) also confirmed these findings. These results indicated that symptomatic relief of T2DM might be related to AEPSa regulating the gut microbiota against the TLR4/NF-κB pathway to protect the intestinal barrier. Therefore, AEPSa might be developed as a prebiotic agent against T2DM by regulating gut microbiota.}, }
@article {pmid36639024, year = {2023}, author = {Li, HY and Huang, SY and Zhou, DD and Xiong, RG and Luo, M and Saimaiti Data Acquisition, A and Han, MK and Gan, RY and Zhu, HL and Li, HB}, title = {Theabrownin inhibits obesity and non-alcoholic fatty liver disease in mice via serotonin-related signaling pathways and gut-liver axis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2023.01.008}, pmid = {36639024}, issn = {2090-1224}, abstract = {INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) with obesity seriously threats public health. Our previous studies showed that dark tea had more potential on regulating lipid metabolism than other teas, and theabrownin (TB) was considered to be a main contributor to the bioactivity of dark tea.<br><br>OBJECTIVES: This in vivo study aims to reveal the effects and molecular mechanisms of TB on NAFLD and obesity, and the role of the gut-liver axis is explored.<br><br>METHODS: The histopathological examinations, biochemical tests, and nuclear magnetic resonance were applied to evaluate the effects of TB on NAFLD and obesity. The untargeted metabolomics was used to find the key molecule for further exploration of molecular mechanisms. The 16S rRNA gene sequencing was used to assess the changes in gut microbiota. The antibiotic cocktail and fecal microbiota transplant were used to clarify the role of gut microbiota.<br><br>RESULTS: TB markedly reduced body weight gain (67.01%), body fat rate (62.81%), and hepatic TG level (51.35%) in the preventive experiment. Especially, TB decreased body weight (32.16%), body fat rate (42.56%), and hepatic TG level (42.86%) in the therapeutic experiment. The mechanisms of action could be the improvement of fatty acid oxidation, lipolysis, and oxidative stress via the regulation of serotonin-related signaling pathways. Also, TB increased the abundance of serotonin-related gut microbiota, such as Akkermansia, Bacteroides and Parabacteroides. Antibiotics-induced gut bacterial dysbiosis disrupted the regulation of TB on serotonin-related signaling pathways in liver, whereas the beneficial regulation of TB on target proteins was regained with the restoration of gut microbiota.<br><br>CONCLUSION: We find that TB has markedly preventive and therapeutic effects on NAFLD and obesity by regulating serotonin level and related signaling pathways through gut microbiota. Furthermore, gut microbiota and TB co-contribute to alleviating NAFLD and obesity. TB could be a promising medicine for NAFLD and obesity.}, }
@article {pmid36638854, year = {2023}, author = {Guo, HH and Shen, HR and Tang, MZ and Sheng, N and Ding, X and Lin, Y and Zhang, JL and Jiang, JD and Gao, TL and Wang, LL and Han, YX}, title = {Microbiota-derived short-chain fatty acids mediate the effects of dengzhan shengmai in ameliorating cerebral ischemia via the gut-brain axis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {116158}, doi = {10.1016/j.jep.2023.116158}, pmid = {36638854}, issn = {1872-7573}, abstract = {Dengzhan shengmai (DZSM) formula, composed of four herbal medicines (Erigeron breviscapus, Panax ginseng, Schisandra chinensis, and Ophiopogon japonicus), is widely used in the recovery period of ischemic cerebrovascular diseases; however, the associated molecular mechanism remains unclear.<br><br>AIM OF THE STUDY: The purpose of this study was to uncover the links between the microbiota-gut-brain axis and the efficacy of DZSM in ameliorating cerebral ischemic diseases.<br><br>MATERIALS AND METHODS: The effects of DZSM on the gut microbiota community and bacteria-derived short-chain fatty acid (SCFA) production were evaluated in vivo using a rat model of cerebral ischemia and in vitro through the anaerobic incubation with fresh feces derived from model animals. Subsequently, the mechanism underlying the role of SCFAs in the DZSM-mediated treatment of cerebral ischemia was explored.<br><br>RESULTS: We found that DZSM treatment significantly altered the composition of the gut microbiota and markedly enhanced SCFA production. The consequent increase in SCFA levels led to the upregulation of the expression of monocarboxylate transporters and facilitated the transportation of intestinal SCFAs into the brain, thereby inhibiting the apoptosis of neurocytes via the regulation of the PI3K/AKT/caspase-3 pathway. The increased intestinal SCFA levels also contributed to the repair of the 2VO-induced disruption of gut barrier integrity and inhibited the translocation of lipopolysaccharide from the intestine to the brain, thus attenuating neuroinflammation. Consequently, cerebral neuropathy and oxidative stress were significantly improved in 2VO model rats, leading to the amelioration of cerebral ischemia-induced cognitive dysfunction. Finally, fecal microbiota transplantation could reproduce the beneficial effects of DZSM on SCFA production and cerebral ischemia.<br><br>CONCLUSIONS: Our findings suggested that SCFAs mediate the effects of DZSM in ameliorating cerebral ischemia via the gut microbiota-gut-brain axis.}, }
@article {pmid36638713, year = {2023}, author = {Wang, Z and Sun, Y and Han, Y and Chen, X and Gong, P and Zhai, P and Yao, W and Ba, Q and Wang, H}, title = {Eucommia bark/leaf extract improves HFD-induced lipid metabolism disorders via targeting gut microbiota to activate the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {110}, number = {}, pages = {154652}, doi = {10.1016/j.phymed.2023.154652}, pmid = {36638713}, issn = {1618-095X}, abstract = {BACKGROUND: The bark of Eucommia ulmoides (a perennial deciduous tree termed eucommia hereafter) has anti-hyperlipidemia effects due to its bioactive components. However, the slow growth of eucommia bark leads to a deficit in this resource. Studies have shown that eucommia leaf has bioactive components similar to those of eucommia bark and anti-hyperlipidemia effects. At present, the strength of the anti-hyperlipidemia effect of eucommia bark and eucommia leaf has not been reported. Their interaction with the gut microbiota and the mechanism by which the gut microbiota exerts anti-hyperlipidemia effects are unclear.<br><br>PURPOSES: Through fecal microbiota transplantation (FMT) experiments, this study aimed to investigate the mechanism by which fecal bacteria suspensions containing chlorogenic acid (CGA), eucommia bark extract (EBE), and eucommia leaves extract (ELE) improve high-fat diet (HFD)-induced lipid metabolism disorders. Difference in anti-hyperlipidemia effects between EBE and ELE and exploring an eucommia bark substitute to improve the sustainable utilization of eucommia were also evaluated.<br><br>RESULTS: EBE and ELE contain eight identical bioactive ingredients, and fecal bacteria suspensions containing EBE and ELE significantly improved HFD-induced lipid metabolism disorders and elevated blood glucose levels. The fecal bacteria suspension of healthy mice containing CGA, EBE, and ELE significantly reduced the relative abundance of Erysipelothrichaceae and Ruminococcaceae and promoted short chain fatty acids (SCFAs) production thereby activating the expression of the SCFA. G protein-coupled receptor 43 (GPR43) gene in colon and epididymal fat tissues. In addition, fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE significantly activated fasting-induced adipose factor (Fiaf) gene expression in colon tissue and inhibited the secretion of lipoprotein lipase (LPL) in liver tissue, thereby inhibiting the synthesis of triglycerides (TG). Changed in the Erysipelotrichaceae and Ruminococcaceae relative abundances were significantly correlated with these target genes. Thus, regulating the abundance of the Erysipelotrichaceae and Ruminococcaceae could serve as a potential target for the role of fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE in the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis. In addition, regarding HFD-induced lipid metabolism disorders and gut microbiota structural disorders, we found no significant difference between ELE and EBE.<br><br>CONCLUSIONS: Our FMT experiments evidenced that EBE and ELE improve lipid metabolism disorders by regulating the gut microbiota, providing a new pathway for treating hyperlipidemia using eucommia dietary therapy. There was no significant difference in the anti-hyperlipidemia effects of ELE and EBE; thus, eucommia leaf could replace eucommia bark in traditional Chinese medicine, so as to achieve a sustainable utilization of eucommia resources.}, }
@article {pmid36638348, year = {2023}, author = {Zeng, X and Li, X and Li, X and Wei, C and Shi, C and Hu, K and Kong, D and Luo, Q and Xu, Y and Shan, W and Zhang, M and Shi, J and Feng, J and Han, Y and Huang, H and Qian, P}, title = {Fecal microbiota transplantation from young mice rejuvenates aged hematopoietic stem cells by suppressing inflammation.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2022017514}, pmid = {36638348}, issn = {1528-0020}, abstract = {Hematopoietic stem cell (HSC) aging is accompanied by hematopoietic reconstitution dysfunction, including loss of regenerative and engraftment ability, myeloid differentiation bias and elevated risks of hematopoietic malignancies. Gut microbiota, a key regulator of host health and immunity, has been recently reported to impact hematopoiesis. However, there is currently limited empirical evidence elucidating the direct impact of gut microbiome on aging hematopoiesis. In this study, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. Further, FMT from young mice rejuvenated aged HSCs with enhanced short-term and long-term hematopoietic repopulation capacity. Mechanistically, single-cell RNA sequencing deciphered that FMT from young mice mitigated inflammatory signals, upregulated FoxO signaling pathway and promoted lymphoid differentiation of HSCs during aging. Finally, integrated microbiome and metabolome analyses uncovered that FMT reshaped gut microbiota construction and metabolite landscape, and Lachnospiraceae and tryptophan-associated metabolites promoted the recovery of hematopoiesis and rejuvenated aged HSCs. Together, our study highlights the paramount importance of the gut microbiota in HSC aging and provides insights into therapeutic strategies for aging-related hematologic disorders.}, }
@article {pmid36637229, year = {2023}, author = {Green, JE and Berk, M and Mohebbi, M and Loughman, A and McGuinness, AJ and Castle, D and Chatterton, ML and Perez, J and Strandwitz, P and Athan, E and Hair, C and Nierenberg, AA and Cryan, JF and Jacka, F}, title = {Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437221150508}, doi = {10.1177/07067437221150508}, pmid = {36637229}, issn = {1497-0015}, abstract = {OBJECTIVES: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD.<br><br>METHODS: The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial (n = 15) of enema-delivered FMT (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD.<br><br>RESULTS: Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD.<br><br>CONCLUSIONS: All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.}, }
@article {pmid36636378, year = {2023}, author = {Guan, X and Sun, Z}, title = {The Role of Intestinal Flora and Its Metabolites in Heart Failure.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {51-64}, pmid = {36636378}, issn = {1178-6973}, abstract = {Intestinal flora is a complex collection of microbial communities that participate in the physiological and pathological activities of the human body through various pathways. In recent years, numerous studies have reported that intestinal flora are involved in the occurrence and development of heart failure (HF) and its metabolic products could play an important role in this progression, suggesting a great value in the clinical treatment of this condition. This study reported the interaction between intestinal flora and HF, and with intestinal flora metabolites, such as short-chain fatty acids, trimethylamine N-oxide and bile acids and urotoxins, considered as the starting point, the mechanism of the roles in HF was summarized. Additionally, the current research status and the development prospects of applying flora and metabolites to the clinical therapeutic decision of HF were discussed.}, }
@article {pmid36631533, year = {2023}, author = {Shrode, RL and Knobbe, JE and Cady, N and Yadav, M and Hoang, J and Cherwin, C and Curry, M and Garje, R and Vikas, P and Sugg, S and Phadke, S and Filardo, E and Mangalam, AK}, title = {Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {526}, pmid = {36631533}, issn = {2045-2322}, support = {T32 GM139776/NH/NIH HHS/United States ; }, mesh = {Humans ; United States/epidemiology ; Female ; *Breast Neoplasms ; Dysbiosis/microbiology ; Bacteria/genetics ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics/analysis ; }, abstract = {As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.}, }
@article {pmid36632334, year = {2022}, author = {Wexler, A}, title = {Mapping the Landscape of Do-it-Yourself Medicine.}, journal = {Citizen science : theory and practice}, volume = {7}, number = {1}, pages = {}, pmid = {36632334}, issn = {2057-4991}, abstract = {The practice of medicine is typically conceptualized as remaining within the boundaries of a hospital or clinic. However, in recent years, patients have been able to gain access to information about medical research as it is ongoing. As a result, there has been a rise in do-it-yourself (DIY) medicine, where individuals treat themselves for medical conditions outside of clinical settings, often mimicking experimental therapies that remain inaccessible to the wider public. For example, in DIY brain stimulation, individuals suffering from depression build at-home electrical headsets using nine-volt batteries, mimicking an experimental neuroscience technique used in scientific laboratories. In DIY fecal transplantation, those with intestinal disorders like C. Difficile and inflammatory bowel disease transplant stool from donors into themselves with the aid of blenders and enemas. In the open Artificial Pancreas System movement, diabetes patients hacked together an artificial pancreas system from their glucose monitors and insulin pumps, years before such a system was approved by the United States Food and Drug Administration (US FDA). To date, scholarship on DIY medicine has largely been relegated to specific medical domains (e.g., neurology, gastroenterology, infectious disease). In this paper, however, I recognize DIY medicine as a cross-cutting phenomenon that has emerged independently across medical domains but shares common features. I map the varieties of DIY medicine across these domains and suggest that four key factors lead to their creation, growth, and uptake. In doing so, this essay sheds light on an understudied area of biomedical citizen science that is likely to grow substantially in the coming decades.}, }
@article {pmid36632246, year = {2022}, author = {Patel, M and Atluri, LM and Gonzalez, NA and Sakhamuri, N and Athiyaman, S and Randhi, B and Gutlapalli, SD and Pu, J and Zaidi, MF and Khan, S}, title = {A Systematic Review of Mixed Studies Exploring the Effects of Probiotics on Gut-Microbiome to Modulate Therapy in Children With Autism Spectrum Disorder.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32313}, pmid = {36632246}, issn = {2168-8184}, abstract = {Autism spectrum disorder(ASD) is a complex neurodevelopmental disorder characterized by social deficits, repetitive typical behaviors, insistence on the same routines, and communication impairments. The prevalence of ASD has increased in the past decade. While we are aware that there is no cure for ASD, attempts are being made to reduce its symptoms and improve the learning, overall growth, and well-being of ASD patients. Gastrointestinal (GI) symptoms are frequent occurrences in patients with ASD, but the underlying mechanisms are unknown. Recent studies show that the microbiota-gut-brain axis is the key modulator of neuropsychiatric health. Although fecal transplants have shown positive outcomes in treating dysbiosis and symptoms of autism, lifestyle modifications such as dietary intervention will prevent and treat this disorder without causing major adverse effects. Probiotics enhance the microbiome to provide necessary metabolites, which help in gut permeability, cognitive function, and immunity. In some studies, children with increased GI symptoms have also shown increased behavioral disturbances. In this study, a systematic review of mixed studies is conducted to obtain more robust and conclusive results. We included randomized controlled studies with larger sample sizes and specifications on probiotics.}, }
@article {pmid36631604, year = {2023}, author = {Mei, T and Noguchi, H and Kuraji, R and Kubo, S and Sato, Y and Kaku, K and Okabe, Y and Onishi, H and Nakamura, M}, title = {Effects of periodontal pathogen-induced intestinal dysbiosis on transplant immunity in an allogenic skin graft model.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {544}, pmid = {36631604}, issn = {2045-2322}, abstract = {Periodontal disease can induce dysbiosis, a compositional and functional alteration in the microbiota. Dysbiosis induced by periodontal disease is known to cause systemic inflammation and may affect transplant immunity. Here, we examined the effects of periodontal disease-related intestinal dysbiosis on transplant immunity using a mouse model of allogenic skin graft in which the mice were orally administered the periodontal pathogen Porphyromonas gingivalis (Pg). For 6 weeks, the Pg group orally received Pg while the control group orally received phosphate-buffered saline solution. After that, both groups received allogenic skin grafts. 16 s rRNA analysis of feces revealed that oral administration of Pg significantly increased three short chain fatty acids (SCFAs) producing genera. SCFA (acetate and propionate) levels were significantly higher in the Pg group (p = 0.040 and p = 0.005). The ratio of regulatory T cells, which are positively correlated with SCFAs, to total CD4+ T cells in the peripheral blood and spleen was significantly greater (p = 0.002 and p < 0.001) in the Pg group by flowcytometry. Finally, oral administration of Pg significantly prolonged skin graft survival (p < 0.001) and reduced pathological inflammation in transplanted skin grafts. In conclusion, periodontal pathogen-induced intestinal dysbiosis may affect transplant immunity through increased levels of SCFAs and regulatory T cells. (198 words).}, }
@article {pmid36631439, year = {2023}, author = {Yuan, X and Zhou, F and Wang, H and Xu, X and Xu, S and Zhang, C and Zhang, Y and Lu, M and Zhang, Y and Zhou, M and Li, H and Zhang, X and Zhang, T and Song, J}, title = {Systemic antibiotics increase microbiota pathogenicity and oral bone loss.}, journal = {International journal of oral science}, volume = {15}, number = {1}, pages = {4}, pmid = {36631439}, issn = {2049-3169}, abstract = {Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.}, }
@article {pmid36629092, year = {2023}, author = {Thacher, PR and Kendrick, EL and Maslanka, M and Muletz-Wolz, CR and Bornbusch, SL}, title = {Fecal microbiota transplants modulate the gut microbiome of a two-toed sloth (Choloepus didactylus).}, journal = {Zoo biology}, volume = {}, number = {}, pages = {}, doi = {10.1002/zoo.21751}, pmid = {36629092}, issn = {1098-2361}, abstract = {The microbes inhabiting an animal's gastrointestinal tracts, collectively known as the gut microbiome, are vital to animal health and wellbeing. For animals experiencing gut distress or infection, modulation of the gut microbiome, for example, via fecal microbiota transplant (FMT), provides a possible disease prevention and treatment method. The beneficial microbes present in the donor's transplanted feces can help combat pathogens, assist in digestion, and rebalance the recipient's microbiota. Investigating the efficacy of FMTs in animal health is a crucial step toward improving management strategies for species under human care. We present a case study of the use of FMTs in a two-toed sloth experiencing abnormally large, clumped, and frequent stools. We used 16 S rRNA amplicon sequencing of fecal samples to (a) compare the microbiomes of the FMT donor, a healthy, cohoused conspecific, and the FMT recipient and (b) assess the influence of multiple rounds of FMTs on the recipient's microbiome and stool consistency and frequency over time. In response to the FMTs, we found that the recipient's microbiome showed trends toward increased diversity, shifted community composition, and altered membership that more resembled the community of the donor. FMT treatment was also associated with marked, yet temporary, alleviation of the recipient's abnormal bowel movements, suggesting a broader impact on gut health. Our results provide valuable preliminary evidence that FMT treatments can augment the recipient's gut microbiome, with potential implications for animal health and management.}, }
@article {pmid36627937, year = {2022}, author = {Yu, J and Cheon, JH}, title = {Microbial Modulation in Inflammatory Bowel Diseases.}, journal = {Immune network}, volume = {22}, number = {6}, pages = {e44}, pmid = {36627937}, issn = {1598-2629}, abstract = {Gut dysbiosis is one of prominent features in inflammatory bowel diseases (IBDs) which are of an unknown etiology. Although the cause-and-effect relationship between IBD and gut dysbiosis remains to be elucidated, one area of research has focused on the management of IBD by modulating and correcting gut dysbiosis. The use of antibiotics, probiotics either with or without prebiotics, and fecal microbiota transplantation from healthy donors are representative methods for modulating the intestinal microbiota ecosystem. The gut microbiota is not a simple assembly of bacteria, fungi, and viruses, but a complex organ-like community system composed of numerous kinds of microorganisms. Thus, studies on specific changes in the gut microbiota depending on which treatment option is applied are very limited. Here, we review previous studies on microbial modulation as a therapeutic option for IBD and its significance in the pathogenesis of IBD.}, }
@article {pmid36627827, year = {2023}, author = {Li, ZM and Kong, CY and Mao, YQ and Huang, JT and Chen, HL and Han, B and Wang, LS}, title = {Ampicillin exacerbates acetaminophen-induced acute liver injury by inducing intestinal microbiota imbalance and butyrate reduction.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1111/liv.15512}, pmid = {36627827}, issn = {1478-3231}, abstract = {BACKGROUND AND AIMS: Antibiotics and acetaminophen (APAP) are widely used worldwide. APAP is the most common cause of acute liver injury and might be used in combination with antibiotics in clinics. However, the impact of antibiotics on APAP-induced acute liver injury (ALI) has rarely been studied.<br><br>METHODS: First, we compared the effects of seven antibiotics on APAP-induced acute liver injury. Then, we analyzed fecal, serum, and liver samples to investigate the impact of the gut microbiota on this process. Finally, we assessed the role of short-chain fatty acids in this process.<br><br>RESULTS: In this work, we found that the ALI was significantly aggravated in the mice treated with ampicillin instead of other antibiotics. Ampicillin exposure reduced the diversity and altered the composition of gut microbiota. The altered gut microbiota aggravated APAP-induced ALF, which was proven by fecal microbiota transplantation from antibiotics-treated mice. Metagenomic analysis showed a significantly decreased Lactobacillus abundance in ampicillin-treated mice. Gavage with Lactobacillus, especially L. rhamnosus, significantly reversed the severer ALF induced by APAP and ampicillin. Moreover, Lactobacillus supplementation increased butyrate-producing clostridia and lowered butyrate levels in ampicillin-treated mice. In accordance, butyrate supplementation could also alleviate ampicillin-aggravated ALI. In addition, inhibition of NFR2 counteracted the protective effect of butyrate on aggravated ALI induced by ampicillin and APAP.<br><br>CONCLUSION: Together, this study revealed a potential health impact of ampicillin that may exacerbate liver damage when co-exposed to excess APAP.}, }
@article {pmid36627762, year = {2023}, author = {Su, SH and Chen, M and Wu, YF and Lin, Q and Wang, DP and Sun, J and Hai, J}, title = {Fecal microbiota transplantation and short-chain fatty acids protected against cognitive dysfunction in a rat model of chronic cerebral hypoperfusion.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/cns.14089}, pmid = {36627762}, issn = {1755-5949}, abstract = {AIMS: Clear roles and mechanisms in explaining gut microbial dysbiosis and microbial metabolites short-chain fatty acids (SCFAs) alterations in chronic cerebral ischemic pathogenesis have yet to be explored. In this study, we investigated chronic cerebral hypoperfusion (CCH)-induced gut microbiota and metabolic profiles of SCFAs as well as the effects and mechanisms of fecal microbiota transplantation (FMT) and SCFAs treatment on CCH-induced hippocampal neuronal injury.<br><br>METHODS: Bilateral common carotid artery occlusion (BCCAo) was used to establish the CCH model. Gut microbiota and SCFAs profiles in feces and hippocampus were evaluated by 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry. RNA sequencing analysis was performed in hippocampal tissues. The potential molecular pathways and differential genes were verified through western blot, immunoprecipitation, immunofluorescence, and ELISA. Cognitive function was assessed via the Morris water maze test. Ultrastructures of mitochondria and synapses were tested through a transmission electron microscope.<br><br>RESULTS: Chronic cerebral hypoperfusion induced decreased fecal acetic and propionic acid and reduced hippocampal acetic acid, which were reversed after FMT and SCFAs administration by changing fecal microbial community structure and compositions. Furthermore, in the hippocampus, FMT and SCFAs replenishment exerted anti-neuroinflammatory effects through inhibiting microglial and astrocytic activation as well as switching microglial phenotype from M1 toward M2. Moreover, FMT and SCFAs treatment alleviated neuronal loss and microglia-mediated synaptic loss and maintained the normal process of synaptic vesicle fusion and release, resulting in the improvement of synaptic plasticity. In addition, FMT and SCFAs supplement prevented oxidative phosphorylation dysfunction via mitochondrial metabolic reprogramming. The above effects of FMT and SCFAs treatment led to the inhibition of CCH-induced cognitive impairment.<br><br>CONCLUSION: Our findings highlight FMT and SCFAs replenishment would be the feasible gut microbiota-based strategy to mitigate chronic cerebral ischemia-induced neuronal injury.}, }
@article {pmid36627187, year = {2023}, author = {Pinto, Y and Frishman, S and Turjeman, S and Eshel, A and Nuriel-Ohayon, M and Shrossel, O and Ziv, O and Walters, W and Parsonnet, J and Ley, C and Johnson, EL and Kumar, K and Schweitzer, R and Khatib, S and Magzal, F and Muller, E and Tamir, S and Tenenbaum-Gavish, K and Rautava, S and Salminen, S and Isolauri, E and Yariv, O and Peled, Y and Poran, E and Pardo, J and Chen, R and Hod, M and Borenstein, E and Ley, RE and Schwartz, B and Louzoun, Y and Hadar, E and Koren, O}, title = {Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2022-328406}, pmid = {36627187}, issn = {1468-3288}, abstract = {OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities.<br><br>DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394&#x2009;women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts.<br><br>RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy.<br><br>CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.}, }
@article {pmid36627028, year = {2023}, author = {Zhang, S and Zeng, L and Ma, J and Xu, W and Qu, Y and Wang, X and An, X and Wang, Q and Wu, Y and Wang, D and Chen, H and Ai, J}, title = {Gut Prevotellaceae-GABAergic septohippocampal pathway mediates spatial memory impairment in high-fat diet-fed ovariectomized mice.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {105993}, doi = {10.1016/j.nbd.2023.105993}, pmid = {36627028}, issn = {1095-953X}, abstract = {Clarifying the risk factors and mechanisms that contribute to the onset of cognitive impairment following estrogen depletion is essential for improving the quality of life of older females. In the current study, using behavioral tests, 16S rDNA sequencing, in vivo and in vitro electrophysiology, optogenetics and chemogenetics, we found that high-fat diet (HFD)-accelerated impairment of hippocampus-dependent memory, gut microbiota, and hippocampal theta rhythmogenesis in ovariectomized (OVX) mice and fecal microbiota transplantation rescued these phenomena. The identification of fasting-activated medial septal neurons showed that PV[+] GABAergic neurons in the medial septal area (MSA) respond to gut sensory signals. Optogenetic activation of septohippocampal PV[+] GABAergic fibers (but not cholinergic fibers) significantly rescued hippocampal theta rhythmogenesis and spatial memory in HFD-fed OVX mice. Resistant starch supplementation (RSHFD) rectified the gut Prevotellaceae and considerably alleviated reduced septal gut-responsive neurons, decreased hippocampal theta rhythm, and impaired hippocampus-dependent memory in HFD-fed OVX mice. Furthermore, chemogenetic inhibition of septal PV[+] GABAergic neurons reversed the neuroprotective effects of resistant starch supplementation. These findings highlight the notable gut-sensory nature of medial septal PV[+] GABAergic neurons. A HFD accelerates estrogen deficiency-induced cognitive impairment by disrupting the gut Prevotellaceae-septo-hippocampal pathway. This study contributes to a better understanding of the precise gut-brain control of cognition and cognitive impairment in postmenopausal females.}, }
@article {pmid36626083, year = {2023}, author = {Wang, W and Yan, Y and Yu, F and Zhang, W and Su, S}, title = {Role of oral and gut microbiota in childhood obesity.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {36626083}, issn = {1874-9356}, abstract = {Childhood obesity not only causes damage to children's respiratory, cardiovascular, endocrine, motor, and other systems but also is a significant risk factor for metabolic diseases such as obesity in adulthood, which has become one of the serious public health problems worldwide. The etiology and pathogenesis of obesity are complex. In addition to genetic and lifestyle factors, recent studies have found that the microbes in the digestive tract play a crucial role in the occurrence and development of obesity. Among them, the gut microbiota has been confirmed to be one of the important pathogenic factors of obesity, which can mediate the occurrence and development of obesity by interfering with the balance of host energy metabolism and inducing low-grade chronic inflammation throughout the host. Targeting the gut microbiota to treat obesity through various methods such as fecal microbiota transplantation, dietary intervention, and probiotic supplementation has become a research hotspot in obesity treatment. In addition, the oral microbiota is also considered closely related to the occurrence and development of obesity due to its regulatory effect on the balance of gut microbiota. Exploring the relationship between oral and gut microbiota and childhood obesity elucidates the pathogenesis and treatment concepts of childhood obesity from a new perspective. It may provide new methods for the prevention and treatment of childhood obesity in the future.}, }
@article {pmid36624625, year = {2023}, author = {Oh, L and Ab Rahman, S and Dubinsky, K and Azanan, MS and Ariffin, H}, title = {Manipulating the Gut Microbiome as a Therapeutic Strategy to Mitigate Late Effects in Childhood Cancer Survivors.}, journal = {Technology in cancer research &amp; treatment}, volume = {22}, number = {}, pages = {15330338221149799}, doi = {10.1177/15330338221149799}, pmid = {36624625}, issn = {1533-0338}, abstract = {Recent studies have identified causal links between altered gut microbiome, chronic inflammation, and inflammation-driven conditions such as diabetes and cardiovascular disease. Childhood cancer survivors (CCS) show late effects of therapy in the form of inflammaging-related disorders as well as microbial dysbiosis, supporting a hypothesis that the conditions are interconnected. Given the susceptibility of the gut microbiome to alteration, a number of therapeutic interventions have been investigated for the treatment of inflammatory conditions, though not within the context of cancer survivorship in children and adolescents. Here, we evaluate the potential for these interventions, which include probiotic supplementation, prebiotics/fiber-rich diet, exercise, and fecal microbiota transplantation for prevention and treatment of cancer treatment-related microbial dysbiosis in survivors. We also make recommendations to improve adherence and encourage long-term lifestyle changes for maintenance of healthy gut microbiome in CCS as a potential strategy to mitigate treatment-related late effects.}, }
@article {pmid36624505, year = {2023}, author = {Green, JE and McGuinness, AJ and Berk, M and Castle, D and Athan, E and Hair, C and Strandwitz, P and Loughman, A and Nierenberg, AA and Cryan, JF and Mohebbi, M and Jacka, F}, title = {Safety and feasibility of faecal microbiota transplant for major depressive disorder: study protocol for a pilot randomised controlled trial.}, journal = {Pilot and feasibility studies}, volume = {9}, number = {1}, pages = {5}, pmid = {36624505}, issn = {2055-5784}, abstract = {BACKGROUND: Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain-axis is now recognised as playing a role in mental and brain health, and promising preclinical and clinical data suggest Faecal Microbiota Transplants (FMT) may be efficacious for treating a range of mental illnesses. However, there are no existing published studies in humans evaluating the efficacy of FMT for MDD.<br><br>METHODS AND DESIGN: This protocol describes an 8-week, triple-blind, 2:1 parallel group, randomised controlled pilot trial (n = 15), of enema-delivered FMT treatment (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. There will be a further 26-week follow-up to monitor longer-term safety. Participants will receive four FMT or placebo enemas over four consecutive days. The primary aims of the study are to evaluate feasibility and safety of FMT as an adjunctive treatment for MDD in adults. Changes in gut microbiota will be assessed as a secondary outcome. Other data will be collected, including changes in depression and anxiety symptoms, and safety parameters.<br><br>DISCUSSION: Modification of the microbiota-gut-brain axis via FMT is a promising potential treatment for MDD, but there are no published rigorous clinical trials evaluating its use. If this study finds that our FMT strategy is safe and feasible, a larger fully powered RCT is planned. Further high-quality research in this field is urgently needed to address unmet need.<br><br>TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12621000932864.}, }
@article {pmid36623885, year = {2023}, author = {Uehara, S and Higuchi, Y and Yoneda, N and Kato, H and Yamazaki, H and Suemizu, H}, title = {The Unique Human N10-Glucuronidated Metabolite Formation from Olanzapine in Chimeric NOG-TKm30 Mice with Humanized Livers.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {}, number = {}, pages = {}, doi = {10.1124/dmd.122.001102}, pmid = {36623885}, issn = {1521-009X}, abstract = {Olanzapine is an antipsychotic agent with species-dependent pharmacokinetic profiles in both humans and animals. In the present study, the metabolic profiles of olanzapine in vitro and in vivo were compared in non-transplanted immunodeficient NOG-TKm30 mice and chimeric mice with humanized livers (hereafter humanized-liver mice). Hepatic microsomal fractions prepared from humanized-liver mice and humans mediated olanzapine N10-glucuronidation, whereas fractions from cynomolgus monkeys, marmosets, minipigs, dogs, rabbits, guinea pigs, rats, CD1 mice, and NOG-TKm30 mice did not. The olanzapine N10-glucuronidation activity in liver microsomes from humanized-liver mice was inhibited by hecogenin, a human UDP-glucuronosyltransferase (UGT) 1A4 inhibitor. In addition, hepatocytes from humanized-liver mice suggest that olanzapine N10-glucuronidation was a major metabolic pathway in the livers of humanized-liver mice. After a single oral dose of olanzapine (10 mg/kg body weight) to humanized-liver mice and control NOG-TKm30 mice, olanzapine N10-glucuronide isomers and olanzapine N4'-glucuronide were detected only in the plasma of humanized-liver mice. In contrast, the area under the curve for N4'-demethylolanzapine, 2-hydroxymethylolanzapine, and 7-hydroxyolanzapine glucuronide was higher in NOG-TKm30 mice than that in humanized-liver mice. The cumulative excreted amounts of olanzapine N10-glucuronide isomers were high in the urine and feces from humanized-liver mice, whereas the cumulative excreted amounts of 2-hydroxymethylolanzapine were higher in NOG-TKm30 mice than in humanized-liver mice. Thus, production of human-specific olanzapine N10-glucuronide was observed in humanized-liver mice, which was consistent with the in vitro glucuronidation data. These results suggest that humanized-liver mice are useful for studying drug oxidation and conjugation of olanzapine in humans. Significance Statement Human-specific olanzapine N10-glucuronide isomers were generated in chimeric NOG-TKm30 mice with humanized livers (humanized-liver mice), and high UGT1A4-dependent N10-glucuronidation was observed in the liver microsomes from humanized-liver mice. Hence, humanized-liver mice may be a suitable model for studying UGT1A4-dependent biotransformation of drugs in humans.}, }
@article {pmid36620981, year = {2023}, author = {Baunwall, SMD and Andreasen, SE and Hansen, MM and Kelsen, J and Høyer, KL and Rågård, N and Eriksen, LL and Støy, S and Rubak, T and Damsgaard, EMS and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection - Authors' reply.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {112-113}, doi = {10.1016/S2468-1253(22)00424-1}, pmid = {36620981}, issn = {2468-1253}, }
@article {pmid36620980, year = {2023}, author = {Krutova, M and Davis, K and Guery, B and Barbut, F}, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {111-112}, doi = {10.1016/S2468-1253(22)00388-0}, pmid = {36620980}, issn = {2468-1253}, }
@article {pmid36620979, year = {2023}, author = {Aby, ES and Rajasingham, R and Enns, EA and Vaughn, BP}, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {110-111}, doi = {10.1016/S2468-1253(22)00353-3}, pmid = {36620979}, issn = {2468-1253}, }
@article {pmid36620978, year = {2023}, author = {Goldenberg, SD and Merrick, B}, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {109-110}, doi = {10.1016/S2468-1253(22)00343-0}, pmid = {36620978}, issn = {2468-1253}, }
@article {pmid36620977, year = {2023}, author = {van Prehn, J and Fitzpatrick, F and Kuijper, EJ and , }, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {109}, doi = {10.1016/S2468-1253(22)00342-9}, pmid = {36620977}, issn = {2468-1253}, }
@article {pmid36620345, year = {2022}, author = {Xiang, H and Liu, QP}, title = {Alterations of the gut microbiota in coronavirus disease 2019 and its therapeutic potential.}, journal = {World journal of gastroenterology}, volume = {28}, number = {47}, pages = {6689-6701}, pmid = {36620345}, issn = {2219-2840}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global health. SARS-CoV-2 infects host cells primarily by binding to angiotensin-converting enzyme 2, which is coexpressed in alveolar type 2 cells and gut epithelial cells. It is known that COVID-19 often presents with gastrointestinal symptoms and gut dysbiosis, mainly characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. In recent years, multiple studies have comprehensively explored gut microbiota alterations in COVID-19 and highlighted the clinical correlation between dysbiosis and COVID-19. SARS-CoV-2 causes gastrointestinal infections and dysbiosis mainly through fecal-oral transmission and the circulatory and immune pathways. Studies have shown that the gut microbiota and its metabolites can regulate the immune response and modulate antiviral effects. In addition, the gut microbiota is closely related to gastrointestinal symptoms, such as diarrhea, a common gastrointestinal symptom among COVID-19. Therefore, the contribution of the gut microbiota in COVID-19 should not be overlooked. Strategies targeting the gut microbiota via probiotics, prebiotics and fecal microbiota transplantation should be considered to treat this patient population in the future. However, the specific alterations and mechanisms as well as the contributions of gut microbiota in COVID-19 should be urgently further explored.}, }
@article {pmid36620003, year = {2022}, author = {Zhang, L and Lang, H and Ran, L and Tian, G and Shen, H and Zhu, J and Zhang, Q and Yi, L and Mi, M}, title = {Long-term high loading intensity of aerobic exercise improves skeletal muscle performance via the gut microbiota-testosterone axis.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1049469}, pmid = {36620003}, issn = {1664-302X}, abstract = {Exercise is reported to play a crucial role in skeletal muscle performance. However, the underlying mechanism is still unknown. Thus, we investigated the effect of high-intensity aerobic exercise on skeletal muscle performance. In this study, the male C57BL/6J mice were accepted by high-intensity aerobic exercise for 8 weeks to establish an exercise model. It was observed that high-intensity aerobic exercise markedly affected the expression of genes in skeletal muscle. Moreover, high-intensity aerobic exercise significantly improved skeletal muscle grip strength and serum testosterone levels. HE staining showed that the cross-sectional area (CSA) of the skeletal muscle was successfully increased after 8 weeks of high-intensity aerobic exercise. Additionally, we found that high-intensity aerobic exercise changed gut microbiota structure by altering the abundance of Akkermansia, Allobaculum, and Lactobacillus, which might be related to testosterone production. However, the beneficial effects disappeared after the elimination of the gut microbiota and recovered after fecal microbiota transplantation (FMT) experiments for 1 week. These results indicated that the beneficial effects of high-intensity aerobic exercise on skeletal muscle were partly dependent on the gut microbiota. Our results suggested that long-term high loading intensity of aerobic exercise could improve skeletal muscle performance, which was probably due to the gut microbiota-testosterone axis.}, }
@article {pmid36618438, year = {2022}, author = {Ramos, RJ and Zhu, C and Joseph, DF and Thaker, S and Lacomb, JF and Markarian, K and Lee, HJ and Petrov, JC and Monzur, F and Buscaglia, JM and Chawla, A and Small-Harary, L and Gathungu, G and Morganstern, JA and Yang, J and Li, J and Pamer, EG and Robertson, CE and Frank, DN and Cross, JR and Li, E}, title = {Metagenomic and bile acid metabolomic analysis of fecal microbiota transplantation for recurrent Clostridiodes difficile and/or inflammatory bowel diseases.}, journal = {Medical research archives}, volume = {10}, number = {10}, pages = {}, pmid = {36618438}, issn = {2375-1916}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infections (rCDI), but has more limited efficacy in treating either ulcerative colitis (UC) or Crohn's disease (CD), two major forms of inflammatory bowel diseases (IBD). We hypothesize that FMT recipients with rCDI and/or IBD have baseline fecal bile acid (BA) compositions that differ significantly from that of their healthy donors and that FMT will normalize the BA compositions.<br><br>AIM: To study the effect of single colonoscopic FMT on microbial composition and function in four recipient groups: 1.) rCDI patients without IBD (rCDI-IBD); 2.) rCDI with IBD (rCDI+IBD); 3.) UC patients without rCDI (UC-rCDI); 4.) CD patients without rCDI (CD-rCDI).<br><br>METHODS: We performed 16S rRNA gene sequence, shotgun DNA sequence and quantitative bile acid metabolomic analyses on stools collected from 55 pairs of subjects and donors enrolled in two prospective single arm FMT clinical trials (Clinical Trials.gov ID NCT03268213, 479696, UC no rCDI &#x2265; 2x IND 1564 and NCT03267238, IND 16795). Fitted linear mixed models were used to examine the effects of four recipient groups, FMT status (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on microbial diversity and composition, bile acid metabolites and bile acid metabolizing enzyme gene abundance.<br><br>RESULTS: The pre-FMT stools collected from rCDI &#xb1; IBD recipients had reduced &#x3b1;-diversity compared to the healthy donor stools and was restored post-FMT. The &#x3b1;-diversity in the pre-FMT stools collected from UC-rCDI or CD-rCDI recipients did not differ significantly from donor stools. FMT normalized some recipient/donor ratios of genus level taxa abundance in the four groups. Fecal secondary BA levels, including some of the secondary BA epimers that exhibit in vitro immunomodulatory activities, were lower in rCDI&#xb1;IBD and CD-rCDI but not UC-rCDI recipients compared to donors. FMT restored secondary BA levels. Metagenomic baiE gene and some of the eight bile salt hydrolase (BSH) phylotype abundances were significantly correlated with fecal BA levels.<br><br>CONCLUSION: Restoration of multiple secondary BA levels, including BA epimers implicated in immunoregulation, are associated with restoration of fecal baiE gene counts, suggesting that the 7-&#x3b1;-dehydroxylation step is rate-limiting.}, }
@article {pmid36615885, year = {2023}, author = {Flaig, B and Garza, R and Singh, B and Hamamah, S and Covasa, M}, title = {Treatment of Dyslipidemia through Targeted Therapy of Gut Microbiota.}, journal = {Nutrients}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/nu15010228}, pmid = {36615885}, issn = {2072-6643}, abstract = {Dyslipidemia is a multifaceted condition with various genetic and environmental factors contributing to its pathogenesis. Further, this condition represents an important risk factor for its related sequalae including cardiovascular diseases (CVD) such as coronary artery disease (CAD) and stroke. Emerging evidence has shown that gut microbiota and their metabolites can worsen or protect against the development of dyslipidemia. Although there are currently numerous treatment modalities available including lifestyle modification and pharmacologic interventions, there has been promising research on dyslipidemia that involves the benefits of modulating gut microbiota in treating alterations in lipid metabolism. In this review, we examine the relationship between gut microbiota and dyslipidemia, the impact of gut microbiota metabolites on the development of dyslipidemia, and the current research on dietary interventions, prebiotics, probiotics, synbiotics and microbiota transplant as therapeutic modalities in prevention of cardiovascular disease. Overall, understanding the mechanisms by which gut microbiota and their metabolites affect dyslipidemia progression will help develop more precise therapeutic targets to optimize lipid metabolism.}, }
@article {pmid36615662, year = {2022}, author = {Zhang, W and Zhang, Y and Li, Y and Ma, D and Zhang, H and Kwok, LY}, title = {Lacticaseibacillus rhamnosus Probio-M9-Driven Mouse Mammary Tumor-Inhibitory Effect Is Accompanied by Modulation of Host Gut Microbiota, Immunity, and Serum Metabolome.}, journal = {Nutrients}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/nu15010005}, pmid = {36615662}, issn = {2072-6643}, abstract = {Gut microbiome may influence tumor growth and cancer treatment efficacy, so it is a potential target for tumor prevention/treatment. This pilot study investigated the preventive and therapeutic effects of a probiotic strain, Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9), against murine mammary cancer. Thirty-six female mice were randomly divided into three groups (n = 12 per group): control (without tumor transplantation), model (tumor transplantation; no probiotic administration), and probiotic (30-day oral gavage of probiotic, started seven days before tumor transplantation). Changes in tumor size were recorded, and blood, tumor tissue, and stool samples were collected at the end of the trial for analyses. Comparing with the model group, the probiotic group had a significantly smaller tumor volume (p < 0.05), a higher fecal microbiota Shannon diversity index, with significant modifications in the gut microbiota structure (p < 0.05), characterized by more Alistipes sp._2, Porphyromonadaceae bacterium_7, and Bacteroidales bacterium 55_9 (p < 0.05). Additionally, Probio-M9 administration elevated the serum IFN-γ, IL-9, IL-13, and IL-27 levels and several metabolites (e.g., pyridoxal, nicotinic acid, 3-hydroxybutyric acid, glutamine; p < 0.05), while reducing IL-5 (p < 0.05). These changes might be associated with the protective effect of Probio-M9 against mammary tumor growth. Thus, probiotic administration could harness host gut microbiome in anti-cancer responses.}, }
@article {pmid36611911, year = {2022}, author = {Elangovan, S and Borody, TJ and Holsinger, RMD}, title = {Fecal Microbiota Transplantation Reduces Pathology and Improves Cognition in a Mouse Model of Alzheimer's Disease.}, journal = {Cells}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/cells12010119}, pmid = {36611911}, issn = {2073-4409}, abstract = {Characterized by the presence of amyloid plaques, neurofibrillary tangles and neuroinflammation, Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no known treatment or cure. Global disease projections warrant an urgent and rapid therapeutic for the treatment of this devastating disease. Fecal microbiota transplantation (FMT) is a widely accepted and safely used treatment for recurrent Clostridium difficile infection and other metabolic diseases such as diabetes mellitus. FMT has also been demonstrated to be a possible AD therapeutic. We examined the potential of FMT for the treatment of AD in a robust, mouse model of the disease and report that a brief, 7-day treatment regimen demonstrated 'plaque-busting' and behavior-modifying effects in treated 5xFAD mice. Importantly, we show that donor age plays an important role in the efficacy of the treatment and these findings warrant further investigation in human trials.}, }
@article {pmid36611848, year = {2022}, author = {Anand, N and Gorantla, VR and Chidambaram, SB}, title = {The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders.}, journal = {Cells}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/cells12010054}, pmid = {36611848}, issn = {2073-4409}, abstract = {Mounting evidence shows that the complex gut microbial ecosystem in the human gastrointestinal (GI) tract regulates the physiology of the central nervous system (CNS) via microbiota and the gut-brain (MGB) axis. The GI microbial ecosystem communicates with the brain through the neuroendocrine, immune, and autonomic nervous systems. Recent studies have bolstered the involvement of dysfunctional MGB axis signaling in the pathophysiology of several neurodegenerative, neurodevelopmental, and neuropsychiatric disorders (NPDs). Several investigations on the dynamic microbial system and genetic-environmental interactions with the gut microbiota (GM) have shown that changes in the composition, diversity and/or functions of gut microbes (termed "gut dysbiosis" (GD)) affect neuropsychiatric health by inducing alterations in the signaling pathways of the MGB axis. Interestingly, both preclinical and clinical evidence shows a positive correlation between GD and the pathogenesis and progression of NPDs. Long-term GD leads to overstimulation of hypothalamic-pituitary-adrenal (HPA) axis and the neuroimmune system, along with altered neurotransmitter levels, resulting in dysfunctional signal transduction, inflammation, increased oxidative stress (OS), mitochondrial dysfunction, and neuronal death. Further studies on the MGB axis have highlighted the significance of GM in the development of brain regions specific to stress-related behaviors, including depression and anxiety, and the immune system in the early life. GD-mediated deregulation of the MGB axis imbalances host homeostasis significantly by disrupting the integrity of the intestinal and blood-brain barrier (BBB), mucus secretion, and gut immune and brain immune functions. This review collates evidence on the potential interaction between GD and NPDs from preclinical and clinical data. Additionally, we summarize the use of non-therapeutic modulators such as pro-, pre-, syn- and post-biotics, and specific diets or fecal microbiota transplantation (FMT), which are promising targets for the management of NPDs.}, }
@article {pmid36610712, year = {2023}, author = {}, title = {Corrigendum to: Efficacy and Outcomes of Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjac195}, pmid = {36610712}, issn = {1876-4479}, }
@article {pmid36610264, year = {2023}, author = {Zheng, M and Zhou, W and Huang, C and Hu, Z and Zhang, B and Lu, Q and Zhao, M}, title = {A single-cell map of peripheral alterations after FMT treatment in patients with systemic lupus erythematosus.}, journal = {Journal of autoimmunity}, volume = {135}, number = {}, pages = {102989}, doi = {10.1016/j.jaut.2022.102989}, pmid = {36610264}, issn = {1095-9157}, abstract = {Systemic lupus erythematosus (SLE) is characterized by loss of self-tolerance and persistent self-aggression, sustained chronic inflammation, production of autoantibodies and multi-system damage, and is largely incurable to date. The gut microbiota and its metabolites, now recognized as crucial environmental triggers of local/systemic immune reactions, have been implicated in the development and progression of SLE. Fecal microbiota transplantation (FMT) is restoration of disturbed microbiota by transplanting foreign gut microbiota from healthy individuals into the gastrointestinal tract of diseased individuals. Our previous clinical trial suggests that FMT is a potentially safe and effective treatment for SLE. In order to elucidate the potential effect of FMT on peripheral immune cells of patients with SLE, we collected PBMCs (n = 30) of 13 SLE patients who participated in the clinical trial before and after the FMT-treatment, and performed single-cell RNA sequencing. The results first revealed that peripheral T lymphocytes of SLE patients decreased and NK cells increased after the FMT treatment. Then, sub-clustering analysis discovered that total CD4[+] T cells highly expressed genes of IL7R, CD28, and CD8[+] T cells highly expressed genes of GZMH and NKG7 after FMT treatment. Moreover, FMT treatment reduced the expression of interferon-related genes (IRGs) in CD4[+] T, CD8[+] T, DP, NK, and B cells of SLE patients. More importantly, interferon-related pathways were more enriched in cells of the FMT non-responder group, and further the interferon genes expression of lymphocytes and myeloid cells was negatively correlated with the efficiency of FMT treatment. Collectively, our data identified various immunophenotypic and associated gene set changes following FMT treatment, illustrating the heterogeneity of response to FMT treatment in SLE.}, }
@article {pmid36610135, year = {2022}, author = {Luo, Z and Xu, W and Yuan, T and Shi, C and Jin, T and Chong, Y and Ji, J and Lin, L and Xu, J and Zhang, Y and Kang, A and Zhou, W and Xie, T and Di, L and Shan, J}, title = {Platycodon grandiflorus root extract activates hepatic PI3K/PIP3/Akt insulin signaling by enriching gut Akkermansia muciniphila in high fat diet fed mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {109}, number = {}, pages = {154595}, doi = {10.1016/j.phymed.2022.154595}, pmid = {36610135}, issn = {1618-095X}, abstract = {BACKGROUND: Increasing hepatic insulin signaling is found to be an important mechanism of Platycodon grandiflorus root to alleviate metabolic syndrome (MetS) symptoms such as insulin resistance, obesity, hyperlipidemia and hepatic steatosis, but the details are not yet clear. Since the main constituents of Platycodon grandiflorus root were hard to be absorbed by gastrointestinal tract, getting opportunity to interact with gut microbiota, we speculate the gut microorganisms may mediate its effect.<br><br>PURPOSE: Our work aimed to confirm the critical role of gut microbes in the intervention of Platycodon grandiflorus root extract (PRE) on MetS, and investigate the mechanism.<br><br>METHODS: Biochemical analyses, glucose tolerance test and hepatic lipidomics analysis were used to evaluate the anti-MetS effect of PRE on high fat diet (HFD) fed mice. Perform 16S rDNA analysis, qPCR analysis and in vitro co-incubation experiment to study its effect on gut microbes, followed by fecal microbiota transplantation (FMT) experiment and antibiotics intervention experiment. Also, the effect of Akkermansia muciniphila treatment on HFD mice was investigated.<br><br>RESULTS: PRE alleviated lipid accumulation and insulin resistance in HFD mice and remodeled the fecal microbiome. It also increased the gene expression of colonic tight junction proteins, alleviated metabolic endotoxemia and inflammation, so that reduced TNF-&#x3b1; induced hepatic JNK-dependent IRS-1 serine phosphorylation and the impairment of PI3K/PIP3/Akt insulin signaling pathway. A. muciniphila was one of the most significantly enriched microbes by PRE treatment, and its administration to HFD mice showed similar effects to PRE, repairing the gut barrier and activating hepatic PI3K/PIP3/Akt pathway. Finally, anti-MetS effect of PRE could be delivered to FMT recipients, and PRE could not further attenuate MetS in gut microbiota depleted mice.<br><br>CONCLUSION: We demonstrated for the first time that PRE alleviated MetS in a gut microbiota dependent manner, and found activation of hepatic insulin signaling mediated by gut A. muciniphila was a potential mechanism of it.}, }
@article {pmid36608164, year = {2023}, author = {Li, J and Liu, H and Guo, F and Guo, R and Zhang, H and He, X and Ming, X and Ma, X and Shang, G and Ji, P and Song, L and Gao, S}, title = {Increased GABAergic projections in the paraventricular nucleus regulate colonic hypersensitivity via oxytocin in a rat model of irritable bowel syndrome.}, journal = {Neuroreport}, volume = {34}, number = {2}, pages = {108-115}, doi = {10.1097/WNR.0000000000001867}, pmid = {36608164}, issn = {1473-558X}, abstract = {Irritable bowel syndrome (IBS) is characterized by gastrointestinal dysmotility and visceral hyperalgesia, and the impaired brain-gut axis is accepted as a crucial cause for the onset of IBS. The objective of this study is to investigate the effects of the adaptive changes in the central neural system induced by stress on IBS-like syndromes in rats. Long-term water avoidance stress (WAS) was used to prepare IBS animals. The changes in neuronal excitation and GABA expression were shown by immunohistochemistry. The mRNA and protein expressions of neurotransmitters were detected with Quantitative reverse-transcription PCR (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). The intestinal transit time, fecal moisture content, and abdominal withdrawal reflex scores of rats were recorded to monitor intestinal motility and visceral hyperalgesia. In the WAS-treated rats with enhanced intestinal motility and visceral hypersensitivity, more GABAergic projections were found in the paraventricular nucleus (PVN) of the hypothalamus, which inhibited the firing rate of neurons and decreased the expression of oxytocin. Exogenous oxytocin improved gut motility and decreased AWR scores. The inhibition of oxytocin by the adaptive GABAergic projection in the PVN might be an important mediator of IBS, which indicates a potential novel therapeutic target.}, }
@article {pmid36605728, year = {2022}, author = {Gangadhar, M and Kottapalli, A and Kottapalli, V}, title = {A Novel Treatment Approach to Treatment-Resistant, Recurrent Clostridium difficile.}, journal = {Case reports in gastroenterology}, volume = {16}, number = {3}, pages = {646-651}, pmid = {36605728}, issn = {1662-0631}, abstract = {A 36-year-old male with a previous medical history of persistent Clostridium difficile presented to clinic for evaluation of diarrheal symptoms intermittently for the last 2 years. He reported recurrent episodes of C. difficile that initially began after prophylactic antibiotic use prior to a tooth extraction. He underwent 12 unsuccessful treatment trials at a nearby clinic with courses of vancomycin, metronidazole, and fidaxomicin. His chronic diarrhea had caused him to endure significant lifestyle alterations over the years. After multiple episodes of incomplete bacterial clearance, he was referred to a university-based tertiary care facility but instead opted for care at a nearby clinic. Upon work-up, his serology was again positive for C. difficile, and he was initiated on a 14-day course of fidaxomicin 200 mg p.o. BID, along with yogurt and probiotic supplementation. Despite fidaxomicin treatment, subsequent serological PCR testing for C. difficile remained positive, consistent with CT abdomen and pelvis findings suspicious for enteritis. His recurrent resistance to standard therapy protocols inspired an unconventional treatment approach: another 14-day course of fidaxomicin 200 mg p.o. BID, followed by fidaxomicin 200 mg p.o. each morning and cholestyramine 4 g p.o. each evening for another 2 weeks, concluded by fecal microbial transplant. Two weeks following this antibiotic regimen and fecal transplant, serology was negative for C. difficile. Subsequent follow-up revealed no evidence of recurrence.}, }
@article {pmid36605506, year = {2022}, author = {Zhang, W and Xie, J and Xia, S and Fan, X and Schmitz-Esser, S and Zeng, B and Zheng, L and Huang, H and Wang, H and Zhong, J and Zhang, Z and Zhang, L and Jiang, M and Hou, R}, title = {Evaluating a potential model to analyze the function of the gut microbiota of the giant panda.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1086058}, pmid = {36605506}, issn = {1664-302X}, abstract = {To contribute to the conservation of endangered animals, the utilization of model systems is critical to analyze the function of their gut microbiota. In this study, the results of a fecal microbial transplantation (FMT) experiment with germ-free (GF) mice receiving giant panda or horse fecal microbiota showed a clear clustering by donor microbial communities in GF mice, which was consistent with the results of blood metabolites from these mice. At the genus level, FMT re-established approximately 9% of the giant panda donor microbiota in GF mice compared to about 32% for the horse donor microbiota. In line with this, the difference between the panda donor microbiota and panda-mice microbiota on whole-community level was significantly larger than that between the horse donor microbiota and the horse-mice microbiota. These results were consistent with source tracking analysis that found a significantly higher retention rate of the horse donor microbiota (30.9%) than the giant panda donor microbiota (4.0%) in GF mice where the microbiota remained stable after FMT. Further analyzes indicated that the possible reason for the low retention rate of the panda donor microbiota in GF mice was a low relative abundance of Clostridiaceae in the panda donor microbiota. Our results indicate that the donor microbiota has a large effect on GF mice microbiota after FMT.}, }
@article {pmid36604442, year = {2023}, author = {Le Guern, R and Grandjean, T and Stabler, S and Bauduin, M and Gosset, P and Kipnis, &#xc9; and Dessein, R}, title = {Gut colonisation with multidrug-resistant Klebsiella pneumoniae worsens Pseudomonas aeruginosa lung infection.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {78}, pmid = {36604442}, issn = {2041-1723}, abstract = {Carbapenemase-producing Enterobacterales (CPE) are spreading rapidly in hospital settings. Asymptomatic CPE gut colonisation may be associated with dysbiosis and gut-lung axis alterations, which could impact lung infection outcomes. In this study, in male C57BL/6JRj mice colonised by CPE, we characterise the resulting gut dysbiosis, and analyse the lung immune responses and outcomes of subsequent Pseudomonas aeruginosa lung infection. Asymptomatic gut colonisation by CPE leads to a specific gut dysbiosis and increases the severity of P. aeruginosa lung infection through lower numbers of alveolar macrophages and conventional dendritic cells. CPE-associated dysbiosis is characterised by a near disappearance of the Muribaculaceae family and lower levels of short-chain fatty acids. Faecal microbiota transplantation restores immune responses and outcomes of lung infection outcomes, demonstrating the involvement of CPE colonisation-induced gut dysbiosis in altering the immune gut-lung axis, possibly mediated by microbial metabolites such as short-chain fatty acids.}, }
@article {pmid36604080, year = {2023}, author = {Liu, Y and Li, P and Pan, W and Zhao, J and Olnood, CG and Liu, Y and Xu, YJ}, title = {Salecan confers anti-inflammatory effects in liver injury via regulating gut microbiota and its metabolites.}, journal = {Carbohydrate polymers}, volume = {302}, number = {}, pages = {120418}, doi = {10.1016/j.carbpol.2022.120418}, pmid = {36604080}, issn = {1879-1344}, abstract = {Salecan, a natural β-glucan and one of the novel food ingredients approved in China, has been shown a variety of positive health effects, yet the mechanism of liver injury remains poorly understood. In addition, β-glucan could induce the shifts in gut microbiota, however, whether modulation of gut microbiota by β-glucan is associated with their positive health effects remain elusive. Here, the anti-inflammatory effects and the underlying mechanism of Salecan supplementation in CCl4-induced liver injury were investigated. After 8 weeks of treatment, we observed that Salecan alleviated liver injury by regulating inflammatory response and M2 macrophage polarization. In addition, Salecan treatment modulated the composition of gut microbiota and antibiotic cocktail treatment indicated that the hepatoprotective effect of Salecan was dependent on the gut microbiota. Fecal microbiota transplantation was used to further verify the mechanism, and we confirmed that microbial colonization partially alleviated liver injury. Besides, microbiota-derived metabolites of Salecan also contributed to the hepatoprotective and anti-inflammatory effect of Salecan against liver injury. These findings supported that Salecan intervention attenuated liver injury by regulating gut microbiota and its metabolites.}, }
@article {pmid36601003, year = {2022}, author = {Shang, J and Cui, W and Guo, R and Zhang, Y and Wang, P and Yu, W and Zheng, X and Wang, T and Dong, Y and Zhao, J and Ding, S and Xiao, J and Ren, Z and Zhao, Z}, title = {The harmful intestinal microbial community accumulates during DKD exacerbation and microbiome-metabolome combined validation in a mouse model.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {964389}, pmid = {36601003}, issn = {1664-2392}, abstract = {OBJECTIVE: Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is associated with gut microbial dysbiosis. We aim to build a diagnostic model to aid clinical practice and uncover a crucial harmful microbial community that contributes to DKD pathogenesis and exacerbation.<br><br>DESIGN: A total of 528 fecal samples from 180 DKD patients and 348 non-DKD populations (138 DM and 210 healthy volunteers) from the First Affiliated Hospital of Zhengzhou University were recruited and randomly divided into a discovery phase and a validation phase. The gut microbial composition was compared using 16S rRNA sequencing. Then, the 180 DKD patients were stratified into four groups based on clinical stages and underwent gut microbiota analysis. We established DKD mouse models and a healthy fecal microbiota transplantation (FMT) model to validate the effects of gut microbiota on DKD and select the potential harmful microbial community. Untargeted metabolome-microbiome combined analysis of mouse models helps decipher the pathogenetic mechanism from a metabolic perspective.<br><br>RESULTS: The diversity of the gut microbiome was significantly decreased in DKD patients when compared with that of the non-DKD population and was increased in the patients with more advanced DKD stages. The DKD severity in mice was relieved after healthy gut microbiota reconstruction. The common harmful microbial community was accumulated in the subjects with more severe DKD phenotypes (i.e., DKD and DKD5 patients and DKD mice). The harmful microbial community was positively associated with the serum injurious metabolites (e.g., cholic acid and hippuric acid).<br><br>CONCLUSION: The fecal microbial community was altered markedly in DKD. Combining the fecal analysis of both human and animal models selected the accumulated harmful pathogens. Partially recovering healthy gut microbiota can relieve DKD phenotypes via influencing pathogens' effect on DKD mice's metabolism.}, }
@article {pmid36600789, year = {2022}, author = {Perez Del Nogal, G and Patel, N}, title = {Refractory Checkpoint Inhibitor Colitis Responsive to Ustekinumab.}, journal = {ACG case reports journal}, volume = {9}, number = {12}, pages = {e00946}, pmid = {36600789}, issn = {2326-3253}, abstract = {Immune checkpoint inhibitors have transformed the treatment of cancer. Nonetheless, multiple immune-related adverse events have been reported, including checkpoint inhibitor colitis. Severe colitis can be complicated by ileus, megacolon, intestinal perforation, and death. Current appropriate treatment includes steroids, followed by antitumor necrosis factor biologic therapy, infliximab. Alternatively, vedolizumab and fecal microbiota transplantation have reported efficacy for refractory cases. In this study, we present the first case report of a patient with steroid-refractory checkpoint inhibitor-induced colitis due to pembrolizumab for Stage IV anaplastic thyroid carcinoma successfully treated with ustekinumab after failure of infliximab, vedolizumab, and fecal microbiota transplantation. This may lead to a better understanding of treatment options for refractory checkpoint inhibitor colitis.}, }
@article {pmid36600636, year = {2023}, author = {Yao, B and Cai, Y and Wang, W and Deng, J and Zhao, L and Han, Z and Wan, L}, title = {The Effect of Gut Microbiota on the Progression of Intervertebral Disc Degeneration.}, journal = {Orthopaedic surgery}, volume = {}, number = {}, pages = {}, doi = {10.1111/os.13626}, pmid = {36600636}, issn = {1757-7861}, abstract = {OBJECTIVE: Intervertebral disc degeneration (IDD) is the main cause of back pain, and its treatment is a serious socio-economic burden. The safety and treatment of fecal microbiota transplantation (FMT) has been established. However, the relationship between FMT and IDD still unclear. We aimed to explore whether FMT plays a role in IDD to provide a reference for the treatment of IDD.<br><br>METHODS: An experimental model of IDD was established using 2-month-old male Sprague-Dawley rats. FMT was performed by intragastric gavage of IDD rats with a fecal bacterial solution. Rat serum, feces, and vertebral disc tissue were collected after surgery for 2 months. The levels of TNF-&#x3b1;, IL-1&#x3b2;, IL-6, matrix metalloproteinase (MMP)-3, MMP-13, Collagen II, and aggrecan in the serum or vertebral disc tissue were measured by an enzyme-linked immunosorbent assay, immunohistochemistry, quantitative real-time polymerase chain reaction, or western blotting. We also examined the pathology of the vertebral disc tissue using hematoxylin and eosin (HE) and safranin O-fast green staining. Finally, we examined the gut microbiota in rat feces using 16&#x2009;S rRNA gene sequencing.<br><br>RESULTS: We found that the expression of TNF-&#x3b1;, IL-1&#x3b2;, IL-6, MMP-3, MMP-13, NLRP3 and Caspase-1 increased in the IDD group rats. In contrast, Collagen II and aggrecan levels were downregulated. Additionally, vertebral disc tissue was severely damaged in the IDD group, with disordered cell arrangement and uneven safranin coloration. FMT reversed the effects of IDD modeling on these factors and alleviated cartilage tissue damage. In addition, FMT increased the gut microbiota diversity and microbial abundance in rats treated with IDD.<br><br>CONCLUSION: Our findings suggest that FMT has a positive effect in maintaining cellular stability in the vertebral disc and alleviating histopathological damage. It affects the diversity and abundance of gut microbiota in rats with IDD. Therefore, FMT may serve as a promising target for amelioration of IDD.}, }
@article {pmid36597735, year = {2023}, author = {Liu, JY and Zhu, YP and Han, BM and Xia, SJ}, title = {[Effects of androgen deprivation therapy for prostate cancer on gut microbiota and treatment].}, journal = {Zhonghua yi xue za zhi}, volume = {103}, number = {2}, pages = {84-88}, doi = {10.3760/cma.j.cn112137-20220822-01789}, pmid = {36597735}, issn = {0376-2491}, abstract = {Androgen deprivation therapy is widely regarded as the first-line therapy for advanced prostate cancer. Although the initial efficacy is significant, clinical complications that arise after the therapy can reduce the patient's life quality, affect the efficacy, and even endanger their health or life due to the progression to castration-resistant prostate cancer (CRPC). The gut microbiota is associated not only with local diseases of the intestinal tract but also with systemic diseases such as liver or neurological diseases, but its relationship with prostate cancer is less frequently studied. Androgen deprivation therapy for prostate cancer affects the gut microbiota of prostate cancer patients, thereby inducing relevant complications and promoting CRPC formation. In this review, we present the microecological effects of androgen deprivation therapy for prostate cancer on gut microbiota from the perspectives of gut microbiota diversity, intestinal microbiota structure, and functional pathways. We also propose corresponding countermeasures, such as fecal microbiota transplantation, oral antibiotics, and oral probiotics, to improve the efficacy and outcome of androgen deprivation therapy for prostate cancer by regulating gut microbiota, and provide new ideas for the diagnosis and treatment of advanced prostate cancer.}, }
@article {pmid36596826, year = {2023}, author = {Xu, TT and Chen, P and Zhang, CD and Shaukat, A and Lin, LX and Yue, K and Ding, WL and Tong, X and Liu, KL and He, YF and Xie, JF and Liu, F and Zhang, C and Zhang, HY and Huang, SC}, title = {Gut microbiome dysregulation drives bone damage in broiler tibial dyschondroplasia by disrupting glucose homeostasis.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {1}, pmid = {36596826}, issn = {2055-5008}, abstract = {Tibial dyschondroplasia (TD) with multiple incentives is a metabolic skeletal disease that occurs in fast-growing broilers. Perturbations in the gut microbiota (GM) have been shown to affect bone homoeostasis, but the mechanisms by which GM modulates bone metabolism in TD broilers remain unknown. Here, using a broiler model of TD, we noted elevated blood glucose (GLU) levels in TD broilers, accompanied by alterations in the pancreatic structure and secretory function and damaged intestinal barrier function. Importantly, faecal microbiota transplantation (FMT) of gut microbes from normal donors rehabilitated the GM and decreased the elevated GLU levels in TD broilers. A high GLU level is a predisposing factor to bone disease, suggesting that GM dysbiosis-mediated hyperglycaemia might be involved in bone regulation. 16S rRNA gene sequencing and short-chain fatty acid analysis revealed that the significantly increased level of the metabolite butyric acid derived from the genera Blautia and Coprococcus regulated GLU levels in TD broilers by binding to GPR109A in the pancreas. Tibial studies showed reduced expression of vascular regulatory factors (including PI3K, AKT and VEFGA) based on transcriptomics analysis and reduced vascular distribution, contributing to nonvascularization of cartilage in the proximal tibial growth plate of TD broilers with elevated GLU levels. Additionally, treatment with the total flavonoids from Rhizoma drynariae further validated the improvement in bone homoeostasis in TD broilers by regulating GLU levels through the regulation of GM to subsequently improve intestinal and pancreatic function. These findings clarify the critical role of GM-mediated changes in GLU levels via the gut-pancreas axis in bone homoeostasis in TD chickens.}, }
@article {pmid36596758, year = {2023}, author = {Shin, J}, title = {Fecal microbiota transplantation is not a magical treatment, but better too early than too late.}, journal = {The Korean journal of internal medicine}, volume = {38}, number = {1}, pages = {3-4}, doi = {10.3904/kjim.2022.377}, pmid = {36596758}, issn = {2005-6648}, }
@article {pmid36596411, year = {2022}, author = {John Kenneth, M and Tsai, HC and Fang, CY and Hussain, B and Chiu, YC and Hsu, BM}, title = {Diet-mediated gut microbial community modulation and signature metabolites as potential biomarkers for early diagnosis, prognosis, prevention and stage-specific treatment of colorectal cancer.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2022.12.015}, pmid = {36596411}, issn = {2090-1224}, abstract = {BACKGROUND: Over the last decade, studies have shown an increased incidence of colorectal cancer (CRC), particularly early onset colorectal cancer (EOCRC). Researchers have demonstrated that dietary behavior, especially among young adults, influences alterations in the gut microbial community, leading to an increased accumulation of pathogenic gut microbiota and a decrease in beneficial ones. Unfortunately, CRC is likely to be diagnosed at a late stage, increasing CRC-related mortality. However, this alteration in the gut microbiota (gut dysbiosis) can be harnessed as a biomarker for non-invasive diagnosis, prognosis, prevention, and treatment of CRC in an effort to prevent late diagnosis and poor prognosis associated with CRC.<br><br>AIM: of Review This review discusses identification of potential biomarkers by targeting diet-mediated gut dysbiosis for the stage-specific diagnosis, prognosis, treatment, and prevention of CRC. Our findings provide a comprehensive insight into the potential of protumorigenic bacteria (e.g.pathogenic Escherichia coli,enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum) and their metabolites (e.g., colibactin and B. fragilis toxin) from gut dysbiosis as biomarkers for the diagnosis of CRC. Key Scientific Concepts of Review Collectively, a detailed understanding of the available data from current studies suggests that, further research on quantification of metabolites and stage-specific pathogenic microbial abundance is required for the diagnosis and treatment of CRC based on microbial dysbiosis. Specifically, future studies on faecal samples, from patient with CRC, should be conducted for F. nucleatum among different opportunistic bacteria, given its repeated occurrence in faecal samples and CRC biopsies in numerous studies. Finally, we discuss the potential of faecal microbial transplantation (FMT) as an intervention to restore damaged gut microbiota during CRC treatment and management.}, }
@article {pmid36595955, year = {2022}, author = {Lynn, MA and Ryan, FJ and Tee, YC and Lynn, DJ}, title = {Protocol to colonize gnotobiotic mice in early life and assess the impact on early life immune programming.}, journal = {STAR protocols}, volume = {3}, number = {4}, pages = {101914}, doi = {10.1016/j.xpro.2022.101914}, pmid = {36595955}, issn = {2666-1667}, abstract = {Understanding how changes in gut microbiota in early life impact immune programming can be difficult to study due to variations in the assembly of the microbiota. In this protocol, we describe how to colonize gnotobiotic/germ-free mice in early life with different microbiota community types (e.g., PAMI and PAMII). We detail several assays to determine whether differential colonization alters immune programming in early life. We also describe how to propagate mouse fecal microbiota transplant material if the donor fecal sample is limited. For complete details on the use and execution of this protocol, please refer to Lynn et al. (2021).[1].}, }
@article {pmid36590421, year = {2022}, author = {Huang, Z and Liu, K and Ma, W and Li, D and Mo, T and Liu, Q}, title = {The gut microbiome in human health and disease-Where are we and where are we going? A bibliometric analysis.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1018594}, pmid = {36590421}, issn = {1664-302X}, abstract = {BACKGROUND: There are trillions of microbiota in our intestinal tract, and they play a significant role in health and disease via interacting with the host in metabolic, immune, neural, and endocrine pathways. Over the past decades, numerous studies have been published in the field of gut microbiome and disease. Although there are narrative reviews of gut microbiome and certain diseases, the whole field is lack of systematic and quantitative analysis. Therefore, we outline research status of the gut microbiome and disease, and present insights into developments and characteristics of this field to provide a holistic grasp and future research directions.<br><br>METHODS: An advanced search was carried out in the Web of Science Core Collection (WoSCC), basing on the term "gut microbiome" and its synonyms. The current status and developing trends of this scientific domain were evaluated by bibliometric methodology. CiteSpace was used to perform collaboration network analysis, co-citation analysis and citation burst detection.<br><br>RESULTS: A total of 29,870 articles and 13,311 reviews were retrieved from the database, which involve 42,900 keywords, 176 countries/regions, 19,065 institutions, 147,225 authors and 4,251 journals. The gut microbiome and disease research is active and has received increasing attention. Co-cited reference analysis revealed the landmark articles in the field. The United States had the largest number of publications and close cooperation with other countries. The current research mainly focuses on gastrointestinal diseases, such as inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), while extra-intestinal diseases are also rising, such as obesity, diabetes, cardiovascular disease, Alzheimer's disease, Parkinson's disease. Omics technologies, fecal microbiota transplantation (FMT) and metabolites linked to mechanism would be more concerned in the future.<br><br>CONCLUSION: The gut microbiome and disease has been a booming field of research, and the trend is expected to continue. Overall, this research field shows a multitude of challenges and great opportunities.}, }
@article {pmid36590298, year = {2022}, author = {Li, Q and Cao, M and Wei, Z and Mei, J and Zhang, Y and Li, M and Li, M and Zhang, Y and Wang, Z}, title = {The protective effect of Buzhong Yiqi decoction on ischemic stroke mice and the mechanism of gut microbiota.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {956620}, pmid = {36590298}, issn = {1662-4548}, abstract = {Buzhong Yiqi decoction (BZYQD) has been developed for preventing or reducing the recurrence of ischemic stroke for a long time in China. However, the mechanism of action of the BZYQD is not completely understood. Our research aims to determine whether the mechanism of action of BZYQD is by regulating gut microbiota using 16SR RNA and fecal microbiota transplantation. In a cerebral ischemia mouse model, the results showed that prophylactic administration of BZYQD could reduce brain infarct volume and improve neurological function and behavior. The prophylactic administration of BZYQD could regulate intestinal microbiota and increase the abundance of butyrate-producing Prevotellaceae_NK3B31_group and probiotic Akkermansia in mice 72 h after surgery. Transplanting BZYQD-administered bacterial flora into antibiotic-depleted mice could reproduce the therapeutic effects of BZYQD. Overall, our study provided molecular insights into the mechanism and impact of BZYQD in the prevention of cerebral ischemic damage and highlighted the potential of regulation of intestinal microbiota as a therapeutic approach for ischemic stroke.}, }
@article {pmid36586523, year = {2022}, author = {Cai, Y and Li, X and Han, Q and Bai, J and Zheng, Q and Sun, R and Liu, R}, title = {Si-Ni-San improves experimental colitis by favoring Akkermensia colonization.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {116067}, doi = {10.1016/j.jep.2022.116067}, pmid = {36586523}, issn = {1872-7573}, abstract = {Ulcerative colitis (UC) is widely believed to be a leading risk factor of colorectal cancer. Gut microbiota is a known vital player in the progression of UC. Si-Ni-San (SNS) has been considered to effectively treat colitis in clinical practice during thousands of years, yet whether SNS ameliorated acute colitis mouse model by modulating intestinal flora has not been distinctly elucidated.<br><br>AIM OF THE STUDY: Our study aimed to elucidate the effect of SNS against acute murine colitis and focused on the underlying mechanisms of SNS targeting gut microbiota.<br><br>MATERIALS AND METHODS: 16S RNA sequencing, molecular biological analysis, and fecal microbiota transplants (FMT) were conducted to reveal the mechanisms of SNS in regulating gut microbiota.<br><br>RESULTS: In our study, SNS dramatically inhibited DSS-induced acute inflammatory responses by improving gut microbiota dysbiosis, as evidenced by decreased abundance proinflammatory species, upregulated abundance of anti-inflammatory species and potentially altered microbiota metabolite metabolism. Additionally, intestinal flora knockout and FMT experiments confirmed that the therapeutic effect of SNS on colitis was dependent on gut microbiota, and specifically on favoring the growth of potential probiotics, Akkermansia genus. Furthermore, we found that SNS alone and SNS combined with Akkermansia muciniphila (A. muciniphila) increased Mucin 2 (MUC2) production, thus enhancing the competitive edge of A. muciniphila among pathogenic gut microbiota.<br><br>CONCLUSION: Our study shed lights on the underlying mechanism of SNS in attenuating acute murine colitis from the perspective of intestinal flora and provides novel insights into the discovery of adjacent therapeutic strategy against colitis based on SNS and probiotics.<br><br>CLASSIFICATION: Gastro-intestinal system.}, }
@article {pmid36586452, year = {2022}, author = {Lin, D and Sun, Q and Liu, Z and Pan, J and Zhu, J and Wang, S and Jia, S and Zheng, M and Li, X and Gong, F}, title = {Gut microbiota and bile acids partially mediate the improvement of fibroblast growth factor 21 on methionine-choline-deficient diet-induced non-alcoholic fatty liver disease mice.}, journal = {Free radical biology &amp; medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2022.12.087}, pmid = {36586452}, issn = {1873-4596}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, inflammation, and fibrosis, as well as gut dysbiosis. Fibroblast growth factor 21 (FGF21), which regulates glucose and lipid metabolism, has been proven to have a good effect on NAFLD. However, the modulating process between FGF21 and gut microbiota remains unclear in treating NAFLD. Here, the fecal microbiota composition of 30 patients with NAFLD who had undergone liver biopsy and 29 matched healthy participants were studied, together with the fecal bile acid (BA) profile. Treatment with FGF21 was given in methionine-choline-deficient (MCD) diet-induced NAFLD model C57BL/6 mice. An antibiotic cocktail and fecal microbiota transplantation were used to further confirm the benefits of FGF21 that were partially attributable to the change in gut microbiota. Patients with NAFLD had higher serum FGF21 levels and dysregulated fecal microbiota compositions and fecal BA profiles. In NAFLD mice, FGF21 significantly reduced steatohepatitis and collagen deposition in vivo and restored intestinal structure. FGF21 treatment also changed gut microbiota composition and regulated dysbiosis in BA metabolism. After treatment with an antibiotic cocktail, FGF21 partially alleviated hepatic and intestinal damage in NAFLD mice. Furthermore, fecal microbiota transplantation from FGF21-treated mice showed benefits similar to FGF21 therapy. The improvement using FGF21 in MCD diet-induced NAFLD mice is partially mediated via gut microbiota and BA. Gut microbiota-regulated BA metabolism may be a potential target of FGF21 in improving NAFLD.}, }
@article {pmid36585803, year = {2022}, author = {Sun, T and Du, H and Li, Z and Xiong, J and Liu, Y and Li, Y and Zhang, W and Liang, F and He, J and Liu, X and Xiang, H}, title = {Decoding the contributions of gut microbiota and cerebral metabolism in acute liver injury mice with and without cognitive dysfunction.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/cns.14069}, pmid = {36585803}, issn = {1755-5949}, abstract = {AIMS: Patients with acute liver injury (ALI) can develop cognitive dysfunction (CD). The study investigated the role of gut microbiota and cerebral metabolism in ALI mice with and without CD.<br><br>METHODS: Male C57BL/6 mice that received thioacetamide were classified into ALI mice with (susceptible) or without (unsusceptible) CD-like phenotypes by hierarchical cluster analysis of behavior. The role of gut microbiota was investigated by 16S ribosomal RNA gene sequencing and feces microbiota transplantation (FMT). [1] H-[[13] C] NMR and electrophysiology were used to detect the changes in cerebral neurotransmitter metabolic and synaptic transition in neurons or astrocytes.<br><br>RESULTS: Apromixlay 55% (11/20) of mice developed CD and FMT from the susceptible group transmitted CD to gut microbiota-depleted mice. Alloprevotella was enriched in the susceptible group. GABA production was decreased in the frontal cortex, while hippocampal glutamine was increased in the susceptible group. Altered Escherichia. Shigella and Alloprevotella were correlated with behaviors and cerebral metabolic kinetics and identified as good predictors of ALI-induced CD. The frequencies of both miniature inhibitory and excitatory postsynaptic currents in hippocampal CA1 and prefrontal cortex were decreased in the susceptible group.<br><br>CONCLUSION: Altered transmitter metabolism and synaptic transmission in the hippocampus and prefrontal cortex and gut microbiota disturbance may lead to ALI-induced CD.}, }
@article {pmid36585700, year = {2022}, author = {Borgers, JSW and Burgers, FH and Terveer, EM and van Leerdam, ME and Korse, CM and Kessels, R and Flohil, CC and Blank, CU and Schumacher, TN and van Dijk, M and Henderickx, JGE and Keller, JJ and Verspaget, HW and Kuijper, EJ and Haanen, JBAG}, title = {Conversion of unresponsiveness to immune checkpoint inhibition by fecal microbiota transplantation in patients with metastatic melanoma: study protocol for a randomized phase Ib/IIa trial.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {1366}, pmid = {36585700}, issn = {1471-2407}, abstract = {BACKGROUND: The gut microbiome plays an important role in immune modulation. Specifically, presence or absence of certain gut bacterial taxa has been associated with better antitumor immune responses. Furthermore, in trials using fecal microbiota transplantation (FMT) to treat melanoma patients unresponsive to immune checkpoint inhibitors (ICI), complete responses (CR), partial responses (PR), and durable stable disease (SD) have been observed. However, the underlying mechanism determining which patients will or will not respond and what the optimal FMT composition is, has not been fully elucidated, and a discrepancy in microbial taxa associated with clinical response has been observed between studies. Furthermore, it is unknown whether a change in the microbiome itself, irrespective of its origin, or FMT from ICI responding donors, is required for reversion of ICI-unresponsiveness. To address this, we will transfer microbiota of either ICI responder or nonresponder metastatic melanoma patients via FMT.<br><br>METHODS: In this randomized, double-blinded phase Ib/IIa trial, 24 anti-PD1-refractory patients with advanced stage cutaneous melanoma will receive an FMT from either an ICI responding or nonresponding donor, while continuing anti-PD-1 treatment. Donors will be selected from patients with metastatic melanoma treated with anti-PD-1 therapy. Two patients with a good response (&#x2265;&#x2009;30% decrease according to RECIST&#xa0;1.1 within the past 24&#xa0;months) and two patients with progression (&#x2265;&#x2009;20% increase according to RECIST&#xa0;1.1 within the past 3&#xa0;months) will be selected as ICI responding or nonresponding donors, respectively. The primary endpoint is clinical benefit (SD, PR or CR) at 12&#xa0;weeks, confirmed on a CT scan at 16&#xa0;weeks. The secondary endpoint is safety, defined as the occurrence of grade&#x2009;&#x2265;&#x2009;3 toxicity. Exploratory endpoints are progression-free survival and changes in the gut microbiome, metabolome, and immune cells.<br><br>DISCUSSION: Transplanting fecal microbiota to restore the patients' perturbed microbiome has proven successful in several indications. However, less is known about the potential role of FMT to improve antitumor immune response. In this trial, we aim to investigate whether administration of FMT can reverse resistance to anti-PD-1 treatment in patients with advanced stage melanoma, and whether the ICI-responsiveness of the feces donor is associated with its effectiveness.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov: NCT05251389 (registered 22-Feb-2022). Protocol V4.0 (08-02-2022).}, }
@article {pmid36585238, year = {2022}, author = {Hajjar, R and Gonzalez, E and Fragoso, G and Oliero, M and Alaoui, AA and Calvé, A and Vennin Rendos, H and Djediai, S and Cuisiniere, T and Laplante, P and Gerkins, C and Ajayi, AS and Diop, K and Taleb, N and Thérien, S and Schampaert, F and Alratrout, H and Dagbert, F and Loungnarath, R and Sebajang, H and Schwenter, F and Wassef, R and Ratelle, R and Debroux, E and Cailhier, JF and Routy, B and Annabi, B and Brereton, NJB and Richard, C and Santos, MM}, title = {Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2022-328389}, pmid = {36585238}, issn = {1468-3288}, abstract = {OBJECTIVE: Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing.<br><br>DESIGN: The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo.<br><br>RESULTS: Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1&#x3b1;, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery.<br><br>CONCLUSION: Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.}, }
@article {pmid36585105, year = {2023}, author = {Chen, BY and Lin, WZ and Li, YL and Bi, C and Du, LJ and Liu, Y and Zhou, LJ and Liu, T and Xu, S and Shi, CJ and Zhu, H and Wang, YL and Sun, JY and Liu, Y and Zhang, WC and Lu, HX and Wang, YH and Feng, Q and Chen, FX and Wang, CQ and Tonetti, MS and Zhu, YQ and Zhang, H and Duan, SZ}, title = {Roles of oral microbiota and oral-gut microbial transmission in hypertension.}, journal = {Journal of advanced research}, volume = {43}, number = {}, pages = {147-161}, doi = {10.1016/j.jare.2022.03.007}, pmid = {36585105}, issn = {2090-1224}, abstract = {INTRODUCTION: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered.<br><br>OBJECTIVES: To characterize the alterations of oral and gut microbiota and their roles in HTN.<br><br>METHODS: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN.<br><br>RESULTS: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition.<br><br>CONCLUSIONS: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.}, }
@article {pmid36581371, year = {2022}, author = {Holmstroem, RB and Dahl, EK and Helms, M and Nielsen, HV and Andersen, JB and Bjerrum, JT and Svane, IM and Ellebaek, E and Seidelin, JB}, title = {Tofacitinib and faecal microbiota transplantation in treating checkpoint inhibitor-induced enterocolitis: case report.}, journal = {BMJ open gastroenterology}, volume = {9}, number = {1}, pages = {}, doi = {10.1136/bmjgast-2022-000989}, pmid = {36581371}, issn = {2054-4774}, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce a wide range of immune-related adverse events (irAEs), potentially affecting any organ. ICI-induced colitis is a frequently reported irAE, whereas enteritis is rare and not well documented.<br><br>CASE PRESENTATION: We are presenting a patient with metastatic melanoma who developed severe ICI-induced enterocolitis multirefractory for glucocorticoids, infliximab and vedolizumab, partially responding to faecal microbiota transplantation and final complete response to tofacitinib.<br><br>CONCLUSION: This case supports that tofacitinib may be an(other) effective agent in managing multirefractory ICI-induced diarrhoea caused by colitis and/or enteritis.}, }
@article {pmid36581324, year = {2023}, author = {Aburahma, A and Stewart, EL and Rana, S and Larsen, R and Ward, CS and Sprague, JE}, title = {Influence of fecal microbial transplant (FMT) between male and female rats on methamphetamine-induced hyperthermia.}, journal = {International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group}, volume = {40}, number = {1}, pages = {2159072}, doi = {10.1080/02656736.2022.2159072}, pmid = {36581324}, issn = {1464-5157}, abstract = {OBJECTIVE: To investigate the effect of bidirectional fecal microbial transplant (FMT) between male and female rats on methamphetamine (MA)-induced hyperthermia.<br><br>METHODS: FMT was performed between male and female rats prior to MA (10 mg/kg, sc) treatment. Core body temperature, plasma drug and norepinephrine (NE) levels were measured and compared between treatment groups. 16S rRNA gene sequencing of bacterial communities between male and female rats was performed.<br><br>RESULTS: MA treatment resulted in significantly higher core body temperatures in male groups (control and FMT-treated) compared to MA-treated female groups (control and FMT-treated). Plasma concentrations of MA and amphetamine were higher in females than males. Whereas, plasma norepinephrine (NE) levels were not different between male and female rats 90 minutes after MA treatment. At the phyla level, the microbiome of male and female control rats were dominated by Firmicutes and Bacteroidetes. Males had a higher relative abundance of Firmicutes and lower relative abundances of Bacteroidetes than females. The FMT procedure changed the recipient group towards their donor with males getting closer to their donors than females. In the control groups following MA treatment, Firmicutes increased and Bacteroides decreased in females and males. Conversely, in the FMT treatment groups following MA treatment, Firmicutes decreased while Bacteroidetes increased in females and males.<br><br>CONCLUSIONS: Although definite differences in the structure and diversity of the gut microbiome were observed using 16S rRNA gene sequencing of bacterial communities between male and female rats, these differences do not seem to contribute to the sex-based differences in MA-induced hyperthermia.}, }
@article {pmid36580630, year = {2022}, author = {Gulati, AS and Nicholson, MR and Khoruts, A and Kahn, SA}, title = {Fecal microbiota transplantation across the lifespan: balancing efficacy, safety, and innovation.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000002167}, pmid = {36580630}, issn = {1572-0241}, abstract = {Fecal microbiota transplantation (FMT) is a rapidly growing therapy aimed at reconstituting the dysbiotic microbiota of a patient with the beneficial stool microbiota of a healthy individual. The efficacy rates of FMT are very robust for recurrent Clostridioides difficile infection in both children and adults. Although complications of FMT have been reported, it is generally felt to be a safe procedure. Novel indications for FMT are being studied, with the hope that ultimately it may be useful for a variety of disorders. As this field continues to grow, however, it is necessary to consider efficacy, safety, and innovation across the lifespan. There are unique concerns regarding FMT as it pertains to children, adults, and the elderly. In this review, we seek to update clinicians, researchers, and regulators on how these factors must be balanced across the lifespan as we move forward with this innovative therapy.}, }
@article {pmid36578000, year = {2022}, author = {Wang, L and Shao, L and Chen, MY and Wang, L and Zhang, W and Tan, FB and Huang, WH}, title = {Effect of ginsenoside compound K on alleviating colitis via modulating gut microbiota.}, journal = {Chinese medicine}, volume = {17}, number = {1}, pages = {146}, pmid = {36578000}, issn = {1749-8546}, abstract = {BACKGROUND: Ginsenoside compound K (GC-K) potentially alleviates ulcerative colitis involved in gut microbiota, which is significantly associated with the occurrence and development of colitis. However, the effect and mechanism of GC-K on anti-colitis in relation to gut microbiota are not clear. This study focused on the prevention and mechanism of GC-K on Dextran sulfate sodium (DSS)-induced colitis of mice pertinent to gut microbiota.<br><br>METHODS: DSS was used to establish a chronic colitis mouse model. Body weight analysis, colon length measurement, HE staining, and inflammatory factors levels were processed in animal experiments. Flow cytometry was employed to analyze Th17/Treg cells in the mouse spleen and blood. 16S rRNA sequencing was utilized to analyze gut microbiota. Fecal microbiota transplantation (FMT) experiment was employed to verify the anti-colitis efficacy of GC-K by reshaping gut microbiota.<br><br>RESULTS: GC-K significantly relieved colitis-related symptoms due to decreased disease activity index (DAI) scores, spleen weight, and increased colon length. Additionally, the tight junction proteins were increased, and the pro-inflammatory cytokines, such as TNF-&#x3b1;, IL-6, IL-1&#x3b2; and IL-17, were decreased after GC-K treatment. Furthermore, Bacteroides spp. significantly increased after modeling. Moreover, FMT experiments confirmed that GC-K-driven gut microbiota greatly relieved DSS-induced colitis.<br><br>CONCLUSION: GC-K alleviated colitis via the modulation of gut microbiota.}, }
@article {pmid36577369, year = {2022}, author = {Wang, Z and Qin, X and Hu, D and Huang, J and Guo, E and Xiao, R and Li, W and Sun, C and Chen, G}, title = {Akkermansia supplementation reverses the tumor-promoting effect of the fecal microbiota transplantation in ovarian cancer.}, journal = {Cell reports}, volume = {41}, number = {13}, pages = {111890}, doi = {10.1016/j.celrep.2022.111890}, pmid = {36577369}, issn = {2211-1247}, abstract = {Ovarian cancer (OC) remains a clinical challenge for its difficulty in early diagnosis and insensitivity to treatments. Gut microbiota modulate multiple carcinoma progression through immunoregulation. The relationship between OC and gut microbiota has not been fully characterized. We find that the feces of patients with OC demonstrate different characteristics from benign controls. After fecal microbiota transplantation (FMT) from patients with OC into OC-bearing mice, the tumor development accelerates. Further, an Akkermansia supplementation with FMT significantly suppresses OC progression in mice. RNA sequencing of tumors shows that T cell activation pathways are upregulated after Akkermansia supplementation with FMT. Moreover, acetate accumulation accompanies Akkermansia abundance elevation, which is associated with enhanced interferon γ (IFNγ) secretion of CD8[+] T cells and also its tumor-killing property. This work highlights the importance of protective gut microbiome in immune surveillance of OC, which connects accumulation of acetate and the cytotoxic function of CD8[+] T cells by increasing IFNγ secretion.}, }
@article {pmid36576900, year = {2022}, author = {Bier, N and Hanson, B and Jiang, ZD and DuPont, HL and Arias, CA and Miller, WR}, title = {A Case of Successful Treatment of Recurrent Urinary Tract Infection by Extended-Spectrum β-Lactamase Producing Klebsiella pneumoniae Using Oral Lyophilized Fecal Microbiota Transplant.}, journal = {Microbial drug resistance (Larchmont, N.Y.)}, volume = {}, number = {}, pages = {}, doi = {10.1089/mdr.2022.0031}, pmid = {36576900}, issn = {1931-8448}, abstract = {Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of the recipient microbiota did not mirror the donor stool taxa at either site, but an increase in the relative proportion of the genus Bacteroides as compared with Prevotella was noted in the stool post-transplant. FMTs may be a promising treatment option for recurrent multidrug-resistant infections.}, }
@article {pmid36574857, year = {2022}, author = {Shi-Long, Z and Lisha, C and Zheng-Yan, Z and Hai-Tao, S and Jia-Jia, L}, title = {Untangling Determinants of gut microbiota and tumor immunologic status through a multi-omics approach in colorectal cancer.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106633}, doi = {10.1016/j.phrs.2022.106633}, pmid = {36574857}, issn = {1096-1186}, abstract = {The changes in gut microbiota have been implicated in colorectal cancer (CRC). The interplays between the host and gut microbiota remain largely unclear, and few studies have investigated these interplays using integrative multi-omics data. In this study, large-scale multi-comic datasets, including microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing of CRC patients, were analyzed individually and integrated through advanced bioinformatics methods. We further examined the clinical relevance of these findings in the mice recolonized with microbiota from human. We found that CRC patients had distinct microbiota compositions compared to healthy controls. A machine-learning model was developed with 28 biomarkers for detection of CRC, which had high accuracy and clinical applicability. We identified multiple significant correlations between genera and well-characterized genes, suggesting the potential role of gut microbiota in tumor immunity. Further analysis showed that specific metabolites worked as profound communicators between these genera and tumor immunity. Integrating microbiota and metabolome perspectives, we catalogued gut taxonomic and metabolomic features that represented the key multi-omics signature of CRC. Furthermore, gut microbiota from CRC patients transplanted to compromise the response of CRC to immunotherapy. These phenotypes were strongly associated with the alterations in gut microbiota, immune cell infiltration as well as multiple metabolic pathways. The comprehensive interplays across multi-comic data of CRC might explain how gut microbiota influenced tumor immunity. Hence, we proposed that modifying the CRC microbiota using healthy donors might serve as a promising strategy to improve response to immunotherapy.}, }
@article {pmid36572703, year = {2022}, author = {Stø, K and Valeur, J and Ueland, T and Malmstrøm, GH and Bjerkeli, V and Trøseid, M and Hov, JR and Holm, K and Vestad, B and Halvorsen, B and Skjelland, M and Skagen, KR}, title = {Fecal level of butyric acid, a microbiome-derived metabolite, is increased in patients with severe carotid atherosclerosis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22378}, pmid = {36572703}, issn = {2045-2322}, abstract = {The short-chain fatty acid (SCFA) butyric acid maintains a healthy gut barrier and vascular endothelium. We aimed to investigate the association between fecal butyric acid, carotid atherosclerosis and risk factors for ischemic stroke. Patients with severe carotid atherosclerosis (i.e. ≥ 50% stenosis) (n = 43) were compared with healthy controls (n = 38). We analyzed fecal SCFAs by gas chromatography, microbiota composition by 16S rRNA sequencing, markers of gut barrier damage and inflammasome activation by immunoassay, and plasma SCFAs by ultra-high performance liquid chromatography-tandem mass spectroscopy. Patients had higher fecal butyric acid level (p = 0.024), along with increased functional potential of microbial butyric acid production (p = 0.031), compared with controls. Dietary fiber intake was comparable. Patients had higher levels of gut barrier damage markers CCL25 and IFABP, and the inflammasome activation marker IL-18, whereas plasma level of butyric was similar. Increased fecal butyric acid was associated with higher BMI, waist-hip ratio, HbA1c, CRP and leukocyte count. Contrary to our hypothesis, patients with severe carotid atherosclerosis had higher fecal butyric acid level, and increased microbial production, compared with controls. Gut barrier damage in patients might indicate decreased absorption of butyric acid and hence contribute to the higher fecal level.}, }
@article {pmid36572070, year = {2022}, author = {Shon, WJ and Jung, MH and Kim, Y and Kang, GH and Choi, EY and Shin, DM}, title = {Sugar-sweetened beverages exacerbate high-fat diet-induced inflammatory bowel disease by altering the gut microbiome: Sweetened beverages enhance fat-induced IBD.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109254}, doi = {10.1016/j.jnutbio.2022.109254}, pmid = {36572070}, issn = {1873-4847}, abstract = {High-fat diets (HFDs) and frequent consumption of sugar-sweetened beverages (SSBs) are potential contributors to increasing inflammatory bowel disease (IBD) incidences. While HFDs have been implicated in mild intestinal inflammation, the role of sucrose in SSBs remains unclear. Therefore, we studied the role of SSBs in IBD pathogenesis in a mouse model and humans. C57BL6/J mice were given ad libitum access to a sucrose solution or plain water for 10 weeks, with or without an HFD. Interestingly, sucrose solution consumption alone did not induce gut inflammation in mice; however, when combined with an HFD, it dramatically increased the inflammation score, submucosal edema, and CD45[+] cell infiltration. 16S ribosomal RNA gene-sequencing revealed that sucrose solution and HFD co-consumption significantly increased the relative abundance of IBD-related pathogenic bacteria when compared with HFD consumption. RNA sequencing and flow cytometry showed that co-consumption promoted pro-inflammatory cytokine and chemokine synthesis, dendritic-cell expansion, and IFN-γ[+]TNF-α[+]CD4[+] and CD8[+] T-cell activation. Fecal microbiota transplantation from HFD- and sucrose water-fed mice into gut-sterilized mice increased the susceptibility to dextran sulfate sodium-induced colitis in the recipient mice. Consistent herewith, high consumption of SSBs and animal fat-rich diets markedly increased systemic inflammation-associated IBD marker expression in humans. In conclusion, SSBs exacerbate HFD-induced colitis by triggering a shift of the gut microbiome into a pathobiome. Our findings provide new insights for the development of strategies aimed at preventing IBD.}, }
@article {pmid36570710, year = {2022}, author = {Guo, XH and Zhu, YL and Yang, L and Li, WJ and Du, XF}, title = {The Effects of Multi-Donor Fecal Microbiota Transplantation Capsules Combined with Thalidomide on Hormone-Dependent Ulcerative Colitis.}, journal = {Infection and drug resistance}, volume = {15}, number = {}, pages = {7495-7501}, pmid = {36570710}, issn = {1178-6973}, abstract = {OBJECTIVE: This study aimed to assess the effects of multi-donor fecal microbiota transplantation (FMT) capsules combined with thalidomide on hormone-dependent ulcerative colitis (UC).<br><br>METHODS: A total of 59 patients with steroid-dependent UC treated at the Gastroenterology Department of the First Affiliated Hospital of Xinxiang Medical University between January 2017 and January 2019 were enrolled in this study. Using a random number table, the patients were divided into two groups: a group treated with FMT capsules (the FMT group) and a group treated with FMT capsules and thalidomide (the FMT+S group). Multi-donor FMT capsules were prepared, and all subjects and stool donors followed the FMT pathway for FMT transplantation. Each patient's Mayo score, C-reactive protein (CRP) level, and level of fecal calprotectin before FMT treatment and at week 1 and week 13 after treatment were recorded. All patients were followed up for 15 weeks.<br><br>RESULTS: A total of 56.7% of the patients (34/59) achieved a therapeutic response at the end of the research period. Compared with the FMT group, the FMT+S group had better clinical benefit (P < 0.05). In the comparison of efficacy at week 1 and week 13 after treatment, the Mayo scores, calprotectin levels, and CRP indexes in the FMT+S group were better than those in the FMT group (P < 0.05). There were no serious adverse events in the treatment process or during follow-up.<br><br>CONCLUSION: A combination of FMT capsules and thalidomide provides a treatment choice for patients with hormone-dependent UC, and it can be used as an adjuvant therapy. However, large-scale, multi-center, and prospective trials are required to further verify the reliability of this treatment.}, }
@article {pmid36569199, year = {2022}, author = {Hadjadj, L and Cassir, N and Saïdani, N and Hoffman, C and Brouqui, P and Astoul, P and Rolain, JM and Baron, SA}, title = {Outbreak of carbapenem-resistant enterobacteria in a thoracic-oncology unit through clonal and plasmid-mediated transmission of the bla OXA-48 gene in Southern France.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1048516}, pmid = {36569199}, issn = {2235-2988}, abstract = {BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) represent an increasing threat to public health, especially in hospitals.<br><br>OBJECTIVES: To investigate an outbreak of CPE in a thoracic-oncology unit by using whole genome sequencing (WGS) and to describe the control measures taken to limit the epidemic, including fecal microbiota transplantation (FMT).<br><br>METHODS: A retrospective study between December 2016 and October 2017 was performed to investigate an outbreak of CPE in a thoracic-oncology unit at the North Hospital in Marseille, France. The isolates were identified, and antimicrobial susceptibility tests were performed. All CPE were sequenced using MiSeq and/or MinIon technologies. Nucleotide variations between plasmids and similarity within the same species were investigated. The origin of this outbreak, its spread, and the decolonization of patients in the ward were also studied.<br><br>RESULTS: Four Citrobacter freundii, one Enterobacter cloacae and four E. hormaechei OXA-48 carbapenemase producers were isolated in eight patients hospitalized the same year in a thoracic-oncology ward. The bla OXA-48 gene was present in a Tn1999.2 transposon located in IncL/M plasmids, with single nucleotide variants (SNV) ranging from 0 to 5. All C. freundii strains belonged to the same ST22 and had more than 99.6% similarity between them. Two strains of E. hormaechei ST1007 were almost identical at 99.98%, while the others belonged to a different ST (ST98, ST114, ST133). No single source was identified. FMT resulted in decolonization in 4/6 patients.<br><br>CONCLUSIONS: WGS demonstrated the dissemination of the bla OXA-48 gene by both clonal (C. freundii ST22 and E. hormaechei ST1007) and plasmid spread (pOXA-48 IncL/M). The origin of this outbreak appeared to be both external and internal to the ward. This evidence of cross-infection supports the urgent need for the implementation of infection control measures to prevent CPE dissemination.}, }
@article {pmid36569149, year = {2022}, author = {Hamamah, S and Gheorghita, R and Lobiuc, A and Sirbu, IO and Covasa, M}, title = {Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1060581}, pmid = {36569149}, issn = {2296-858X}, abstract = {Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbial composition in recipients. Currently, FMT is approved in the USA to treat recurrent and refractory Clostridioides difficile infection and has been shown to have great efficacy. As such, significant research has been directed toward understanding the potential role of FMT in other conditions associated with gut microbiota dysbiosis such as obesity, type 2 diabetes mellitus, metabolic syndrome, neuropsychiatric disorders, inflammatory bowel disease, irritable bowel syndrome, decompensated cirrhosis, cancers and graft-versus-host disease. This review examines current updates and efficacy of FMT in treating conditions other than Clostridioides difficile infection. Further, protocols for administration of FMT are also discussed including storage of fecal samples in stool banks, inclusion/exclusion criteria for donors, fecal sample preparation and methods of treatment administration. Overall, understanding the mechanisms by which FMT can manipulate gut microbiota to provide therapeutic benefit as well as identifying potential adverse effects is an important step in clarifying its long-term safety and efficacy in treating multiple conditions in the future.}, }
@article {pmid36568836, year = {2022}, author = {Matzaras, R and Nikopoulou, A and Protonotariou, E and Christaki, E}, title = {Gut Microbiota Modulation and Prevention of Dysbiosis as an Alternative Approach to Antimicrobial Resistance: A Narrative Review.}, journal = {The Yale journal of biology and medicine}, volume = {95}, number = {4}, pages = {479-494}, pmid = {36568836}, issn = {1551-4056}, abstract = {Background: The importance of gut microbiota in human health is being increasingly studied. Imbalances in gut microbiota have been associated with infection, inflammation, and obesity. Antibiotic use is the most common and significant cause of major alterations in the composition and function of the gut microbiota and can result in colonization with multidrug-resistant bacteria. Methods: The purpose of this review is to present existing evidence on how microbiota modulation and prevention of gut dysbiosis can serve as tools to combat antimicrobial resistance. Results: While the spread of antibiotic-resistant pathogens requires antibiotics with novel mechanisms of action, the number of newly discovered antimicrobial classes remains very low. For this reason, the application of alternative modalities to combat antimicrobial resistance is necessary. Diet, probiotics/prebiotics, selective oropharyngeal or digestive decontamination, and especially fecal microbiota transplantation (FMT) are under investigation with FMT being the most studied. But, as prevention is better than cure, the implementation of antimicrobial stewardship programs and strict infection control measures along with newly developed chelating agents could also play a crucial role in decreasing colonization with multidrug resistant organisms. Conclusion: New alternative tools to fight antimicrobial resistance via gut microbiota modulation, seem to be effective and should remain the focus of further research and development.}, }
@article {pmid36567449, year = {2022}, author = {Xu, K and Guo, Y and Wang, Y and Ren, Y and Low, V and Cho, S and Ping, L and Peng, K and Li, X and Qiu, Y and Liu, Q and Li, Z and Wang, Z}, title = {Decreased Enterobacteriaceae translocation due to gut microbiota remodeling mediates the alleviation of premature aging by a high-fat diet.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e13760}, doi = {10.1111/acel.13760}, pmid = {36567449}, issn = {1474-9726}, abstract = {Aging-associated microbial dysbiosis exacerbates various disorders and dysfunctions, and is a major contributor to morbidity and mortality in the elderly, but the underlying cause of this aging-related syndrome is confusing. SIRT6 knockout (SIRT6 KO) mice undergo premature aging and succumb to death by 4 weeks, and are therefore useful as a premature aging research model. Here, fecal microbiota transplantation from SIRT6 KO mice into wild-type (WT) mice phenocopies the gut dysbiosis and premature aging observed in SIRT6 KO mice. Conversely, an expanded lifespan was observed in SIRT6 KO mice when transplanted with microbiota from WT mice. Antibiotic cocktail treatment attenuated inflammation and cell senescence in KO mice, directly suggesting that gut dysbiosis contributes to the premature aging of SIRT6 KO mice. Increased Enterobacteriaceae translocation, driven by the overgrowth of Escherichia coli, is the likely mechanism for the premature aging effects of microbiome dysregulation, which could be reversed by a high-fat diet. Our results provide a mechanism for the causal link between gut dysbiosis and aging, and support a beneficial effect of a high-fat diet for correcting gut dysbiosis and alleviating premature aging. This study provides a rationale for the integration of microbiome-based high-fat diets into therapeutic interventions against aging-associated diseases.}, }
@article {pmid36567333, year = {2022}, author = {Su, SH and Wu, YF and Lin, Q and Zhang, L and Wang, DP and Hai, J}, title = {Fecal microbiota transplantation and replenishment of short-chain fatty acids protect against chronic cerebral hypoperfusion-induced colonic dysfunction by regulating gut microbiota, differentiation of Th17 cells, and mitochondrial energy metabolism.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {313}, pmid = {36567333}, issn = {1742-2094}, abstract = {BACKGROUND: Little is known about the association between gut microbiota and intestinal injury under a state of chronic cerebral hypoperfusion (CCH). Here, the effects of gut microbiota and short-chain fatty acids (SCFAs), as important metabolic products, on intestinal function and potential mechanisms after CCH were investigated.<br><br>METHODS: Rats were subjected to bilateral common carotid artery occlusion (BCCAo) to induce CCH. The gut microbiota and metabolites of SCFAs were assessed by 16S rRNA sequencing and targeted metabolomics, respectively. Transcriptomic analysis of colon tissues was also conducted. Subsequently, potential molecular pathways and differentially expressed genes were verified by western blot, immunoprecipitation, and immunofluorescence analyses. Furthermore, the integrity of the colonic barrier was evaluated by hematoxylin and eosin and mucin 2 staining and expression levels of tight junction proteins. Besides, colonic inflammation was further assessed by flow cytometry and expression levels of inflammatory cytokines. In addition, colonic mitochondrial dysfunction was analyzed via membrane potential, reactive oxygen species, electron transport chain (ETC) activities, adenosine triphosphate content, and mitochondrial ultrastructure.<br><br>RESULTS: CCH modified gut microbial composition and microbial metabolism of SCFAs, which may be associated with inhibition of mitochondrial ETC activities and oxidative phosphorylation, leading to dysregulation of mitochondrial energy metabolism. Furthermore, CCH induced differentiation of pathogenic Th17 cells, promoted the formation of complexes of interferon regulatory factor 4 and signal transducer and activator of transcription 3 (STAT3), and increased the phosphorylation of STAT3. This was associated with an impairment of colonic barrier function and chronic colonic inflammation. In contrast, FMT and SCFA replenishment ameliorated CCH-induced gut microbial dysbiosis by increasing the intestinal content of Ruminococcus_sp_N15_MGS_57 and modulating microbial metabolism of SCFAs by increasing acetic acid contents associated with an improvment of the balance between Tregs and Th17 cells, mitochondrial ETC activities, and oxidative phosphorylation to prevent colonic inflammation and dysregulation of mitochondrial energy metabolism.<br><br>CONCLUSION: These findings indicate that FMT and SCFA replenishment present a promising therapeutic strategy against colonic dysfunction under a state of chronic cerebral ischemia.}, }
@article {pmid36567320, year = {2022}, author = {Kim, KH and Chung, Y and Huh, JW and Park, DJ and Cho, Y and Oh, Y and Jeong, H and Yoon, J and Kang, JH and Shin, HS and Kim, HC and Kwon, SK and Seo, KY and Oh, SH and Seong, JK and Ha, SJ and Nam, KT and Kim, JF}, title = {Gut microbiota of the young ameliorates physical fitness of the aged in mice.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {238}, pmid = {36567320}, issn = {2049-2618}, abstract = {BACKGROUND: Aging is a natural process that an organism gradually loses its physical fitness and functionality. Great efforts have been made to understand and intervene in this deteriorating process. The gut microbiota affects host physiology, and dysbiosis of the microbial community often underlies the pathogenesis of host disorders. The commensal microbiota also changes with aging; however, the interplay between the microbiota and host aging remains largely unexplored. Here, we systematically examined the ameliorating effects of the gut microbiota derived from the young on the physiology and phenotypes of the aged.<br><br>RESULTS: As the fecal microbiota was transplanted from young mice at 5 weeks after birth into 12-month-old ones, the thickness of the muscle fiber and grip strength were increased, and the water retention ability of the skin was enhanced with thickened stratum corneum. Muscle thickness was also marginally increased in 25-month-old mice after transferring the gut microbiota from the young. Bacteria enriched in 12-month-old mice that received the young-derived microbiota significantly correlated with the improved host fitness and altered gene expression. In the dermis of these mice, transcription of Dbn1 was most upregulated and DBN1-expressing cells increased twice. Dbn1-heterozygous mice exhibited impaired skin barrier function and hydration.<br><br>CONCLUSIONS: We revealed that the young-derived gut microbiota rejuvenates the physical fitness of the aged by altering the microbial composition of the gut and gene expression in muscle and skin. Dbn1, for the first time, was found to be induced by the young microbiota and to modulate skin hydration. Our results provide solid evidence that the gut microbiota from the young improves the vitality of the aged. Video Abstract.}, }
@article {pmid36564805, year = {2022}, author = {Li, X and Li, R and Ji, B and Zhao, L and Wang, J and Yan, T}, title = {Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {614}, pmid = {36564805}, issn = {1479-5876}, abstract = {BACKGROUND: Antibody-mediated rejection (AMR) remains one of the major barriers for graft survival after kidney transplantation. Our previous study suggested a gut microbiota dysbiosis in kidney transplantation recipients with AMR. However, alternations in gut microbial function and structure at species level have not been identified. In the present study, we investigated the metagenomic and metabolic patterns of gut microbiota in AMR patients to provide a comprehensive and in-depth understanding of gut microbiota dysbiosis in AMR.<br><br>METHODS: We enrolled 60 kidney transplantation recipients, 28 showed AMR and 32 were non-AMR controls with stable post-transplant renal functions. Shotgun sequencing and untargeted LC/MS metabolomic profiling of fecal samples were performed in kidney transplantation recipients with AMR and controls.<br><br>RESULTS: Totally, we identified 311 down-regulated and 27 up-regulated gut microbial species associated with AMR after kidney transplantation, resulting in the altered expression levels of 437 genes enriched in 22 pathways, of which 13 were related to metabolism. Moreover, 32 differential fecal metabolites were found in recipients with AMR. Among them, alterations in 3b-hydroxy-5-cholenoic acid, L-pipecolic acid, taurocholate, and 6k-PGF1alpha-d4 directly correlated with changes in gut microbial species and functions. Specific differential fecal species and metabolites were strongly associated with clinical indexes (Cr, BUN, etc.), and could distinguish the recipients with AMR from controls as potential biomarkers.<br><br>CONCLUSIONS: Altogether, our findings provided a comprehensive and in-depth understanding of the correlation between AMR and gut microbiota, which is important for the etiological and diagnostic study of AMR after kidney transplantation.}, }
@article {pmid36564793, year = {2022}, author = {Juottonen, H and Moghadam, NN and Murphy, L and Mappes, J and Galarza, JA}, title = {Host's genetic background determines the outcome of reciprocal faecal transplantation on life-history traits and microbiome composition.}, journal = {Animal microbiome}, volume = {4}, number = {1}, pages = {67}, pmid = {36564793}, issn = {2524-4671}, abstract = {BACKGROUND: Microbes play a role in their host's fundamental ecological, chemical, and physiological processes. Host life-history traits from defence to growth are therefore determined not only by the abiotic environment and genotype but also by microbiota composition. However, the relative importance and interactive effects of these factors may vary between organisms. Such connections remain particularly elusive in Lepidoptera, which have been argued to lack a permanent microbiome and have microbiota primarily determined by their diet and environment. We tested the microbiome specificity and its influence on life-history traits of two colour genotypes of the wood tiger moth (Arctia plantaginis) that differ in several traits, including growth. All individuals were grown in the laboratory for several generations with standardized conditions. We analyzed the bacterial community of the genotypes before and after a reciprocal frass (i.e., larval faeces) transplantation and followed growth rate, pupal mass, and the production of defensive secretion.<br><br>RESULTS: After transplantation, the fast-growing genotype grew significantly slower compared to the controls, but the slow-growing genotype did not change its growth rate. The frass transplant also increased the volume of defensive secretions in the fast-growing genotype but did not affect pupal mass. Overall, the fast-growing genotype appeared more susceptible to the transplantation than the slow-growing genotype. Microbiome differences between the genotypes strongly suggest genotype-based selective filtering of bacteria from the diet and environment. A novel cluster of insect-associated Erysipelotrichaceae was exclusive to the fast-growing genotype, and specific Enterococcaceae were characteristic to the slow-growing genotype. These Enterococcaceae became more prevalent in the fast-growing genotype after the transplant, which suggests that a&#xa0;slower growth rate is&#xa0;potentially related to their presence.<br><br>CONCLUSIONS: We show that reciprocal frass transplantation can reverse some genotype-specific life-history traits in a lepidopteran host. The results indicate that genotype-specific selective filtering can fine-tune the bacterial community at specific life stages and tissues like the larval frass, even against a background of a highly variable community with stochastic assembly. Altogether, our findings suggest that the host's genotype can influence its susceptibility to being colonized by microbiota, impacting key life-history traits.}, }
@article {pmid36564273, year = {2022}, author = {Stoll, ML}, title = {Therapeutic alteration of the microbiota in rheumatic diseases: Hype or potential?.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {}, number = {}, pages = {101806}, doi = {10.1016/j.berh.2022.101806}, pmid = {36564273}, issn = {1532-1770}, abstract = {Multiple studies have demonstrated abnormalities in the contents of the fecal microbiota in patients with a variety of forms of arthritis. This has prompted interest in microbial-altering therapy as a therapeutic tool. While antibiotics as a long-term therapeutic tool have largely fallen out of favor, there have been multiple studies evaluating probiotics in rheumatoid arthritis, spondyloarthritis, or systemic sclerosis; a small number of studies have tested fecal microbial transplantation (FMT) in rheumatic diseases. Although probiotics were well tolerated, few studies detected meaningful clinical benefit regardless of indication. Likewise, one of the two randomized studies evaluating FMT showed minimal clinical benefit, while the other demonstrated worsening compared to sham treatment. In this review article, I summarize the literature on probiotics and FMT in rheumatic diseases, discuss potential reasons for the absence of demonstrable benefit, and suggest avenues of future direction of research.}, }
@article {pmid36563827, year = {2022}, author = {Deng, J and Zou, X and Liang, Y and Zhong, J and Zhou, K and Zhang, J and Zhang, M and Wang, Z and Sun, Y and Li, M}, title = {Hypoglycemic effects of different molecular weight konjac glucomannans via intestinal microbiota and SCFAs mediated mechanism.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ijbiomac.2022.12.160}, pmid = {36563827}, issn = {1879-0003}, abstract = {The hypoglycemic effects of konjac glucomannans (KGMs) are well recognized, and our previous study showed KGMs with different molecular weight have different hypoglycemic effects on diabetes rats, but the detailed mechanisms still remain unclear. In this study, KGMs with medium molecular weight (KGM-M, 757.1 kDa) and low molecular weight (KGM-L, 87.3 kDa) were utilized to investigate the possible mechanism on hypoglycemic effects of type 2 diabetic (T2DM) rats. The results revealed that KGM-M had better effects than KGM-L on decreasing fasting blood glucose, mitigating insulin resistance and improving inflammation. Further mechanism analysis showed that KGM-M better enriched gut flora diversity and the abundance of Ruminococcus and Lachnoclostridium, which was accompanied by increased short chain fatty acids (SCFAs) production and expression of G protein-coupled receptors (GPCRs), and improved regulation on bile acid synthesis. Antibiotics treatment eliminated the beneficial effects of KGMs on gut flora, SCFAs, GPCRs and bile acid synthesis. By contrast, fecal microbiota transplantation (FMT) treatment restored the structure of intestinal microbiota. And after FMT treatment, KGM-M displayed higher hypoglycemic activity than KGM-L, probably due to the better effects on intestinal microbiota, SCFAs production, GPCRs expression and bile acid synthesis inhibition.}, }
@article {pmid36561896, year = {2022}, author = {Elsayed, OH and Ercis, M and Pahwa, M and Singh, B}, title = {Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {2927-2943}, pmid = {36561896}, issn = {1176-6328}, abstract = {INTRODUCTION: Bipolar disorder (BD) is a chronic mental illness impacting 1-2% of the population worldwide and causing high rates of functional impairment. Patients with BD spend most of their time in depressive episodes and up to one-third of patients do not respond to adequate doses of medications. Although no consensus exists for definition of treatment-resistant bipolar depression (TRBD), failure of symptoms improvement despite an adequate trial of two therapeutic agents is a common theme of TRBD. In this paper, we review the evidence base of therapeutic interventions, challenges, and potential future directions for TRBD.<br><br>METHODS: We conducted a literature search for randomized controlled trials on PubMed for the treatment of TRBD and ongoing trials for the treatment of TRBD/bipolar depression on clinicaltrials.gov.<br><br>RESULTS: Several therapeutic agents have been investigated for TRBD. Adjunctive pramipexole and modafinil have data supporting short-term efficacy in TRBD, along with limited data for racemic intravenous ketamine. Celecoxib augmentation of escitalopram and treatment with metformin in patients with insulin resistance showed promising results. Right unilateral electroconvulsive therapy displayed statistically significant response rate and improvement, but not remission compared to pharmacotherapy. Trials for transcranial magnetic stimulation (TMS) have failed to show a significant difference from sham treatment in TRBD.<br><br>FUTURE TRENDS: Pharmacological treatments with novel mechanisms of actions like brexpiprazole and vortioxetine are being investigated following successes in unipolar depression. Modified TMS protocols such as accelerated TMS are under investigation. Innovative approaches like psychedelic-assisted psychotherapy, interleukin-2, fecal microbiota transplantation and multipotent stromal cells are being studied.<br><br>CONCLUSION: Evidence on current treatment modalities for TRBD is limited with low efficacy. More research is needed for successful treatment of TRBD. Effective therapies and innovative approaches to treatment are being investigated and could show promise.}, }
@article {pmid36561217, year = {2022}, author = {Zhang, Y and Zhou, Y and Cui, W and Wang, Z and Wang, X and Wu, F and Wang, P and Wang, T and Yu, W and Wang, L and Shang, J and Zhao, Z}, title = {Characterization and diagnostic value of the gut microbial composition in patients with minimal change disease.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {1070569}, pmid = {36561217}, issn = {1664-042X}, abstract = {Background: Minimal change disease (MCD) is one of the most common causes of primary nephrotic syndrome with high morbidity. This study aimed to explore the typical alterations of gut microbiota in MCD and establish a non-invasive classifier using key gut microbiome. We also aimed to evaluate the therapeutic efficiency of gut microbiota intervention in MCD through animal experiments. Methods: A total of 222 stool samples were collected from MCD patients and healthy controls at the First Affiliated Hospital of Zhengzhou University and Shandong Provincial Hospital for 16S rRNA sequencing. Optimum operational taxonomic units (OTUs) were obtained for constructing a diagnostic model. MCD rat models were established using doxorubicin hydrochloride for exploring the therapeutic efficiency of gut microbial intervention through fecal microbiota transplantation (FMT). Results: The α-diversity of gut microbiota decreased in MCD patients when compared with healthy controls. The relative abundance of bacterial species also changed significantly. We constructed a diagnostic model based on eight optimal OTUs and it achieved efficiency of 97.81% in discovery cohort. The high efficiency of diagnostic model was also validated in the patients with different disease states and cross-regional cohorts. The treatment partially recovered the gut microbial dysbiosis in patients with MCD. In animal experiments, likewise, the gut microbiota changed sharply in MCD rats. However, gut microbial interventions did not reduce urinary protein or pathological kidney damage. Conclusion: Gut Microbiota shifts sharply in both patients and rats with MCD. Typical microbial changes can be used as biomarkers for MCD diagnosis. The gut microbiota compositions in patients with MCD tended to normalize after treatment. However, the intervention of gut microbiota seems to have no therapeutic effect on MCD.}, }
@article {pmid36560636, year = {2022}, author = {Ács, N and Holohan, R and Dunne, LJ and Fernandes, AR and Clooney, AG and Draper, LA and Ross, RP and Hill, C}, title = {Comparing In Vitro Faecal Fermentation Methods as Surrogates for Phage Therapy Application.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560636}, issn = {1999-4915}, support = {SFI/15/ERCD/3189/SFI_/Science Foundation Ireland/Ireland ; }, abstract = {The human microbiome and its importance in health and disease have been the subject of numerous research articles. Most microbes reside in the digestive tract, with up to 10[12] cells per gram of faecal material found in the colon. In terms of gene number, it has been estimated that the gut microbiome harbours >100 times more genes than the human genome. Several human intestinal diseases are strongly associated with disruptions in gut microbiome composition. Less studied components of the gut microbiome are the bacterial viruses called bacteriophages that may be present in numbers equal to or greater than the prokaryotes. Their potential to lyse their bacterial hosts, or to act as agents of horizontal gene transfer makes them important research targets. In this study in vitro faecal fermentation systems were developed and compared for their ability to act as surrogates for the human colon. Changes in bacterial and viral composition occurred after introducing a high-titre single phage preparation both with and without a known bacterial host during the 24 h-long fermentation. We also show that during this timeframe 50 mL plastic tubes can provide data similar to that generated in a sophisticated faecal fermenter system. This knowledge can guide us to a better understanding of the short-term impact of bacteriophage transplants on the bacteriomes and viromes of human recipients.}, }
@article {pmid36558532, year = {2022}, author = {Komorniak, N and Martynova-Van Kley, A and Nalian, A and Wroński, M and Kaseja, K and Kowalewski, B and Kaźmierczak-Siedlecka, K and Łoniewski, I and Kaczmarczyk, M and Podsiadło, K and Bogdański, P and Palma, J and Stachowska, E}, title = {Association between Fecal Microbiota, SCFA, Gut Integrity Markers and Depressive Symptoms in Patients Treated in the Past with Bariatric Surgery-The Cross-Sectional Study.}, journal = {Nutrients}, volume = {14}, number = {24}, pages = {}, pmid = {36558532}, issn = {2072-6643}, abstract = {(1) Background: Depressive symptoms often appear after surgical treatment. (2) Methods: We involved 41 adults who underwent bariatric surgery a minimum of 6 months before the study and had the Beck scale ≥12. We analysed patients' mental state, gut barrier markers, faecal short chain fatty acids, and microbiota. (3) Results: Gut microbiota composition differed significantly among patients undergoing two different types of surgery (F = 1.64, p = 0.00002). Additionally, we discovered an association between short chain fatty acids and the Beck scale (F = 1.22, p = 0.058). The rearrangement of bacterial metabolites may be due to the patients' use of increased dietary protein, with insufficient intake of products containing vegetable fiber (Diet Quality Index (DQI-I)adequacy 22.55 (±3.46) points). (4) Conclusions: Bariatric surgery affects the gut microbiota, which may play an important role in the development of depressive and gastrointestinal symptoms in patients after bariatric surgery. Low fiber consumption and increased levels of faecal isobutyric acid may lead to intestinal inflammation. There is a need for further research on this topic including a larger sample size.}, }
@article {pmid36558359, year = {2022}, author = {Bustamante, JM and Dawson, T and Loeffler, C and Marfori, Z and Marchesi, JR and Mullish, BH and Thompson, CC and Crandall, KA and Rahnavard, A and Allegretti, JR and Cummings, BP}, title = {Impact of Fecal Microbiota Transplantation on Gut Bacterial Bile Acid Metabolism in Humans.}, journal = {Nutrients}, volume = {14}, number = {24}, pages = {}, pmid = {36558359}, issn = {2072-6643}, support = {R21AT010956/NH/NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included Desulfovibrio fairfieldensis and Clostridium hylemonae. To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. Bacteroides ovatus and Phocaeicola dorei were positively correlated with unconjugated bile acids. Bifidobacterium adolescentis, Collinsella aerofaciens, and Faecalibacterium prausnitzii were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation.}, }
@article {pmid36557703, year = {2022}, author = {Tun, KM and Hsu, M and Batra, K and Lo, CH and Laeeq, T and Vongsavath, T and Mohammed, S and Hong, AS}, title = {Efficacy and Safety of Fecal Microbiota Transplantation in Treatment of Clostridioides difficile Infection among Pediatric Patients: A Systematic Review and Meta-Analysis.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557703}, issn = {2076-2607}, abstract = {BACKGROUND AND AIMS: Cases of Clostridioides difficile infection have been rising among the pediatric and adolescent population. Fecal microbiota transplantation (FMT) has emerged as an alternative therapy for recurrent C. difficile infection. We aim to perform the first systematic review and meta-analysis investigating the safety and efficacy of fecal microbiota transplantation for C. difficile infection in children and adolescents.<br><br>METHODS: A literature search was performed using variations of the keywords "pediatrics", "C. difficile infection", and "fecal microbiota transplantation" in PubMed, EMBASE, CINAHL, Cochrane, and Google Scholar from inception to 30 June 2022. The resulting 575 articles were independently screened by three authors. Fourteen studies that satisfied the eligibility criteria were included in the meta-analysis.<br><br>RESULTS: The pooled success rate of FMT in the overall cohort was 86% (95% confidence interval: 77-95%; p < 0.001; I[2] = 70%). There were 38 serious adverse events in 36 patients with a pooled rate of 2.0% (95% confidence interval: 0.0-3.0%; p = 0.1; I[2] = 0.0%) and 47 adverse events in 45 patients with a pooled rate of 15% (95% confidence interval: 5.0-25.0%; p = 0.02; I[2] = 54.0%). There was no death associated with FMT.<br><br>CONCLUSIONS: FMT was concluded to be an effective and safe therapy in pediatric and adolescent patients with C. difficile infection. Underlying comorbidities may impede the efficacy. A rigorous screening process of the donors is recommended prior to embarking on FMT. There is no universal and cost-effective way to monitor the long-term outcomes of FMT. While promising, metagenomic sequencing may not be available in settings with limited resources. Robust data from randomized clinical trials is warranted.}, }
@article {pmid36557677, year = {2022}, author = {Quaranta, G and Guarnaccia, A and Fancello, G and Agrillo, C and Iannarelli, F and Sanguinetti, M and Masucci, L}, title = {Fecal Microbiota Transplantation and Other Gut Microbiota Manipulation Strategies.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557677}, issn = {2076-2607}, abstract = {The gut microbiota is composed of bacteria, archaea, phages, and protozoa. It is now well known that their mutual interactions and metabolism influence host organism pathophysiology. Over the years, there has been growing interest in the composition of the gut microbiota and intervention strategies in order to modulate it. Characterizing the gut microbial populations represents the first step to clarifying the impact on the health/illness equilibrium, and then developing potential tools suited for each clinical disorder. In this review, we discuss the current gut microbiota manipulation strategies available and their clinical applications in personalized medicine. Among them, FMT represents the most widely explored therapeutic tools as recent guidelines and standardization protocols, not only for intestinal disorders. On the other hand, the use of prebiotics and probiotics has evidence of encouraging findings on their safety, patient compliance, and inter-individual effectiveness. In recent years, avant-garde approaches have emerged, including engineered bacterial strains, phage therapy, and genome editing (CRISPR-Cas9), which require further investigation through clinical trials.}, }
@article {pmid36557658, year = {2022}, author = {Talapko, J and Včev, A and Meštrović, T and Pustijanac, E and Jukić, M and Škrlec, I}, title = {Homeostasis and Dysbiosis of the Intestinal Microbiota: Comparing Hallmarks of a Healthy State with Changes in Inflammatory Bowel Disease.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557658}, issn = {2076-2607}, abstract = {The gut microbiota, which represent a community of different microorganisms in the human intestinal tract, are crucial to preserving human health by participating in various physiological functions and acting as a metabolic organ. In physiological conditions, microbiota-host partnership exerts homeostatic stability; however, changes in intestinal microbiota composition (dysbiosis) are an important factor in the pathogenesis of inflammatory bowel disease and its two main disease entities: ulcerative colitis and Crohn's disease. The incidence and prevalence of these inflammatory conditions have increased rapidly in the last decade, becoming a significant problem for the healthcare system and a true challenge in finding novel therapeutic solutions. The issue is that, despite numerous studies, the etiopathogenesis of inflammatory bowel disease is not completely clear. Based on current knowledge, chronic intestinal inflammation occurs due to altered intestinal microbiota and environmental factors, as well as a complex interplay between the genetic predisposition of the host and an inappropriate innate and acquired immune response. It is important to note that the development of biological and immunomodulatory therapy has led to significant progress in treating inflammatory bowel disease. Certain lifestyle changes and novel approaches-including fecal microbiota transplantation and nutritional supplementation with probiotics, prebiotics, and synbiotics-have offered solutions for dysbiosis management and paved the way towards restoring a healthy microbiome, with only minimal long-term unfavorable effects.}, }
@article {pmid36556089, year = {2022}, author = {Mirsepasi-Lauridsen, HC}, title = {Therapy Used to Promote Disease Remission Targeting Gut Dysbiosis, in UC Patients with Active Disease.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36556089}, issn = {2077-0383}, abstract = {Ulcerative colitis (UC) is a relapsing non-transmural chronic inflammatory disease of the colon characterized by bloody diarrhea. The etiology of UC is unknown. The goal is to reduce the inflammation and induce disease remission in UC patients with active disease. The aim of this study is to investigate the innovative treatment method used to promote disease remission in UC patients with active disease targeting gut dysbiosis. Immunosuppressants such as TNF-α blocker are used to promote disease remission in UC, but it is expensive and with side effects. Probiotic, prebiotic and diet are shown to be effective in maintaining disease remission. Fecal microbiota transplantation (FMT) might be the future therapy option to promote disease remission in UC patients with active disease. However, correct manufacturing and administration of the FMT are essential to achieve successful outcome. A few cohorts with FMT capsules show promising results in UC patients with active disease. However, randomized controlled clinical trials with long-term treatment and follow-up periods are necessary to show FMT capsules' efficacy to promote disease remission in UC patients.}, }
@article {pmid36555774, year = {2022}, author = {Nita, IB and Ilie, OD and Ciobica, A and Hritcu, LD and Dobrin, I and Doroftei, B and Dobrin, R}, title = {Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia.}, journal = {International journal of molecular sciences}, volume = {23}, number = {24}, pages = {}, pmid = {36555774}, issn = {1422-0067}, abstract = {Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host's eubiosis. Based on combinations of specific keywords, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) for the established interval (2018-2022) and identified twenty two eligible cases, restricted only to human patients' experiences. Up until the writing of this manuscript, it has been revealed that the administration of specific lactic acid bacteria strains (Lactobacillus and Bifidobacterium), or those combined with vitamin D and selenium, maintain the integrity of the gut flora, preventing antagonistic effects including inflammation, antipsychotic-related body weight gain (olanzapine) and other metabolic dysfunctionalities. However, there are multiple antipsychotics that exert a potent effect upon gut flora, influencing a plethora of pathways and creating a dysbalance ratio between beneficial and opportunistic pathogens. Risperidone, amisulpride, and clozapine are just a few examples, but the current literature is unfortunately inconsistent and reported data is contradictory, which is why we support additional studies in this context. Moreover, we further argue the utility of studying how distinct controlled substances influence microbial communities, considering that ketamine is proved to alleviate depressive-like behavior as opposed to amphetamine and phencyclidine, which are known substances to trigger SCZ-like symptoms in experimental models. Probiotics may be regarded as the most consequential vehicle through which the gut flora can be successfully influenced, in adequate doses exerting a beneficial role as an alternative approach to alleviate SCZ symptoms.}, }
@article {pmid36555600, year = {2022}, author = {Tyszka, M and Maciejewska-Markiewicz, D and Biliński, J and Lubas, A and Stachowska, E and Basak, GW}, title = {Increased Intestinal Permeability and Stool Zonulin, Calprotectin and Beta-Defensin-2 Concentrations in Allogenic Hematopoietic Cell Transplantation Recipients.}, journal = {International journal of molecular sciences}, volume = {23}, number = {24}, pages = {}, pmid = {36555600}, issn = {1422-0067}, abstract = {Significant progress has been made in understanding the connection between intestinal barrier function and allogenic hematopoietic cell transplantation (allo-HCT) recipients' outcomes. The purpose of this study was to further evaluate gut barrier permeability and other potential intestinal barrier disruption markers in the allo-HCT setting. Fifty-one patients were enrolled in the study. Intestinal permeability was assessed with the sugar absorption test and faecal concentrations of the zonulin, calprotectin and beta-defensin-2 levels in the peri-transplantation period. Most patients undergoing allo-HCT in our department had a disrupted intestinal barrier at the baseline, which was associated with older age and higher Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Regardless of this, we observed a further increase in gut barrier permeability after allo-HCT in most patients. However, there was no association between permeability assay and other markers (zonulin, calprotectin and beta-defensin-2). Patients with acute GVHD had significantly higher median calprotectin concentrations after allo-HCT compared with the patients without this complication. Our findings indicate that gut barrier damage develops prior to allo-HCT with progression after the procedure and precedes further complications, but did not prove other markers to be useful surrogates of intestinal permeability.}, }
@article {pmid36552041, year = {2022}, author = {Patel, D and Desai, C and Singh, D and Soppina, V and Parwani, K and Patel, F and Mandal, P}, title = {Synbiotic Intervention Ameliorates Oxidative Stress and Gut Permeability in an In Vitro and In Vivo Model of Ethanol-Induced Intestinal Dysbiosis.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/biomedicines10123285}, pmid = {36552041}, issn = {2227-9059}, abstract = {Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD's pathophysiology is unknown. However, acetaldehyde's toxic effects cause oxidative stress and intestinal permeability. This study investigates the influence of a synbiotic (a combination of aged garlic extract (AGE) and Lactobacillus rhamnosus MTCC1423) on colonic oxidative stress and inflammation in ALD male Wistar rats and Caco2 cells. MDA measurement by HPLC in CaCo2 cells, blood serum, and colon tissue demonstrated that synbiotic treatment in the ALD model reduces oxidative stress. Further, fecal high-throughput 16S rRNA gene sequencing revealed the microbiome's shift towards Firmicutes in the synbiotic group compared to ethanol. In addition, DCFDA labeling and H/E staining demonstrate that the synbiotic is beneficial in inhibiting the development of ALD. In the colon, the synbiotic reduces the activation of CYP2E1 and the inflammatory markers TNF-a and IL-6 while elevating the mRNA expression of ZO-1, occludin, and IL-10. Synbiotics colonize Lactobacillus to restore barrier function and microbiota and reduce colon oxidative stress. Thus, a synbiotic combination can be used in ALD treatment.}, }
@article {pmid36552029, year = {2022}, author = {Feng, J and Ma, H and Huang, Y and Li, J and Li, W}, title = {Ruminococcaceae_UCG-013 Promotes Obesity Resistance in Mice.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/biomedicines10123272}, pmid = {36552029}, issn = {2227-9059}, abstract = {Alterations in the gut microbiome have been linked to obesity and type 2 diabetes, in epidemiologic studies and studies of fecal transfer effects in germ-free mice. Here, we aimed to identify the effects of specific gut microbes on the phenotype of mice fed a high-fat diet (HFD). After eight weeks of HFD feeding, male C57BL/6J mice in the HFD group ranking in the upper and lower quartiles for body weight gain were considered obese prone and obese resistant, respectively. 16S rRNA gene sequencing was used to determine the composition of the intestinal microbiota, and fecal transplantation (FMT) was conducted to determine whether the microbiota plays a causal role in phenotypic variation. Ruminococcaceae_UCG-013 was more abundant in the gut microbes of mice with a lean phenotype than in those with an obese phenotype. Ruminococcaceae_UCG-013 was identified as the most significant biomarker for alleviating obesity by random forest analysis. In a correlation analysis of serum parameters and body weight, Ruminococcaceae_UCG-013 was positively associated with serum HDL-C levels and negatively associated with serum TC, TG, and LDL-C levels. To conclude, Ruminococcaceae_UCG-013 was identified as a novel microbiome biomarker for obesity resistance, which may serve as a basis for understanding the critical gut microbes responsible for obesity resistance. Ruminococcaceae_UCG-013 may serve as a target for microbiome-based diagnoses and treatments in the future.}, }
@article {pmid36551772, year = {2022}, author = {Tian, P and Gao, J and Liang, L and Cui, B and Hu, Q and Zhou, W and Li, B and Liu, Y and Chen, T and Rao, J and Wei, H}, title = {Fecal Microbiota Transplantation Could Improve Chronic Diarrhea in Cynomolgus Monkey by Alleviating Inflammation and Modulating Gut Microbiota.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/biomedicines10123016}, pmid = {36551772}, issn = {2227-9059}, abstract = {Chronic diarrhea is associated with enteric dysbiosis and provokes the overuse of antibiotics. Fecal microbiota transplantation (FMT) is a promising therapy, but it shows discrepant clinical efficacy. Bacterial colonization in recipients has been studied, although little is known about the role of gut fungi and Archaea after FMT. In this study, we evaluated the efficacy of human-derived FMT on spontaneous chronic diarrhea cynomolgus monkeys and revealed the effector mechanisms. We demonstrated that FMT can mitigate the appearance of diarrheal symptoms and inhibit the increase in interleukin-6, interleukin-8, interleukin-1β, and interferon-γ and the decrease in interleukin-10 in serum. We confirmed that FMT restored the disturbance of gut bacteria by reducing the relative abundances of potential pathogens, including Cloacibacillus porcorum, Desulfovibrio desulfuricans, Erysipelotrichaceae bacterium 5_2_54FAA, and Erysipelotrichaceae bacterium 21_3, and increasing the levels of Lactobacillus fermentum and Lactobacillus ruminis CAG_367 in diarrheal monkeys. The metabolic pathways of healthy and FMT monkeys' gut bacteria were enriched in amino acid metabolism, carbohydrate metabolism, and lipid metabolism, while the metabolic pathways of pre-FMT monkeys' gut bacteria were enriched in antibiotic production. Moreover, a higher Ascomycota/Basidiomycota ratio, higher Aspergillus levels, and lower Trichosporon asahii abundance were present in intestinal fungi after FMT. Although the abundance of the Archaea Methanosphaera stastmanae did not change significantly, it was inversely correlated with the anti-inflammatory factor IL-4 after FMT. These results support the further development and application of FMT for chronic diarrhea.}, }
@article {pmid36551258, year = {2022}, author = {Petakh, P and Isevych, V and Kamyshnyi, A and Oksenych, V}, title = {Weil's Disease-Immunopathogenesis, Multiple Organ Failure, and Potential Role of Gut Microbiota.}, journal = {Biomolecules}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/biom12121830}, pmid = {36551258}, issn = {2218-273X}, abstract = {Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. In this review, we have described in detail the immunopathogenesis of leptospirosis, the influence of cytokines, genetic susceptibility on the course of the disease, and the evasion of the immune response. These data are combined with information about immunological and pathomorphological changes in the kidneys, liver, and lungs, which are most affected by Weil's disease. The review also suggests a possible role of the gut microbiota in the clinical course of leptospirosis, the main mechanisms of the influence of gut dysbiosis on damage in the liver, kidneys, and lungs through several axes, i.e., gut-liver, gut-kidney, and gut-lungs. Modulation of gut microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research.}, }
@article {pmid36550632, year = {2022}, author = {Li, J and Liang, J and Zeng, M and Sun, K and Luo, Y and Zheng, H and Li, F and Yuan, W and Zhou, H and Liu, J and Sun, H}, title = {Oxymatrine ameliorates white matter injury by modulating gut microbiota after intracerebral hemorrhage in mice.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/cns.14066}, pmid = {36550632}, issn = {1755-5949}, abstract = {INTRODUCTION: White matter injury (WMI) significantly affects neurobehavioral recovery in intracerebral hemorrhage (ICH) patients. Gut dysbiosis plays an important role in the pathogenesis of neurological disorders. Oxymatrine (OMT) has therapeutic effects on inflammation-mediated diseases. Whether OMT exerts therapeutic effects on WMI after ICH and the role of gut microbiota involved in this process is largely unknown.<br><br>METHODS: Neurological deficits, WMI, gut microbial composition, intestinal barrier function, and systemic inflammation were investigated after ICH. Fecal microbiota transplantation (FMT) was performed to elucidate the role of gut microbiota in the pathogenesis of ICH.<br><br>RESULTS: OMT promoted long-term neurological function recovery and ameliorated WMI in the peri-hematoma region and distal corticospinal tract (CST) region after ICH. ICH induced significant and persistent gut dysbiosis, which was obviously regulated by OMT. In addition, OMT alleviated intestinal barrier dysfunction and systemic inflammation. Correlation analysis revealed that gut microbiota alteration was significantly correlated with inflammation, intestinal barrier permeability, and neurological deficits after ICH. Moreover, OMT-induced gut microbiota alteration could confer protection against neurological deficits and intestinal barrier disruption.<br><br>CONCLUSIONS: Our study demonstrates that OMT ameliorates ICH-induced WMI and neurological deficits by modulating gut microbiota.}, }
@article {pmid36550591, year = {2022}, author = {Li, Y and Yang, L and Li, J and Gao, W and Zhao, Z and Dong, K and Duan, W and Dai, B and Guo, R}, title = {Antidepression of Xingpijieyu formula targets gut microbiota derived from depressive disorder.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/cns.14049}, pmid = {36550591}, issn = {1755-5949}, abstract = {OBJECTIVE: This investigation aims to determine the antidepressant role of Xingpijieyu formula (XPJYF) mediated via gut microbiota (GM)-brain axis.<br><br>METHODS: We collected fecal microbiota from patients with depressive disorder (DD) and cultured microbiota in vitro. Some of microbiota were transplanted into germ-free rats with the intragastric administration of XPJYF grain at the dose of 1.533&#xa0;g/kg/day. The behaviors were studied by forced swimming test, open field test, sucrose preference test, and body weight. Products of hypothalamus-pituitary-adrenocortical (HPA) axis, neurotransmitter, and serum cytokines were investigated by enzyme linked immunosorbent assay. Glial fibrillary acidic protein (GFAP), a biomarker of astrocyte, was quantified using immunofluorescence. Microbiota culturing in vitro after XPJYF treatment was analyze by 16&#x2009;s RNA sequencing technology. We used lipopolysaccharide (LPS) to mimic activated rat primary astrocyte in vitro. Brain-derived neurotrophic factor (BDNF), cytokines, and oxidative stress factors were determined by western blotting, and glycometabolism in astrocyte was investigated by 2-deoxy-D-glucose (2-DG) uptake, adenosine triphosphate (ATP), and glucose-1-phosphate (G1P) kits.<br><br>RESULTS: Microbiota composition during 8&#xa0;mg/ml of XPJYF (H12-8) for 12&#x2009;h showed the more consistency. Lactococcus is enriched in DD-derived microbiota composition, and Biffdobacterium and Lactobacillus in H12-8 group. GLUCOSE1PMETAB-PWY and PWY-7328 of which biofunctions were dominantly encoded by Biffdobacterium were the top two of altered pathways. XPJYF improved behaviors and repressed astrocyte activation in depression rats. XPJYF elevated 2-DG uptake, ATP, glucose-1-phosphate, and brain-derived neurotrophic factor (BDNF), and inhibited cytokines and oxidative stress in LPS-induced astrocyte.<br><br>CONCLUSION: XPJYF treatment targets inflammation, activation, and glycometabolim in astrocyte via gut microbiota modulation, thereby improve animal behaviors, HPA axis dysfunction, and neurotransmitter synthesis in depression rats.}, }
@article {pmid36550389, year = {2022}, author = {Zhao, M and Jiang, G and Zhou, H and Li, J and Xiang, W and Li, S and Wang, H and Zhou, J}, title = {Gut microbiota: a potential target for improved cancer therapy.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00432-022-04546-5}, pmid = {36550389}, issn = {1432-1335}, abstract = {Drug resistance and toxicity are major challenges observed during cancer treatment. In recent years, gut microbiota has been found to be strongly associated with the efficacy, toxicity, and side effects of chemotherapy, radiotherapy, and immunotherapy. Both preclinical studies and clinical trials have demonstrated the potential of microbiota modulation for cancer treatment. The human gut microbiota has exciting prospects for developing biomarkers to predict the outcome of cancer treatment. Moreover, multiple approaches can alter the gut microbiota composition, including faecal microbiota transplantation (FMT), probiotics, antibiotics (ATB), and diet. We describe the mechanisms by which the gut microbiota influences the efficacy and toxicity of cancer therapy, disease-related biomarkers, and methods to target the gut microbiota to improve outcomes. The purpose of this review is to provide new ideas for optimising cancer therapy by providing up-to-date information on the relationship between gut microbiota and cancer therapy, and hopes to find new targets for cancer treatment from human microbiota.}, }
@article {pmid36549470, year = {2022}, author = {Cavestro Giulia, M and Mannucci, A and Balaguer, F and Hampel, H and Kupfer, SS and Repici, A and Sartore-Bianchi, A and Seppälä Toni, T and Valentini, V and Boland Clement, R and Brand, RE and Buffart, TE and Burke, CA and Caccialanza, R and Cannizzaro, R and Cascinu, S and Cercek, A and Crosbie, EJ and Danese, S and Dekker, E and Daca-Alvarez, M and Deni, F and Dominguez-Valentin, M and Eng, C and Goel, A and Guillem Josè, G and Houwen, B and Kahi, C and Kalady, MF and Kastrinos, F and Kühn, F and Laghi, L and Latchford, A and Liska, D and Lynch, P and Malesci, A and Mauri, G and Meldolesi, E and Møller, P and Monahan, KJ and Moslein, G and Murphy, CC and Nass, K and Ng, K and Oliani, C and Papaleo, E and Patel, SG and Puzzono, M and Remo, A and Ricciardiello, L and Ripamonti Carla, I and Siena, S and Singh, SK and Stadler, ZK and Stanich, PP and Syngal, S and Turi, S and Urso Emanuele, D and Valle, L and Vanni Valeria, S and Vilar, E and Vitellaro, M and You, YN and Yurgelun, MB and Zuppardo Raffaella, A and Stoffel, EM and ,  and ,  and ,  and , }, title = {Delphi initiative for early-onset colorectal cancer (DIRECt). International Management Guidelines.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2022.12.006}, pmid = {36549470}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), comprised of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC.<br><br>METHODS: After reviewing the published literature, a Delphi methodology was employed to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of &#x2265;80%.<br><br>RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. Based on current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors.The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients.<br><br>CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.}, }
@article {pmid36548856, year = {2022}, author = {Li, K and Yang, J and Zhou, X and Wang, H and Ren, Y and Huang, Y and Liu, H and Zhong, Z and Peng, G and Zheng, C and Zhou, Z}, title = {The Mechanism of Important Components in Canine Fecal Microbiota Transplantation.}, journal = {Veterinary sciences}, volume = {9}, number = {12}, pages = {}, doi = {10.3390/vetsci9120695}, pmid = {36548856}, issn = {2306-7381}, abstract = {Fecal microbiota transplantation (FMT) is a potential treatment for many intestinal diseases. In dogs, FMT has been shown to have positive regulation effects in treating Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), canine parvovirus (CPV) enteritis, acute diarrhea (AD), and acute hemorrhagic diarrhea syndrome (AHDS). FMT involves transplanting the functional components of a donor's feces into the gastrointestinal tract of the recipient. The effective components of FMT not only include commensal bacteria, but also include viruses, fungi, bacterial metabolites, and immunoglobulin A (IgA) from the donor feces. By affecting microbiota and regulating host immunity, these components can help the recipient to restore their microbial community, improve their intestinal barrier, and induce anti-inflammation in their intestines, thereby affecting the development of diseases. In addition to the above components, mucin proteins and intestinal epithelial cells (IECs) may be functional ingredients in FMT as well. In addition to the abovementioned indications, FMT is also thought to be useful in treating some other diseases in dogs. Consequently, when preparing FMT fecal material, it is important to preserve the functional components involved. Meanwhile, appropriate fecal material delivery methods should be chosen according to the mechanisms these components act by in FMT.}, }
@article {pmid36545204, year = {2022}, author = {He, G and Chen, T and Huang, L and Zhang, Y and Feng, Y and Qu, S and Yin, X and Liang, L and Yan, J and Liu, W}, title = {Tremella fuciformis polysaccharide reduces obesity in high-fat diet-fed mice by modulation of gut microbiota.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1073350}, pmid = {36545204}, issn = {1664-302X}, abstract = {Obesity is a metabolic disease associated with gut microbiota and low-grade chronic inflammation. Tremella fuciformis is a medicinal and edible fungus; polysaccharide (TP) is the main active component, which has a variety of biological activities, such as hypoglycemic and hypolipidemic. However, the anti-obesity effects and potential mechanisms of TP have never been reported. This study was conducted to elucidate the inhibitory effect of TP on high-fat diet (HFD)-induced obesity in mice. Mice were split into five groups: normal chow diet (NCD) group, NCD_TP_H group, HFD group, HFD_TP_L group and HFD_TP_H group. Our study showed that TP inhibited high-fat diet-induced weight gain and fat accumulation in mice and reduced blood glucose, hyperlipidemia and inflammation. TP also improved gut microbiota disorders by reducing the Firmicutes/Bacteroidetes ratio and modulating the relative abundance of specific gut microbiota. We also found that the anti-obesity and gut microbiota-modulating effects of TP could be transferred to HFD-fed mice via faecal microbiota transplantation (FMT), confirming that the gut microbiota was one of the targets of TP for obesity inhibition. Further studies showed that TP increased the production of short-chain fatty acids and the secretion of intestinal hormones. Our studies showed that TP inhibited obesity by modulating inflammation and the microbe-gut-brain axis, providing a rationale for developing TP to treat obesity and its complications.}, }
@article {pmid36544550, year = {2022}, author = {Li, Y and Wang, Y and Zhang, T}, title = {Fecal Microbiota Transplantation in Autism Spectrum Disorder.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {2905-2915}, pmid = {36544550}, issn = {1176-6328}, abstract = {Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that begin in infancy. In recent years, the incidence of ASD in the world is increasing year by year. At present, the etiology and pathogenesis of ASD are not clear, and effective treatments are still lacking. In addition to neurobehavioral symptoms, children with ASD often have obvious gastrointestinal symptoms. Gut microbiota is a large microbial community in the human gut, which is closely related to the nervous system and can affect brain development and behavior through the neuroendocrine, neuroimmune and autonomic nervous systems, forming a microbiota-gut-brain axis connection. Recent studies have shown that children with ASD have significant gut microbiota and metabolic disorders, and fecal microbiota transplantation (FMT) is expected to improve ASD-related symptoms by regulating gut microbiota and metabolism. This review paper will therefore focus on FMT in the treatment of ASD, and FMT is effective in improving gastrointestinal and neurobehavioral symptoms in children with ASD.}, }
@article {pmid36544495, year = {2022}, author = {Wortelboer, K and Koopen, AM and Herrema, H and de Vos, WM and Nieuwdorp, M and Kemper, EM}, title = {From fecal microbiota transplantation toward next-generation beneficial microbes: The case of Anaerobutyricum soehngenii.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1077275}, pmid = {36544495}, issn = {2296-858X}, abstract = {The commensal gut microbiota is important for human health and well-being whereas deviations of the gut microbiota have been associated with a multitude of diseases. Restoration of a balanced and diverse microbiota by fecal microbiota transplantation (FMT) has emerged as a potential treatment strategy and promising tool to study causality of the microbiota in disease pathogenesis. However, FMT comes with logistical challenges and potential safety risks, such as the transfer of pathogenic microorganisms, undesired phenotypes or an increased risk of developing disease later in life. Therefore, a more controlled, personalized mixture of cultured beneficial microbes might prove a better alternative. Most of these beneficial microbes will be endogenous commensals to the host without a long history of safe and beneficial use and are therefore commonly referred to as next-generation probiotics (NGP) or live biotherapeutic products (LBP). Following a previous FMT study within our group, the commensal butyrate producer Anaerobutyricum spp. (previously named Eubacterium hallii) was found to be associated with improved insulin-sensitivity in subjects with the metabolic syndrome. After the preclinical testing with Anaerobutyricum soehngenii in mice models was completed, the strain was produced under controlled conditions and several clinical studies evaluating its safety and efficacy in humans were performed. Here, we describe and reflect on the development of A. soehngenii for clinical use, providing practical guidance for the development and testing of NGPs and reflecting on the current regulatory framework.}, }
@article {pmid36544282, year = {2023}, author = {Bai, X and Xu, Q and Zhang, W and Wang, C}, title = {The Gut-Eye Axis: Correlation Between the Gut Microbiota and Autoimmune Dry Eye in Individuals With Sjögren Syndrome.}, journal = {Eye &amp; contact lens}, volume = {49}, number = {1}, pages = {1-7}, doi = {10.1097/ICL.0000000000000953}, pmid = {36544282}, issn = {1542-233X}, abstract = {The impact of gut microbiota on human health, autoimmunity, and disease occurrence has long been recognized since the advancement of metagenomic sequencing technology has enabled a new level of perspective on the human microbiome. Emerging findings also suggest the existence of a gut-eye axis, wherein gut dysbiosis may be a crucial factor affecting the onset and progression of multiple ocular diseases. Sjögren syndrome (SS) is a chronic autoimmune disease mainly affecting the exocrine glands, primarily the lacrimal gland in the eye, resulting in severe dry eye. Although there are currently various treatments for environmental dry eye, the efficacy for SS-related autoimmune dry eye is limited, and new and more effective therapies still need to be explored. The latest studies have demonstrated that the gut microbiota plays a key role in the pathogenesis of autoimmune dry eye. This review describes the effect of gut microbiota on the ocular surface of autoimmune dry eye; introduces the presumable pathways forming the "gut dysbiosis-ocular surface-lacrimal gland axis"; discusses the advantages of restoring intestinal microecology to treat dry eye by fecal microbiota transplantation or probiotics, which are expected to provide perspectives into the correlation between the gut microbiome and dry eye; enhance our understanding of the pathogenesis in autoimmune dry eye; and be useful in the development of future interventions of dry eye by regulating the gut microbiota.}, }
@article {pmid36543925, year = {2022}, author = {Ahn, EH and Liu, X and Alam, AM and Kang, SS and Ye, K}, title = {Helicobacter hepaticus augmentation triggers Dopaminergic degeneration and motor disorders in mice with Parkinson's disease.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {36543925}, issn = {1476-5578}, abstract = {Gut dysbiosis contributes to Parkinson's disease (PD) pathogenesis. Gastrointestinal disturbances in PD patients, along with gut leakage and intestinal inflammation, take place long before motor disorders. However, it remains unknown what bacterial species in gut microbiomes play the key role in driving PD pathogenesis. Here we show that Helicobacter hepaticus (H. hepaticus), abundant in gut microbiota from rotenone-treated human α-Synuclein gene (SNCA) transgenic mice and PD patients, initiates α-Synuclein pathology and motor deficits in an AEP-dependent manner in SNCA mice. Chronic Dextran sodium sulfate (DSS) treatment, an inflammatory inducer in the gut, activates AEP (asparagine endopeptidase) that cleaves α-Synuclein N103 and triggers its aggregation, promoting inflammation in the gut and the brain and motor defects in SNCA mice. PD fecal microbiota transplant or live H. hepaticus administration into antibiotics cocktail (Abx)-pretreated SNCA mice induces α-Synuclein pathology, inflammation in the gut and brain, and motor dysfunctions, for which AEP is indispensable. Hence, Helicobacter hepaticus enriched in PD gut microbiomes may facilitate α-Synuclein pathologies and motor impairments via activating AEP.}, }
@article {pmid36543914, year = {2022}, author = {Chioma, OS and Mallott, EK and Chapman, A and Van Amburg, JC and Wu, H and Shah-Gandhi, B and Dey, N and Kirkland, ME and Blanca Piazuelo, M and Johnson, J and Bernard, GR and Bodduluri, SR and Davison, S and Haribabu, B and Bordenstein, SR and Drake, WP}, title = {Gut microbiota modulates lung fibrosis severity following acute lung injury in mice.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {1401}, doi = {10.1038/s42003-022-04357-x}, pmid = {36543914}, issn = {2399-3642}, abstract = {Independent studies demonstrate the significance of gut microbiota on the pathogenesis of chronic lung diseases; yet little is known regarding the role of the gut microbiota in lung fibrosis progression. Here we show, using the bleomycin murine model to quantify lung fibrosis in C57BL/6 J mice housed in germ-free, animal biosafety level 1 (ABSL-1), or animal biosafety level 2 (ABSL-2) environments, that germ-free mice are protected from lung fibrosis, while ABSL-1 and ABSL-2 mice develop mild and severe lung fibrosis, respectively. Metagenomic analysis reveals no notable distinctions between ABSL-1 and ABSL-2 lung microbiota, whereas greater microbial diversity, with increased Bifidobacterium and Lactobacilli, is present in ABSL-1 compared to ABSL-2 gut microbiota. Flow cytometric analysis reveals enhanced IL-6/STAT3/IL-17A signaling in pulmonary CD4 + T cells of ABSL-2 mice. Fecal transplantation of ABSL-2 stool into germ-free mice recapitulated more severe fibrosis than transplantation of ABSL-1 stool. Lactobacilli supernatant reduces collagen 1 A production in IL-17A- and TGFβ1-stimulated human lung fibroblasts. These findings support a functional role of the gut microbiota in augmenting lung fibrosis severity.}, }
@article {pmid36542917, year = {2022}, author = {Wu, Z and Tian, E and Chen, Y and Dong, Z and Peng, Q}, title = {Gut microbiota and its roles in the pathogenesis and therapy of endocrine system diseases.}, journal = {Microbiological research}, volume = {268}, number = {}, pages = {127291}, doi = {10.1016/j.micres.2022.127291}, pmid = {36542917}, issn = {1618-0623}, abstract = {A new field of microbial research is the relationship between microorganisms and multicellular hosts. It is known that gut microbes can cause various endocrine system diseases, such as diabetes and thyroid disease. Changes in the composition or structure and the metabolites of gut microbes may cause gastrointestinal disorders, including ulcers or intestinal perforation and other inflammatory and autoimmune diseases. In recent years, reports on the interactions between intestinal microorganisms and endocrine system diseases have been increasingly documented. In the meantime, the treatment based on gut microbiome has also been paid much attention. For example, fecal microbiota transplantation is found to have a therapeutic effect on many diseases. As such, understanding the gut microbiota-endocrine system interactions is of great significance for the theranostic of endocrine system diseases. Herein, we summarize the relations of gut microbiome with endocrine system diseases, and discuss the potentials of regulating gut microbiome in treating those diseases. In addition, the concerns and possible solutions regarding the gut microbiome-based therapy are discussed.}, }
@article {pmid36537602, year = {2022}, author = {Santacroce, L and Di Domenico, M and Montagnani, M and Jirillo, E}, title = {Antibiotic Resistance And Microbiota Response.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/1381612829666221219093450}, pmid = {36537602}, issn = {1873-4286}, abstract = {BACKGROUND: Use of antibiotics has dramatically eradicated bacterial infections in humans and animals. However, antibiotic overdose and abuse are responsible for the emergence of so-called multi-drug resistant bacteria. Interaction between antibiotics and gut microbiota: Gut microbiota deserves many functions in the host, and, among them, integrity of epithelial barrier and enhancement of protective immune responses are included. There is evidence that antibiotic treatment decreases the diversity of gut microbiota species, also provoking metabolic changes, increased susceptibility to colonization and decrease of antimicrobial peptide secretion, leading to antibiotic resistance.<br><br>SPECIFIC AIMS: In this review the major mechanisms involved in antibiotic resistance will be illustrated. However, novel findings on the potential use of alternative treatments to overcome antibiotic resistance will be elucidated. In this regard, special emphasis will be placed on microcins, prebiotics, probiotics and postbiotics, as well as phage therapy and fecal microbial transplantation.}, }
@article {pmid36537331, year = {2022}, author = {Wang, S and Cui, J and Jiang, S and Zheng, C and Zhao, J and Zhang, H and Zhai, Q}, title = {Early life gut microbiota: Consequences for health and opportunities for prevention.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-25}, doi = {10.1080/10408398.2022.2158451}, pmid = {36537331}, issn = {1549-7852}, abstract = {The gut microbiota influences many aspects of the host, including immune system maturation, nutrient absorption and metabolism, and protection from pathogens. Increasing evidences from cohort and animal studies indicate that changes in the gut microbiota early in life increases the risk of developing specific diseases early and later in life. Therefore, it is becoming increasingly important to identify specific disease prevention or therapeutic solutions targeting the gut microbiota, especially during infancy, which is the window of the human gut microbiota establishment process. In this review, we provide an overview of current knowledge concerning the relationship between disturbances in the gut microbiota early in life and health consequences later in life (e.g., necrotizing enterocolitis, celiac disease, asthma, allergies, autism spectrum disorders, overweight/obesity, diabetes and growth retardation), with a focus on changes in the gut microbiota prior to disease onset. In addition, we summarize and discuss potential microbiota-based interventions early in life (e.g., diet adjustments, probiotics, prebiotics, fecal microbiota transplantation, environmental changes) to promote health or prevent the development of specific diseases. This knowledge should aid the understanding of early life microbiology and inform the development of prediction and prevention measures for short- and long-term health disorders based on the gut microbiota.}, }
@article {pmid36537141, year = {2022}, author = {Nie, C and Xie, X and Liu, H and Yuan, X and Ma, Q and Tu, A and Zhang, M and Chen, Z and Li, J}, title = {Galactooligosaccharides ameliorate dietary advanced glycation end product-induced intestinal barrier damage in C57BL/6 mice by modulation of the intestinal microbiome.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d2fo02959f}, pmid = {36537141}, issn = {2042-650X}, abstract = {Advanced glycation end products (AGEs) are increasingly recognized as potentially pathogenic components of processed foods, and long-term consumption of dietary AGEs triggers disruption of the intestinal barrier integrity and increases the risk of chronic diseases. Galactooligosaccharides (GOS) as prebiotics can modulate the intestinal microbiota and improve the intestinal barrier integrity. In this study, we aimed to investigate whether GOS could ameliorate the intestinal barrier damage induced by AGEs. The results showed an increased number of goblet cells (AGEs vs. H-GOS, 133.4 vs. 174.7, p < 0.05) and neutral mucin area (PAS positive area, 7.29% vs. 10.05%, p < 0.05). Upregulated expressions of occludin and claudin-1 and improved intestinal barrier integrity were observed in the H-GOS group. Using 16S rRNA sequencing analysis, we found that GOS significantly reduced the high enrichment of Akkermansia (16.95% vs. 1.29%, p < 0.05) induced by dietary AGEs while increasing the content of short-chain fatty acids. Fecal microbiota transplantation (FMT) showed that AGE-induced damage to the intestinal mucus barrier was reversed in the H-GOS transplanted group. Collectively, GOS ameliorated dietary AGE-induced intestinal barrier damage by reversing the dysregulated state of the intestinal microbiota. Our study lays the foundation for further research on dietary guidelines for populations with high AGE diets.}, }
@article {pmid36536532, year = {2022}, author = {Bloom, PP and Young, VB}, title = {Microbiome therapeutics for the treatment of recurrent Clostridioides difficile infection.}, journal = {Expert opinion on biological therapy}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/14712598.2022.2154600}, pmid = {36536532}, issn = {1744-7682}, abstract = {INTRODUCTION: The gut microbiome is implicated in Clostridioides difficile infection (CDI) and recurrent CDI (rCDI).<br><br>AREAS COVERED: This review covers the mechanisms by which microbiome therapeutics treat rCDI, their efficacy and safety, and clinical trial design considerations for future research.<br><br>EXPERT OPINION: Altering the chemical environment of the gut and reconstituting colonization resistance is a promising strategy for preventing and treating rCDI. Fecal microbiota transplant (FMT) is safe and effective for the treatment of rCDI. However, limitations of FMT have prompted investigation into alternative microbiome therapeutics. These alternative microbiome therapies require further evaluation, and adaptive trial designs should be strongly considered to more rapidly discern variables including the need for bowel preparation, timing and selection of pre-treatment antibiotics, and dose and duration of microbiome therapeutics. A broad range of adverse events must be prospectively evaluated in these controlled trials, as microbiome therapeutics have the potential for numerous effects. Future studies will lead to a greater understanding of the mechanisms by which microbiome therapies can break the cycle of rCDI, which should ultimately yield a personalized approach to rCDI treatment that restores an individual's specific deficit(s) in colonization resistance to C. difficile.}, }
@article {pmid36535571, year = {2022}, author = {Yan, M and Man, S and Liang, Y and Ma, L and Guo, L and Huang, L and Gao, W}, title = {Diosgenin alleviates nonalcoholic steatohepatitis through affecting liver-gut circulation.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106621}, doi = {10.1016/j.phrs.2022.106621}, pmid = {36535571}, issn = {1096-1186}, abstract = {Nonalcoholic steatohepatitis (NASH), as the aggressive form of nonalcoholic fatty liver disease (NAFLD), rapidly becomes the leading cause of end-stage liver disease or liver transplantation. Nowadays, there has no approved drug for NASH treatment. Diosgenin possesses multiple beneficial effects towards inhibition of lipid accumulation, cholesterol metabolism, fibrotic progression and inflammatory response. However, there has been no report concerning its effects on NASH so far. Using methionine and choline-deficient (MCD) feeding mice, we evaluated the anti-NASH effects of diosgenin. 16S rDNA was used to investigate gut microbiota composition. Transcriptome sequencing, LC/MS and GC/MS analysis were used to evaluate bile acids (BAs) metabolism and their related pathway. Compared with the MCD group, diosgenin treatment improved the hepatic dysfunction, especially decreased the serum and hepatic TC, TG, ALT, AST and TBA to nearly 50%. Content of BAs, especially CA and TCA, were decreased from 59.30 and 26.00 to 39.71 and 11.48ng/mg in liver and from 0.96 and 2.1 to 0.47 and 1.13μg/mL in serum, and increased from 7.01 and 11.08 to 3.278 and 5.11ng/mg in feces, respectively. Antibiotic and fecal microbiota transplantation (FMT) treatment further confirmed the therapeutic effect of diosgenin on gut microbiota, especially Clostridia (LDA score of 4.94), which regulated BAs metabolism through the hepatic FXR-SHP and intestinal FXR-FGF15 pathways. These data indicate that diosgenin prevents NASH by altering Clostridia and BAs metabolism. Our results shed light on the mechanisms of diosgenin in treating NASH, which pave way for the design of novel clinical therapeutic strategies.}, }
@article {pmid36535435, year = {2022}, author = {Zhang, L and Zhang, Y and Zou, Z and Jiang, X and Mao, L and Xia, Y and Fan, Y and Li, N and Jiang, Z and Qin, X and Jiang, Y and Liu, G and Qiu, F and Zhang, J and Chen, C}, title = {Disruption of the lung-gut-brain axis is responsible for cortex damage induced by pulmonary exposure to zinc oxide nanoparticles.}, journal = {Toxicology}, volume = {}, number = {}, pages = {153390}, doi = {10.1016/j.tox.2022.153390}, pmid = {36535435}, issn = {1879-3185}, abstract = {Increasing demonstrations pointed out that gut microbiota is important for interactions affecting host health in response to metal nanomaterials exposure. However, the effect of gut microbiota on the cortex damage caused by pulmonary exposure to zinc oxide nanoparticles (ZnONPs) remains mainly unknown. In this research, 48 8-week-old C57BL/6J mice were intratracheally instilled with 0.6mg/kg ZnONPs in the presence or absence of antibiotics (ABX) treatment. Besides, 24 8-week-old C57BL/6J mice were treated with or without fecal microbiota transplantation (FMT) after the intraperitoneal administration of ABX. Our results demonstrated for the first time that dysbiosis induced by ABX treatment significantly aggravated cortex damage induced by pulmonary exposure to ZnONPs. Such damage might highly occur through the induction of oxidative stress, manifested by the enhancement of antioxidative enzymes and products of lipid peroxidation. However, ferroptosis was not involved in this process. Interestingly, our data revealed that ABX treatment exacerbated the alterations of gut-brain peptides (including Sst, Sstr2, and Htr4) induced by ZnONPs in both gut and cortex tissues. Moreover, fecal microbiota transplantation (FMT) was able to alleviate cerebral cortex damage, oxidative stress, and alterations of gut-brain peptides induced by pulmonary exposure to ZnONPs. The results together indicate that pulmonary exposure to ZnONPs causes cerebral cortex damage possibly via the disruption of the lung-gut-brain axis. These findings not only propose valuable insights into the mechanism of ZnONPs neurotoxicity but also provide a potential therapeutic method against brain disorders induced by pulmonary exposure to ZnONPs. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the current study are available from the The corresponding author on reasonable request.}, }
@article {pmid36532458, year = {2022}, author = {Zhou, Y and Zhou, C and Zhang, A}, title = {Gut microbiota in acute leukemia: Current evidence and future directions.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1045497}, pmid = {36532458}, issn = {1664-302X}, abstract = {Gut microbiota includes a large number of microorganisms inhabiting the human gastrointestinal tract, which show a wide range of physiological functions, including digestion, metabolism, immunity, neural development, etc., and are considered to play an increasingly important role in health and disease. A large number of studies have shown that gut microbiota are closely associated with the onset and development of several diseases. In particular, the interaction between gut microbiota and cancer has recently attracted scholars' attention. Acute leukemia (AL) is a common hematologic malignancy, especially in children. Microbiota can affect hematopoietic function, and the effects of chemotherapy and immunotherapy on AL are noteworthy. The composition and diversity of gut microbiota are important factors that influence and predict the complications and prognosis of AL after chemotherapy or hematopoietic stem cell transplantation. Probiotics, prebiotics, fecal microbiota transplantation, and dietary regulation may reduce side effects of leukemia therapy, improve response to treatment, and improve prognosis. This review concentrated on the role of the gut microbiota in the onset and development of AL, the response and side effects of chemotherapy drugs, infection during treatment, and therapeutic efficacy. According to the characteristics of gut microbes, the applications and prospects of microbial preparations were discussed.}, }
@article {pmid36532422, year = {2022}, author = {Liu, X and Zhang, M and Wang, X and Liu, P and Wang, L and Li, Y and Wang, X and Ren, F}, title = {Fecal microbiota transplantation restores normal fecal composition and delays malignant development of mild chronic kidney disease in rats.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1037257}, pmid = {36532422}, issn = {1664-302X}, abstract = {Chronic kidney disease (CKD) is associated with gut microbiome dysbiosis, but the role of intestinal flora in CKD treatment remains to be elucidated. Fecal microbiota transplantation (FMT) can be utilized to re-establish healthy gut microbiota for a variety of diseases, which offers new insight for treating CKD. First, 5/6 nephrectomy rats (Donor CKD) and sham rats (Donor Sham) were used as donors for FMT, and fecal metagenome were analyzed to explore potential therapeutic targets. Then, to assess the effect of FMT on CKD, sterilized 1/2 nephrectomy rats were transplanted with fecal microbiota from Donor sham (CKD/Sham) or Donor CKD (CKD/CKD) rats, and 1/2 nephrectomy rats without FMT (CKD) or no nephrectomy (Sham) were used as model control or normal control. Results showed that Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 were enriched in Donor CKD, while Lactobacillus johnsonii and Lactobacillus intestinalis were reduced. In addition, the increased abundance of microbial functions included tryptophan metabolism and lysine degradation contributing to the accumulation of protein-bound uremic toxins (PBUTs) in Donor CKD. Genome analysis indicated that FMT successfully differentiated groups of gut microbes and altered specific gut microbiota after 1 week of treatment, with Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 increasing in CKD/CKD group as well as Lactobacillus johnsonii and Lactobacillus intestinalis being improved in CKD/Sham group. In comparison to CKD group, substantial PBUT buildup and renal damage were observed in CKD/CKD. Interestingly, compared to CKD or CKD/CKD group, tryptophan metabolism and lysine degradation were efficiently suppressed in CKD/Sham group, while lysine biosynthesis was promoted. Therefore, FMT considerably reduced PBUTs accumulation. After FMT, PBUTs and renal function in CKD/Sham rats remained the same as in Sham group throughout the experimental period. In summary, FMT could delay the malignant development of CKD by modifying microbial amino acid metabolism through altering the microenvironment of intestinal flora, thereby providing a novel potential approach for treating CKD.}, }
@article {pmid36532416, year = {2022}, author = {Li, H and Li, N and Lu, Q and Yang, J and Zhao, J and Zhu, Q and Yi, S and Fu, W and Luo, T and Tang, J and Zhang, Y and Yang, G and Liu, Z and Xu, J and Chen, W and Zhu, J}, title = {Chronic alcohol-induced dysbiosis of the gut microbiota and gut metabolites impairs sperm quality in mice.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1042923}, pmid = {36532416}, issn = {1664-302X}, abstract = {Studies have indicated that the ethanol exposure impairs the gut microbiota, At the same time, high levels of alcohol exposure damage sperm in mice. However, whether the gut microbiota is involved in mediating the effects of alcohol on sperm quality remains unclear. This study aimed to assess the effect of chronic alcohol consumption on intestinal microbiota in mice and analyze the potential pathophysiological effect of altered intestinal microbiota on sperm quality. We established a mouse model of chronic alcohol consumption by allowing male C57 mice to freely ingest 10% ethanol for 10 weeks, and collected the fecal microbiota of the male mice in the chronic drinking group (alcohol) and the control group (control) and transplanted the specimens into the transplant groups (the alcohol-fecal microbiota transplantation [FMT] group and the control-FMT group). Sperm quality was significantly decreased in the alcohol-FMT group compared with the control-FMT group. Gut microbiota analysis revealed that the abundance of 11 operational taxonomic units (OTUs) was altered in the alcohol-FMT group. Nontargeted metabolomics identified 105 differentially altered metabolites, which were mainly annotated to amino acids, lipids, glycerophosphoethanolamine, organic oxygenic compounds, organic acids and their derivatives, steroids, and flavonoids. In particular, the oxidative phosphorylation pathway, which is the key to spermatogenesis, was significantly enriched in the alcohol-FMT group. Moreover, compared with the control-FMT group, the alcohol-FMT group presented significantly higher serum endotoxin and inflammatory cytokine levels, with more pronounced T cell and macrophage infiltration in the intestinal lamina propria and elevated levels of testicular inflammatory cytokines. In addition, RNA sequencing showed significant differences in the expression of testis-related genes between the alcohol-FMT group and the control-FMT group. In particular, the expression of genes involved in gamete meiosis, testicular mitochondrial function, and the cell division cycle was significantly reduced in alcohol-FMT mice. In conclusion, these findings indicated that intestinal dysbiosis induced by chronic alcohol consumption may be an important factor contributing to impaired sperm quality. Chronic alcohol consumption induces intestinal dysbiosis, which then leads to metabolic disorders, elevated serum endotoxin and inflammatory cytokine levels, testicular inflammation, abnormal expression of related genes, and ultimately, impaired sperm quality. These findings are potentially useful for the treatment of male infertility.}, }
@article {pmid36532026, year = {2022}, author = {Kang, Y and Ren, P and Kuang, X and Li, L and Kang, X and Yang, Y}, title = {Editorial: Improve metabolic and autoimmune diseases by regulating gut microbiota.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1091805}, doi = {10.3389/fimmu.2022.1091805}, pmid = {36532026}, issn = {1664-3224}, }
@article {pmid36530877, year = {2022}, author = {Zhang, X and Ishikawa, D and Ohkusa, T and Fukuda, S and Nagahara, A}, title = {Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1068567}, pmid = {36530877}, issn = {2296-858X}, abstract = {Inflammatory bowel disease (IBD) is a chronic intestinal mucosal inflammatory disease with complex etiology. Traditional anti-inflammatory treatment regimens have yielded unsatisfactory results. As research continues to deepen, it has been found that the gut microbiota of patients with IBD is generally altered. The presence of microorganisms in the human gastrointestinal tract is inextricably linked to the regulation of health and disease. Disruption of the microbiotic balance of microbiota in the gastrointestinal tract is called dysbiosis, which leads to disease. Therefore, in recent years, the exploration of therapeutic methods to restore the homeostasis of the gut microbiota has attracted attention. Moreover, the use of the well-established fecal microbiota transplantation (FMT) regimen for the treatment of Clostridioides difficile infection has attracted the interest of IBD researchers. Therefore, there are an increasing number of clinical studies regarding FMT for IBD treatment. However, a series of questions regarding FMT in the treatment of IBD warrants further investigation and discussion. By reviewing published studies, this review explored hot topics such as the efficacy, safety, and administration protocol flow of FMT in the treatment of IBD. Different administration protocols have generally shown reassuring results with significant efficacy and safety. However, the FMT treatment regimen needs to be further optimized. We believe that in the future, individual customized or standard FMT implementation will further enhance the relevance of FMT in the treatment of IBD.}, }
@article {pmid36530444, year = {2022}, author = {Zhang, S and Deng, F and Chen, J and Chen, F and Wu, Z and Li, L and Hou, K}, title = {Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes: A systematic review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1075201}, pmid = {36530444}, issn = {2235-2988}, abstract = {There is a strong link between fecal microbiota and the development of type 1 diabetes. As an emerging therapeutic modality, fecal microbiota transplantation has been shown to be safe and effective in the treatment of many intestinal and extraintestinal diseases. Various studies have found that fecal microbiota transplantation can treat diseases by correcting patients' immune disorders. Besides, many studies have found that fecal microbiota transplantation can improve glycemic control and insulin resistance in diabetic patients. Therefore, this paper reviews the mechanism of action of fecal microbiota transplantation on autoimmune-mediated T1DM and the current research progress, feasibility, and issues that need to be addressed in the future development of fecal microbiota transplantation in the treatment of autoimmune-mediated T1DM.}, }
@article {pmid36529248, year = {2022}, author = {Li, B and Xu, M and Wang, Y and Feng, L and Xing, H and Zhang, K}, title = {Gut microbiota: A new target for traditional Chinese medicine in the treatment of depression.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {116038}, doi = {10.1016/j.jep.2022.116038}, pmid = {36529248}, issn = {1872-7573}, abstract = {The causes of depression are complex. Many factors are involved in its pathogenesis, including the individual's biological and social environment. Although numerous studies have reported that the gut microbiota plays a significant role in depression, drugs that regulate the gut microbiota to treat depression have not yet been comprehensively reviewed. At the same time, more and more attention has been paid to the characteristics of traditional Chinese medicine (TCM) in improving depression by regulating gut microbiota. In ancient times, fecal microbiota transplantation was recorded in TCM for the treatment of severe diseases. There are also records in Chinese ancient books about the use of TCM to adjust gut microbiota to treat diseases, which has opened up a unique research field in TCM. Therefore, this article focuses on the pharmacological effects, targets, and mechanisms of TCM in improving depression by mediating the influence of gut microbiota.<br><br>AIM OF THIS REVIEW: To summarize the role the gut microbiota plays in depression, highlight potential regulatory targets, and elucidate the anti-depression mechanisms of TCMs through regulation of the gut microbiota.<br><br>METHODS: A systematic review of 256 clinical trials and pharmaceutical studies published until June 2022 was conducted in eight electronic databases (Web of Science, PubMed, SciFinder, Research Gate, ScienceDirect, Google Scholar, Scopus, and China Knowledge Infrastructure), according to the implemented PRISMA criteria, using the search terms "traditional Chinese medicine," "depression," and "gut microbiota."<br><br>RESULTS: Numerous studies reported the effects of different gut bacteria on depression and that antidepressants work through the gut microbiota. TCM preparations based on compound Chinese medicine, the Chinese Materia Medica, and major bioactive components exerted antidepressant-like effects by improving levels of neurotransmitters, short-chain fatty acids, brain-derived neurotrophic factor, kynurenine, and cytokines via regulation of the gut microbiota.<br><br>CONCLUSION: This review summarized the anti-depression effects of TCM on the gut microbiota, providing evidence that TCMs are safe and effective in the treatment of depression and may provide a new therapeutic approach.}, }
@article {pmid36527519, year = {2022}, author = {Yousefi, B and Babaeizad, A and Banihashemian, SZ and Feyzabadi, ZK and Dadashpour, M and Pahlevan, D and Ghaffari, H and Eslami, M}, title = {Gastrointestinal Tract, Microbiota and Multiple Sclerosis (MS) and the Link Between Gut Microbiota and CNS.}, journal = {Current microbiology}, volume = {80}, number = {1}, pages = {38}, pmid = {36527519}, issn = {1432-0991}, abstract = {Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions that can lead to severe neurological defects. Evidence is mounting that immune function is crucial in neuroinflammatory illnesses like MS. Through its impact on systemic immunological reactions, the large microbial population known as the gut microbiota has been linked to both human health and disease. The gut-brain axis (GBA) therefore encompasses neurological, immunological, and hormonal pathways, and microbiota can have a number of effects on the immune system, influencing MS. Recent research revealed a bidirectional relationship between metabolites originating from the gut microbiota, namely short-chain fatty acids (SCFAs). Intestinal epithelial cells are influenced by SCFAs, which also boosts the secretion of -Defensins and regenerating islet-derived III (REGIII) proteins. These proteins reduce intestinal pathogens, induce T-reg differentiation, and modulate immune responses by reducing IL-1 and IL-6 expression and increasing IL-10. Nutrition and psychological stress are two of the most significant elements that can directly and indirectly change the microbiota compositions along with other environmental influencing factors. An important regulator of intestinal physiology in the gut-brain-microbiota axis is butyrate, a well-known SCFA. Intestinal dysbiosis, altered intestinal barrier function, behavioral abnormalities, and activation of the hypothalamic-pituitary-adrenal (HPA) axis are all brought on by exposure. Probiotics, bacterial metabolite supplementation, fecal matter transplantation, defined microbial communities, and dietary intervention are some methods for modifying the composition of the gut microbiota that may be used to affect disease-related immune dysfunction and serve as the foundation for a new class of therapeutics.}, }
@article {pmid36525272, year = {2022}, author = {Lahtinen, P and Juuti, A and Luostarinen, M and Niskanen, L and Liukkonen, T and Tillonen, J and Kössi, J and Ilvesmäki, V and Viljakka, M and Satokari, R and Arkkila, P}, title = {Effectiveness of Fecal Microbiota Transplantation for Weight Loss in Patients With Obesity Undergoing Bariatric Surgery: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {5}, number = {12}, pages = {e2247226}, doi = {10.1001/jamanetworkopen.2022.47226}, pmid = {36525272}, issn = {2574-3805}, abstract = {IMPORTANCE: Severe obesity is a major health concern. However, a few patients remain resistant to bariatric surgery and other treatments. Animal studies suggest that weight may be altered by fecal microbiota transplantation (FMT) from a lean donor.<br><br>OBJECTIVE: To determine whether FMT from a lean donor reduces body weight and further improves the results of bariatric surgery.<br><br>This double-blinded, placebo-controlled, multicenter, randomized clinical trial was conducted in 2018 to 2021 among adult individuals with severe obesity treated at 2 bariatric surgery centers in Finland and included 18 months of follow-up. Patients eligible for bariatric surgery were recruited for the study. Data were analyzed from March 2021 to May 2022.<br><br>INTERVENTIONS: FMT from a lean donor or from the patient (autologous placebo) was administered by gastroscopy into the duodenum. Bariatric surgery was performed 6 months after the baseline intervention using laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG).<br><br>MAIN OUTCOMES AND MEASURES: The main outcome was weight reduction measured as the percentage of total weight loss (TWL).<br><br>RESULTS: Forty-one patients were recruited to participate in the study and were included in the final analysis (29 women [71.1%]; mean [SD] age, 48.7 [8.7] years; mean [SD] body mass index, 42.5 [6.0]). A total of 21 patients received FMT from a lean donor, and 20 received an autologous placebo. Six months after FMT, 34 patients underwent LRYGB and 4 underwent LSG. Thirty-four patients (82.9%) attended the last visit 18 months after the baseline visit. The percentage of TWL at 6 months was 4.8% (95% CI, 2.7% to 7.0%; P&#x2009;<&#x2009;.001) in the FMT group and 4.6% (95% CI, 1.5% to 7.6%; P&#x2009;=&#x2009;.006) in the placebo group, but no difference was observed between the groups. At 18 months from the baseline (ie, 12 months after surgery), the percentage of TWL was 25.3% (95% CI, 19.5 to 31.1; P&#x2009;<&#x2009;.001) in the FMT group and 25.2% (95% CI, 20.2 to 30.3; P&#x2009;<&#x2009;.001) in the placebo group; however, no difference was observed between the groups.<br><br>CONCLUSIONS AND RELEVANCE: FMT did not affect presurgical and postsurgical weight loss. Further studies are needed to elucidate the possible role of FMT in obesity.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03391817.}, }
@article {pmid36522083, year = {2023}, author = {Sun, B and Liu, M and Tang, L and Zhou, X and Hu, C and Chen, L}, title = {Variability in fecal metabolome depending on age, PFBS pollutant, and fecal transplantation in zebrafish: A non-invasive diagnosis of health.}, journal = {Journal of environmental sciences (China)}, volume = {127}, number = {}, pages = {530-540}, doi = {10.1016/j.jes.2022.06.019}, pmid = {36522083}, issn = {1001-0742}, abstract = {To protect the wellbeing of research animals, certain non-invasive measures are in increasing need to facilitate an early diagnosis of health and toxicity. In this study, feces specimen was collected from adult zebrafish to profile the metabolome fingerprint. Variability in fecal metabolite composition was also distinguished as a result of aging, perfluorobutanesulfonate (PFBS) toxicant, and fecal transplantation. The results showed that zebrafish feces was very rich in a diversity of metabolites that belonged to several major classes, including lipid, amino acid, carbohydrate, vitamin, steroid hormone, and neurotransmitter. Fecal metabolites had functional implications to multiple physiological activities, which were characterized by the enrichment of digestion, absorption, endocrine, and neurotransmission processes. The high richness and functional involvement of fecal metabolites pinpointed feces as an abundant source of diagnostic markers. By comparison between young and aged zebrafish, fundamental modifications of fecal metabolomes were caused by aging progression, centering on the neuroactive ligand-receptor interaction pathway. Exposure of aged zebrafish to PFBS pollutant also significantly disrupted the metabolomic structure in feces. Of special concern were the changes in fecal hormone intermediates after PFBS exposure, which was concordant with the in vivo endocrine disrupting effects of PFBS. Furthermore, it was intriguing that transplantation of young zebrafish feces efficiently mitigated the metabolic perturbation of PFBS in aged recipients, highlighting the health benefits of therapeutic strategies based on gut microbiota manipulation. In summary, the present study provides preliminary clues to evidence the non-invasive advantage of fecal metabolomics in the early diagnosis and prediction of physiology and toxicology.}, }
@article {pmid36520071, year = {2022}, author = {Man, S and Xie, L and Liu, X and Wang, G and Liu, C and Gao, W}, title = {Diosgenin relieves oxaliplatin-induced pain by affecting TLR4/NF-κB inflammatory signaling and the gut microbiota.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d2fo02877h}, pmid = {36520071}, issn = {2042-650X}, abstract = {Diosgenin extracted from fenugreek, yam and other foods exhibits a wide range of pharmacological activities, especially for the treatment of pain and other nervous system diseases. However, its role in oxaliplatin-induced peripheral neuropathy (OIPN) is unclear. To explore its detailed mechanism on the pain caused by chemotherapy, we carried out this experiment. In this study, the effects of diosgenin on injured PC12 cells and OIPN mice were examined. The results showed that diosgenin not only protected PC12 from injury, but also reduced the mechanical withdrawal threshold and cold hyperalgesia in OIPN mice. Diosgenin inhibited oxidative stress, the cell glial fibrillary acidic protein, and the pro-inflammatory cytokines such as tumor necrosis factor-α, toll-like receptor 4 and nuclear factor-κB in the brain. Furthermore, the fecal microbiota transplantation experiment indicated that diosgenin improved OIPN through regulation of the gut microbiota. All in all, diosgenin ameliorates peripheral neuropathy and is worthy of further study in the treatment of neuropathic pain.}, }
@article {pmid36519447, year = {2022}, author = {Wei, S and Bahl, MI and Baunwall, SMD and Dahlerup, JF and Hvas, CL and Licht, TR}, title = {Gut microbiota differs between treatment outcomes early after fecal microbiota transplantation against recurrent Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2084306}, doi = {10.1080/19490976.2022.2084306}, pmid = {36519447}, issn = {1949-0984}, abstract = {AbstarctIn fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (CDI), clinical outcomes are usually determined after 8 weeks. We hypothesized that the intestinal microbiota changes earlier than this timepoint, and analyzed fecal samples obtained 1 week after treatment from 64 patients diagnosed with recurrent CDI and included in a randomized clinical trial, where the infection was treated with either vancomycin-preceded FMT (N = 24), vancomycin (N = 16) or fidaxomicin (N = 24). In comparison with non-responders, patients with sustained resolution after FMT had increased microbial alpha diversity, enrichment of Ruminococcaceae and Lachnospiraceae, depletion of Enterobacteriaceae, more pronounced donor microbiota engraftment, and resolution of gut microbiota dysbiosis. We found that a constructed index, based on markers for the identified genera Escherichia and Blautia, successfully predicted clinical outcomes at Week 8, which exemplifies a way to utilize clinically feasible methods to predict treatment failure. Microbiota changes were restricted to patients who received FMT rather than antibiotic monotherapy, indicating that FMT confers treatment response in a different way than antibiotics. We suggest that early identification of microbial community structures after FMT is of clinical value to predict response to the treatment.}, }
@article {pmid36519027, year = {2022}, author = {Tateishi, AT and Okuma, Y}, title = {Onco-biome in pharmacotherapy for lung cancer: a narrative review.}, journal = {Translational lung cancer research}, volume = {11}, number = {11}, pages = {2332-2345}, doi = {10.21037/tlcr-22-299}, pmid = {36519027}, issn = {2218-6751}, abstract = {BACKGROUND AND OBJECTIVE: The gut microbiota (GM) was recently recognized to play an important role in modulating systemic immune responses and is known to influence the effects or adverse events of immune checkpoint blockade (ICB) or carcinogenesis by crosstalk with regulators of cancer-related immunity, and this relationship is complex and multifactorial. Diversity in the gut microbiome and the abundance of specific bacterial species have been identified to be associated with better response and prognosis. Therefore, the purpose of the current interest in the gut microbiome is to enable modulation of the immune system in donor cancer patients by the administration of specific bacterial species and enabling their dominance. To understand this "terra incognita" is to uncover the role of the mechanisms underlying unknown organ functions, and this knowledge will lead to enhanced immunotherapy for lung cancer patients.<br><br>METHODS: In this article, we summarized the literature on the relationship between the microbiome and lung cancer and the potential of the microbiome as a therapeutic target.<br><br>KEY CONTENT AND FINDINGS: This article is organized into the following sections: introduction, methods, microbiota and cancer development, microbiota and lung cancer treatment, future directions, and conclusion.<br><br>CONCLUSIONS: The gut microbiome is currently becoming the hallmark of cancer research and has an established and critical role in regulating antitumor immunity and the response to ICB in patients with lung cancers.}, }
@article {pmid36517893, year = {2022}, author = {Liu, Y and Zhong, X and Lin, S and Xu, H and Liang, X and Wang, Y and Xu, J and Wang, K and Guo, X and Wang, J and Yu, M and Li, C and Xie, C}, title = {Limosilactobacillus reuteri and caffeoylquinic acid synergistically promote adipose browning and ameliorate obesity-associated disorders.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {226}, doi = {10.1186/s40168-022-01430-9}, pmid = {36517893}, issn = {2049-2618}, abstract = {OBJECTIVE: High intake of caffeoylquinic acid (CQA)-rich dietary supplements, such as green coffee bean extracts, offers health-promoting effects on maintaining metabolic homeostasis. Similar to many active herbal ingredients with high pharmacological activities but low bioavailability, CQA has been reported as a promising thermogenic agent with anti-obesity properties, which contrasts with its poor oral absorption. Intestinal tract is the first site of CQA exposure and gut microbes might react quickly to CQA. Thus, it is of interest to explore the role of gut microbiome and microbial metabolites in the beneficial effects of CQA on obesity-related disorders.<br><br>RESULTS: Oral CQA supplementation effectively enhanced energy expenditure by activating browning of adipose and thus ameliorated obesity-related metabolic dysfunctions in high fat diet-induced obese (DIO) mice. Here, 16S rRNA gene amplicon sequencing revealed that CQA treatment remodeled the gut microbiota to promote its anti-obesity actions, as confirmed by antibiotic treatment and fecal microbiota transplantation. CQA enriched the gut commensal species Limosilactobacillus reuteri (L. reuteri) and stimulated the production of short-chain fatty acids, especially propionate. Mono-colonization of L. reuteri or low-dose CQA treatment did not reduce adiposity in DIO mice, while their combination elicited an enhanced thermogenic response, indicating the synergistic effects of CQA and L. reuteri on obesity. Exogenous propionate supplementation mimicked the anti-obesity effects of CQA alone or when combined with L. reuteri, which was ablated by the monocarboxylate transporter (MCT) inhibitor 7ACC1 or MCT1 disruption in inguinal white adipose tissues to block propionate transport.<br><br>CONCLUSIONS: Our data demonstrate a functional axis among L. reuteri, propionate, and beige fat tissue in the anti-obesity action of CQA through the regulation of thermogenesis. These findings provide mechanistic insights into the therapeutic use of herbal ingredients with poor bioavailability via their interaction with the gut microbiota. Video Abstract.}, }
@article {pmid36514447, year = {2022}, author = {Pendrasik, K and Gocel, O and Winter, K and Małecka-Wojciesko, E}, title = {Faecal microbiota transplantation as a non-standard therapy for the treatment of Clostridioides difficile in an ulcerative colitis patient.}, journal = {Przeglad gastroenterologiczny}, volume = {17}, number = {4}, pages = {338-341}, doi = {10.5114/pg.2022.121825}, pmid = {36514447}, issn = {1895-5770}, }
@article {pmid36514019, year = {2022}, author = {Podolanczuk, AJ and Kim, JS and Cooper, CB and Lasky, JA and Murray, S and Oldham, JM and Raghu, G and Flaherty, KR and Spino, C and Noth, I and Martinez, FJ and , }, title = {Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial.}, journal = {BMC pulmonary medicine}, volume = {22}, number = {1}, pages = {475}, pmid = {36514019}, issn = {1471-2466}, support = {UH3HL145266/HL/NHLBI NIH HHS/United States ; U24 HL145265/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Acetylcysteine/therapeutic use ; *Idiopathic Pulmonary Fibrosis/drug therapy/genetics ; Vital Capacity ; Treatment Outcome ; Double-Blind Method ; Genotype ; }, abstract = {BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few treatment options. N-acetylcysteine (NAC) is a well-tolerated, inexpensive treatment with antioxidant and anti-fibrotic properties. The National Heart, Lung, and Blood Institute (NHLBI)-sponsored PANTHER (Prednisone Azathioprine and NAC therapy in IPF) trial confirmed the harmful effects of immunosuppression in IPF, and did not show a benefit to treatment with NAC. However, a post hoc analysis revealed a potential beneficial effect of NAC in a subgroup of individuals carrying a specific genetic variant, TOLLIP rs3750920 TT genotype, present in about 25% of patients with IPF. Here, we present the design and rationale for the Phase III, multi-center, randomized, double-blind, placebo-controlled Prospective Treatment Efficacy in IPF Using Genotype for NAC Selection (PRECISIONS) clinical trial.<br><br>METHODS: The PRECISIONS trial will randomize 200 patients with IPF and the TOLLIP rs3750920 TT genotype 1:1 to oral N-acetylcysteine (600&#xa0;mg tablets taken three times a day) or placebo for a 24-month duration. The primary endpoint is the composite of time to 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or death from any cause. Secondary endpoints include change in patient-reported outcome scores and proportion of participants with treatment-emergent adverse events. Biospecimens, including blood, buccal, and fecal will be collected longitudinally for future research purposes. Study participants will be offered enrollment in a home spirometry substudy, which explores time to 10% relative FVC decline measured at home, and its comparison with study visit FVC.<br><br>DISCUSSION: The sentinel observation of a potential pharmacogenetic interaction between NAC and TOLLIP polymorphism highlights the urgent, unmet need for better, molecularly focused, and precise therapeutic strategies in IPF. The PRECISIONS clinical trial is the first study to use molecularly-focused techniques to identify patients with IPF most likely to benefit from treatment. PRECISIONS has the potential to shift the paradigm in how trials in this condition are designed and executed, and is the first step toward personalized medicine for patients with IPF. Trial Registration ClinicalTrials.gov identifier: NCT04300920. Registered March 9, 2020. https://clinicaltrials.gov/ct2/show/NCT04300920.}, }
@article {pmid36513509, year = {2022}, author = {Křížová, L and Benešová, I and Špaček, J and Petruželka, L and Vočka, M}, title = {Fecal microbiota transplantation - new possibility to influence the results of therapy of cancer patients.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {35}, number = {6}, pages = {436-440}, doi = {10.48095/ccko2022436}, pmid = {36513509}, issn = {1802-5307}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Carcinoma, Non-Small-Cell Lung ; *Lung Neoplasms ; *Melanoma ; }, abstract = {BACKGROUND: The intestinal microbio-me is essential for the function of the human body, it affects not only metabolism and digestion, but also the immune and neurobehavioral systems. The composition of the human intestinal microbio-me has been of interest to many scientific teams around the world in recent years, aided by the rapid development of molecular genetics methods. Intestinal microbio-me imbalance (so-called dysbio-sis) can help develop several pathological conditions such as autoimmune diseases or can be involved in the process of carcinogenesis. Microbio-me research in oncology has so far focused most on the effect of intestinal microbio-me composition on the effectiveness of checkpoint inhibitors. Differences in the relative proportions of individual bacterial strains and the overall microbio-me diversity in patients treated with checkpoint inhibitors appear to be related to the efficacy of this therapy. Many projects are currently studying the possibility of manipulating the composition of the intestinal microbio-me, especially by means of fecal microbial transplantation (FMT). Two published clinical studies have confirmed that it is possible to overcome resistance to checkpoint inhibitor therapy in malignant melanoma with this method and to re-establish a clinical response after FMT. One of the problems of this effort is the significant diversity in the composition of the microbio-me in different populations. Therefore, knowledge of the microbial composition in a particular population is of key importance. The Department of Oncology of the 1st Faculty of Medicine at Charles University and the General University Hospital in Prague is part of this effort, where a program to investigate intestinal microbio-me composition in patients with non-small cell lung cancer, renal cell carcinoma and malignant melanoma during checkpoint inhibitor therapy has been running for several years.<br><br>PURPOSE: The aim of the publication is to demonstrate the current information and the importance of fecal transplantation in oncology and also to present our currently ongoing research project.}, }
@article {pmid36512976, year = {2023}, author = {Shuwen, H and Yangyanqiu, W and Jian, C and Boyang, H and Gong, C and Jing, Z}, title = {Synergistic effect of sodium butyrate and oxaliplatin on colorectal cancer.}, journal = {Translational oncology}, volume = {27}, number = {}, pages = {101598}, doi = {10.1016/j.tranon.2022.101598}, pmid = {36512976}, issn = {1936-5233}, abstract = {BACKGROUND: Oxaliplatin (OXA) is a chemotherapy agent commonly used in the treatment of colorectal cancer (CRC). Sodium butyrate (NaB) has an antitumor effect.<br><br>METHODS: In total, 30 patients in stage III who completed 8 cycles of chemotherapy regimens were recruited for this study. The patients were divided into good and bad groups based on the chemotherapy efficacy. Gas chromatography-mass spectrometry (GC/MS) was used to detect microbial metabolites in stool samples from CRC patients. Cell counting kit-8 (CCK-8), Annexin-V APC/7-AAD double staining, Transwell assays, scratch-wound assays, and EdU assays were used to detect cell proliferation, apoptosis, invasion and migration, respectively. Fluoroelectron microscopy was used to observe the cell structures. To verify the inhibitory effect of NaB and OXA at animal level, a subcutaneous transplanted tumor model was established. Finally, 16S sequencing technology was used to detect intestinal bacteria. GC-MS was used to detect metabolites in mouse stools.<br><br>RESULTS: NaB was a differential metabolite that affected the efficacy of OXA. NAB and oxaliplatin can synergically inhibit cell proliferation, migration and invasion, and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of oxaliplatin and sodium butyrate on tumor in mice. In addition, the intestinal microbe detection and microbial metabolite detection in fecal samples from mice showed significant differences between butyrate-producing bacteria and NaB.<br><br>CONCLUSION: NaB and OXA can synergistically inhibit the proliferation, invasion and metastasis of CRC cells and promote the apoptosis of CRC cells. NaB, as an OXA synergist, has the potential to become a new clinical adjuvant in CRC chemotherapy.}, }
@article {pmid36511953, year = {2022}, author = {Barbut, F and Eckert, C and Lalande, V and Le Neindre, K and Couturier, J}, title = {[Clostridioides difficile: updated recommendations].}, journal = {La Revue du praticien}, volume = {72}, number = {7}, pages = {703-709}, pmid = {36511953}, issn = {2101-017X}, mesh = {Humans ; Aged ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/epidemiology/therapy ; Clostridioides ; *Bacterial Toxins ; Fidaxomicin ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {UPDATED RECOMMENDATIONS Clostridioides difficile is a spore-forming anaerobic enteropathogen responsible for a wide spectrum of clinical features ranging from mild uncomplicated diarrhoea to severe debilitating disease, toxic megacolon, or even perforation and sometimes death. Risk factors for CDI include age >65 years, previous hospitalization and recent antibiotic therapy. Main virulence factors of C. difficile are toxins A (TcdA) and B (TcdB). The emergence and dissemination of a new hypervirulent strain (027/NAP/BI) in 2005 has stimulated clinical and basic research on C. difficile. Major advances have been made regarding the CDI epidemiology (better recognition of community acquired CDI), diagnosis (molecular tests) and therapy (new drugs such as fidaxomicin, bezlotoxumab, and fecal microbiota transplantation) aspects. These advances have allowed the updating of management recommendations, under the aegis of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Antibiotic treatment of CDI depends on both the severity of the infection, and the risk/number of recurrences. Prevention of CDI requires an antimicrobial stewardship policy and the implementation of contact precautions for the infected patients.}, }
@article {pmid36511706, year = {2022}, author = {Fang, H and Feng, X and Xu, T and Zhong, R and Lu, D and Zhang, H and Shen, W and Zhao, Y and Chen, L and Wang, J}, title = {Gut-Spleen Axis: Microbiota via Vascular and Immune Pathways Improve Busulfan-Induced Spleen Disruption.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0058122}, doi = {10.1128/msphere.00581-22}, pmid = {36511706}, issn = {2379-5042}, abstract = {Fecal microbiota transplantation (FMT) is an effective means of modulating gut microbiota for the treatment of many diseases, including Clostridioides difficile infections. The gut-spleen axis has been established, and this is involved in the development and function of the spleen. However, it is not understood whether gut microbiota can be used to improve spleen function, especially in spleens disrupted by a disease or an anti-cancer treatment. In the current investigation, we established that alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue anticancer drug busulfan-disrupted spleen vasculature and spleen function. A10-FMT improved the gene and/or protein expression of genes involved in vasculature development, increased the cell proliferation rate, enhanced the endothelial progenitor cell capability, and elevated the expression of the cell junction molecules to increase the vascularization of the spleen. This investigation found for the first time that the reestablishment of spleen vascularization restored spleen function by improving spleen immune cells and iron metabolism. These findings may be used as a strategy to minimize the side effects of anti-cancer drugs or to improve spleen vasculature-related diseases. IMPORTANCE Alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue busulfan disrupted spleen vasculature. A10-FMT improved the cell proliferation rate, endothelial progenitor cell capability, and cell junction molecules to increase vasculature formation in the spleen. This reestablishment restored spleen function by improving spleen immune cells and iron metabolism. These findings are useful for the treatment of spleen vasculature-related diseases.}, }
@article {pmid36509451, year = {2022}, author = {Raue, KD and David, BT and Fessler, RG}, title = {The spinal cord-gut-immune axis and its implications on therapeutic development for spinal cord injury.}, journal = {Journal of neurotrauma}, volume = {}, number = {}, pages = {}, doi = {10.1089/neu.2022.0264}, pmid = {36509451}, issn = {1557-9042}, abstract = {Spinal cord injury (SCI) affects approximately 1.3 million people living in the United States. Most research efforts have been focused on reversing paralysis, as this is arguably the most defining feature of SCI. The damage due to SCI, however, extends past paralysis and includes other debilitating outcomes including immune dysfunction and gut dysbiosis. Recent efforts are now investigating the pathophysiology of and developing therapies for these more distal manifestations of SCI. One exciting avenue is the spinal cord-gut-immune axis, which proposes that gut dysbiosis amplifies lesion inflammation and impairs SCI recovery. This review will highlight the most recent findings regarding gut and immune dysfunction following SCI, and discuss how the CNS, gut, and immune system all coalesce to form a bidirectional axis that can impact SCI recovery. Finally, important considerations into how the spinal cord-gut-immune axis fits within the larger framework of therapeutic development (i.e., probiotics, fecal transplants, dietary modifications) will be discussed, emphasizing the lack of interdepartmental investigation and the missed opportunity to maximize therapeutic benefit in SCI.}, }
@article {pmid36507830, year = {2022}, author = {Bonetto, S and Boano, V and Valenzi, E and Saracco, GM and Pellicano, R}, title = {Non-pharmacological strategies to treat irritable bowel syndrome: 2022 update.}, journal = {Minerva gastroenterology}, volume = {68}, number = {4}, pages = {475-481}, doi = {10.23736/S2724-5985.22.03202-8}, pmid = {36507830}, issn = {2724-5365}, abstract = {Irritable bowel syndrome (IBS) is a chronic functional disorder characterized by abdominal pain associated with changes in stool frequency or form, in absence of organic disease. The treatment of IBS is often challenging and should be individually adjusted according to the prevalent symptomatology. Pharmacological treatment for IBS with diarrhea includes peripheral opioid agonists, bile acid sequestrants and antibiotics, while IBS with constipation can be treated with soluble fibers, osmotic agents or prokinetics. In case of abdominal pain, the available pharmacological options are antispasmodics, peripheral opioid agonists or antidepressants. Along with pharmacotherapy, non-pharmacological interventions should be considered as they can play an important role in symptom control. The first-line approach includes lifestyle modifications and dietary advice. Microbiota manipulation through probiotics, prebiotics and symbiotics is a widely used strategy, although the evidence upon the most effective among these in specific IBS subtypes is still unclear. Fecal microbiota transplantation is still in experimental phase for IBS, but it is giving promising results. Psychological therapies may be effective in patients with IBS, despite their application can be limited by long duration, high costs and poor patient's acceptance. Alternative medicine approaches, such as acupuncture, body relaxation techniques, dietary supplements or Chinese herbs, have been proposed; however, the evidence upon their efficacy and safety is still controversial.}, }
@article {pmid36504550, year = {2022}, author = {Li, ZJ and Gou, HZ and Zhang, YL and Song, XJ and Zhang, L}, title = {Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value.}, journal = {World journal of gastroenterology}, volume = {28}, number = {44}, pages = {6213-6229}, pmid = {36504550}, issn = {2219-2840}, abstract = {Primary sclerosing cholangitis (PSC) is an autoimmune disease characterized by chronic cholestasis, a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis. Gut microbes, consisting of microorganisms colonized in the human gut, play an important role in nutrient intake, metabolic homeostasis, immune regulation, and immune regulation; however, their presence might aid PSC development. Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC. Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria. Dysbiosis of the intestinal flora leads to increased intestinal permeability, homing of intestinal lymphocytes, entry of bacteria and their associated metabolites, such as bile acids, into the liver, stimulation of hepatic immune activation, and promotion of PSC. Currently, PSC effective treatment is lacking. However, a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases (alcoholic liver disease, metabolic fatty liver, cirrhosis, and autoimmune liver disease). In addition, antibiotics, fecal microbiota transplantation, and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis, suggesting their effectiveness for PSC treatment. Therefore, this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.}, }
@article {pmid36504032, year = {2023}, author = {Hallowell, HA and Gao, AL and Suez, J}, title = {Double-edged sword: impact of fecal microbiome transplants on the gut resistome.}, journal = {Current opinion in gastroenterology}, volume = {39}, number = {1}, pages = {16-22}, doi = {10.1097/MOG.0000000000000894}, pmid = {36504032}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: Fecal microbiome transplants (FMT) show promise in treating various diseases, such as Clostridioides difficile infections. FMT have also demonstrated the capacity to modulate the collection of antibiotic resistance genes (ARGs), termed the resistome, within the gut. The purpose of this review was to critically evaluate the literature regarding the interaction between FMT and the gut resistome and determine whether FMT could be used specifically to reduce ARG carriage in the gut.<br><br>RECENT FINDINGS: Several studies have demonstrated a decrease in ARG carriage post-FMT administration in various disease states, including recurrent C. difficile infection and after antibiotic usage. However, other studies have reported an expansion of the resistome following FMT. Most studies contained small patient cohorts regardless of the outcome and showed heterogeneity in responses.<br><br>SUMMARY: Research on resistome modulation by FMT is preliminary, and human studies currently lack consensus regarding benefits and risks. From a safety perspective, screening donor samples for ARGs in addition to antibiotic-resistant organisms may be advisable. Additional studies on the mechanisms underlying heterogeneity between studies and individuals are required before FMT is considered an efficient approach for resistome amelioration.}, }
@article {pmid36503158, year = {2022}, author = {Fujikawa, H and Shimizu, H and Nambu, R and Takeuchi, I and Matsui, T and Sakamoto, K and Gocho, Y and Miyamoto, T and Yasumi, T and Yoshioka, T and Arai, K}, title = {Monogenic inflammatory bowel disease with STXBP2 mutations is not resolved by hematopoietic stem cell transplantation but can be alleviated via immunosuppressive drug therapy.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {}, number = {}, pages = {109203}, doi = {10.1016/j.clim.2022.109203}, pmid = {36503158}, issn = {1521-7035}, abstract = {STXBP2, encoding syntaxin-binding protein 2, is involved in intracellular organelle trafficking and is associated with familial hemophagocytic lymphohistiocytosis type 5. Although STXBP2 mutations reportedly cause monogenic inflammatory bowel disease, the clinical course and underlying pathogenic mechanisms remain unclear. We identified a novel mutation in STXBP2 [c.1197delC, p.Ala400fs] in a boy with congenital intractable diarrhea and hemophagocytic lymphohistiocytosis (HLH). HLH was treated with intravenous prednisolone, cyclosporine, and dexamethasone palmitate. Hematopoietic stem cell transplantation (HSCT) along with prophylaxis for graft-versus-host-disease was performed at 5 months of age. Additionally, colonoscopies done before and after HSCT showed mild colitis with cryptitis. The patient showed elevated fecal calprotectin levels and persistent diarrhea even after HSCT and required partial parenteral nutrition. While anti-inflammatory treatment reduced diarrhea, it was not completely normalized even after HSCT, suggesting that the pathogenesis of inflammatory bowel disease associated with STXBP2 mutations involves both hyperinflammation and functional epithelial barrier defects.}, }
@article {pmid36501055, year = {2022}, author = {Huang, L and Liu, Z and Wu, P and Yue, X and Lian, Z and He, P and Liu, Y and Zhou, R and Zhao, J}, title = {Puerariae lobatae Radix Alleviates Pre-Eclampsia by Remodeling Gut Microbiota and Protecting the Gut and Placental Barriers.}, journal = {Nutrients}, volume = {14}, number = {23}, pages = {}, doi = {10.3390/nu14235025}, pmid = {36501055}, issn = {2072-6643}, abstract = {Pre-eclampsia (PE) is a serious pregnancy complication, and gut dysbiosis is an important cause of it. Puerariae lobatae Radix (PLR) is a medicine and food homologous species; however, its effect on PE is unclear. This study aimed to investigate the efficacy of PLR in alleviating PE and its mechanisms. We used an NG-nitro-L-arginine methyl ester (L-NAME)-induced PE mouse model to examine the efficacy of preventive and therapeutic PLR supplementation. The results showed that both PLR interventions alleviated hypertension and proteinuria, increased fetal and placental weights, and elevated the levels of VEGF and PlGF. Moreover, PLR protected the placenta from oxidative stress via activating the Nrf2/HO-1/NQO1 pathway and mitigated placental damage by increasing intestinal barrier markers (ZO-1, Occludin, and Claudin-1) expression and reducing lipopolysaccharide leakage. Notably, preventive PLR administration corrected gut dysbiosis in PE mice, as evidenced by the increased abundance and positive interactions of beneficial bacteria including Bifidobacterium, Blautia, and Turicibacter. Fecal microbiota transplantation confirmed that the gut microbiota partially mediated the beneficial effects of PLR on PE. Our findings revealed that modulating the gut microbiota is an effective strategy for the treatment of PE and highlighted that PLR might be used as an intestinal nutrient supplement in PE patients.}, }
@article {pmid36499254, year = {2022}, author = {Kim, JE and Roh, YJ and Choi, YJ and Lee, SJ and Jin, YJ and Song, HJ and Seol, AY and Son, HJ and Hong, JT and Hwang, DY}, title = {Dysbiosis of Fecal Microbiota in Tg2576 Mice for Alzheimer's Disease during Pathological Constipation.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, doi = {10.3390/ijms232314928}, pmid = {36499254}, issn = {1422-0067}, abstract = {Tg2576 transgenic mice for Alzheimer's disease (AD) exhibited significant phenotypes for neuropathological constipation, but no research has been conducted on the association of the fecal microbiota with dysbiosis. The correlation between fecal microbiota composition and neuropathological constipation in Tg2576 mice was investigated by examining the profile of fecal microbiota and fecal microbiota transplantation (FMT) in 9-10-month-old Tg2576 mice with the AD phenotypes and constipation. Several constipation phenotypes, including stool parameters, colon length, and histopathological structures, were observed prominently in Tg2576 mice compared to the wild-type (WT) mice. The fecal microbiota of Tg2576 mice showed decreases in Bacteroidetes and increases in the Firmicutes and Proteobacteria populations at the phylum level. The FMT study showed that stool parameters, including weight, water content, and morphology, decreased remarkably in the FMT group transplanted with a fecal suspension of Tg2576 mice (TgFMT) compared to the FMT group transplanted with a fecal suspension of WT mice (WFMT). The distribution of myenteric neurons and the interstitial cells of Cajal (ICC), as well as the enteric nervous system (ENS) function, remained lower in the TgFMT group. These results suggest that the neuropathological constipation phenotypes of Tg2576 mice may be tightly linked to the dysbiosis of the fecal microbiota.}, }
@article {pmid36496175, year = {2022}, author = {Mitra, S and Dash, R and Al Nishan, A and Ummey Habiba, S and Soo Moon, I}, title = {Brain modulation by the gut microbiota: from disease to therapy.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2022.12.001}, pmid = {36496175}, issn = {2090-1224}, abstract = {BACKGROUND: The gut microbiota (GM) and brain are strongly associated, which significantly affects neuronal development and disorders. GM-derived metabolites modulate neuronal function and influence many cascades in age-related neurodegenerative disorders (NDDs). Because of the dual role of GM in neuroprotection and neurodegeneration, understanding the balance between beneficial and harmful bacteria is crucial for applying this approach to clinical therapies.<br><br>AIM: of the review This review briefly discusses the role of the gut-brain relationship in promoting brain and cognitive function. Although a healthy gut environment is helpful for brain function, gut dysbiosis can disrupt the brain's environment and create a vicious cycle of degenerative cascades. The ways in which the GM population can affect brain function and the development of neurodegeneration are also discussed. In the treatment and management of NDDs, the beneficial effects of methods targeting GM populations and their derivatives, including probiotics, prebiotics, and fecal microbial transplantation (FMT) are also highlighted. Key scientific concept of the review In this review, we aimed to provide a deeper understanding of the mechanisms of the gut microbe-brain relationship and their twin roles in neurodegeneration progression and therapeutic applications. Here, we attempted to highlight the different pathways connecting the brain and gut, together with the role of GM in neuroprotection and neuronal development. Furthermore, potential roles of GM metabolites in the pathogenesis of brain disorders and in strategies for its treatment are also investigated. By analyzing existing in vitro and clinical studies, this review attempts to identify new and promising therapeutic strategies for central nervous system (CNS) disorders. As the connection between the gut microbe-brain relationship and responses to NDD treatments is less studied, this review will provide new insights into the global mechanisms of GM modulation in disease progression, and identify potential future perspectives for developing new therapies to treat NDDs.}, }
@article {pmid36495561, year = {2022}, author = {Hocking, L and Ianiro, G and Leong, RW and Iqbal, T and Kao, D and Cabling, M and Stockwell, S and Romanelli, RJ and Marjanovic, S}, title = {Faecal microbiota transplantation for recurrent C. difficile infections: challenges and improvement opportunities for clinical practice and healthcare systems.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.17309}, pmid = {36495561}, issn = {1365-2036}, abstract = {BACKGROUND: There is growing interest in faecal microbiota transplantation (FMT) as a treatment for recurrent Clostridioides difficile infection (CDI), but evidence on the diverse requirements for safe, effective and accessible services is fragmented and limited.<br><br>AIMS: To identify key components of FMT provision relating to the patient care pathway, stool donor pathway and wider healthcare system, and to explore variation in practice METHODS: We conducted a narrative review of the literature and consultations with key clinical experts in the field. Evidence is drawn from high-income country contexts, with an emphasis on Australia, Canada, Italy and the United Kingdom as case example countries.<br><br>RESULTS: We identify and discuss key challenges to do with healthcare capacity (workforce, FMT and stool banking facilities), donors and donations, patient access and choice of FMT delivery routes, regulation, costs and reimbursement. We also identify improvement opportunities to increase awareness of FMT and referral processes, physician training, maintaining patient registries and outcome monitoring metrics, in-country regulatory harmonisation and tackling reimbursement challenges and discuss future research needs.<br><br>CONCLUSION: Effectively bringing FMT to patients in a healthcare system requires much more than just the existence of a clinically effective procedure. With FMT being a potentially effective treatment option for recurrent CDI for many patients, a well-rounded understanding of how appropriate FMT capacity can be built and nurtured is important for both healthcare providers and policymakers seeking to improve patient care.}, }
@article {pmid36495304, year = {2022}, author = {Wang, X and Wu, J and Huang, R and Wang, S}, title = {Moxibustion improved the effect of fecal microbiota transplantation donor to dextran sulfate sodium-induced colitis in mice.}, journal = {Anatomical record (Hoboken, N.J. : 2007)}, volume = {}, number = {}, pages = {}, doi = {10.1002/ar.25135}, pmid = {36495304}, issn = {1932-8494}, abstract = {Fecal microbiota transplantation (FMT) is beneficial for several gastrointestinal diseases because it alters the intestinal microbiota of recipients. The efficacy of FMT is related to the microbial structure and composition of the donor. Mild moxibustion is a non-invasive and safe traditional Chinese therapy that can regulate the gut microbiota. In this study, we investigated whether moxibustion improved the efficacy of FMT in donors using a dextran sulfate sodium (DSS)-induced colitis mouse model. Normal mice were treated with mild moxibustion at acupoints ST25 and ST36 for 7 days. DSS (2%) was administered for 7 days to induce colitis. FMT was performed on Day 8 and lasted for 7 days. The effect of FMT on mice with DSS was observed on Day 21. Using hematoxylin and eosin staining and immunofluorescence, we analyzed the pathology and cell proliferation after FMT in DSS mice. In addition, using 16 S rDNA sequencing analysis, we investigated the gut microbiota of mice. The results indicated that moxibustion altered the colonic microbial community and increased the relative abundance of specific bacteria without changes in morphology and physiological function in normal mice. FMT using donors with moxibustion reduced body weight loss, inflammation, abnormal microbial community structure, and the relative abundance of some bacteria. These results provide potential strategies for the safe and targeted improvement of FMT donors.}, }
@article {pmid36494024, year = {2022}, author = {Yandle, Z and Gonzalez, G and Carr, M and Matthijnssens, J and De Gascun, C}, title = {A Viral Metagenomic Protocol for Nanopore Sequencing of Group A Rotavirus.}, journal = {Journal of virological methods}, volume = {}, number = {}, pages = {114664}, doi = {10.1016/j.jviromet.2022.114664}, pmid = {36494024}, issn = {1879-0984}, abstract = {AIM: Development of an unbiased methodology using Oxford Nanopore Technology (ONT) sequencing to obtain whole-genome sequences (WGS) of Rotavirus A (RVA) from clinical samples.<br><br>METHODS: 157 RVA qRT-PCR positive faecal samples were enriched by virus-like particle (VLP) purification and host nuclease digestion to enhance the detection of viral nucleic acids and cDNA generated as per the NetoVIR protocol. ONT sequencing was then performed using the ONT Native Barcoding kit (SQK-LSK-109) on the GridION platform. Data was basecalled, demultiplexed and assembled into near complete RVA genomes. The accuracy and quality of the obtained sequences was assessed by comparing to Sanger sequencing and RVA reference genomes.<br><br>RESULTS: The developed protocol generated 146 near-complete RVA WGS out of the 157 RVA-positive clinical samples. The quality of the assembled genomes was assessed by comparison against publicly-available sequences with results showing 98.76% &#xb1; 0.03% similarity and >90% genome coverage. A concordance assessment was performed comparing the identity of partial RVA VP7 and VP4 segments obtained by Sanger sequencing (n=51) against corresponding nanopore sequences which demonstrated an overall identity of 100.0% &#xb1; 0.02%.<br><br>CONCLUSIONS: The nanopore protocol generated both high quality and accurate RVA WGS extracted from faecal samples. This protocol can be extended to other viral agents in other sample types.}, }
@article {pmid36484924, year = {2022}, author = {Kawabata, S and Takagaki, M and Nakamura, H and Nishida, T and Terada, E and Kadono, Y and Izutsu, N and Takenaka, T and Matsui, Y and Yamada, S and Fukuda, T and Nakagawa, R and Kishima, H}, title = {Association of Gut Microbiome with Early Brain Injury After Subarachnoid Hemorrhage: an Experimental Study.}, journal = {Translational stroke research}, volume = {}, number = {}, pages = {}, pmid = {36484924}, issn = {1868-601X}, abstract = {The occurrence of early brain injury (EBI) following subarachnoid hemorrhage (SAH) is crucial in the prognosis of SAH; however, no effective treatment for EBI has been developed. Gut microbiome (GM) composition influences the outcome of various diseases, including ischemic stroke. Here, we evaluated whether prior GM alteration could prevent EBI following SAH. We altered the GM of 7-week-old male rats by administering antibiotic-containing water for 2 weeks and performing fecal microbiome transplantation after antibiotic induction. Composition of the GM was profiled using 16S rRNA. We induced SAH by injecting blood in the subarachnoid space of control rats and rats with altered GM. We evaluated EBI indicators such as neurological score, brain water content, Evans blue extravasation, and neuronal injury. Additionally, we studied inflammatory cells using immunohistochemistry, immunocytochemistry, quantitative PCR, and flow cytometry. EBI was significantly averted by alterations in GM using antibiotics. The altered GM significantly prevented neutrophil infiltration into the brain among inflammatory cells, and this anti-inflammatory effect was observed immediately following SAH onset. The altered GM also prevented neutrophil extracellular trap formation in the brain and blood, indicating the systemic protective effect. The cause of the protective effect was attributed to a significant decrease in aged neutrophils (CXCR4[high] CD62L[low]) by the altered GM. These protective effects against EBI disappeared when the altered GM was recolonized with normal flora. Our findings demonstrated that EBI following SAH is associated with GM, which regulated neutrophil infiltration.}, }
@article {pmid36484871, year = {2022}, author = {Gu, X and Chen, ZH and Zhang, SC}, title = {Fecal microbiota transplantation in childhood: past, present, and future.}, journal = {World journal of pediatrics : WJP}, volume = {}, number = {}, pages = {}, pmid = {36484871}, issn = {1867-0687}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been well described in the treatment of pediatric diseases; however, the latest updates regarding its use in children are unclear and the concepts involved need to be revisited.<br><br>DATA SOURCES: We performed advanced searches in the MEDLINE, EMBASE, and Cochrane databases using the keywords "Fecal microbiota transplantation OR Fecal microbiota transfer" in the [Title/Abstract] to identify relevant articles published in English within the last five years. To identify additional studies, reference lists of review articles and included studies were manually searched. Retrieved manuscripts (case reports, reviews, and abstracts) were assessed by the authors.<br><br>RESULTS: Among the articles, studies were based on the mechanism (n&#x2009;=&#x2009;28), sample preparation (n&#x2009;=&#x2009;9), delivery approaches (n&#x2009;=&#x2009;23), safety (n&#x2009;=&#x2009;26), and indications (n&#x2009;=&#x2009;67), including Clostridium difficile infection (CDI) and recurrent C. difficile infection (rCDI; n&#x2009;=&#x2009;21), non-alcoholic fatty liver disease (NAFLD; n&#x2009;=&#x2009;10), irritable bowel syndrome (IBS; n&#x2009;=&#x2009;5), inflammatory bowel disease (IBD; n&#x2009;=&#x2009;15), diabetes (n&#x2009;=&#x2009;5), functional constipation (FC; n&#x2009;=&#x2009;4), and autism spectrum disorder (ASD; n&#x2009;=&#x2009;7).<br><br>CONCLUSIONS: Concepts of FMT in pediatric diseases have been updated with respect to underlying mechanisms, methodology, indications, and safety. Evidence-based clinical trials for the use of FMT in pediatric diseases should be introduced to resolve the challenges of dosage, duration, initiation, and the end point of treatment.}, }
@article {pmid36483198, year = {2022}, author = {Zhou, J and Zhang, R and Guo, P and Li, P and Huang, X and Wei, Y and Yang, C and Zhou, J and Yang, T and Liu, Y and Shi, S}, title = {Effects of intestinal microbiota on pharmacokinetics of cyclosporine a in rats.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1032290}, doi = {10.3389/fmicb.2022.1032290}, pmid = {36483198}, issn = {1664-302X}, abstract = {BACKGROUND: Intestinal microbiota has been confirmed to influencing the pharmacokinetic processes of a variety of oral drugs. However, the pharmacokinetic effects of the gut microbiota on cyclosporine A, a drug with a narrow therapeutic window, remain to be studied.<br><br>METHOD: Twenty-one rats were randomly divided into three groups: (a) control group (CON), (b) antibiotic treatment group (ABT) and (c) fecal microbe transplantation group (FMT). The ABT group was administrated with water containing multiple antibiotics to deplete microorganisms. FMT was with the same treatment, followed by oral administration of conventional rat fecal microorganisms for normalization.<br><br>RESULT: The bioavailability of CSA increased by 155.6% after intestinal microbes were consumed by antibiotics. After intestinal microbiota reconstruction by fecal transplantation, the increased bioavailability was significantly reduced and basically returned to the control group level. Changes in gut microbiota alter the protein expression of CYP3A1, UGT1A1 and P-gp in liver. The expressions of these three proteins in ABT group were significantly lower than those in CON and FMT groups. The relative abundance of Alloprevolleta and Oscillospiraceae UCG 005 was negatively correlated with CSA bioavailability while the relative abundance of Parasutterella and Eubacterium xylanophilum group was negatively correlated with CSA bioavailability.<br><br>CONCLUSION: Intestinal microbiota affects the pharmacokinetics of CSA by regulating the expression of CYP3A1, UGT1A1 and P-GP.}, }
@article {pmid36479654, year = {2022}, author = {Garoufalia, Z and Gefen, R and Emile, SH and Silva-Alvarenga, E and Freund, MR and Horesh, N and Wexner, SD}, title = {Outcomes of graciloplasty in the treatment of fecal incontinence: a systematic review and meta-analysis of the literature.}, journal = {Techniques in coloproctology}, volume = {}, number = {}, pages = {}, pmid = {36479654}, issn = {1128-045X}, abstract = {BACKGROUND: Patients with refractory fecal incontinence symptoms can be treated with several surgical procedures including graciloplasty. Reported outcomes and morbidity rates of this procedure are highly variable. The aim of this study was to assess continence rate and safety of dynamic and adynamic graciloplasty.<br><br>METHODS: PubMed and Google Scholar databases were systematically searched from inception until January 2022 according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Reviews, animal studies, studies with patients&#x2009;<&#x2009;18&#xa0;years or&#x2009;<&#x2009;10 patients, with no success rate reported or non-English text, were excluded. Main outcome measures were overall continence and morbidity rates of each technique.<br><br>RESULTS: Fourteen studies were identified, incorporating a total of 450 patients (337 females), published between 1980 and 2021. Most common etiology of incontinence (35.5%-n&#x2009;=&#x2009;160) was obstetric trauma followed by anorectal trauma (20%-n&#x2009;=&#x2009;90). The weighted mean rate of continence after dynamic graciloplasty was 69.1% (95% CI 0.53-0.84%, I[2]&#x2009;=&#x2009;90%) compared to 71% (95% CI 0.54-0.87, I[2]&#x2009;=&#x2009;82.5%) after adynamic. Although the weighted mean short-term complication rate was lower in the dynamic group (26% versus 40%), when focusing on complications requiring intervention under general anesthesia, there was a much higher incidence (43.4% versus 10.5%) in the dynamic group. The weighted mean rate of long-term complications was 59.4% (95% CI 0.13-1.04%, I[2]&#x2009;=&#x2009;97.7%) in the dynamic group, almost twice higher than in the adynamic group [30% (95% CI -&#x2009;0.03 to 0.63), I[2]&#x2009;=&#x2009;95.8%]. Median follow-up ranged from 1 to 13&#xa0;years.<br><br>CONCLUSIONS: Our data suggest that graciloplasty may be considered for incontinent patients. Dynamic graciloplasty may harbor higher risk for reoperation and complications compared to adynamic.&#xa0;The fact that the functional results between adynamic and dynamic graciloplasty are equivalent and the morbidity rate of adynamic graciloplasty is significantly lower reinforce the graciloplasty as an option to treat appropriately selected patients with fecal incontinence.}, }
@article {pmid36479155, year = {2022}, author = {Philips, CA and Ahamed, R and Rajesh, S and Singh, S and Tharakan, A and Abduljaleel, JK and Augustine, P}, title = {Clinical outcomes and gut microbiota analysis of severe alcohol-associated hepatitis patients undergoing healthy donor fecal transplant or pentoxifylline therapy: single-center experience from Kerala.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goac074}, doi = {10.1093/gastro/goac074}, pmid = {36479155}, issn = {2052-0034}, abstract = {BACKGROUND: Severe alcohol-associated hepatitis (SAH) patients with infections have a high short-term mortality rate. Gut microbiota dysbiosis plays an important role in the pathogenesis of SAH. Preliminary studies have demonstrated long-term benefits with healthy donor fecal microbiota transplantation (FMT). Data on FMT compared with pentoxifylline for SAH and relevant gut microbial changes are lacking in literature.<br><br>METHODS: From January 2019 to February 2021, retrospective analysis of a single hospital's records revealed 47 SAH patients undergoing FMT (100&#x2009;mL/day via nasoduodenal tube for 7&#x2009;days) and 25 matched patients receiving pentoxifylline (400&#x2009;mg/8 h for 28&#x2009;days). The primary end point was a 6-month survival rate. Secondary end points included incidence of ascites, hepatic encephalopathy, infections, acute kidney injury, and gut microbiota changes between post-therapy groups. Biomarker discovery and network analysis were also performed to identify significant taxa of gut microbiota in post-treatment groups in retrospectively stored stool samples.<br><br>RESULTS: All were males. The 6-month survival rate was higher in the patients undergoing FMT than in patients receiving pentoxifylline (83.0% vs 56.0%, P&#x2009;=&#x2009;0.012). At the end of 6-month follow-up, the incidences of clinically significant ascites (56.0% vs 25.5%, P&#x2009;=&#x2009;0.011), hepatic encephalopathy (40.0% vs 10.6%, P&#x2009;=&#x2009;0.003), and critical infections (52.0% vs 14.9%, P&#x2009;<&#x2009;0.001) in patients administered pentoxifylline were significantly higher than those in patients treated with FMT. At 3&#x2009;months, biomarker analysis revealed a significant abundance of Bifidobacterium and Eggerthella in the FMT group and the pentoxifylline group, respectively. At 6&#x2009;months, Bifidobacterium in the FMT group and pathogenic Aerococcaceae in the pentoxifylline group were notable. Network analysis showed beneficial taxa (Bifidobacterium) as a central influencer in those undergoing FMT at 6&#x2009;months.<br><br>CONCLUSIONS: Healthy donor FMT improved survival rate and reduced liver-related complications compared with pentoxifylline. These clinical benefits were associated with favorable modulation of intestinal bacterial communities. Difficult-to-treat SAH patients may be safely bridged to transplantation using FMT. Controlled trials evaluating long-term outcomes are an unmet need.}, }
@article {pmid36478314, year = {2022}, author = {Akita, Y and Higashiyama, M and Kurihara, C and Ito, S and Nishii, S and Mizoguchi, A and Inaba, K and Tanemoto, R and Sugihara, N and Hanawa, Y and Wada, A and Horiuchi, K and Okada, Y and Narimatsu, K and Komoto, S and Tomita, K and Takei, F and Satoh, Y and Saruta, M and Hokari, R}, title = {Ameliorating Role of Hydrogen-Rich Water Against NSAID-Induced Enteropathy via Reduction of ROS and Production of Short-Chain Fatty Acids.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {36478314}, issn = {1573-2568}, abstract = {BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, the mechanism of which is involved in oxidative stress, can be lethal due to hemorrhage. Thus, we aimed to investigate the effect of hydrogen-rich water (HRW), in terms of oxidative stress, on intestinal mucosal damage as well as changes in the gut microbiome and the short-chain fatty acids (SCFAs) content in feces.<br><br>METHODS: Hydrogen-rich water was orally administered for 5 days to investigate the effectiveness of indomethacin-induced enteropathy in mice. Small intestinal damage and luminal reactive oxygen species (ROS) were evaluated to investigate the ameliorating effects of hydrogen. Then, components of the gut microbiome were analyzed; fecal microbiota transplantation (FMT) was performed using the cecal contents obtained from mice drinking HRW. The cecal contents were analyzed for the SCFAs content. Finally, cells from the macrophage cell line RAW264 were co-cultured with the supernatants of cecal contents.<br><br>RESULTS: Hydrogen-rich water significantly ameliorated IND-induced enteropathy histologically and reduced the expression of IND-induced inflammatory cytokines. Microscopic evaluation revealed that luminal ROS was significantly reduced and that HRW did not change the gut microbiota; however, FMT from HRW-treated animals ameliorated IND-induced enteropathy. The SCFA content in the cecal contents of HRW-treated animals was significantly higher than that in control animals. The supernatant had significantly increased interleukin-10 expression in RAW264 cells in vitro.<br><br>CONCLUSION: Hydrogen-rich water ameliorated NSAID-induced enteropathy, not only via direct antioxidant effects but also via anti-inflammatory effects by increasing luminal SCFAs. These results suggest that hydrogen may have therapeutic potential in small intestinal inflammatory diseases.}, }
@article {pmid36476497, year = {2022}, author = {Corriero, A and Gadaleta, RM and Puntillo, F and Inchingolo, F and Moschetta, A and Brienza, N}, title = {The central role of the gut in intensive care.}, journal = {Critical care (London, England)}, volume = {26}, number = {1}, pages = {379}, pmid = {36476497}, issn = {1466-609X}, abstract = {Critically ill patients undergo early impairment of their gut microbiota (GM) due to routine antibiotic therapies and other environmental factors leading to intestinal dysbiosis. The GM establishes connections with the rest of the human body along several axes representing critical inter-organ crosstalks that, once disrupted, play a major role in the pathophysiology of numerous diseases and their complications. Key players in this communication are GM metabolites such as short-chain fatty acids and bile acids, neurotransmitters, hormones, interleukins, and toxins. Intensivists juggle at the crossroad of multiple connections between the intestine and the rest of the body. Harnessing the GM in ICU could improve the management of several challenges, such as infections, traumatic brain injury, heart failure, kidney injury, and liver dysfunction. The study of molecular pathways affected by the GM in different clinical conditions is still at an early stage, and evidence in critically ill patients is lacking. This review aims to describe dysbiosis in critical illness and provide intensivists with a perspective on the potential as adjuvant strategies (e.g., nutrition, probiotics, prebiotics and synbiotics supplementation, adsorbent charcoal, beta-lactamase, and fecal microbiota transplantation) to modulate the GM in ICU patients and attempt to restore eubiosis.}, }
@article {pmid36475195, year = {2022}, author = {Kanlioz, M and Ekici, U and Ferhatoğlu, MF}, title = {Total Gastrointestinal Flora Transplantation in the Treatment of Leaky Gut Syndrome and Flora Loss.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e31071}, doi = {10.7759/cureus.31071}, pmid = {36475195}, issn = {2168-8184}, abstract = {Introduction The aim of this work was to treat patients with leaky gut syndrome (LGS) and gastrointestinal flora loss in a simple, inexpensive, permanent and effective way without the need for further treatment. Methods A total gastrointestinal flora transplantation (TGFT) procedure is performed by simultaneously transferring the "flora" taken from approximately 30 different anatomical sites, from the mouth to the anus, of healthy donors to the corresponding anatomical site of the patient using the endoscopic lavage method. Results Of the patients, 25 (44.6%) were female and 31 (55.4%) were male, totaling 56 (100%). The mean age was 32.88±15.78 years. Among the 56 patients enrolled in the study, TGFT had no efficacy in one patient, five patients underwent repeat TGFT during a mean follow-up period of 23.73±16.74 months, and the treatment was permanent in 50 patients; our success rate during the follow-up period was 89.3%. Conclusion In LGS, TGFT should be the gold standard treatment.}, }
@article {pmid36474346, year = {2022}, author = {Wang, D and Pham, VT and Steinert, RE and Zhernakova, A and Fu, J}, title = {Microbial vitamin production mediates dietary effects on diabetic risk.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2154550}, doi = {10.1080/19490976.2022.2154550}, pmid = {36474346}, issn = {1949-0984}, abstract = {Adequate levels of essential vitamins are important for the prevention of diabetes. While the main efforts to address this are currently focused on the intake of vitamin supplements, improving and maintaining intrinsic vitamin production capacity, which is determined by gut microbes, has received insufficient attention. In this study, we systematically investigated the relationship between gut microbial vitamin production and factors related to diabetes and cardiometabolic health in a deeply phenotyped cohort, Lifelines-DEEP (N = 1,135). We found that blood glucose-related factors, lipids, circulating inflammation, and fecal short-chain fatty acids are associated with gut microbial vitamin production. Use of laxatives and metformin are associated with increased levels of vitamin B1/B6 biosynthesis pathways. We further reveal a mediatory role for microbial vitamin B1/B2 production on the influence of fruit intake on diabetes risk. This study provides preliminary evidence for microbiome-targeted vitamin metabolism interventions to promote health.}, }
@article {pmid36473618, year = {2022}, author = {Liu, CS and Hu, YX and Luo, ZY and Qiu, CW and Deng, XH and Chen, FL}, title = {Xianglian pill modulates gut microbial production of succinate and induces regulatory T cells to alleviate ulcerative colitis in rats.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {116007}, doi = {10.1016/j.jep.2022.116007}, pmid = {36473618}, issn = {1872-7573}, abstract = {Xianglian pill (XLP), a traditional Chinese formula, is widely used as treatment for ulcerative colitis (UC) in China. However, the mechanism of its therapeutic effect is still unclear.<br><br>AIM OF THE STUDY: Our previous studies showed a low oral bioavailability and a predominant distribution of major XLP ingredients in the gut. In the present study, we aimed to explore the mechanism of action of XLP on UC with respect to the regulation of gut microecology.<br><br>MATERIALS AND METHODS: UC model rats established using 5% dextran sulfate sodium were treated with XLP. After the treatment period, bodyweight, colon length, histopathology, and inflammatory changes were evaluated. Further, changes in gut microbiota structure were detected via 16S rRNA sequencing, and microbial metabolites in feces were analyzed via a metabolomic assay. Antibiotic intervention and fecal microbiota transplantation were also employed to explore the involvement of gut microbiota, while the level of regulatory T cells (Tregs) in mesenteric lymph nodes was determined via flow cytometry. Transcriptome sequencing was also performed to determine colonic gene changes.<br><br>RESULTS: XLP alleviated colonic injury, inflammation, and gut microbial dysbiosis in UC model rats and also changed microbial metabolite levels. Particularly, it significantly decreased succinate level in the tyrosine pathway. We also observed that fecal microbiota derived from XLP-treated rats conferred resilience to UC model rats. However, this therapeutic effect of XLP on UC was inhibited by succinate. Moreover, XLP increased the level of anti-inflammatory cellular Tregs via gut microbiota. However, this beneficial effect was counteracted by succinate supplementation. Further, XLP induced the differentiation of Treg possibly by the regulation of the PHD2/HIF-1&#x3b1; pathway via decreasing microbial succinate production.<br><br>CONCLUSIONS: Our findings indicated that XLP exerts its therapeutic effects on UC mainly via the gut microbiota-succinate-Treg differentiation axis.}, }
@article {pmid36473615, year = {2022}, author = {Zádori, ZS and Király, K and Al-Khrasani, M and Gyires, K}, title = {Interactions between NSAIDs, opioids and the gut microbiota - Future perspectives in the management of inflammation and pain.}, journal = {Pharmacology &amp; therapeutics}, volume = {}, number = {}, pages = {108327}, doi = {10.1016/j.pharmthera.2022.108327}, pmid = {36473615}, issn = {1879-016X}, abstract = {The composition of intestinal microbiota is influenced by a number of factors, including medications, which may have a substantial impact on host physiology. Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are among those widely used medications that have been shown to alter microbiota composition in both animals and humans. Although much effort has been devoted to identify microbiota signatures associated with these medications, much less is known about the underlying mechanisms. Mucosal inflammation, changes in intestinal motility, luminal pH and bile acid metabolism, or direct drug-induced inhibitory effect on bacterial growth are all potential contributors to NSAID- and opioid-induced dysbiosis, however, only a few studies have addressed directly these issues. In addition, there is a notable overlap between the microbiota signatures of these drugs and certain diseases in which they are used, such as spondyloarthritis (SpA), rheumatoid arthritis (RA) and neuropathic pain associated with type 2 diabetes (T2D). The aims of the present review are threefold. First, we aim to provide a comprehensive up-to-date summary on the bacterial alterations caused by NSAIDs and opioids. Second, we critically review the available data on the possible underlying mechanisms of dysbiosis. Third, we review the current knowledge on gut dysbiosis associated with SpA, RA and neuropathic pain in T2D, and highlight the similarities between them and those caused by NSAIDs and opioids. We posit that drug-induced dysbiosis may contribute to the persistence of these diseases, and may potentially limit the therapeutic effect of these medications by long-term use. In this context, we will review the available literature data on the effect of probiotic supplementation and fecal microbiota transplantation on the therapeutic efficacy of NSAIDs and opioids in these diseases.}, }
@article {pmid36472469, year = {2022}, author = {Gan, B and Sun, N and Lai, J and Wan, Z and Li, L and Wang, Y and Zeng, Y and Zeng, D and Pan, K and Fang, J and Shu, G and Wang, H and Xin, J and Ni, X}, title = {Dynamic Monitoring of Changes in Fecal Flora of Giant Pandas in Mice: Co-Occurrence Network Reconstruction.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0199122}, doi = {10.1128/spectrum.01991-22}, pmid = {36472469}, issn = {2165-0497}, abstract = {Giant pandas are uniquely vulnerable mammals in western China. It is important to develop an animal model to explore the intestinal flora of giant pandas to understand the relationship between digestive diseases and flora. Existing animal models of intestinal flora focus on human flora-associated animals, such as mice, and there is a very limited amount of knowledge regarding giant panda flora-associated animals. To fill this gap, fecal microorganisms from giant pandas were transplanted into pseudosterile and germfree mice using single and multiple gavages. Fecal samples were collected from mice at four time points after transplantation for microbial community analysis. We determined that compared to pseudosterile mice, the characteristics of intestinal flora in pandas were better reproduced in germfree mice. There was no significant difference in microbial diversity between germfree mice and giant panda gut microbes from day 3 to day 21. Germfree mice at the phylum level possessed large amounts of Firmicutes and Proteobacteria, and at the genus level, Escherichia-Shigella, Clostridium sensu stricto 1, and Streptococcus dominated the intestinal flora structure. The microbial community co-occurrence network based on indicator species indicated that germfree mice transplanted with fecal bacteria tended to form a microbial community co-occurrence network similar to that of giant pandas, while pseudosterile mice tended to restore the microbial community co-occurrence network originally present in these mice. Our data are helpful for the study of giant panda flora-associated animals and provide new insights for the in vitro study of giant panda intestinal flora. IMPORTANCE The giant panda is a unique vulnerable mammal in western China, and its main cause of death is digestive system diseases regardless of whether these animals are in the wild or in captivity. The relationship between the intestinal flora and the host exerts a significant impact on the nutrition and health of the giant pandas. However, the protected status of the giant panda has made in vivo, repeatable, and large-sample sampling studies of their intestinal flora difficult. This greatly hinders the research depth of the giant panda intestinal flora from the source. The development and utilization of specific animal models to simulate the structure and characteristics of the intestinal flora provide another means to deal with these research limitations. However, current research examining giant panda flora-associated animals is limited. This study is the first to reveal dynamic changes in the fecal flora of giant pandas in mice after transplantation.}, }
@article {pmid36472435, year = {2022}, author = {Zhang, B and Yang, L and Ning, H and Cao, M and Chen, Z and Chen, Q and Lian, G and Tang, H and Wang, Q and Wang, J and Lin, Z and Wen, J and Liu, Y and Xuan, J and Li, X and Lin, A and He, J and Zhang, L and Hou, X and Zeng, Q and Xiao, C}, title = {A Matching Strategy To Guide Donor Selection for Ulcerative Colitis in Fecal Microbiota Transplantation: Meta-Analysis and Analytic Hierarchy Process.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0215921}, doi = {10.1128/spectrum.02159-21}, pmid = {36472435}, issn = {2165-0497}, abstract = {Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of ulcerative colitis (UC). However, preliminary trials showed that only a subset of patients responded to FMT, and the heterogeneity in donor gut microbiota probably played important roles in patients' responses, implying the significance of matching an appropriate donor to a specified patient. We developed a strategy to build a donor-recipient matching model to guide rational donor selection for UC in FMT. We collected and uniformly reanalyzed 656 fecal 16S rRNA gene sequencing samples (350 from UC patients and 306 from healthy subjects) from 9 studies. Significantly lower α-diversity indexes were observed in UC patients by random effects model. Thirty-four bacterial genera and 34 predicted pathways were identified with significant odds ratios and classification potentials for UC patients. Based on six bacterial indicators, including richness, overall distance, genera, and pathways (beneficial and harmful), the analytic hierarchy process-based donor-recipient matching model was set to rank and select appropriate donors for patients with UC. Finally, the model showed favorable classification powers (>70%) for FMT effectiveness in two previous clinical trials. This study revealed the dysbiosis of fecal bacterial diversity, composition, and predicted pathways of patients with UC by meta-analysis and hereby developed a donor-recipient matching strategy to guide donor selection for UC in FMT. This strategy can also be applied to other diseases associated with gut microbiota. IMPORTANCE Modulation of gut microbiota by FMT from donors has been applied to the treatment of UC and yielded variable effectiveness in clinical trials. One possibility is that this variable effectiveness was related to donor selection, as a patient's response to FMT may rely on the capability of the used donor's microbiota to restore the specific gut disturbances of the patient. However, the biggest issues on the practical level are what should be considered in the selection process and how to set up such a donor-recipient matching model. In this study, we presented a bacterial profile-based donor-recipient matching strategy to guide donor selection for UC in FMT by first meta-analysis of 656 fecal 16S rRNA gene sequencing samples from 9 studies to identify significant indicators and then setting up the model by an analytic hierarchy process. The applicability and accuracy of this model were verified in the data sets from two previous FMT clinical studies. Our data indicate that the donor-recipient matching model built in this study enables researchers to rationally select donors for UC patients in FMT clinical practice, although it needs more samples and prospective trials for validation. The strategy adopted in this study to leverage existing data sets to build donor-recipient matching models for precision FMT is feasible for other diseases associated with gut microbiota.}, }
@article {pmid36469298, year = {2022}, author = {Pande, A and Sharma, S and Khillan, V and Rastogi, A and Arora, V and Shasthry, SM and Vijayaraghavan, R and Jagdish, R and Kumar, M and Kumar, G and Mondot, S and Dore, J and Sarin, SK}, title = {Fecal microbiota transplantation compared with prednisolone in severe alcoholic hepatitis patients: a randomized trial.}, journal = {Hepatology international}, volume = {}, number = {}, pages = {}, pmid = {36469298}, issn = {1936-0541}, abstract = {BACKGROUND: Severe alcoholic hepatitis (SAH) has high 90-day mortality. Prednisolone therapy has shown modest survival benefits over placebo at 28 but not 90 days. Fecal microbial transplantation (FMT) has shown promise in these patients. We compared the efficacy and safety of the two therapies in SAH patients.<br><br>METHODS: Steroid eligible SAH patients were randomized in an open-label study to prednisolone (n&#x2009;=&#x2009;60) 40&#xa0;mg/day for 28&#xa0;days (assessed at day-7 for continuation) or healthy donor FMT (n&#x2009;=&#x2009;60) through naso-duodenal tube, daily for seven days. Primary outcome of study was day-90 survival.<br><br>RESULTS: Patients in prednisolone and FMT arms were comparable at baseline (discriminant function score 65&#x2009;&#xb1;&#x2009;16.2 and 68&#x2009;&#xb1;&#x2009;14, MELD score 17.1 and 16.5, respectively). Of 120 patients, 112 [prednisolone-57; FMT-55] completed trial. As per intention-to-treat analysis, 90-day survival was achieved by 56.6% (34/60) patients in prednisolone and 75% (45/60) in FMT group (p&#x2009;=&#x2009;0.044, FMT HR&#x2009;=&#x2009;0.528, 95%CI 0.279-0.998). Secondary outcome of 28-day survival [78.33% (47/60) and 88.33% (53/60) (p&#x2009;=&#x2009;0.243, FMT HR&#x2009;=&#x2009;0.535, 95%CI 0.213-1.34)] with comparable severity scores over time between both arms. Infections accounted for 11 (19.3%) and 2 (3.6%) deaths in prednisolone and FMT groups, respectively (p&#x2009;=&#x2009;0.01). Path-tracing showed a slow establishment of microbiota and alpha diversity (Shannon index) improvement by day-28 (p&#x2009;=&#x2009;0.029). FMT resulted in 23 new taxa by day-28, reduction from baseline in pathogenic taxa [Campylobacter (19-fold, p&#x2009;=&#x2009;0.035), anaerobes (Parcubacteria, Weisella and Leuconostocaceae)], and increase of Alphaproteobacteria [~&#x2009;sevenfold, p&#x2009;=&#x2009;0.047] and Thaumarcheota (known ammonia oxidizer, p&#x2009;=&#x2009;0.06). Lachnospiraceae (p&#x2009;=&#x2009;0.008), Prevotella and Viellonella communities in gut favored survival (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: In severe alcoholic hepatitis, FMT is safe and improves 90-day survival and reduces infections by favorably modulating microbial communities. It can be a useful alternative to prednisolone therapy.}, }
@article {pmid36469257, year = {2022}, author = {Sankararaman, S and Noriega, K and Velayuthan, S and Sferra, T and Martindale, R}, title = {Gut Microbiome and Its Impact on Obesity and Obesity-Related Disorders.}, journal = {Current gastroenterology reports}, volume = {}, number = {}, pages = {}, pmid = {36469257}, issn = {1534-312X}, abstract = {PURPOSE OF REVIEW: The prevalence of overweight and obesity has been increasing worldwide at an alarming rate. Gut microbiota intimately influence host energy metabolism, and immune response. Studies indicate a prominent role of gut dysbiosis in propagating inflammation that is associated with the development of obesity and obesity-related disorders such as type 2 diabetes mellitus, metabolic syndrome, and non-alcoholic fatty liver disease. This article will review the current literature on gut microbiome and its impact on obesity and obesity-related disorders.<br><br>RECENT FINDINGS: An altered gut microbial composition in obesity and obesity-related disorders is associated with enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability, increased production of proinflammatory metabolites, such as lipopolysaccharides, resulting in systemic inflammation and insulin resistance. Gut microbiota modulation can be achieved either by dietary manipulation or by administration of probiotics, prebiotics, synbiotics, and/or fecal microbiota transplantation aiming at the improvement of the gut dysbiosis in obesity and metabolic disorders. Further clinical trials are required to better elucidate the dose, and frequency of these interventions and also their long-term impact on host metabolism.}, }
@article {pmid36468853, year = {2022}, author = {Zhang, B and Zhao, C and Zhang, X and Li, X and Zhang, Y and Liu, X and Yin, J and Li, X and Wang, J and Wang, S}, title = {An Elemental Diet Enriched in Amino Acids Alters the Gut Microbial Community and Prevents Colonic Mucus Degradation in Mice with Colitis.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0088322}, doi = {10.1128/msystems.00883-22}, pmid = {36468853}, issn = {2379-5077}, abstract = {The role of dietary amino acids or intact proteins in the progression of colitis remains controversial, and the mechanism involving gut microbes is unclear. Here, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of dextran sulfate sodium (DSS)-induced colitis in mice. Our results showed that the ED induced remission of colitis in mice. Notably, ED treatment reduced the abundance of the mucolytic bacteria Akkermansia and Bacteroides, which was attributed to decreased colonic protein fermentation. Consistently, the activities of mucolytic enzymes were decreased, leading to protection against mucus layer degradation and microbial invasion. Fecal microbiota transplantation from ED-fed mice reshaped microbial ecology and alleviated intestinal inflammation in recipient mice. The ED failed to induce remission of colitis in pseudogermfree mice. Together, our results demonstrate the critical role of the gut microbiota in the prevention of colitis by an ED. IMPORTANCE The prevalence of inflammatory bowel disease is rapidly increasing and has become a global burden. Several specific amino acids have been shown to benefit mucosal healing and colitis remission. However, the role of amino acids or intact proteins in diets and enteral nutrition formulas is controversial, and the mechanisms involving gut microbes remain unclear. In this study, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of colitis in mice. The underlying mechanisms were explored by utilizing fecal microbiota transplantation and pseudogermfree mice. ED treatment reduced the abundance of mucolytic bacteria, thereby protecting the mucus layer from microbial invasion and degradation. For the first time, we convincingly demonstrated the critical role of gut microbiota in the effects of the ED. This study may provide new insights into the gut microbiota-diet interaction and its role in human health.}, }
@article {pmid36468073, year = {2022}, author = {Yang, L and Li, W and Zhang, X and Tian, J and Ma, X and Han, L and Wei, H and Meng, W}, title = {The evaluation of different types fecal bacteria products for the treatment of recurrent Clostridium difficile associated diarrhea: A systematic review and network meta-analysis.}, journal = {Frontiers in surgery}, volume = {9}, number = {}, pages = {927970}, pmid = {36468073}, issn = {2296-875X}, abstract = {PURPOSE: To determine the efficacy of different types of fecal microbiota transplantation for the treatment of recurrent clostridium difficile associated diarrhea (RCDAD).<br><br>METHODS: We searched PubMed, Embase, The Cochrane Library, Web of Science, China Biomedical Medicine (CBM), China National Knowledge Infrastructure (CNKI) and WanFang database. We also tracked the references found in systematic reviews of RCDAD treated with fecal microbiota transplantation. We included randomized controlled trials (RCTs) comparing different types of fecal microbiota transplantation with other methods for the treatment of RCDAD. The search period was from the date of inception of this treatment method to January 16, 2022. Two reviewers independently screened the published literature, extracted the data and assessed the risk of bias. Systematic review and network meta-analysis were conducted using RevMan 5.4, Stata 16.0 and R 4.1.2 software.<br><br>RESULTS: Ten RCTs involving 765 patients were included in this network meta-analysis. The results showed that treatment with fresh fecal bacteria and frozen fecal bacteria were better than vancomycin, fresh vs. vancomycin [odds ratio, (OR)&#x2009;=&#x2009;8.98, 95% confidence interval (95% CI) (1.84, 43.92)], frozen vs. vancomycin [OR&#x2009;=&#x2009;7.44, 95% CI (1.39, 39.75)]. However, there were no statistically significant differences in cure rate [fresh vs. frozen: OR&#x2009;=&#x2009;1.21, 95% CI (0.22, 6.77); fresh vs. lyophilized, OR&#x2009;=&#x2009;1.95, 95% CI (0.20, 19.44); frozen vs. lyophilized, OR&#x2009;=&#x2009;1.62, 95% CI (0.30, 8.85)]. The Surface Under the Cumulative Ranking (SUCRA) indicated that fresh fecal bacteria were the best treatment for RCDAD.<br><br>CONCLUSIONS: Fresh fecal bacteria are the best treatment of RCDAD, frozen fecal bacteria and lyophilized fecal bacteria can achieve the same effect. Fecal microbiota transplantation is worthy of clinical and commercial application.}, }
@article {pmid36467356, year = {2022}, author = {Dong, YH and Hu, JJ and Deng, F and Chen, XD and Li, C and Liu, KX and Zhao, BC}, title = {Use of dexmedetomidine to alleviate intestinal ischemia-reperfusion injury via intestinal microbiota modulation in mice.}, journal = {Annals of translational medicine}, volume = {10}, number = {21}, pages = {1161}, pmid = {36467356}, issn = {2305-5839}, abstract = {BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a serious condition with unacceptable mortality rates. Our previous study revealed a protective effect of dexmedetomidine (DEX) on intestinal I/R injury, but its underlying mechanism remains unclear. Gut microbiota imbalance is associated with the progression of I/R injury. We hypothesized that DEX would attenuate intestinal I/R injury via modulating gut microbiota.<br><br>METHODS: An I/R injury model was established in C57BL/6 mice in the presence or absence of DEX preconditioning. Some mice were treated with antibiotics to deplete intestinal bacteria. Fecal microbiota transplantation (FMT) was performed by transplanting the feces of DEX-pretreated mice into a new batch of I/R mice. We analyzed the expression of Bacteroidetes and Firmicutes in feces, survival rate, and inflammatory cytokines.<br><br>RESULTS: DEX reversed I/R-induced bacterial abnormalities by increasing the ratio of Firmicutes to Bacteroidetes [DEX + I/R 3.02&#xb1;0.36 vs. normal saline (NS) + I/R 0.82&#xb1;0.15; 95% CI: 0.80-3.60; P<0.05] and was accompanied by increased 72-hour survival (0.40&#xb1;0.16 vs. 0.10&#xb1;0.09; P<0.05). The protective effect of DEX did not significantly differ from that of DEX + antibiotics. Furthermore, the bacteria of the DEX-pretreated mice decreased the release of inflammatory factors.<br><br>CONCLUSIONS: This study revealed that DEX can alleviate intestinal I/R injury through a microbiota-related mechanism, providing a potential avenue for the management of intestinal I/R injury.}, }
@article {pmid36467061, year = {2022}, author = {Wang, R and Liu, M and Ren, G and Luo, G and Wang, Z and Ge, Z and Pu, Q and Ren, W and Yang, S}, title = {Zhilong Huoxue Tongyu Capsules' Effects on ischemic stroke: An assessment using fecal 16S rRNA gene sequencing and untargeted serum metabolomics.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1052110}, pmid = {36467061}, issn = {1663-9812}, abstract = {Zhilong Huoxue Tongyu capsule (ZHTC) is an effective traditional Chinese medicine compound for the treatment of ischemic stroke, which is widely used in clinical ischemic stroke patients. However, it is uncertain whether ZHTC affects ischemic stroke through gut microbiota and serum metabolites. In this study, a rat model of middle cerebral artery occlusion (MCAO) was prepared. By evaluating motor nerve function score, cerebral infarct size, brain tissue damage and intestinal barrier damage, it was found that ZHTC improved stroke-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, fecal microbial transplantation (FMT), untargeted metabolomics, and spearman correlation analysis of gut microbiota and serum metabolites, we found that ZHTC can regulate the abundance of p_Firmicutes, p_Bacteroidota,p_Proteobacteria, g_Prevotella, and g_Lactobacillus, and regulated 23 differential metabolites. Spearman correlation analysis found that Arginine was positively correlated with p_Firmicutes, o_Clostridiales, c_Clostridia, and negatively correlated with p_Bacteroidetes, c_Bacteroidia,o_Bacteroidales; L-Lysine was negatively correlated with f_Christensenellaceae; L-methionine was positively correlated with o_Lactobacillales, f_Lactobacillaceae, and g_Lactobacillus. Altogether, this study shows for the first time that ZHTC can ameliorate ischemic stroke by modulating gut microbiota and metabolic disturbances. This lays the foundation for further revealing the causal relationship between ZHTC, gut dysbiosis, plasma metabolite levels and ischemic stroke, and provides a scientific explanation for the ameliorating effect of ZHTC on ischemic stroke.}, }
@article {pmid36466675, year = {2022}, author = {El Haddad, L and Mendoza, JF and Jobin, C}, title = {Bacteriophage-mediated manipulations of microbiota in gastrointestinal diseases.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1055427}, pmid = {36466675}, issn = {1664-302X}, abstract = {Although some gastrointestinal diseases could be managed using various antibiotics regimen, this therapeutic approach lacks precision and damages the microbiota. Emerging literature suggests that phages may play a key role in restoring the gut microbiome balance and controlling disease progression either with exogenous phage intervention or filtered fecal transplantation or even engineered phages. In this review, we will discuss the current phage applications aiming at controlling the bacterial population and preventing infection, inflammation, and cancer progression in the context of gastrointestinal diseases.}, }
@article {pmid36466673, year = {2022}, author = {Wang, Y and Zhang, Z and Liu, B and Zhang, C and Zhao, J and Li, X and Chen, L}, title = {A study on the method and effect of the construction of a humanized mouse model of fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1031758}, pmid = {36466673}, issn = {1664-302X}, abstract = {The gestation period is critical for the health of the mother and fetus. Malnutrition or over nutrition during pregnancy may cause gestational diseases that can result in adverse pregnancy outcomes. Fecal microbiota transplantation (FMT) can be used to re-establish new gut microbiota to treat a variety of diseases and construct a model to investigate the nutritional health during pregnancy. Therefore, this study investigated whether human-derived gut microbiota during pregnancy could colonize the intestines of mice. Moreover, we determined the time and method of intervention for FMT. Based on this information, a humanized mouse model of FMT was constructed to simulate the human intestinal microecology during pregnancy, and serve as a useful animal model for the study of nutritional health and disease during pregnancy. Germ-free (GF) and specific pathogen free (SPF) C57BL/6J mice were selected for humanized gestational FMT and the transplantation outcomes were evaluated. The results demonstrated that the gestational intestinal microbiota colonized the intestines of mice, allowing researchers to construct a humanized mouse model of gestational FMT. The main intestinal flora of the gestational period were transplanted into GF mice, with the gestational flora being similar to the flora of GF mice after transplantation. However, antibiotics could not eliminate the original microbial flora in SPF mice, and the flora was complex and variable after FMT with little increase in abundance. Background flora had a significant impact on the outcomes assessment. The results were better in GF mice than in SPF mice, and after microbiota transplantation, a superior effect was observed on day 21 compared to days 7 and 14.}, }
@article {pmid36466655, year = {2022}, author = {Wei, W and Wang, S and Xu, C and Zhou, X and Lian, X and He, L and Li, K}, title = {Gut microbiota, pathogenic proteins and neurodegenerative diseases.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {959856}, pmid = {36466655}, issn = {1664-302X}, abstract = {As the world's population ages, neurodegenerative diseases (NDs) have brought a great burden to the world. However, effective treatment measures have not been found to alleviate the occurrence and development of NDs. Abnormal accumulation of pathogenic proteins is an important cause of NDs. Therefore, effective inhibition of the accumulation of pathogenic proteins has become a priority. As the second brain of human, the gut plays an important role in regulate emotion and cognition functions. Recent studies have reported that the disturbance of gut microbiota (GM) is closely related to accumulation of pathogenic proteins in NDs. On the one hand, pathogenic proteins directly produced by GM are transmitted from the gut to the central center via vagus nerve. On the other hand, The harmful substances produced by GM enter the peripheral circulation through intestinal barrier and cause inflammation, or cross the blood-brain barrier into the central center to cause inflammation, and cytokines produced by the central center cause the production of pathogenic proteins. These pathogenic proteins can produced by the above two aspects can cause the activation of central microglia and further lead to NDs development. In addition, certain GM and metabolites have been shown to have neuroprotective effects. Therefore, modulating GM may be a potential clinical therapeutic approach for NDs. In this review, we summarized the possible mechanism of NDs caused by abnormal accumulation of pathogenic proteins mediated by GM to induce the activation of central microglia, cause central inflammation and explore the therapeutic potential of dietary therapy and fecal microbiota transplantation (FMT) in NDs.}, }
@article {pmid36466637, year = {2022}, author = {Elokil, AA and Chen, W and Mahrose, K and Elattrouny, MM and Abouelezz, KFM and Ahmad, HI and Liu, HZ and Elolimy, AA and Mandouh, MI and Abdelatty, AM and Li, S}, title = {Early life microbiota transplantation from highly feed-efficient broiler improved weight gain by reshaping the gut microbiota in laying chicken.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1022783}, pmid = {36466637}, issn = {1664-302X}, abstract = {Starting phase of laying chicken life is the building stone for rearing and production stages. Since, fecal microbial transplantation (FMT) regulates the gut microbial diversity and affects the productive performance of the bird. The aim of this study is to evaluate the effect of FMT from feed-efficient broiler chicken could program the diversity of gut microbiota and growth of recipient native slow growing egg-laying chicks. For this, a total of 150 (one-day-old) Jing Hong chicks were randomly assigned into two groups, each group consisted of 5 replicates (n = 15 bird/ replicate). The control group (CON) and FMT recipient birds (FMT) fed on basal diet, the FMT group received an oral daily dose of FMT prepared from Cobb-500 chickens. The FMT performed from the 1d to 28d of age, through the experimental period, feed intake and body weight were recorded weekly. At the end of a 28-day trial, carcass traits were assessed and cecal samples were collected for microbiome assessment via 16S rRNA-based metagenomic analysis to characterize the diversity and functions of microbial communities. The data were statistically analyzed using R software. Body weight and body weight gain increased, and FCR decreased (p = 0.01) in FMT group. The relative abundance of Firmicutes and the Firmicutes/Bacteroidetes (F/B) ratio were increased due to FMT administration (p = 0.01). A higher relative abundance of Lactobacillus, Lactococcus, and Bifidobacterium were presented in the FMT group. Meanwhile, Enterococcus, Helicobacter, and Bacteroides were more abundant in the CON group (p < 0.01). Kyoto encyclopedia of genes and genomes (KEGG) pathways for microbial functions regarding amino acid metabolism, secondary metabolites biosynthesis, carbohydrate metabolism, energy metabolism, and enzyme families, cofactors, and vitamins were significantly annotated in the FMT group. Overall, FMT administration from the donor of highly feed-efficient broilers improved weight gain by reshaping a distinct gut microbiome, which may be related to the metabolism and health in the recipients laying chicks, providing new insight on the application of the FMT technique for early life programming of laying chickens.}, }
@article {pmid36461391, year = {2022}, author = {Liu, X and Zhang, Y and Li, W and Yin, J and Zhang, B and Wang, J and Wang, S}, title = {Differential responses on gut microbiota and microbial metabolome of 2'-fucosyllactose and galactooligosaccharide against DSS-induced colitis.}, journal = {Food research international (Ottawa, Ont.)}, volume = {162}, number = {Pt B}, pages = {112072}, doi = {10.1016/j.foodres.2022.112072}, pmid = {36461391}, issn = {1873-7145}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Prebiotics ; *Colitis/chemically induced ; Metabolome ; }, abstract = {Prebiotics are effective in modulating gut microbiota and may further benefit colitis remission. 2'-fucosyllactose (2'FL) and galactooligosaccharide (GOS) are the main prebiotics in human and animal milk, respectively. This study aimed to investigate the colitis-preventing effects of 2'FL and GOS, and explore the underlying mechanisms involving the gut microbiota. The chronic colitis was induced by 1.5 % dextran sulfate sodium (DSS) for 4 consecutive cycles and manifested as aggravation of colitis symptoms, gut barrier disruption, and colonic inflammation. We found that 2'FL was more effective than GOS against colitis at the same dosage (500 mg/kg bw). 2'FL and GOS have a differential response on gut microbiota, reflecting the inhibition of Romboutsia and the enrichment of Akkermansia, Bifidobacterium, Faecalibaculum, and unclassified_f_Lachnosipiaceae. In addition, the differential response on microbial metabolome was reflected in the elevation of secondary bile acids, which activated Takeda G protein-coupled receptor 5 (TGR5) and further suppressed the nuclear factor-κB (NF-κB) pathway. Furthermore, fecal bacterial transplantation confirmed the critical role of gut microbiota in the prevention of colitis by 2'FL and GOS. Overall, microbiota and microbial metabolites are essential parts of 2'FL and GOS against colitis, and their differential responses may account for different effects in alleviating colitis.}, }
@article {pmid36461273, year = {2022}, author = {Tang, Q and Wang, C and Jin, G and Li, Y and Hou, H and Wang, X and Guo, Q and Liu, T and Wang, S and Dai, X and Wang, B and Cao, H}, title = {Early life dietary emulsifier exposure predisposes the offspring to obesity through gut microbiota-FXR axis.}, journal = {Food research international (Ottawa, Ont.)}, volume = {162}, number = {Pt A}, pages = {111921}, doi = {10.1016/j.foodres.2022.111921}, pmid = {36461273}, issn = {1873-7145}, mesh = {Female ; Pregnancy ; Mice ; Animals ; *Gastrointestinal Microbiome ; Dysbiosis ; Mice, Inbred C57BL ; Obesity ; Emulsifying Agents/adverse effects ; Bile Acids and Salts ; Polysorbates ; Inflammation ; }, abstract = {The prevalence of obesity is increasing rapidly around the world, and there is growing evidence that obesity is closely related to diet and gut microbiota. Early life adverse exposures have profound effects on gut microbiota. However, the effects of maternal emulsifier polysorbate 80 (P80) exposure in early life on obesity of offspring remains unclear. Female C57BL/6 mice were free access to water containing 1 % P80 during pregnancy and lactation to investigate the effects of maternal P80 exposure on gut microbiota and obesity susceptibility of offspring, while bile acid composition and the FGF15-FXR axis were also analyzed. Maternal P80 exposure significantly impaired intestinal development and barrier function and increased intestinal low-grade inflammation in offspring mice. Maternal P80 exposure led to gut dysbiosis in offspring at 3 weeks of age, which was characterized by increased potentially harmful bacteria, Prevotella, Helicobacter and Ruminococcus and Mucin degrading bacteria, Akkermansia. Interestingly, mice transplanted with the fecal microbiota of offspring exposed to maternal P80 showed more serious intestinal barrier impairment and increased low-grade inflammation than that received microbiota of offspring fed with normal diet. After a high-fat diet, Maternal P80 exposed offspring showed more severe in gut dysbiosis and obesity, accompanied by alternation in bile acid profile and up regulation of the FXR-FGF15 axis. Conclusively, early life emulsifier exposure predisposes the offspring to obesity through gut microbiota-FXR axis. The findings will provide new insights into effects of P80 on health.}, }
@article {pmid36457852, year = {2022}, author = {Wu, L and Lu, XJ and Lin, DJ and Chen, WJ and Xue, XY and Liu, T and Xu, JT and Xie, YT and Li, MQ and Lin, WY and Zhang, Q and Wu, QP and He, XX}, title = {Washed microbiota transplantation improves patients with metabolic syndrome in South China.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1044957}, pmid = {36457852}, issn = {2235-2988}, mesh = {Humans ; *Metabolic Syndrome/therapy ; Cholesterol, LDL ; RNA, Ribosomal, 16S/genetics ; Retrospective Studies ; China ; Triglycerides ; *Atherosclerosis ; *Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Metabolic syndrome (MS) is a growing public health problem worldwide. The clinical impact of fecal microbiota transplantation (FMT) from healthy donors in MS patients is unclear, especially in southern Chinese populations. This study aimed to investigate the effect of washed microbiota transplantation (WMT) in MS patients in southern China.<br><br>METHODS: The clinical data of patients with different indications receiving 1-3 courses of WMT were retrospectively collected. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared, such as fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c)), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein (non-HDL-c), systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. At the same time, comprehensive efficacy evaluation and atherosclerotic cardiovascular disease (ASCVD) grade assessment were performed on MS patients. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of MS patients before and after transplantation.<br><br>RESULTS: A total of 237 patients were included, including 42 in the MS group and 195 in the non-MS group. For MS patients, WMT significantly improved the comprehensive efficacy of MS in short term 40.48% (p<0.001), medium term 36.00% (p=0.003), and long term 46.15% (p=0.020). Short-term significantly reduced FBG (p=0.023), TG (p=0.030), SBP (p=0.026) and BMI (p=0.031), and increased HDL-c (p=0.036). The medium term had a significant reduction in FBG (p=0.048), TC (p=0.022), LDL-c (p=0.043), non-HDL-c (p=0.024) and BMI (p=0.048). WMT had a significant short term (p=0.029) and medium term (p=0.011) ASCVD downgrading effect in the high-risk group of MS patients. WMT improved gut microbiota in MS patients.<br><br>CONCLUSION: WMT had a significant improvement effect on MS patients and a significant downgrade effect on ASCVD risk in the high-risk group of patients with MS. WMT could restore gut microbiota homeostasis in MS patients. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of MS.}, }
@article {pmid36456838, year = {2022}, author = {Liu, H and Kang, X and Yang, X and Yang, H and Kuang, X and Ren, P and Yan, H and Shen, X and Kang, Y and Li, L and Wang, X and Guo, L and Tong, M and Fan, W}, title = {Compound Probiotic Ameliorates Acute Alcoholic Liver Disease in Mice by Modulating Gut Microbiota and Maintaining Intestinal Barrier.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {36456838}, issn = {1867-1314}, abstract = {Alcoholic liver disease (ALD) is a worldwide health threaten lack of effective treatment. Gut dysbiosis and concomitant augmented intestinal permeability are strongly implicated in the pathogenesis and progression of ALD. Research on the protective effect of probiotics on ALD is limited, and more effective intestinal microecological regulators and the related mechanisms still need to be further explored. In the present study, the protective effects and mechanisms of a compound probiotic against acute alcohol-induced liver injury in vivo were explod. It was showed that the compound probiotic ameliorated liver injury in acute ALD mice and stabilized the levels of ALT, AST, and TG in serum. The compound probiotic reversed acute alcohol-induced gut dysbiosis and maintained the intestinal barrier integrity by upregulating the production of mucus and the expression of tight junction (TJ) proteins and thus reduced LPS level in liver. Meanwhile, the compound probiotic reduced inflammation level by inhibiting TLR4/NF-κB signaling pathway and suppressed oxidative stress level in liver. Furthermore, the compound probiotic alleviated liver lipid accumulation by regulating fatty acid metabolism-associated genes and AMPK-PPARα signaling pathway. Noteworthy, fecal microbiota transplantation (FMT) realized comparable protective effect with that of compound probiotic. In conclusion, present study demonstrates the beneficial effects and underlying mechanism of the compound probiotic against acute alcohol-induced liver injury. It provides clues for development of novel strategy for treatment of ALD.}, }
@article {pmid36454023, year = {2022}, author = {Cumpelik, A and Cody, E and Yu, SM and Grasset, EK and Dominguez-Sola, D and Cerutti, A and Heeger, PS}, title = {Cutting Edge: Neutrophil Complement Receptor Signaling Is Required for BAFF-Dependent Humoral Responses in Mice.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {}, number = {}, pages = {}, doi = {10.4049/jimmunol.2200410}, pmid = {36454023}, issn = {1550-6606}, abstract = {T cell-independent (TI) B cell responses to nonprotein Ags involve multiple cues from the innate immune system. Neutrophils express complement receptors and activated neutrophils can release BAFF, but mechanisms effectively linking neutrophil activation to TI B cell responses are incompletely understood. Using germline and conditional knockout mice, we found that TI humoral responses involve alternative pathway complement activation and neutrophil-expressed C3a and C5a receptors (C3aR1/C5aR1) that promote BAFF-dependent B1 cell expansion and TI Ab production. Conditional absence of C3aR1/C5aR1 on neutrophils lowered serum BAFF levels, led to fewer Peyer's patch germinal center B cells, reduced germinal center B cells IgA class-switching, and lowered fecal IgA levels. Together, the results indicate that sequential activation of complement on neutrophils crucially supports humoral TI and mucosal IgA responses through upregulating neutrophil production of BAFF.}, }
@article {pmid36451382, year = {2022}, author = {Chen, Q and Zhang, Z and Bei, S and Wang, X and Zhu, Y}, title = {Efficacy of oral fecal microbiota transplantation in recurrent bowel disease: A protocol for systematic review and meta-analysis.}, journal = {Medicine}, volume = {101}, number = {47}, pages = {e31477}, doi = {10.1097/MD.0000000000031477}, pmid = {36451382}, issn = {1536-5964}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Irritable Bowel Syndrome/therapy ; Quality of Life ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; Chronic Disease ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {BACKGROUND: Recurrent bowel disease (RBD) refers to the chronic, recurrent intestinal diseases, including recurrent Clostridium Difficile Infection (rCDI), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), etc., these diseases have similar clinical characteristics, that is, abdominal pain, diarrhea, repeated attacks, prolonged recovery, etc. Clinically, there are relevant reports on the use of oral capsule fecal microbiota transplantation (oFMT) to treat RBD. However, both the advantages and disadvantages of clinical efficacy have been reported; there are some contradictions, the study sample size is too small, and the purpose of this systematic review was to evaluate the efficacy and safety of oral capsule fecal microbiota transplantation in the treatment of RBD.<br><br>METHODS: This systematic review will include articles identified through electronic searches of the PubMed, EMbase, and Cochrane Library. From inception to July 1, 2022. Two reviewers will independently search the database to conduct data extraction and assessment of study quality. Based on heterogeneity tests, data will be integrated using fixed or random effect models. RevMan V.5.4 will be used for data analysis. The results are expressed as the risk ratio of dichotomous data and the mean difference of continuous data.<br><br>RESULTS: We analyzed the clinical remission or cure rate, IBS-SSS, quality of life, anxiety, depression, total adverse effects, and total severe adverse effects (TSAE) in patients with RBD.<br><br>CONCLUSION: This systematic review evaluated the efficacy and safety of oFMT in the treatment of RBD to provide more comprehensive evidence.}, }
@article {pmid36451045, year = {2022}, author = {Thomas, AR and Liu, C and Tong, YT and Tan, D and Altan, M and Siddiqui, BA and Shatila, M and Khan, A and Thomas, AS and Wang, Y}, title = {Characteristics and outcomes of cancer patients with pre-existing microscopic colitis after exposure to PD-1 and PD-L1 inhibitors.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {36451045}, issn = {1432-1335}, abstract = {PURPOSE: Immune checkpoint inhibitors (ICIs) are frequently associated with adverse events, often affecting the gastrointestinal tract. We conducted this study to determine the characteristics and outcomes of cancer patients with pre-existing microscopic colitis (MC) who underwent ICI treatment.<br><br>METHODS: In this retrospective study, we identified 10 patients with pre-existing MC who received ICIs at our center 01/2010-06/2020. Clinical characteristics and disease outcomes were recorded.<br><br>RESULTS: Of 124 screened patients with MC before ICI exposure, 10 had sufficient data to be included in the study. Melanoma (40%) and lung cancer (30%) were the most prevalent cancer types, with 70% of stage IV cancer. Patients received either anti-programmed death 1 regimen (8, 80%) or anti-programmed death ligand 1 agent (2, 20%). Six patients (60%) had collagenous colitis, and 4 (40%) had lymphocytic colitis. The median time from MC diagnosis to ICI initiation was 4&#xa0;years, with 1 patient on budesonide within 2&#xa0;months of ICI initiation. Eight patients (80%) developed colitis exacerbations after ICI &#xa0;and required selective immunosuppression. One patient received a compassionate-use fecal transplantation. The median time from ICI to colitis exacerbation was 14&#xa0;days, with 40% and 50% of patients experiencing grade 3 diarrhea and grade 2 colitis, respectively, leading to hospitalization in 3 patients. Six patients received steroids and vedolizumab with no colitis recurrence. Of 8 patients who had colitis exacerbation, 6 resumed ICI therapy afterward; with 5 receiving concomitant vedolizumab for secondary prophylaxis.<br><br>CONCLUSION: Our findings suggest that ICI exposure increases the risk of exacerbation of underlying colitis necessitating and responding to potent immunosuppression therapy.}, }
@article {pmid36450880, year = {2022}, author = {Xiao, L and Zhou, Y and Bokoliya, S and Lin, Q and Hurley, M}, title = {Bone loss is ameliorated by fecal microbiota transplantation through SCFA/GPR41/ IGF1 pathway in sickle cell disease mice.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {20638}, pmid = {36450880}, issn = {2045-2322}, support = {R56 HL147048-01/GF/NIH HHS/United States ; }, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation ; Insulin-Like Growth Factor I ; *Bone Diseases, Metabolic ; *Anemia, Sickle Cell/therapy ; Feces ; }, abstract = {Bone loss is common in sickle cell disease (SCD), but the molecular mechanisms is unclear. Serum insulin-like growth factor 1 (IGF1) was low in SCD subjects and SCD mice. To determine if decreased IGF1 associated with low bone mass in SCD is due to reduced SCFA production by gut microbiota, we performed reciprocal fecal microbiota transplantation (FMT) between healthy control (Ctrl) and SCD mice. uCT and histomorphometry analysis of femur showed decreased bone volume/total volume (BV/TV), trabecular number (Tb.N), osteoblast surface/bone surface (Ob.S/BS), mineralizing surface/ bone surface (MS/BS), inter-label thickness (Ir.L.Th) in SCD mice were significantly improved after receiving Ctrl feces. Bone formation genes Alp, Col1, Runx2, and Dmp1 from SCD mice were significantly decreased and were rescued after FMT from Ctrl feces. Transplantation of Ctrl feces increased the butyrate, valerate, and propionate levels in cecal content of SCD mice. Decreased G-coupled protein receptors 41 and 43 (GPR41 and GPR43) mRNA in tibia and lower IGF1 in bone and serum of SCD mice were partially restored after FMT from Ctrl feces. These data indicate that the healthy gut microbiota of Ctrl mice is protective for SCD bone loss through regulating IGF1 in response to impaired bacterial metabolites SCFAs.}, }
@article {pmid36450285, year = {2022}, author = {Ousey, J and Boktor, JC and Mazmanian, SK}, title = {Gut microbiota suppress feeding induced by palatable foods.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2022.10.066}, pmid = {36450285}, issn = {1879-0445}, abstract = {Feeding behaviors depend on intrinsic and extrinsic factors including genetics, food palatability, and the environment.[1][,][2][,][3][,][4][,][5] The gut microbiota is a major environmental contributor to host physiology and impacts feeding behavior.[6][,][7][,][8][,][9][,][10][,][11][,][12] Here, we explored the hypothesis that gut bacteria influence behavioral responses to palatable foods and reveal that antibiotic depletion (ABX) of the gut microbiota in mice results in overconsumption of several palatable foods with conserved effects on feeding dynamics. Gut microbiota restoration via fecal transplant into ABX mice is sufficient to rescue overconsumption of high-sucrose pellets. Operant conditioning tests found that ABX mice exhibit intensified motivation to pursue high-sucrose rewards. Accordingly, neuronal activity in mesolimbic brain regions, which have been linked with motivation and reward-seeking behavior,[3] was elevated in ABX mice after consumption of high-sucrose pellets. Differential antibiotic treatment and functional microbiota transplants identified specific gut bacterial taxa from the family S24-7 and the genus Lactobacillus whose abundances associate with suppression of high-sucrose pellet consumption. Indeed, colonization of mice with S24-7 and Lactobacillus johnsonii was sufficient to reduce overconsumption of high-sucrose pellets in an antibiotic-induced model of binge eating. These results demonstrate that extrinsic influences from the gut microbiota can suppress the behavioral response toward palatable foods in mice.}, }
@article {pmid36444412, year = {2022}, author = {Karakavuk, T and Gül, C and Karakavuk, M and Gül, A and Erkunt Alak, S and Can, H and Ün, C and Döşkaya, M and Gürüz, AY and Değirmenci Döşkaya, A}, title = {Biotechnological Based Recombinant Protein Vaccines Developed Against Toxoplasmosis.}, journal = {Turkiye parazitolojii dergisi}, volume = {46}, number = {4}, pages = {342-357}, doi = {10.4274/tpd.galenos.2022.41636}, pmid = {36444412}, issn = {2146-3077}, mesh = {Humans ; Female ; Pregnancy ; Sheep ; Animals ; Biotechnology ; *Toxoplasma/genetics ; Goats ; Animals, Domestic ; *Toxoplasmosis ; Recombinant Proteins ; }, abstract = {Toxoplasma gondii (T. gondii) that can infect most warm-blooded animals and humans, is an obligate intracellular apicomplexan parasite with a wide host range. About one-third of the world's population is infected with this parasite. While toxoplasmosis progresses asymptomatically in individuals with a strong immune system, it can cause serious clinical manifestations and death in immunocompromised individuals. The parasite is transmitted to humans through the consumption of water and food contaminated with cat feces, as well as raw or undercooked animal products, congenital infection and blood/organ transplantation. Additionally, T. gondii is often observed in farm animals such as sheep and goats. Clinical manifestations and abortions caused by T. gondii in sheep and goats lead to enormous economic loss worldwide. There is a commercial vaccine against T. gondii, called Toxovax (MSD, New Zealand) that can only be used in sheep. For these reasons, there is a need for innovative T. gondii vaccine that is harmless, easily produced, which can prevent losses and be used in all living things. Advances in immunology, molecular biology, genetic, biotechnology and proteomics bring new perspectives to vaccine studies. Studies in innovative vaccine studies against T. gondii have accelerated with the discovery of new antigens by in vitro screenings, and bioinformatic analyzes, the use of various expression systems and new adjuvant types. Recombinant protein vaccines are biotechnological vaccines that are frequently preferred due to their rapid and easy production in various expression systems, availability of very and high purity products, ease of manipulation and stimulation of both cellular and humoral immune responses. Recombinant protein vaccines, developed by biotechnological methods, are promising tools for providing a protective immune response against toxoplasmosis. In this review, an overview of the parasite complex life cycle, its pathogenesis, humoral and cellular immune responses in the host, and recombinant protein vaccine studies developed against the parasite are presented.}, }
@article {pmid36442762, year = {2022}, author = {Liu, C and Song, C and Wang, Y and Xiao, Y and Zhou, Z and Cao, G and Sun, X and Liu, Y}, title = {Deep-fried Atractylodes lancea rhizome alleviates spleen deficiency diarrhea-induced short-chain fatty acid metabolic disorder in mice by remodeling the intestinal flora.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {115967}, doi = {10.1016/j.jep.2022.115967}, pmid = {36442762}, issn = {1872-7573}, abstract = {Atractylodes lancea (Thunb.) DC. is a Chinese herb that has been commonly used to treat spleen-deficiency diarrhea (SDD) in China for over a thousand years. However, the underlying mechanism of its antidiarrheal activity is not fully understood.<br><br>AIM OF THE STUDY: The antidiarrheal effects of the ethanol extract of deep-fried A. lancea rhizome (EEDAR) due to spleen deficiency induced by folium sennae (SE) were determined on the regulation of the short-chain fatty acid (SCFA) metabonomics induced by the intestinal flora.<br><br>MATERIALS AND METHODS: The effects of EEDAR on a SE-induced mouse model of SDD were evaluated by monitoring the animal weight, fecal water content, diarrhea-grade rating, goblet cell loss, and pathological changes in the colon. The expression of inflammatory factors (tumor necrosis factor [TNF]-&#x3b1;, interleukin [IL]-1&#x3b2;, IL-6, IL-10), aquaporins (AQP3, AQP4, and AQP8), and tight junction markers (ZO-1, occludin, claudin-1) in colon tissues were determined using quantitative polymerase chain reaction and western blotting. SCFA metabonomics in the feces of mice treated with EEDAR was evaluated using gas chromatography-mass spectrometry. Furthermore, 16S rDNA sequencing was used to determine the effect of EEDAR on the intestinal flora of SDD mice, and fecal microbiota transplantation (FMT) was used to confirm whether the intestinal flora was essential for the anti-SDD effect of EEDAR.<br><br>RESULTS: Treatment with EEDAR significantly improved the symptoms of mice with SDD by inhibiting the loss of colonic cup cells, alleviating colitis, and promoting the expression of AQPs and tight junction markers. More importantly, the effect of EEDAR on the increase of SCFA content in mice with SDD was closely related to the gut microbiota composition. EEDAR intervention did not significantly improve intestinal inflammation or the barrier of germ-free SDD mice, but FMT was effective.<br><br>CONCLUSION: EEDAR alleviated SE-induced SDD in mice, as well as the induced SCFA disorder by regulating the imbalance of the intestinal microbiota.}, }
@article {pmid36441203, year = {2022}, author = {Bishop, EJ and Tiruvoipati, R}, title = {Management of Clostridioides difficile infection in adults and challenges in clinical practice: review and comparison of current IDSA/SHEA, ESCMID and ASID guidelines.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {}, number = {}, pages = {}, doi = {10.1093/jac/dkac404}, pmid = {36441203}, issn = {1460-2091}, abstract = {Clostridioides difficile infection (CDI) remains a significant clinical challenge both in the management of severe and severe-complicated disease and the prevention of recurrence. Guidelines released by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America (IDSA/SHEA) and ESCMID had some consensus as well as some discrepancies in disease severity classification and treatment recommendations. We review and compare the key clinical strategies from updated IDSA/SHEA, ESCMID and current Australasian guidelines for CDI management in adults and discuss relevant issues for clinicians, particularly in the management of severe-complicated infection. Updated IDSA/SHEA and ESCMID guidelines now reflect the increased efficacy of fidaxomicin in preventing recurrence and have both promoted fidaxomicin to first-line therapy with an initial CDI episode in both non-severe and severe disease and endorsed the role of bezlotoxumab in the prevention of recurrent infection. Vancomycin remains acceptable therapy and metronidazole is not preferred. For severe-complicated infection the IDSA/SHEA recommends high-dose oral ± rectal vancomycin and IV metronidazole, whilst in an important development, ESCMID has endorsed fidaxomicin and tigecycline as part of combination anti-CDI therapy, for the first time. The role of faecal microbiota transplantation (FMT) in second CDI recurrence is now clearer, but timing and mode of FMT in severe-complicated refractory disease still requires further study.}, }
@article {pmid36440358, year = {2022}, author = {Zhang, H and Duan, Y and Cai, F and Cao, D and Wang, L and Qiao, Z and Hong, Q and Li, N and Zheng, Y and Su, M and Liu, Z and Zhu, B}, title = {Next-Generation Probiotics: Microflora Intervention to Human Diseases.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {5633403}, pmid = {36440358}, issn = {2314-6141}, mesh = {Humans ; *Gastrointestinal Microbiome ; Ecosystem ; *Probiotics/therapeutic use ; Intestines ; }, abstract = {With the development of human genome sequencing and techniques such as intestinal microbial culture and fecal microbial transplantation, newly discovered microorganisms have been isolated, cultured, and researched. Consequently, many beneficial probiotics have emerged as next-generation probiotics (NGPs). Currently, "safety," "individualized treatment," and "internal interaction within the flora" are requirements of a potential NGPs. Furthermore, in the complex ecosystem of humans and microbes, it is challenging to identify the relationship between specific strains, specific flora, and hosts to warrant a therapeutic intervention in case of a disease. Thus, this review focuses on the progress made in NGPs and human health research by elucidating the limitations of traditional probiotics; summarizing the functions and strengths of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, Eubacterium hallii, and Roseburia spp. as NGPs; and determining the role of their intervention in treatment of certain diseases. Finally, we aim to provide a reference for developing new probiotics in the future.}, }
@article {pmid36439840, year = {2022}, author = {Li, Z and Ke, H and Wang, Y and Chen, S and Liu, X and Lin, Q and Wang, P and Chen, Y}, title = {Global trends in Akkermansia muciniphila research: A bibliometric visualization.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1037708}, pmid = {36439840}, issn = {1664-302X}, abstract = {BACKGROUND: Akkermansia muciniphila is a member of the gut microbiome, using mucin as sources of carbon, nitrogen, and energy. Since the first discovery of this unique bacterium in 2004, A. muciniphila has been extensively studied. It is considered a promising "next-generation beneficial microbe." The purpose of this paper is to sort out the research status and summarize the hotspots through bibliometric analysis of the publications of A. muciniphila.<br><br>METHODS: The publications about A. muciniphila from January 2004 to February 2022 were obtained from the Web of Science Core Collection. Visualization analyses were performed using three bibliometric tools and GraphPad Prism.<br><br>RESULTS: A total of 1,478 published documents were analyzed. Annual publication number grew from 1 in 2004 to 336 in 2021, with China being the leading producer (33.36%). De Vos, Willem M was the most productive author with the highest H-index (documents&#x2009;=&#x2009;56, H-index&#x2009;=&#x2009;37), followed by Cani, Patrice D (documents&#x2009;=&#x2009;35, H-index&#x2009;=&#x2009;25). And Scientific Reports published the most papers. PNAS was the keystone taxa in this field, with high betweenness centrality (0.11) and high frequency. The keywords with high frequency in recent years include: oxidative stress, diet, metformin, fecal microbiota transplantation, short-chain fatty acids, polyphenols, microbiota metabolites and so on. The keyword "oxidative stress" was observed to be increasing in frequency recently.<br><br>CONCLUSION: Over time, the scope of the research on the clinical uses of A. muciniphila has gradually increased, and was gradually deepened and developed toward a more precise level. A. muciniphila is likely to remain a research hotspot in the foreseeable future and may contribute to human health.}, }
@article {pmid36439220, year = {2022}, author = {Zhang, F and Yang, P and Chen, Y and Wang, R and Liu, B and Wang, J and Yuan, M and Zhang, L}, title = {Bibliometric and visual analysis of fecal microbiota transplantation research from 2012 to 2021.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1057492}, pmid = {36439220}, issn = {2235-2988}, mesh = {Humans ; Fecal Microbiota Transplantation ; Bibliometrics ; *Enterocolitis, Pseudomembranous ; *Gastrointestinal Microbiome ; Chlorhexidine ; *Dermatitis ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapy for diseases associated with intestinal flora imbalance that has attracted increasing attention in recent years. This study aims to provide an overview of research trends in the field, and act as a reference point for future scientific research by analyzing the state of current research, identifying hotspots, and potential frontiers of FMT.<br><br>METHODS: Articles relating to FMT that were published between the years 2012 and 2021 were retrieved from the Web of Science Core Collection. Bibliometric analysis was performed using Microsoft Excel and CiteSpace.<br><br>RESULTS: A total of 2,403 English language articles relating to FMT research were published over the last ten years. Most of this research was carried out in the United States of America, with Harvard Medical school being the most productive institution. Much of the research was published in the PLoS One journal. Alexander Khoruts was identified as a prominent, productive researcher in the field. Keyword analysis revealed that research hot spots included gut microbiota, Clostridium difficile infection (CDI), and diseases. Burst detection indicated that future research frontiers include clinical practice guidelines and strategies.<br><br>CONCLUSION: Our analysis explored hot spots and emerging trends in the FMT field. Indications for use of FMT extended from digestive system diseases to other systemic diseases. Additionally, areas such as risk assessment and control, along with application methods were also a focus of current research. Moreover, research relating to optimization of clinical practice has excellent prospects.}, }
@article {pmid36439219, year = {2022}, author = {Wang, J and Chen, J and Chen, M}, title = {Commentary: Effect of fecal microbiota transplantation on non-alcoholic fatty liver disease: A randomized clinical trial.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1056394}, pmid = {36439219}, issn = {2235-2988}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Non-alcoholic Fatty Liver Disease/therapy ; }, }
@article {pmid36438048, year = {2022}, author = {Orr, MR}, title = {The biodiversity dose-response curve translates theory and practice from ecological restoration into research and clinical priorities for fecal microbiota transplantation.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1059148}, pmid = {36438048}, issn = {2296-858X}, abstract = {Discoveries of the beneficial effects of gut microbiota have led to efforts to cultivate healthy gut flora to treat disease. The field of ecological restoration specializes on reestablishment of desired species in disturbed ecosystems, which suggests that it may be applicable to microbe restoration in the gut. Common language can lower barriers to interdisciplinary insights. Here I introduce the concept of a "biodiversity dose-response curve" to translate ideas from ecological restoration into research and clinical priorities for fecal microbiota transplantation (FMT). The curve is based on a relationship between ecosystem structure, measured as species diversity found in both nature and gut ecosystems, and ecosystem function, which are the measurable parameters that contribute to ecosystem and human health. I explain why the biodiversity dose-response curve may follow the ecological model of a "rivet-redundancy" relationship, in which the overlap of multiple organisms' functional contributions to a system mask the impact of initial losses of diversity, but, at a certain level of loss, function declines sharply. (Imagine an airplane that flies with a few rivets missing, until it loses enough to fail.) The biodiversity dose-response curve indicates that seemingly healthy individuals may be suboptimal donors; it highlights the importance of recipient diet in FMT success; and it introduces the concept of "passive restoration" into the field of gut medicine. These insights, which may help to explain low success rates of FMT in the treatment of non-Clostridium dificile conditions, are less apparent in the absence of interdisciplinary integration.}, }
@article {pmid36432617, year = {2022}, author = {Tang, W and Yuan, M and Li, Z and Lin, Q and Zhen, Y and Li, Z and Zhou, H and Xia, F}, title = {Polyphenol-Rich Liupao Tea Extract Prevents High-Fat Diet-Induced MAFLD by Modulating the Gut Microbiota.}, journal = {Nutrients}, volume = {14}, number = {22}, pages = {}, doi = {10.3390/nu14224930}, pmid = {36432617}, issn = {2072-6643}, mesh = {Male ; Mice ; Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Polyphenols/pharmacology ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; *Liver Diseases ; *Metabolic Diseases ; *Digestive System Diseases ; Tea ; }, abstract = {The modulation of gut microbiota dysbiosis might regulate the progression of metabolic-associated fatty liver disease (MAFLD). Here, we found that polyphenol-rich Liupao tea extract (PLE) prevents high-fat diet (HFD)-induced MAFLD in ApoE[-/-] male mice accompanied by protection of the intestinal barrier and downregulation of lipopolysaccharide (LPS)-related Toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) signaling in the liver. Fecal microbiome transplantation (FMT) from PLE-and-HFD-treated mice delayed MAFLD development significantly compared with FMT from HFD-treated mice. In this case, 16S rRNA gene sequencing revealed that Rikenellaceae and Odoribacter were significantly enriched and that Helicobacter was significantly decreased in not only the HFD+PLE group but also the HFD+PLE-FMT group. Furthermore, the level of 3-sulfodeoxycholic acid was significantly decreased in the HFD+PLE-FMT group compared with the HFD-FMT group. In conclusion, our data demonstrate that PLE could modulate the MAFLD phenotype in mice and that this effect is partly mediated through modulation of the gut microbiota.}, }
@article {pmid36431177, year = {2022}, author = {Zhi, W and Yuan, X and Song, W and Jin, G and Li, Y}, title = {Fecal Microbiota Transplantation May Represent a Good Approach for Patients with Focal Segmental Glomerulosclerosis: A Brief Report.}, journal = {Journal of clinical medicine}, volume = {11}, number = {22}, pages = {}, doi = {10.3390/jcm11226700}, pmid = {36431177}, issn = {2077-0383}, abstract = {This is the first report of fecal microbiota transplantation (FMT) in patients with chronic kidney disease. The patient was subjected to focal segmental glomerulosclerosis (FSGS), with onset in April 2021. The main manifestation featured abnormal renal function and no proteinuria at the level of nephrotic syndrome. In May 2021, she showed biopsy-proven FSGS and was treated with glucocorticoid. However, after glucocorticoid reduction, the patient's serum creatinine increased again, so she adjusted the dosage and continued use until now. In April 2022, the patient was prescribed the FMT capsules. After FMT, the renal function remained stable, urinary protein decreased, reaching the clinical standard of complete remission, and there was no recurrence after glucocorticoid reduction. Furthermore, the patient showed significantly decreased hyperlipidemia, triglyceride (TG) and cholesterol (CHO) after FMT. During FMT, the level of cytokines fluctuated slightly, but returned to the pre-transplantation level after three months. From this, we conclude that FMT is a potential adjuvant therapy for FSGS, and patients can benefit from improving renal function and dyslipidemia.}, }
@article {pmid36429112, year = {2022}, author = {Qi, X and Liu, Y and Hussein, S and Choi, G and Kimchi, ET and Staveley-O'Carroll, KF and Li, G}, title = {The Species of Gut Bacteria Associated with Antitumor Immunity in Cancer Therapy.}, journal = {Cells}, volume = {11}, number = {22}, pages = {}, doi = {10.3390/cells11223684}, pmid = {36429112}, issn = {2073-4409}, support = {R01 CA250536/NH/NIH HHS/United States ; R01 DK130340/NH/NIH HHS/United States ; R01 CA208396/NH/NIH HHS/United States ; I01 BX004065/BX/BLRD VA/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Bacteria ; *Probiotics/therapeutic use ; *Neoplasms/therapy ; }, abstract = {Both preclinical and clinical studies have demonstrated that the modulation of gut microbiota could be a promising strategy for enhancing antitumor immune responses and reducing resistance to immunotherapy in cancer. Various mechanisms, including activation of pattern recognition receptors, gut commensals-produced metabolites and antigen mimicry, have been revealed. Different gut microbiota modulation strategies have been raised, such as fecal microbiota transplantation, probiotics, and dietary selection. However, the identification of gut bacteria species that are either favorable or unfavorable for cancer therapy remains a major challenge. Herein, we summarized the findings related to gut microbiota species observed in the modulation of antitumor immunity. We also discussed the different mechanisms underlying different gut bacteria's functions and the potential applications of these bacteria to cancer immunotherapy in the future.}, }
@article {pmid36425787, year = {2022}, author = {Fang, J and Yu, CH and Li, XJ and Yao, JM and Fang, ZY and Yoon, SH and Yu, WY}, title = {Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {997018}, pmid = {36425787}, issn = {2235-2988}, mesh = {Humans ; Dysbiosis/therapy/microbiology ; *Non-alcoholic Fatty Liver Disease/diagnosis/therapy/metabolism ; *Gastrointestinal Microbiome ; *Liver Neoplasms ; }, abstract = {The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing recently and has become one of the most common clinical liver diseases. Since the pathogenesis of NAFLD has not been completely elucidated, few effective therapeutic drugs are available. As the "second genome" of human body, gut microbiota plays an important role in the digestion, absorption and metabolism of food and drugs. Gut microbiota can act as an important driver to advance the occurrence and development of NAFLD, and to accelerate its progression to cirrhosis and hepatocellular carcinoma. Growing evidence has demonstrated that gut microbiota and its metabolites directly affect intestinal morphology and immune response, resulting in the abnormal activation of inflammation and intestinal endotoxemia; gut dysbiosis also causes dysfunction of gut-liver axis via alteration of bile acid metabolism pathway. Because of its composition diversity and disease-specific expression characteristics, gut microbiota holds strong promise as novel biomarkers and therapeutic targets for NAFLD. Intervening intestinal microbiota, such as antibiotic/probiotic treatment and fecal transplantation, has been a novel strategy for preventing and treating NAFLD. In this article, we have reviewed the emerging functions and association of gut bacterial components in different stages of NAFLD progression and discussed its potential implications in NAFLD diagnosis and therapy.}, }
@article {pmid36425405, year = {2022}, author = {Seekatz, AM and Safdar, N and Khanna, S}, title = {The role of the gut microbiome in colonization resistance and recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {15}, number = {}, pages = {17562848221134396}, pmid = {36425405}, issn = {1756-283X}, abstract = {UNLABELLED: The species composition of the human gut microbiota is related to overall health, and a healthy gut microbiome is crucial in maintaining colonization resistance against pathogens. Disruption of gut microbiome composition and functionality reduces colonization resistance and has been associated with several gastrointestinal and non-gastrointestinal diseases. One prime example is Clostridioides difficile infection (CDI) and subsequent recurrent infections that occur after the development of systemic antibiotic-related dysbiosis. Standard-of-care antibiotics used for both acute and recurrent infections do not address dysbiosis and often worsen the condition. Moreover, monoclonal antibodies, recommended in conjunction with standard-of-care antibiotics for the prevention of recurrent CDI in patients at high risk of recurrence, reduce recurrences but do not address the underlying dysbiosis. Fecal microbiota transplantation (FMT) is an evolving therapeutic strategy in which microbes are harvested from healthy donor stool and transplanted into the gut of a recipient to restore the gut microbiome. Although effective in the prevention of recurrent CDI, some existing challenges include screening and the standardization of stool acquisition and processing. Recent safety alerts by the US Food and Drug Administration raised concern about the possibility of transmission of multidrug-resistant organisms or severe acute respiratory syndrome coronavirus 2 via FMT. Increased knowledge that microbes are beneficial in restoring the gut microbiome has led to the clinical development of several newer biotherapeutic formulations that are more regulated than FMT, which may allow for improved restoration of the gut microbiome and prevention of CDI recurrence. This review focuses on mechanisms by which gut microbiome restoration could influence colonization resistance against the pathogen C. difficile.<br><br>PLAIN LANGUAGE SUMMARY: The Role of the Gut Microbiome in Clostridioides difficile Infection Introduction: A rich and diverse gut microbiome is key to immune system regulation and colonization resistance against pathogens.A disruption in the gut microbiome composition can make the gut more vulnerable to diseases such as Clostridioides difficile infection (CDI), caused by the bacterium C. difficile.CDI management presents a therapeutic dilemma, as it is usually treated with antibiotics that can treat the infection but also can damage the microbiome.Treatment of CDI using antibiotics can further reduce microbial diversity and deplete beneficial bacteria from the gut leading to a condition called dysbiosis.Antibiotic treatment can be followed by therapies that restore the gut microbiota, boost colonization resistance, and prevent the development of antimicrobial resistance.It is important to evaluate treatment options to determine their safety and effectiveness. Methods: The researchers provided an overview of the mechanisms that the gut microbiome uses to prevent colonization of the gut by pathogens.They subsequently reviewed the efficacy and shortcomings of the following treatments for CDI: -&#x2003;Antibiotics-&#x2003;Monoclonal antibodies-&#x2003;Fecal microbiota transplantation (FMT) Results: Commensal intestinal bacteria prevent colonization of the gut by pathogens using mechanisms such as: -&#x2003;Competition for key nutrients-&#x2003;Production of inhibitory bile acids-&#x2003;Short-chain fatty acid production-&#x2003;Lowering the luminal pH-&#x2003;Production of bacteriocinsAntibiotic therapy is recommended as a standard treatment for CDI. However, patients are vulnerable to recurrent CDI after discontinuation of the therapy.Monoclonal antibodies that inactivate C. difficile toxins may be recommended along with antibiotics to prevent recurrent CDI. However, this approach does not restore the microbiome.FMT is one method of microbial restoration, where stool is harvested from a healthy donor and transplanted into a patient's colon.Although FMT has shown some efficacy in the treatment of recurrent CDI, the procedure is not standardized.Safety concerns have been raised about the possibility of transmission of multidrug-resistant pathogens via FMT. Conclusion: Treatment methods that can efficiently restore the diversity of the gut microbiome are crucial in preventing recurrence of CDI.}, }
@article {pmid36424781, year = {2022}, author = {Rastogi, S and Singh, A and Nandy, A and Gupta, A and Agarwal, J and Kostova, I}, title = {Can the Therapeutic Spectrum of Probiotics be Extended: Exploring Potential of Gut Microbiome.}, journal = {Recent advances in anti-infective drug discovery}, volume = {}, number = {}, pages = {}, doi = {10.2174/2772434418666221124124317}, pmid = {36424781}, issn = {2772-4352}, abstract = {Natural therapeutic microorganisms provide a potent alternative healthcare treatment nowadays, with the potential to prevent several human diseases. These health-boosting living organisms, probiotics mostly belong to Gram-positive bacteria such as Lactobacillus, Bifidobacterium, Streptococcus, Saccharomyces, Bacillus and Enterococcus. Initiated almost a century ago, the probiotic application has come a long way. The present review is focused on the potential therapeutic role of probiotics in ameliorating multiple infections, such as upper respiratory tract infections and viral respiratory infections, including Covid-19; liver diseases and hepatic encephalopathy; neurological and psychiatric disorders; autoimmune diseases, particularly rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. Apart from these, the therapeutic exacerbations of probiotics in urinary tract infections have been extremely promising, and several approaches are reviewed and presented here. We also present upcoming and new thrust areas where probiotic therapeutic interventions are showing promising results, like faecal microbial transplant and vaginal microbial transplant.}, }
@article {pmid36424592, year = {2022}, author = {Gu, X and Miao, Z and Wang, Y and Yang, Y and Yang, T and Xu, Y}, title = {New Baitouweng decoction combined with fecal microbiota transplantation alleviates DSS-induced colitis in rats by regulating gut microbiota metabolic homeostasis and the STAT3/NF-κB signaling pathway.}, journal = {BMC complementary medicine and therapies}, volume = {22}, number = {1}, pages = {307}, pmid = {36424592}, issn = {2662-7671}, mesh = {Rats ; Animals ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; NF-kappa B/metabolism ; Dextran Sulfate/pharmacology ; *Colitis ; *Colitis, Ulcerative/therapy/metabolism ; Signal Transduction ; Homeostasis ; }, abstract = {AIM OF THE STUDY: We aimed to elucidate the synergistic effect and potential mechanism of New Baitouweng Decoction (NBD) combined with fecal microbiota transplantation (FMT) in rats with DSS-induced ulcerative colitis (UC).<br><br>MATERIALS AND METHODS: Colitis was induced by 5% (w/v) dextran sulfate sodium (DSS) in drinking water for 7&#x2009;days. NBD or NBD combined with FMT were administered to the colitis rats. Body weight and disease activity index were measured, and the colon histological change was imaged to further examine the efficacy of NBD and FMT. The specific effects of NBD on STAT3/NF-&#x3ba;B signaling pathway and gut microbiota in rats with UC were also investigated.<br><br>RESULTS: The efficacy of NBD in combination with FMT was demonstrated by the lower disease activity index scores; increased tight junction proteins expression; and a lower expression of macrophage marker (F4/80) in colon tissues. NBD combined with FMT elevated the concentrations of short-chain fatty acids and inhibited activation of the JAK2/STAT3/NF-&#x3ba;B related proteins. Furthermore, 16SrDNA sequencing indicated that the gut microbiota in rats with UC was perturbed, in contrast to that in healthy rats. After treatment with NBD and FMT, the diversity and abundance of intestinal flora showed clear improvements. Spearman correlation analysis indicated a strong correlation between specific microbiota and fecal concentrations of acetate, propionate and butyrate.<br><br>CONCLUSIONS: The protective mechanism of NBD combined with FMT may be linked to regulation NF-&#x3ba;B/STAT3 and restoration of the intestinal flora.}, }
@article {pmid36422528, year = {2022}, author = {Franc, A and Vetchý, D and Fülöpová, N}, title = {Commercially Available Enteric Empty Hard Capsules, Production Technology and Application.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {15}, number = {11}, pages = {}, pmid = {36422528}, issn = {1424-8247}, abstract = {Currently, there is a growing need to prepare small batches of enteric capsules for individual therapy or clinical evaluation since many acidic-sensitive substances should be protected from the stomach's acidic environment, including probiotics or fecal material, in the fecal microbiota transplantation (FMT) process. A suitable method seems to be the encapsulation of drugs or lyophilized alternatively frozen biological suspensions in commercial hard enteric capsules prepared by so-called Enteric Capsule Drug Delivery Technology (ECDDT). Manufacturers supply these types of capsules, made from pH-soluble polymers, in products such as AR Caps[®], EnTRinsic[TM], and Vcaps[®] Enteric, or capsules made of gelling polymers that release their content as the gel erodes over time when passing through the digestive tract. These include DRcaps[®], EMBO CAPS[®] AP, BioVXR[®], or ACGcaps™ HD. Although not all capsules in all formulations meet pharmaceutical requirements for delayed-release dosage forms in disintegration and dissolution tests, they usually find practical application. This literature review presents their composition and properties. Since ECDDT is a new technology, this article is based on a limited number of references.}, }
@article {pmid36422003, year = {2022}, author = {Zhuang, Y and Zeng, R and Liu, X and Yang, L and Chan, Z}, title = {Neoagaro-Oligosaccharides Ameliorate Chronic Restraint Stress-Induced Depression by Increasing 5-HT and BDNF in the Brain and Remodeling the Gut Microbiota of Mice.}, journal = {Marine drugs}, volume = {20}, number = {11}, pages = {}, pmid = {36422003}, issn = {1660-3397}, mesh = {Animals ; Mice ; *Brain-Derived Neurotrophic Factor/metabolism ; Depression/drug therapy/etiology ; *Gastrointestinal Microbiome ; Serotonin ; Interleukin-18 ; Mice, Inbred C57BL ; Brain/metabolism ; Oligosaccharides/pharmacology/therapeutic use ; Disease Models, Animal ; }, abstract = {Neoagaro-oligosaccharides (NAOs) belong to the algae oligosaccharides. NAOs have been found to have diverse biological activities. However, the effects of NAOs on depression and their underlying mechanism have not been thoroughly studied. A chronic restraint stress (CRS)-induced C57BL/6J mouse model was used to assess the antidepressant effects of NAOs. Anxiety and depression behaviors were assessed by open field tests (OFT) and forced swimming tests (FST), while interleukin 18 (IL-18), 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) were the molecular biomarkers of depression. Fecal microbiota transplantation (FMT) was performed. The results showed that NAO treatment significantly improved the body weight of depressed mice and reduced the central area time in the OFT and immobility time in the FST. NAO treatment decreased the levels of IL-18 in the serum and increased the levels of 5-HT in the serum and whole brain and of BDNF in the whole brain. NAO treatment mitigated the gut microbiota dysbiosis in the depressed mice and reversed the decreased levels of short-chain fatty acids (SCFAs) in the cecum of the depressed mice. FMT indicated that the gut microbiota is, indeed, linked to depression, which was reflected in the changes in weight gain and behaviors. In a word, NAOs effectively reversed the CRS-induced mice model of depression, which depended on the changes in the gut microbiota and SCFAs, as well as its modulation of 5-HT and BDNF.}, }
@article {pmid36420886, year = {2022}, author = {Zhang, LN and Yuan, WL and Ye, M and Yin, L and Wang, SJ}, title = {Changes in the intestinal microbiota of patients with Parkinson's disease and their clinical significance.}, journal = {International journal of clinical pharmacology and therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.5414/CP204285}, pmid = {36420886}, issn = {0946-1965}, abstract = {OBJECTIVE: To investigate the differences and their clinical significance in the intestinal microbiota in patients with Parkinson's disease (PD) in comparison to those in healthy controls.<br><br>MATERIALS AND METHODS: 20 patients with PD who received treatment in the First Affiliated Hospital of Bengbu Medical College between January 2019 and December 2019 were selected as the research subjects to form the PD group, while 20 age- and gender-matched healthy volunteers were selected as the control group. Fecal samples from the two groups were collected, and the V4 region of 16S-ribosomal ribonucleic acid was selected for high-throughput sequencing analysis to explore any differences, as well as their significance, in the intestinal microbiota abundance at the class, family, and genus levels between the two study groups.<br><br>RESULTS: The operational taxonomic unit cluster analysis revealed a high degree of overlap between the patients with PD and the controls. Compared with the controls, the relative abundance of Coriobacteriia and Coriobacteriaceae was increased in the PD group (p&#xa0;<&#xa0;0.01), while the relative abundance of Lachnospiraceae was significantly lower (p&#xa0;<&#xa0;0.01). The relative abundance of Collinsella, Escherichia, and Fusobacterium in the PD group was significantly higher than in the control group (p&#xa0;<&#xa0;0.05).<br><br>CONCLUSION: Compared with the healthy subjects, the abundance of specific microflora was significantly different in the PD patients at the class, family, and genus level. Intestinal flora may act as a potential biomarker for PD and provide a theoretical basis for microflora transplantation therapy.}, }
@article {pmid36420262, year = {2022}, author = {Wang, X and Li, L and Bai, M and Zhao, J and Sun, X and Gao, Y and Yu, H and Chen, X and Zhang, C}, title = {Dietary supplementation with Tolypocladium sinense mycelium prevents dyslipidemia inflammation in high fat diet mice by modulation of gut microbiota in mice.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {977528}, pmid = {36420262}, issn = {1664-3224}, mesh = {Mice ; Humans ; Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Inflammation/prevention &amp; control ; Obesity/prevention &amp; control ; *Dyslipidemias/etiology/prevention &amp; control ; Dietary Supplements ; *Metabolic Diseases ; Mycelium ; }, abstract = {Obesity is a risk factor for many serious health problems, associated with inflammation, hyperlipidemia, and gut dysbiosis. Prevention of obesity is especially important for human health. Tolypocladium sinense is one of the fungi isolated from Chinese caterpillar fungus, which is a traditional Chinese medicine with putative gut microbiota modulation effects. Here, we established a high-fat diet (HFD)-induced hyperlipidemia mice model, which was supplemented with lyophilized T. sinense mycelium (TSP) daily to evaluate its anti-obesity effects. The results indicated that TSP supplementation can effectively alleviate the inflammatory response and oxidative stress levels caused by obesity. TSP significantly prevented obesity and suppressed dyslipidemia by regulating the expression of lipid metabolism genes in the liver. TSP is also effective in preventing the HFD-induced decline in short-chain fatty acid (SCFA) content. Gut microbiota profiling showed that TSP supplementation reversed HFD diet-induced bacterial abundance and also altered the metabolic pathways of functional microorganisms, as revealed by KEGG analysis. It is noteworthy that, correlation analysis reveals the up-regulated gut microbiota (Lactobacillus and Prevotella_9) are closely correlated with lipid metabolism parameters, gene expression of liver lipid metabolism and inflammatory. Additionally, the role of TSP in the regulation of lipid metabolism was reconfirmed by fecal microbiota transplantation. To sum up, our results provide the evidence that TSP may be used as prebiotic agents to prevent obesity by altering the gut microbiota, alleviating the inflammatory response and regulating gene expression of liver lipid metabolism.}, }
@article {pmid36418892, year = {2022}, author = {Zou, MY and Wang, YJ and Liu, Y and Xiong, SQ and Zhang, L and Wang, JH}, title = {Huangshan Floral Mushroom Polysaccharide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Th17/Treg Balance in a Gut Microbiota-Dependent Manner.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e2200408}, doi = {10.1002/mnfr.202200408}, pmid = {36418892}, issn = {1613-4133}, abstract = {SCOPE: Ulcerative colitis (UC) is a common chronic recurrent inflammatory bowel disease. This study attempts to reveal the improvement mechanism of floral mushroom polysaccharide (FMPS) on UC from the perspective of coordinated interaction between intestinal microbes and intestinal helper T cell 17 (Th17)/regulatory T cell (Treg) balance.<br><br>METHODS AND RESULTS: Dextran sulfate sodium (DSS)-induced colitis mice model is used for the experiment. The results suggest that FMPS up-regulated the expression of occludin, ZO-1, and MUC2, and down-regulated the secretion of TNF-&#x3b1;, IL-1&#x3b2;, and IL-6 in colitis mice. Importantly, FMPS restores intestinal Th17/Treg balance. Meanwhile, FMPS can regulate intestinal microorganisms and improve the level of short-chain fatty acids (SCFAs) in colitis mice. Intestinal microbial depletion and fecal microbiota transplantation (FMT) experiments reveal that FMPS ameliorated UC is mediated by intestinal microbiome. Flow cytometry further proves that FMPS restores intestinal Th17/Treg balance in a microbial-dependent manner.<br><br>CONCLUSION: These results indicate that FMPS has the potential to improve UC, and its mechanism depends on the restoration of Th17/Treg balance mediated by intestinal microorganisms. Therefore, it is suggested that FMPS dietary supplement can be potentially used to intervene UC.}, }
@article {pmid36417859, year = {2022}, author = {Zhao, C and Bao, L and Qiu, M and Wu, K and Zhao, Y and Feng, L and Xiang, K and Zhang, N and Hu, X and Fu, Y}, title = {Commensal cow Roseburia reduces gut-dysbiosis-induced mastitis through inhibiting bacterial translocation by producing butyrate in mice.}, journal = {Cell reports}, volume = {41}, number = {8}, pages = {111681}, doi = {10.1016/j.celrep.2022.111681}, pmid = {36417859}, issn = {2211-1247}, mesh = {Female ; Cattle ; Mice ; Animals ; Humans ; Dysbiosis/complications ; Bacterial Translocation ; Butyrates/pharmacology ; *Gastrointestinal Microbiome/physiology ; *Mastitis/complications ; }, abstract = {The precise mechanism by which gut dysbiosis contributes to the pathogenesis of extraintestinal diseases and how commensal microbes mediate these processes remain unclear. Here, we show that cows with mastitis had marked gut dysbiosis, characterized by the enrichment of opportunistic pathogenic Escherichia_Shigella and the depletion of commensal Roseburia. Fecal microbiota transplantation from donor cows with mastitis (M-FMT) to recipient mice significantly caused mastitis and changed the gut and mammary microbiota in mice. Notably, M-FMT facilitated the translocation of pathobiont from the gut into the mammary gland, and the depletion of Enterobacteriaceae alleviated M-FMT-induced mastitis in mice. In contrast, commensal Roseburia intestinalis improved M-FMT-induced mastitis and microbial dysbiosis in the gut and mammary gland and limited bacterial translocation by producing butyrate, which was associated with inflammatory signaling inhibition and barrier repair. Our research suggests that commensal Roseburia alleviates gut-dysbiosis-induced mastitis, although further studies in dairy cows and humans are needed.}, }
@article {pmid36414201, year = {2022}, author = {Liu, Q and Xu, Z and Dai, M and Su, Q and Leung Chan, FK and Ng, SC}, title = {Fecal microbiota transplantations and the role of bacteriophages.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2022.11.012}, pmid = {36414201}, issn = {1469-0691}, abstract = {BACKGROUND: Bacteriophages are a major component of the human gut microbiota. Emerging evidence suggests that gut bacteriophages play important roles in the intricate dynamics with bacteria and their transfer may be associated with the efficacy of fecal microbiota transplantation (FMT).<br><br>OBJECTIVES: To summarize our current knowledge of the changes in gut bacteriophage communities during FMT and their association with FMT outcome.<br><br>SOURCES: PubMed, Web of Science, and Google Scholar were searched for articles on FMT and bacteriophages published between May 2013 and Jan 2022.<br><br>CONTENT: Preclinical and clinical studies have reported associations between gut bacteriophage profiles and FMT. FMT was associated with donor-specific engraftment of bacteriophages, characterized by increased viral diversity and richness and the bacteriophage composition resembled the donor's profile after FMT. Limited studies showed that cure after FMT was more likely when an increased fraction of the recipient enteric virome was occupied by donor-derived taxa including Caudovirales in Clostridioides difficile infection (CDI). Fecal virome transplant (FVT) involving the transfer of the gut virome communities alone may also induce phenotypical and microbiome improvement in various diseases.<br><br>IMPLICATIONS: The accumulating evidence that bacteriophages play roles in FMT efficacy has attracted considerable interest. Better characterization of bacteriophages and understanding of their underlying mechanisms in FMT are warranted.}, }
@article {pmid36414164, year = {2022}, author = {Lee, EH and Lee, SK and Cheon, JH and Koh, H and Lee, JA and Kim, CH and Kim, J and Lee, KH and Lee, SJ and Kim, JH and Ahn, JY and Jeong, SJ and Ku, NS and Yong, D and Yoon, SS and Yeom, JS and Choi, JY}, title = {Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2022.11.007}, pmid = {36414164}, issn = {1532-2939}, abstract = {BACKGROUND: The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonising MDRO.<br><br>AIM: To compare the efficacy of different FMT methods to optimise the success rate of decolonisation in patients with MDRO carriage.<br><br>METHODS: This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube.<br><br>FINDINGS: A total of 57 patients underwent FMT for MDRO decolonisation. The colonoscopy group required the shortest time for decolonisation, whereas the EGD group required the longest (24.9 vs. 190.4 days, p = 0.022). The decolonisation rate in the oral capsule group was comparable to that in the EGD group (84.6% vs. 85.7%, p = 0.730). An important clinical factor associated with decolonisation failure was antibiotic use after FMT (odds ratio = 6.810, p = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT.<br><br>CONCLUSION: Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonisation.}, }
@article {pmid36412458, year = {2022}, author = {Mahmoudi, H and Hossainpour, H}, title = {Application and development of fecal microbiota transplantation in the treatment of gastrointestinal and metabolic diseases: A review.}, journal = {Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association}, volume = {}, number = {}, pages = {}, doi = {10.4103/sjg.sjg_131_22}, pmid = {36412458}, issn = {1998-4049}, abstract = {Fecal microbiota transplantation (FMT) restores a balanced intestinal flora, which helps to cure recurrent Clostridium difficile infections (RCDI). FMT has also been used to treat other gastrointestinal diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation, as well as a variety of non-GI disorders. The purpose of this review is to discuss gut microbiota and FMT treatment of GI and non-GI diseases. An imbalanced gut microbiota is known to predispose one to Clostridium difficile infections (CDI), IBD, and IBS. However, the complex role of the gut microbiota in maintaining health is a newer concept that is being increasingly studied. The microbiome plays a major role in cellular immunity and metabolism and has been implicated in the pathogenesis of non-GI autoimmune diseases, chronic fatigue syndrome, obesity, and even some neuropsychiatric disorders. Many recent studies have reported that viral gastroenteritis can affect intestinal epithelial cells, and SARS-CoV-2 virus has been identified in the stool of infected patients. FMT is a highly effective cure for RCDI, but a better understanding of the gut microbiota in maintaining health and controlled studies of FMT in a variety of conditions are needed before FMT can be accepted and used clinically.}, }
@article {pmid36409919, year = {2022}, author = {Chen, X and Hashimoto, D and Ebata, K and Takahashi, S and Shimizu, Y and Shinozaki, R and Hasegawa, Y and Kikuchi, R and Senjo, H and Yoneda, K and Zhang, Z and Harada, S and Hayase, E and Ara, T and Ohigashi, H and Iwakura, Y and Nakamura, K and Ayabe, T and Teshima, T}, title = {Reactive granulopoiesis depends on T-cell production of IL-17A and neutropenia-associated alteration of gut microbiota.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {48}, pages = {e2211230119}, doi = {10.1073/pnas.2211230119}, pmid = {36409919}, issn = {1091-6490}, mesh = {Mice ; Animals ; Interleukin-17 ; T-Lymphocytes ; *Gastrointestinal Microbiome ; Mice, Knockout ; *Neutropenia ; }, abstract = {Granulopoiesis in the bone marrow adjusts cellular output as demand for neutrophils changes. Reactive granulopoiesis is induced by profound neutropenia, but its mechanism remains to be clarified. We herein explored its mechanisms using mouse models of syngeneic hematopoietic stem cell transplantation (SCT) and 5-fluorouracil-induced neutropenia. After SCT, T cell production of IL-17A was up-regulated. Neutrophil recovery was significantly delayed in IL-17A-deficient or T cell-deficient RAG1[-/-] mice, and adoptive transfer of wild-type (WT) T cells facilitated neutrophil engraftment. Gut decontamination with oral antibiotics suppressed T cell production of IL-17A and impaired neutrophil recovery. Transplantation of fecal microbiota collected from neutropenic, not naive, mice promoted neutrophil recovery in these mice, suggesting that neutropenia-associated microbiota had a potential to stimulate reactive granulopoiesis. Our study uncovered a cross talk between gut microbiota and neutropenia after SCT and chemotherapy.}, }
@article {pmid36408726, year = {2022}, author = {Wang, L and Shao, L and Chen, MY and Wang, L and Yang, P and Tan, FB and Zhang, W and Huang, WH}, title = {Panax notoginseng Alleviates Colitis via the Regulation of Gut Microbiota.}, journal = {The American journal of Chinese medicine}, volume = {}, number = {}, pages = {1-21}, doi = {10.1142/S0192415X23500076}, pmid = {36408726}, issn = {1793-6853}, abstract = {Gut microbiota are significantly associated with the occurrence and development of inflammatory bowel disease (IBD). Panax notoginseng saponins (PNS) could be used for colitis and to modulate gut microbiota. However, the mechanism behind the effects of PNS on anti-colitis that are pertinent to gut microbiota is largely unknown. This study aimed to evaluate the anti-colitis effects of PNS and explore the involved mechanism as it is related to gut microbiota. Results showed that PNS significantly alleviated dextran sulfate sodium (DSS)-induced colitis. Meanwhile, after PNS treatment, the tight junction proteins were enhanced and proinflammatory cytokines, such as TNF-[Formula: see text], IL-6, IL-1[Formula: see text], and IL-17, were decreased. Furthermore, Bacteroides spp. were significantly increased after modeling, while PNS reduced their abundance and significantly increased the amount of Akkermansia spp. in vivo. Importantly, Akkermansia spp. and Bacteroides spp. were correlated with the IBD disease indicators. Moreover, fecal microbiota transplantation (FMT) experiments confirmed that PNS-reshaped gut microbiota significantly alleviated DSS-induced colitis, while A. muciniphila significantly reduced the levels of the LPS-induced cellular inflammatory factors IL-1[Formula: see text] and TNF-[Formula: see text]. In conclusion, PNS alleviated colitis pertinent to the upregulation of Akkermania spp. and downregulation of Bacteroides spp. in the gut.}, }
@article {pmid36407764, year = {2022}, author = {Melamed, E and Palmer, JL and Fonken, C}, title = {Advantages and limitations of experimental autoimmune encephalomyelitis in breaking down the role of the gut microbiome in multiple sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {15}, number = {}, pages = {1019877}, pmid = {36407764}, issn = {1662-5099}, abstract = {Since the first model of experimental autoimmune encephalomyelitis (EAE) was introduced almost a century ago, there has been an ongoing scientific debate about the risks and benefits of using EAE as a model of multiple sclerosis (MS). While there are notable limitations of translating EAE studies directly to human patients, EAE continues to be the most widely used model of MS, and EAE studies have contributed to multiple key breakthroughs in our understanding of MS pathogenesis and discovery of MS therapeutics. In addition, insights from EAE have led to a better understanding of modifiable environmental factors that can influence MS initiation and progression. In this review, we discuss how MS patient and EAE studies compare in our learning about the role of gut microbiome, diet, alcohol, probiotics, antibiotics, and fecal microbiome transplant in neuroinflammation. Ultimately, the combination of rigorous EAE animal studies, novel bioinformatic approaches, use of human cell lines, and implementation of well-powered, age- and sex-matched randomized controlled MS patient trials will be essential for improving MS patient outcomes and developing novel MS therapeutics to prevent and revert MS disease progression.}, }
@article {pmid36406749, year = {2022}, author = {Hashim, HM and Makpol, S}, title = {A review of the preclinical and clinical studies on the role of the gut microbiome in aging and neurodegenerative diseases and its modulation.}, journal = {Frontiers in cellular neuroscience}, volume = {16}, number = {}, pages = {1007166}, pmid = {36406749}, issn = {1662-5102}, abstract = {As the world population ages, the burden of age-related health problems grows, creating a greater demand for new novel interventions for healthy aging. Advancing aging is related to a loss of beneficial mutualistic microbes in the gut microbiota caused by extrinsic and intrinsic factors such as diet, sedentary lifestyle, sleep deprivation, circadian rhythms, and oxidative stress, which emerge as essential elements in controlling and prolonging life expectancy of healthy aging. This condition is known as gut dysbiosis, and it affects normal brain function via the brain-gut microbiota (BGM) axis, which is a bidirectional link between the gastrointestinal tract (GIT) and the central nervous system (CNS) that leads to the emergence of brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Here, we reviewed the role of the gut microbiome in aging and neurodegenerative diseases, as well as provided a comprehensive review of recent findings from preclinical and clinical studies to present an up-to-date overview of recent advances in developing strategies to modulate the intestinal microbiome by probiotic administration, dietary intervention, fecal microbiota transplantation (FMT), and physical activity to address the aging process and prevent neurodegenerative diseases. The findings of this review will provide researchers in the fields of aging and the gut microbiome design innovative studies that leverage results from preclinical and clinical studies to better understand the nuances of aging, gut microbiome, and neurodegenerative diseases.}, }
@article {pmid36406423, year = {2022}, author = {Li, J and Lv, JL and Cao, XY and Zhang, HP and Tan, YJ and Chu, T and Zhao, LL and Liu, Z and Ren, YS}, title = {Gut microbiota dysbiosis as an inflammaging condition that regulates obesity-related retinopathy and nephropathy.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1040846}, pmid = {36406423}, issn = {1664-302X}, abstract = {Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage. Epidemiological data demonstrated that the high morbidity of T2DM occurs as a result of obesity and gradually develops into serious complications. To date, the mechanisms that underlie this observation are still ill-defined. In view of the effect of obesity on the gut microflora, Lepr[db/db] mice underwent antibiotic treatment and microbiota transplants to modify the gut microbiome to investigate whether microbes are involved in the development of diabetic nephropathy (DN) and/or diabetic retinopathy (DR). The mouse feces were collected for bacterial 16S ribosomal RNA gene sequencing. Cytokines including TNF-α, TGF-β1, IFN-γ, IL-1β, IL-6, IL-17A, IL-10, and VEGFA were detected by enzyme-linked immunosorbent assay (ELISA), flow cytometry, real-time PCR and immunofluorescent assay. Eyes and kidney were collected for histopathological assay. Intestinal permeability was also detected using Evans Blue. The results showed that obesity influenced metabolic variables (including fast/fed glucose, insulin, and triglyceride), retinopathy and nephropathy, and the gut microbiota. Obesity mainly reduced the ratio of Bacteroidetes/Firmicutes and influenced relative abundance of Proteobacteria, Actinobacteria, and Spirochetes. Obesity also increased intestinal permeability, metabolic endotoxemia, cytokines, and VEGFA. Microbiota transplants confirm that obesity aggravates retinopathy and nephropathy through the gut microbiota. These findings suggest that obesity exacerbates retinopathy and nephropathy by inducing gut microbiota dysbiosis, which further enhanced intestinal permeability and chronic low-grade inflammation.}, }
@article {pmid36405622, year = {2022}, author = {Samuthpongtorn, C and Kantagowit, P and Pittayanon, R and Patcharatrakul, T and Gonlachanvit, S}, title = {Fecal microbiota transplantation in irritable bowel syndrome: A meta-analysis of randomized controlled trials.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1039284}, pmid = {36405622}, issn = {2296-858X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has been proposed as a potential treatment for irritable bowel syndrome (IBS); however, the consensus regarding its efficacy and safety is limited.<br><br>MATERIALS AND METHODS: We performed a systematic search of the literature using PubMed, EMBASE, Ovid MEDLINE, and Cochrane. Meta-analyses were conducted in relative risk (RR) or standard mean difference (SMD) using 95% confidence intervals (CI). Cochrane risk-of-bias 2 tool (RoB2) was employed to evaluate the study quality.<br><br>RESULT: Of 2,589 potential records, 7 studies with 9 cohorts involving 505 participants were included. Meta-analyses showed no significant difference in the short-term (12 weeks) and long-term (12 months) global improvement of IBS symptoms of FMT vs. placebo (RR 0.63, 95% CI 0.39-1.00 and RR 0.88, 95% CI 0.53-1.45, respectively). There were statistically significant differences of short-term IBS-SSS improvement (SMD -0.58, 95% CI -1.09 to -0.88) and short-term IBS-QoL improvement (SMD 0.67, 95% CI 0.43-0.91). Eight from 9 studies (88.9%) had a low risk of bias. The subgroup analysis revealed the short-term global symptoms improvement in studies with low-risk of bias (RR 0.53, 95% CI 0.35-0.81), studies with well-defined donors (RR 0.31, 95% CI 0.14-0.72), and studies with FMT using colonoscopy (RR 0.66, 95% CI 0.47-0.92). Major FMT adverse events are transient and rapidly self-limiting.<br><br>CONCLUSION: FMT significantly improved IBS-SSS and IBS-QoL in the short-term period in IBS patients. However, global symptom improvement showed no significance. Well-defined donors and appropriate fecal administration routes appear to be important factors for the successful outcomes of FMT in IBS.<br><br>[www.crd.york.ac.uk/prospero], identifier [CRD42021246101].}, }
@article {pmid36405609, year = {2022}, author = {Yadegar, A and Nabavi-Rad, A and Ochoa-Repáraz, J and Ohkusa, T and Wang, YD}, title = {Editorial: Gut microbiota and gastrointestinal disorders.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1079787}, pmid = {36405609}, issn = {2296-858X}, }
@article {pmid36399701, year = {2022}, author = {Ponce, DM and Alousi, AM and Nakamura, R and Slingerland, J and Calafiore, M and Sandhu, KS and Barker, JN and Devlin, SM and Shia, J and Giralt, SA and Perales, MA and Moore, GF and Fatmi, S and Soto, C and Gomes, AL and Giardina, P and Marcello, LT and Yan, X and Tang, T and Dreyer, K and Chen, J and Daley, WL and Peled, JU and van den Brink, MRM and Hanash, A}, title = {A phase 2 study of Interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2021015111}, pmid = {36399701}, issn = {1528-0020}, abstract = {Graft vs. host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, Interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating safety and efficacy of a novel recombinant human Interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD (NCT02406651; https://clinicaltrials.gov/ct2/show/NCT02406651). The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. 19/27 patients (70%; 80% CI: 56-79) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders exhibited a distinct fecal microbiota composition characterized by expansion of commensal anaerobes, which correlated with increased overall microbial α-diversity, suggesting improvement of GVHD-associated dysbiosis. This work demonstrates a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD. This work was supported by funding from Evive Biotech., The Society of Memorial Sloan Kettering Cancer Center, and the National Institutes of Health.}, }
@article {pmid36398264, year = {2022}, author = {Han, J and Zeng, A and Hou, Z and Xu, Y and Zhao, H and Wang, B and Guan, W and An, Y and Liang, S and Ma, Y}, title = {Identification of diagnostic markers related to fecal and plasma metabolism in primary Sjögren's syndrome.}, journal = {American journal of translational research}, volume = {14}, number = {10}, pages = {7378-7390}, pmid = {36398264}, issn = {1943-8141}, abstract = {BACKGROUND: Accurate diagnostic techniques for patients with primary Sjögren's syndrome (pSS) are needed. This study aimed to investigate new biomarkers related to fecal and plasma metabolism from pSS patients.<br><br>METHODS: The feces and plasma of 21 pSS patients and 18 controls admitted to the Second Hospital of Shanxi Medical University were collected for analysis. Metabolites in feces and plasma were quantified using liquid chromatography-mass spectrometry. The metabolic pathway alterations caused by pSS were studied and the expression of metabolites in the intersecting pathway was analyzed in the feces and plasma of pSS patients. Metabolites that showed the same alterations in feces and plasma in pSS patients were considered as diagnostic markers and receiver operating characteristic curves were generated to analyze the sensitivity of these markers in diagnosing pSS.<br><br>RESULTS: There were 114 and 92 upregulated metabolites and 54 and 125 downregulated metabolites in the feces and plasma of pSS patients, respectively. These metabolites were enriched in 8 pathways for feces and 12 pathways for plasma. Arginine biosynthesis, Linoleic acid metabolism, Tyrosine metabolism, Taurine and hypotaurine metabolism were pathways enriched by metabolites in both samples. Twelves metabolites were enriched in the above four pathways, while only 9,10-12,13-Diepoxyoctadecanoate, Tyramine, 9-OxoODE and 2-Hydroxyethanesulfonate showed the same trend. The candidate diagnostic markers were all predictive, with better diagnostic sensitivity in plasma samples.<br><br>CONCLUSIONS: 9,10-12,13-Diepoxyoctadecanoate, Tyramine, 9-OxoODE, 2-Hydroxyethanesulfonate were metabolism-related diagnostic markers for pSS feces and plasma.}, }
@article {pmid36396738, year = {2022}, author = {Ninkov, M and Schmerk, CL and Moradizadeh, M and Parvathy, SN and Figueredo, R and Burton, JP and Silverman, MS and Fernandes, R and Maleki Vareki, S and Haeryfar, SMM}, title = {Improved MAIT cell functions following fecal microbiota transplantation for metastatic renal cell carcinoma.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {}, number = {}, pages = {1-14}, pmid = {36396738}, issn = {1432-0851}, abstract = {Strategies to modify the gut microbiome in cancer patients using fecal microbiota transplantation (FMT) have gained momentum as a therapeutic intervention. However, how FMT impacts innate-like, antimicrobial T lymphocytes is unclear. In this study, we assessed peripheral blood (PB) mucosa-associated invariant T (MAIT) cell frequencies and functions in patients with metastatic renal cell carcinoma (mRCC) before and seven days after they received FMT as part of a clinical trial. We found comparable MAIT cell frequencies in healthy controls and mRCC patients. In contrast, γδ T cells exhibited a numerical decline in mRCC, which was partially reversed by FMT. We also found a significant increase in the PB CD4[+] MAIT cell compartment of mRCC patients with or without FMT. Paired sample analyses revealed CD69 upregulation on MAIT cells accompanied by decreased PD-1 levels post-FMT. These changes were unique to MAIT cells as non-MAIT T lymphocytes showed either no trend or a trend in the opposite direction. Importantly, FMT did not render MAIT cells exhausted as also judged by their stable expression of TIM-3, LAG-3, BTLA, CTLA-4, TIGIT and VISTA. These findings were corroborated in functional assays in which MAIT cells were stimulated with MR1 ligands or with a combination of IL-12 and IL-18 to produce inflammatory cytokines and granzyme B. Indeed, when stimulated ex vivo with IL-12 and IL-18, MAIT cells mounted a more rigorous TNF-α response post-FMT. In conclusion, FMT improves MAIT cell functions, which should serve patients well in subsequent microbial challenges in the face of cancer-elicited immunosuppression. Trial Registration: https://clinicaltrials.gov/ Identifier: NCT04163289 (registration date: November 14, 2019).}, }
@article {pmid36395738, year = {2022}, author = {Zhang, W and Huang, J and Gao, F and You, Q and Ding, L and Gong, J and Zhang, M and Ma, R and Zheng, S and Sun, X and Zhang, Y}, title = {Lactobacillus reuteri normalizes altered fear memory in male Cntnap4 knockout mice.}, journal = {EBioMedicine}, volume = {86}, number = {}, pages = {104323}, pmid = {36395738}, issn = {2352-3964}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disease, characterized by deficits in social communication, restricted and repetitive behaviours, and impaired fear memory processing. Severe gastrointestinal dysfunction and altered gut microbiome have been reported in ASD patients and animal models. Contactin associated protein-like 4 (CNTNAP4) has been suggested to be a novel risk gene, though its role in ASD remains unelucidated.<br><br>METHODS: Cntnap4[-/-] mice were generated to explore its role in ASD-related behavioural abnormalities. Electrophysiological recording was employed to examine GABAergic transmission in the basolateral amygdala (BLA) and prefrontal cortex. RNA-sequencing was performed to assess underlying mechanisms. 16S rDNA analysis was performed to explore changes in faecal microbial composition. Male Cntnap4[-/-] mice were fed with Lactobacillus reuteri (L.&#xa0;reuteri) or faecal microbiota to evaluate the effects of microbiota supplementation on the impaired fear conditioning mediated by Cntnap4 deficiency.<br><br>FINDINGS: Male Cntnap4[-/-] mice manifested deficiency in social behaviours and tone-cue fear conditioning. Notably, reduced GABAergic transmission and GABA receptor expression were found in the BLA but not the prefrontal cortex. In addition, gut Lactobacillus were less abundant in male Cntnap4[-/-] mice, and L.&#xa0;reuteri treatment or faecal microbiota transplantation rescued abnormal tone-cued fear memory and improved local GABAergic transmission in the BLA of male Cntnap4[-/-] mice.<br><br>INTERPRETATION: Cntnap4 shapes GABAergic transmission of amygdala and fear conditioning, and microbial intervention represents a promising therapy in ASD intervention.<br><br>FUNDING: National Natural Science Foundation of China, Science and Technology Planning Project of Guangzhou, Guangzhou Medical University, and China Postdoctoral Science Foundation.}, }
@article {pmid36394926, year = {2022}, author = {Fedotova, MM and Prokopyeva, VD and Dochkin, VA and Boguta, VD and Fedorova, OS}, title = {[Methods of gut microbiota correction for treatment and prevention of food allergy: a review of current research].}, journal = {Voprosy pitaniia}, volume = {91}, number = {5}, pages = {16-28}, doi = {10.33029/0042-8833-2022-91-5-16-28}, pmid = {36394926}, issn = {0042-8833}, mesh = {Humans ; Child ; *Gastrointestinal Microbiome ; *Food Hypersensitivity/prevention &amp; control ; Bifidobacterium ; Intestinal Mucosa ; Lactobacillus ; }, abstract = {Food allergy (FA) is an actual problem in pediatric practice. The gut microbiota plays a crucial role in food sensitization development, since the maturation of immune system occurs under the influence of intestinal microorganisms. Immunoregulatory activity of gut microbiota is associated with the increase of IgA production and promotion of the barrier function of intestinal epithelium. Gut microbiota influence the activity of T-regulatory cells, as well. Violation of gut biocenosis, which occurs under the influence of various factors (artificial feeding, past diseases, the use of antibiotics, etc.), can lead to a shift in the balance of the immune system towards the increase of Th2-profile cytokines and the subsequent formation of hypersensitivity to food allergens. In this regard, the correction of the gut microbiome is a promising method of FA control, due to the ability of intestinal bacteria influence the production of T-regulatory cells and thus suppress allergy immune response. The aim of the review is to analyze experimental and clinical studies exploring effectiveness of methods modifying intestinal microbiota in order to treat and prevent FA. Material and methods. The analysis of the literature in eLIBRARY, MedLine and PubMed databases was carried out. Results. The analysis revealed the lack of rigorous evidence that pre-, pro- and synbiotics significantly increase the effectiveness of standard therapy of FA. However, the use of bifidobacteria, lactobacilli, lactic acid bacteria, in combination with the basic therapy of FA has general positive effect on the clinical outcome, especially in case of gastrointestinal symptoms. Also, the results of some studies indicate the effectiveness of synbiotics (Bifidobacterium breve M-16V, Lactobacillus rhamnosus GG in combination with oligosaccharides) for the prevention of FA in patients at risk of developing allergic diseases in the long-term period. Conclusion. At present, fecal microbiota transplantation is promising method for FA treatment. Polysaccharides fermented by the microflora, are also actively studied. Experimental studies and clinical trials are required to obtain substantiated conclusions about feasibility of these methods for treatment and prevention of FA.}, }
@article {pmid36389774, year = {2022}, author = {Fujimoto, K and Uematsu, S}, title = {Phage therapy for Clostridioides difficile infection.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1057892}, pmid = {36389774}, issn = {1664-3224}, mesh = {Humans ; *Clostridioides difficile ; *Phage Therapy ; *Clostridium Infections/therapy/microbiology ; Fecal Microbiota Transplantation ; Diarrhea/therapy ; }, abstract = {Clostridioides difficile is endemic in the intestinal tract of healthy people. However, it is responsible for many healthcare-associated infections, such as nosocomial diarrhea following antibiotic treatment. Importantly, there have been cases of unsuccessful treatment and relapse related to the emergence of highly virulent strains of C. difficile and resistance to antimicrobial agents. Fecal microbiota transplantation (FMT) is considered an effective therapy for recurrent C. difficile infection. However, its safety is of concern because deaths caused by antibiotic-resistant bacterial infections after FMT were reported. Therefore, the development of effective C. difficile-specific treatments is urgently needed. In this review, we summarize the importance of phage therapy against C. difficile, and describe a novel next-generation phage therapy developed using metagenomic data.}, }
@article {pmid36389768, year = {2022}, author = {Zhou, G and Zhang, N and Meng, K and Pan, F}, title = {Interaction between gut microbiota and immune checkpoint inhibitor-related colitis.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1001623}, pmid = {36389768}, issn = {1664-3224}, mesh = {Humans ; Immune Checkpoint Inhibitors/adverse effects ; *Gastrointestinal Microbiome ; *Colitis/chemically induced/therapy ; Fecal Microbiota Transplantation ; *Neoplasms ; }, abstract = {Immune checkpoint inhibitors (ICIs) have become a promising therapeutic strategy for malignant tumors, improving patient prognosis, along with a spectrum of immune-related adverse events (irAEs), including gastrointestinal toxicity, ICI-related colitis (IRC), and diarrhea. The gut microbiota has been suggested as an important regulator in the pathogenesis of IRC, and microbiota modulations like probiotics and fecal microbiota transplantation have been explored to treat the disease. This review discusses the interaction between the gut microbiota and IRC, focusing on the potential pathogenic mechanisms and promising interventions.}, }
@article {pmid36389714, year = {2022}, author = {Zou, X and Wang, L and Xiao, L and Wang, S and Zhang, L}, title = {Gut microbes in cerebrovascular diseases: Gut flora imbalance, potential impact mechanisms and promising treatment strategies.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {975921}, pmid = {36389714}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Cerebrovascular Disorders/therapy ; Brain/metabolism ; *Microbiota ; Bacteria ; }, abstract = {The high morbidity, mortality, and disability rates associated with cerebrovascular disease (CeVD) pose a severe danger to human health. Gut bacteria significantly affect the onset, progression, and prognosis of CeVD. Gut microbes play a critical role in gut-brain interactions, and the gut-brain axis is essential for communication in CeVD. The reflection of changes in the gut and brain caused by gut bacteria makes it possible to investigate early warning biomarkers and potential treatment targets. We primarily discussed the following three levels of brain-gut interactions in a systematic review of the connections between gut microbiota and several cerebrovascular conditions, including ischemic stroke, intracerebral hemorrhage, intracranial aneurysm, cerebral small vessel disease, and cerebral cavernous hemangioma. First, we studied the gut microbes in conjunction with CeVD and examined alterations in the core microbiota. This enabled us to identify the focus of gut microbes and determine the focus for CeVD prevention and treatment. Second, we discussed the pathological mechanisms underlying the involvement of gut microbes in CeVD occurrence and development, including immune-mediated inflammatory responses, variations in intestinal barrier function, and reciprocal effects of microbial metabolites. Finally, based on the aforementioned proven mechanisms, we assessed the effectiveness and potential applications of the current therapies, such as dietary intervention, fecal bacterial transplantation, traditional Chinese medicine, and antibiotic therapy.}, }
@article {pmid36389141, year = {2022}, author = {Dong, W and Zheng, J and Huang, Y and Tan, H and Yang, S and Zhang, Z and Liang, X and Liu, H and Zeng, G and Xu, H and Jiang, X and Zhong, W}, title = {Sodium butyrate treatment and fecal microbiota transplantation provide relief from ulcerative colitis-induced prostate enlargement.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1037279}, pmid = {36389141}, issn = {2235-2988}, mesh = {Humans ; Male ; Mice ; Animals ; Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy ; Butyric Acid ; *Prostatic Hyperplasia/therapy ; Prostate ; *Gastrointestinal Microbiome ; }, abstract = {The ability to regulate the gut environment has resulted in remarkable great breakthroughs in the treatment of several diseases. Several studies have found that the regulation of the gut environment might provide relief from the symptoms of benign prostatic hyperplasia. However, the correlation between the gut microenvironment and the colon and prostate glands is still unknown. We found that ulcerative colitis (UC) induced an increase in prostate volumes that could be reversed by sodium butyrate (NaB) and fecal microbiota transplantation (FMT). The mechanism by which UC induced changes in the prostate gland was examined via RNA-Seq. The results show that the expression level of GPER was significantly lower in the prostate gland of UC mices than in normal mices. The expression of GPER could be increased via treatment with NaB or FMT. We found that prostate tissues exhibited higher butryic acid levels after they were treated with NaB or FMT. In experiments conducted in vitro, NaB or the fecal filtrate (FF) from healthy mice up-regulated of the expression of GPER, inhibited cell growth, and induced apoptosis in BPH-1 cells. These changes could be alleviated by treatment with the G15 or in GPER-silenced cells.}, }
@article {pmid36387852, year = {2022}, author = {Acharya, KD and Friedline, RH and Ward, DV and Graham, ME and Tauer, L and Zheng, D and Hu, X and de Vos, WM and McCormick, BA and Kim, JK and Tetel, MJ}, title = {Differential effects of Akkermansia-enriched fecal microbiota transplant on energy balance in female mice on high-fat diet.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1010806}, pmid = {36387852}, issn = {1664-2392}, support = {U24 DK076169/DK/NIDDK NIH HHS/United States ; R01 DK061935/DK/NIDDK NIH HHS/United States ; U2C DK093000/DK/NIDDK NIH HHS/United States ; R01 DK109677/DK/NIDDK NIH HHS/United States ; R01 DK125407/DK/NIDDK NIH HHS/United States ; }, mesh = {Female ; Mice ; Male ; Animals ; *Diet, High-Fat/adverse effects ; Akkermansia ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Obesity/etiology/therapy/metabolism ; Weight Gain ; *Hyperglycemia ; }, abstract = {Estrogens protect against weight gain and metabolic disruption in women and female rodents. Aberrations in the gut microbiota composition are linked to obesity and metabolic disorders. Furthermore, estrogen-mediated protection against diet-induced metabolic disruption is associated with modifications in gut microbiota. In this study, we tested if estradiol (E2)-mediated protection against obesity and metabolic disorders in female mice is dependent on gut microbiota. Specifically, we tested if fecal microbiota transplantation (FMT) from E2-treated lean female mice, supplemented with or without Akkermansia muciniphila, prevented high fat diet (HFD)-induced body weight gain, fat mass gain, and hyperglycemia in female recipients. FMT from, and cohousing with, E2-treated lean donors was not sufficient to transfer the metabolic benefits to the E2-deficient female recipients. Moreover, FMT from lean donors supplemented with A. muciniphila exacerbated HFD-induced hyperglycemia in E2-deficient recipients, suggesting its detrimental effect on the metabolic health of E2-deficient female rodents fed a HFD. Given that A. muciniphila attenuates HFD-induced metabolic insults in males, the present findings suggest a sex difference in the impact of this microbe on metabolic health.}, }
@article {pmid36386919, year = {2022}, author = {Liu, TH and Zhao, L and Zhang, CY and Li, XY and Wu, TL and Dai, YY and Sheng, YY and Ren, YL and Xue, YZ}, title = {Gut microbial evidence chain in high-salt diet exacerbates intestinal aging process.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {1046833}, pmid = {36386919}, issn = {2296-861X}, abstract = {Although excessive salt consumption appears to hasten intestinal aging and increases susceptibility to cardiovascular disease, the molecular mechanism is unknown. In this study, mutual validation of high salt (HS) and aging fecal microbiota transplantation (FMT) in C56BL/6 mice was used to clarify the molecular mechanism by which excessive salt consumption causes intestinal aging. Firstly, we observed HS causes vascular endothelial damage and can accelerate intestinal aging associated with decreased colon and serum expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and increased malondialdehyde (MDA); after transplantation with HS fecal microbiota in mice, vascular endothelial damage and intestinal aging can also occur. Secondly, we also found intestinal aging and vascular endothelial damage in older mice aged 14 months; and after transplantation of the older mice fecal microbiota, the same effect was observed in mice aged 6-8 weeks. Meanwhile, HS and aging significantly changed gut microbial diversity and composition, which was transferable by FMT. Eventually, based on the core genera both in HS and the aging gut microbiota network, a machine learning model was constructed which could predict HS susceptibility to intestinal aging. Further investigation revealed that the process of HS-related intestinal aging was highly linked to the signal transduction mediated by various bacteria. In conclusion, the present study provides an experimental basis of potential microbial evidence in the process of HS related intestinal aging. Even, avoiding excessive salt consumption and actively intervening in gut microbiota alteration may assist to delay the aging state that drives HS-related intestinal aging in clinical practice.}, }
@article {pmid36384941, year = {2022}, author = {Lane, VA and Lall, A and Jaffray, B}, title = {Single institution experience of cloacal malformation.}, journal = {Journal of pediatric surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jpedsurg.2022.10.035}, pmid = {36384941}, issn = {1531-5037}, abstract = {INTRODUCTION: The aim of this study is to report on the outcomes of patients born with cloacal malformation, managed at a single institution more than the last 28 years. The focus of this study is the long term renal and colorectal outcomes.<br><br>METHODS: Patients were identified from the departmental database from 1994 to 2021. The medical records and operative notes were retrospectively reviewed.<br><br>RESULTS: Twenty-one patients fulfilled the inclusion criteria. Eleven long common channel (LCC) and ten short common channel (SCC) cloacae patients were identified. Median age at the time of primary reconstruction was 11 months in both groups. In the LCC group, seven (63.6%) patients underwent a Total Urogenital Mobilisation (TUM), and 4 (36.4%) required a vaginal replacement. 6/11 (54.5%) of patients required drainage of a hydrocolpos. In the SCC group, four patients required a TUM, two patients underwent mobilisation of the rectum and vagina alone, and three underwent rectal mobilisation alone. Two patients have required renal transplant for congenital renal dysplasia, and two have developed chronic renal failure associated with the sequalae of vesicoureteric reflux. Eleven (52.3%) of the patients manage their bowels with an antegrade continent enema (ACE), and two of the LCC cloaca are defunctioned with a colostomy. Clean intermittent catheterisation is performed by 12 (57%) of the patients, either per urethra or via a Mitrofanoff channel.<br><br>CONCLUSION: The urinary and faecal continence are the main challenges in the management of cloaca patients. Many require surgical intervention to achieve social continence.<br><br>LEVEL OF EVIDENCE: Level IV.}, }
@article {pmid36383683, year = {2022}, author = {Schwabkey, ZI and Wiesnoski, DH and Chang, CC and Tsai, WB and Pham, D and Ahmed, SS and Hayase, T and Ortega Turrubiates, MR and El-Himri, RK and Sanchez, CA and Hayase, E and Frenk Oquendo, AC and Miyama, T and Halsey, TM and Heckel, BE and Brown, AN and Jin, Y and Raybaud, M and Prasad, R and Flores, I and McDaniel, L and Chapa, V and Lorenzi, PL and Warmoes, MO and Tan, L and Swennes, AG and Fowler, S and Conner, M and McHugh, K and Graf, T and Jensen, VB and Peterson, CB and Do, KA and Zhang, L and Shi, Y and Wang, Y and Galloway-Pena, JR and Okhuysen, PC and Daniel-MacDougall, CR and Shono, Y and Burgos da Silva, M and Peled, JU and van den Brink, MRM and Ajami, N and Wargo, JA and Reddy, P and Valdivia, RH and Davey, L and Rondon, G and Srour, SA and Mehta, RS and Alousi, AM and Shpall, EJ and Champlin, RE and Shelburne, SA and Molldrem, JJ and Jamal, MA and Karmouch, JL and Jenq, RR}, title = {Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.}, journal = {Science translational medicine}, volume = {14}, number = {671}, pages = {eabo3445}, doi = {10.1126/scitranslmed.abo3445}, pmid = {36383683}, issn = {1946-6242}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Propionates ; *Hematopoietic Stem Cell Transplantation ; Verrucomicrobia ; Mucus/metabolism ; Mucins/metabolism ; Diet ; *Neutropenia/metabolism ; *Neoplasms/metabolism ; }, abstract = {Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant (n = 119), the fecal microbiome was characterized at onset of severe neutropenia. A total of 63 patients (53%) developed a subsequent fever, and their fecal microbiome displayed increased relative abundances of Akkermansia muciniphila, a species of mucin-degrading bacteria (P = 0.006, corrected for multiple comparisons). Two therapies that induce neutropenia, irradiation and melphalan, similarly expanded A. muciniphila and additionally thinned the colonic mucus layer in mice. Caloric restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Antibiotic treatment to eradicate A. muciniphila before caloric restriction preserved colonic mucus, whereas A. muciniphila reintroduction restored mucus thinning. Caloric restriction of unirradiated mice raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila in vitro with propionate reduced utilization of mucin as well as of fucose. Treating irradiated mice with an antibiotic targeting A. muciniphila or propionate preserved the mucus layer, suppressed translocation of flagellin, reduced inflammatory cytokines in the colon, and improved thermoregulation. These results suggest that diet, metabolites, and colonic mucus link the microbiome to neutropenic fever and may guide future microbiome-based preventive strategies.}, }
@article {pmid36382711, year = {2022}, author = {Tian, D and Xu, W and Pan, W and Zheng, B and Yang, W and Jia, W and Liu, Y and Garstka, MA and Gao, Y and Yu, H}, title = {Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA-induced MEK1/2 signaling pathway.}, journal = {The EMBO journal}, volume = {}, number = {}, pages = {e111139}, doi = {10.15252/embj.2022111139}, pmid = {36382711}, issn = {1460-2075}, abstract = {Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest-derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation. We found that the hypoganglionosis intestinal microenvironment negatively influenced the ENCC functional phenotype in vitro and in vivo. Combining 16S rDNA sequencing and targeted mass spectrometry revealed microbial dysbiosis and reduced short-chain fatty acid (SCFA) production in the hypoganglionic gut. FMT increased the abundance of Bacteroides and Clostridium, SCFA production, and improved outcomes following ENCC transplantation. SCFAs alone stimulated ENCC proliferation, migration, and supported ENCC transplantation. Transcriptome-wide mRNA sequencing identified MAPK signaling as the top differentially regulated pathway in response to SCFA exposure, and inhibition of MEK1/2 signaling abrogated the SCFA-mediated effects on ENCC. This study demonstrates that FMT improves cell therapy for hypoganglionosis via short-chain fatty acid metabolism-induced MEK1/2 signaling.}, }
@article {pmid36382190, year = {2022}, author = {Fang, X and Miao, R and Wei, J and Wu, H and Tian, J}, title = {Advances in multi-omics study of biomarkers of glycolipid metabolism disorder.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {5935-5951}, pmid = {36382190}, issn = {2001-0370}, abstract = {Glycolipid metabolism disorder are major threats to human health and life. Genetic, environmental, psychological, cellular, and molecular factors contribute to their pathogenesis. Several studies demonstrated that neuroendocrine axis dysfunction, insulin resistance, oxidative stress, chronic inflammatory response, and gut microbiota dysbiosis are core pathological links associated with it. However, the underlying molecular mechanisms and therapeutic targets of glycolipid metabolism disorder remain to be elucidated. Progress in high-throughput technologies has helped clarify the pathophysiology of glycolipid metabolism disorder. In the present review, we explored the ways and means by which genomics, transcriptomics, proteomics, metabolomics, and gut microbiomics could help identify novel candidate biomarkers for the clinical management of glycolipid metabolism disorder. We also discuss the limitations and recommended future research directions of multi-omics studies on these diseases.}, }
@article {pmid36381829, year = {2022}, author = {Nassar, ST and Tasha, T and Desai, A and Bajgain, A and Ali, A and Dutta, C and Pasha, K and Paul, S and Abbas, MS and Venugopal, S}, title = {Fecal Microbiota Transplantation Role in the Treatment of Alzheimer's Disease: A Systematic Review.}, journal = {Cureus}, volume = {14}, number = {10}, pages = {e29968}, pmid = {36381829}, issn = {2168-8184}, abstract = {Alzheimer's, a neurodegenerative disease that starts slowly and worsens progressively, is the leading cause of dementia worldwide. Recent studies have linked the brain with the gut and its microbiota through the microbiota-gut-brain axis, opening the door for gut-modifying agents (e.g., prebiotics and probiotics) to influence our brain's cognitive function. This review aims to identify and summarize the effects of fecal microbiota transplantation (FMT) as a gut-microbiota-modifying agent on the progressive symptoms of Alzheimer's disease (AD). This systematic review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A systematic search was done using Google Scholar, PubMed, PubMed Central, and ScienceDirect databases in June 2022. The predefined criteria upon which the studies were selected are English language, past 10 years of narrative reviews, observational studies, case reports, and animal studies involving Alzheimer's subjects as no previous meta-analysis or systematic reviews were done on this subject. Later, a quality assessment was done using the available assessment tool based on each study type. The initial search generated 4,302 studies, yielding 13 studies to be included in the final selection: 1 cohort, 2 case reports, 2 animal studies, and 8 narrative reviews. Our results showed that FMT positively affected AD subjects (whether mice or humans). In humans, the FMT effect was measured by the Mini-Mental State Examination (MMSE), showing improvement in Alzheimer's symptoms of mood, memory, and cognition. However, randomized and nonrandomized clinical trials are essential for more conclusive results.}, }
@article {pmid36380385, year = {2022}, author = {Yan, J and Pan, Y and Shao, W and Wang, C and Wang, R and He, Y and Zhang, M and Wang, Y and Li, T and Wang, Z and Liu, W and Wang, Z and Sun, X and Dong, S}, title = {Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {195}, pmid = {36380385}, issn = {2049-2618}, mesh = {Rats ; Animals ; *Gastrointestinal Microbiome/physiology ; Propionates ; Fatty Acids, Volatile ; Verrucomicrobia ; *Vascular Calcification/drug therapy ; }, abstract = {BACKGROUND: Vascular calcification is a major cause of the high morbidity and mortality of cardiovascular diseases and is closely associated with the intestinal microbiota. Short-chain fatty acids (SCFAs) are derived from the intestinal microbiota and can also regulate intestinal microbiota homeostasis. However, it remains unclear whether exogenous supplementation with propionate, a SCFA, can ameliorate vascular calcification by regulating the intestinal microbiota. This study was conducted to explore the roles of propionate and the intestinal microbiota in the process of vascular calcification.<br><br>METHODS: In total, 92 patients were enrolled consecutively as the observational cohort to analyse the relationship between SCFAs and vascular calcification in both blood and faecal samples. A rat model of vascular calcification was induced by vitamin D3 and nicotine (VDN) to validate the effect of propionate. Differences in the intestinal microbiota were analysed by 16S ribosomal RNA gene sequencing. Faecal microbiota transplantation and Akkermansia muciniphila transplantation experiments were performed to evaluate the functions of the intestinal microbiota.<br><br>RESULTS: The results of the observational cohort study revealed that the levels of SCFAs (particularly propionate) in both blood and faecal samples independently correlated negatively with calcification scores (P < 0.01). To verify the activities of propionate, it was provided to VDN-treated rats, and oral or rectal propionate delivery reshaped the intestinal microbiota, resulted in elevated SCFA production, improved intestinal barrier function and alleviated inflammation, ultimately ameliorating vascular calcification. Furthermore, we demonstrated that transplantation of the propionate-modulated intestinal microbiota induced beneficial outcomes similar to those with oral or rectal propionate administration. Interestingly, linear discriminant analysis (LDA) effect size (LEfSe) revealed that oral or rectal propionate administration and propionate-modulated intestinal microbiota transplantation both enriched primarily Akkermansia. Subsequently, we demonstrated that Akkermansia supplementation could ameliorate VDN-induced vascular calcification in rats.<br><br>CONCLUSIONS: Propionate can significantly ameliorate vascular calcification in VDN-treated rats, and this effect is mediated by intestinal microbiota remodelling. The findings in our study indicate that the intestinal tract-vessel axis is a promising target for alleviating vascular calcification. Video Abstract.}, }
@article {pmid36380056, year = {2022}, author = {Zhang, C and Shi, Y and Burch, M and Olthoff, B and Ericsson, AC and Franklin, CL}, title = {Transfer efficiency and impact on disease phenotype of differing methods of gut microbiota transfer.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {19621}, pmid = {36380056}, issn = {2045-2322}, support = {U42 OD010918/NH/NIH HHS/United States ; U42 OD010918/NH/NIH HHS/United States ; U42 OD010918/NH/NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/genetics ; Fecal Microbiota Transplantation/methods ; *Colitis/chemically induced/genetics ; Phenotype ; *Microbiota ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {To test causal relationships between complex gut microbiota (GM) and host outcomes, researchers frequently transfer GM between donor and recipient mice via embryo transfer (ET) rederivation, cross-fostering (CF), and co-housing. In this study, we assess the influence of the transfer method and the differences in baseline donor and recipient microbiota richness, on transfer efficiency. Additionally, recipient mice were subjected to DSS-induced chronic colitis to determine whether disease severity was affected by GM transfer efficiency or features within the GM. We found that the recipient's genetic background, the baseline richness of donor and recipient GM, and the transfer method all influenced the GM transfer efficiency. Recipient genetic background and GM both had significant effects on DSS colitis severity and, unexpectedly, the transfer method was strongly associated with differential disease severity regardless of the other factors.}, }
@article {pmid36380005, year = {2022}, author = {Lordick, F and Hacker, U and Hoffmeister, A and Bläker, H and Gockel, I}, title = {[What is confirmed in the treatment of colon cancer?].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {12}, pages = {1250-1256}, pmid = {36380005}, issn = {2731-7099}, mesh = {Male ; Female ; Humans ; *Colorectal Neoplasms/diagnosis ; Colonoscopy ; Occult Blood ; *Colonic Neoplasms/diagnosis ; *Adenoma/diagnosis ; }, abstract = {Colorectal cancer is the second most common cancer diagnosed in Germany and is the third most frequent cause of cancer-related death in both males and females. The majority of colorectal cancers occur via the adenoma-carcinoma sequence of origin. This means that colorectal cancers can be endoscopically detected in premalignant stages and can be curatively treated within the framework of early detection. Screening colonoscopy and, to a lesser extent, fecal occult blood testing, have led to a reduction in the colon cancer-related incidence and mortality. The acceptance and the use of screening colonoscopy should therefore be developed further. Treatment strategies for colorectal cancer are based on TNM staging, supplemented by anatomical and histopathological risk features as well as individual patient characteristics and treatment preferences. The molecular tumor profile is increasingly used to complement decision-making in the surgical, adjuvant and palliative treatment of colorectal cancer. Colon and rectal cancer have many similarities; however, they differ in the preoperative, surgical and adjuvant treatment strategies. This article focuses on colon cancer.}, }
@article {pmid36378195, year = {2022}, author = {Liu, X and Zhang, Y and Li, W and Zhang, B and Yin, J and Liuqi, S and Wang, J and Peng, B and Wang, S}, title = {Fucoidan Ameliorated Dextran Sulfate Sodium-Induced Ulcerative Colitis by Modulating Gut Microbiota and Bile Acid Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {47}, pages = {14864-14876}, doi = {10.1021/acs.jafc.2c06417}, pmid = {36378195}, issn = {1520-5118}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Dextran Sulfate/adverse effects ; *Colitis, Ulcerative/chemically induced/drug therapy ; Disease Models, Animal ; *Colitis/chemically induced/drug therapy/metabolism ; Colon/metabolism ; Inflammation/pathology ; Ursodeoxycholic Acid ; Mice, Inbred C57BL ; }, abstract = {Gut dysbiosis and bile acid (BA) metabolism disturbance are involved in the pathogenesis of ulcerative colitis. This study aimed to investigate the effect of fucoidan on BA metabolism and gut microbiota in dextran sulfate sodium-induced colitis mice. Our results showed that fucoidan effectively suppressed colonic inflammation and repaired the gut barrier. In addition, fucoidan increased the relative abundance of the Lachnospiraceae family, such as Turicibacter, Muribaculum, Parasutterella, and Colidextribacter, followed by an increase in short-chain fatty acids, especially in butyrate. Moreover, fucoidan modulated bile acid metabolism by elevating cholic acid, ursodeoxycholic acid, deoxycholic acid, and lithocholic acid and decreasing β-muricholic acid, which led to activation of FXR and TGR5 and further enhanced the gut barrier and suppressed colonic inflammation. Our results revealed that the effect of fucoidan alleviating colitis was largely mediated by gut microbiota, which was confirmed by the fecal transplantation experiment. Collectively, these findings provided the basis for fucoidan as a potential functional food for colitis.}, }
@article {pmid36376894, year = {2022}, author = {Zhu, H and Li, G and Liu, J and Xu, X and Zhang, Z}, title = {Gut microbiota is associated with the effect of photoperiod on seasonal breeding in male Brandt's voles (Lasiopodomys brandtii).}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {194}, pmid = {36376894}, issn = {2049-2618}, mesh = {Animals ; Humans ; Male ; Photoperiod ; *Gastrointestinal Microbiome/genetics ; *Melatonin/metabolism ; Seasons ; Arvicolinae/physiology ; }, abstract = {BACKGROUND: Seasonal breeding in mammals has been widely recognized to be regulated by photoperiod, but the association of gut microbiota with photoperiodic regulation of seasonal breeding has never been investigated.<br><br>RESULTS: In this study, we investigated the association of gut microbiota with photoperiod-induced reproduction in male Brandt's voles (Lasiopodomys brandtii) through a long-day and short-day photoperiod manipulation experiment and fecal microbiota transplantation (FMT) experiment. We found photoperiod significantly altered reproductive hormone and gene expression levels, and gut microbiota of voles. Specific gut microbes were significantly associated with the reproductive hormones and genes of voles during photoperiod acclimation. Transplantation of gut microbes into recipient voles induced similar changes in three hormones (melatonin, follicle-stimulating hormone, and luteinizing hormone) and three genes (hypothalamic Kiss-1, testicular Dio3, and Dio2/Dio3 ratio) to those in long-day and short-day photoperiod donor voles and altered circadian rhythm peaks of recipient voles.<br><br>CONCLUSIONS: Our study firstly revealed the association of gut microbiota with photoperiodic regulation of seasonal breeding through the HPG axis, melatonin, and Kisspeptin/GPR54 system. Our results may have significant implications for pest control, livestock animal breeding, and human health management. Video Abstract.}, }
@article {pmid36376576, year = {2022}, author = {Piovezani Ramos, G and Camilleri, M}, title = {Current and Future Therapeutic Options for Irritable Bowel Syndrome with Diarrhea and Functional Diarrhea.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {36376576}, issn = {1573-2568}, abstract = {Irritable bowel syndrome with diarrhea and functional diarrhea are disorders of gut-brain interaction presenting with chronic diarrhea; they have significant impact on quality of life. The two conditions may exist as a continuum and their treatment may overlap. Response to first-line therapy with antispasmodics and anti-diarrheal agents is variable, leaving several patients with suboptimal symptom control and need for alternative therapeutic options. Our aim was to discuss current pharmacologic options and explore alternative therapeutic approaches and future perspectives for symptom management in irritable bowel syndrome with diarrhea and functional diarrhea. We conducted a search of PubMed, Cochrane, clinicaltrial.gov, major meeting abstracts for publications on current, alternative, and emerging drugs for irritable bowel syndrome with diarrhea and functional diarrhea. Currently approved therapeutic options for patients with first-line refractory irritable bowel syndrome with diarrhea and functional diarrhea include serotonin-3 receptor antagonists, eluxadoline and rifaximin. Despite their proven efficacy, cost and availability worldwide impact their utilization. One-third of patients with disorders of gut-brain interaction with diarrhea have bile acid diarrhea and may benefit from drugs targeting bile acid synthesis and excretion. Further understanding of underlying pathophysiology of irritable bowel syndrome with diarrhea and functional diarrhea related to bile acid metabolism, gastrointestinal transit, and microbiome has led to evaluation of novel therapeutic approaches, including fecal microbiota transplantation and enterobacterial "crapsules". These opportunities to treat disorders of gut-brain interaction with diarrhea should be followed with formal studies utilizing large samples of well-characterized patients at baseline and validated response outcomes as endpoints for regulatory approval.}, }
@article {pmid36372864, year = {2022}, author = {Weingarden, AR and Treiger, O and Ulsh, L and Limketkai, B and Goldenberg, D and Okafor, P and Sonu, I and Stollman, N and Neshatian, L}, title = {Delivery of Fecal Material to Terminal Ileum Is Associated with Long-Term Success of Fecal Microbiota Transplantation.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {36372864}, issn = {1573-2568}, support = {T32 DK007056/DK/NIDDK NIH HHS/United States ; T32DK007056-46/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (CDI). However, 10-20% of patients still fail to recover following FMT. There is a need to understand why these failures occur and if there are modifiable factors that can be addressed by clinicians performing FMT.<br><br>AIMS: We sought to identify factors related to the FMT procedure itself which could impact FMT outcomes. We also aimed to identify patient demographics which might be associated with FMT outcomes and whether any factors were associated with early FMT failure compared to late CDI recurrence.<br><br>METHODS: We performed a retrospective multicenter cohort analysis of FMT procedures between October 2005 and November 2020. We collected data on patient demographics, details of the FMT procedure, and procedure outcomes. Using univariate and multivariate regression, we evaluated whether these factors were associated with long-term FMT success, early FMT failure (less than 60&#xa0;days following procedure), or late CDI recurrence (more than 60&#xa0;days following procedure).<br><br>RESULTS: Long-term success of FMT was strongly correlated with any delivery of stool to the terminal ileum (Odds Ratio [OR] 4.83, 95% confidence interval [CI] 1.359-17.167) and underlying neurologic disease (OR 8.012, 95% CI 1.041-61.684). Lower bowel prep quality was significantly associated with both early FMT failure (p&#x2009;=&#x2009;0.034) and late CDI recurrence (p&#x2009;=&#x2009;0.050).<br><br>CONCLUSIONS: Delivery of stool to the terminal ileum is significantly associated with long-term success following FMT. This is a relatively safe practice which could easily be incorporated into the standard of care for colonoscopic FMT.}, }
@article {pmid36372205, year = {2022}, author = {Xiang, Q and Yan, X and Shi, W and Li, H and Zhou, K}, title = {Early gut microbiota intervention in premature infants: Application perspectives.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2022.11.004}, pmid = {36372205}, issn = {2090-1224}, abstract = {BACKGROUND: Preterm birth is the leading cause of death in children under the age of five. One of the major factors contributing to the high risk of diseases and deaths in premature infants is the incomplete development of the intestinal immune system. The gut microbiota has been widely recognized as a critical factor in promoting the development and function of the intestinal immune system after birth. However, the gut microbiota of premature infants is at high risk of dysbiosis, which is highly associated with adverse effects on the development and education of the early life immune system. Early intervention can modulate the colonization and development of gut microbiota and has a long-term influence on the development of the intestinal immune system.<br><br>AIM OF REVIEW: This review aims to summarize the characterization, interconnection, and underlying mechanism of gut microbiota and intestinal innate immunity in premature infants, and to discuss the status, applicability, safety, and prospects of different intervention strategies in premature infants, thus providing an overview and outlook of the current applications and remaining gaps of early intervention strategies in premature infants.<br><br>This review is focused on three key concepts. Firstly, the gut microbiota of premature infants is at high risk of dysbiosis, resulting in dysfunctional intestinal immune system processes. Secondly, contributing roles of early intervention have been observed in improving the intestinal environment and promoting gut microbiota colonization, which is significant in the development and function of gut immunity in premature infants. Thirdly, different strategies of early intervention, such as probiotics, fecal microbiota transplantation, and nutrients, show different safety, applicability, and outcome in premature infants, and the underlying mechanism is complex and poorly understood.}, }
@article {pmid36371983, year = {2022}, author = {Yao, Y and Sun, S and Gu, J and Ni, H and Zhong, K and Xu, Q and Zhou, D and Wang, X and Gao, L and Zhu, X}, title = {Roux-en-Y reconstruction alleviates radical gastrectomy-induced colitis via down-regulation of the butyrate/NLRP3 signaling pathway.}, journal = {EBioMedicine}, volume = {86}, number = {}, pages = {104347}, pmid = {36371983}, issn = {2352-3964}, abstract = {BACKGROUND: Different methods for digestive tract reconstruction have a complex impact on the nutritional status of gastric cancer (GC) patients after radical gastrectomy. Previous studies reported that Roux-en-Y (R-Y) reconstruction resulted in obvious weight reduction and improvement in type 2 diabetes in obese patients. We investigated the relationship between R-Y reconstruction, gut microbiota, and the NLRP3 inflammasome in GC patients with poor basic nutrition.<br><br>METHODS: Changes in the gut microbiota after radical gastrectomy accomplished by different methods of digestive tract reconstruction were investigated via fecal microbiota transplantation. The underlying mechanisms were also explored by analyzing the role of the microbiota, butyrate, and the NLRP3 inflammasome in the colon tissues of colitis model mice and GC patients after radical gastrectomy.<br><br>FINDINGS: R-Y reconstruction effectively relieved intestinal inflammation and facilitated nutrient absorption. 16S rRNA analysis revealed that gavage transplantation with the fecal microbiota of R-Y reconstruction patients could reverse dysbacteriosis triggered by radical gastrectomy and elevate the relative abundance of some short-chain fatty acid (SCFA)-producing bacteria. Subsequently, butyrate negatively regulated the NLRP3-mediated inflammatory signaling pathway to inhibit the activation of macrophages and the secretion of pro-inflammatory mediators such as caspase-1 and interleukin (IL)-1&#x3b2;, decreasing the level of intestinal inflammation and promoting nutrient absorption.<br><br>INTERPRETATION: R-Y reconstruction induced colonization with SCFA-producing bacteria to alleviate radical gastrectomy-induced colitis by down-regulating the NLRP3 signaling pathway. This can be a new strategy and theoretical basis for the management of the postoperative nutritional status of GC patients.<br><br>FUNDING: This work was supported by the National Nature Science Foundation of China (81974375), the BoXi cultivation program (BXQN202130), and the Project of Youth Foundation in Science and Education of the Department of Public Health of Suzhou (KJXW2018001).}, }
@article {pmid36369072, year = {2022}, author = {Gu, J and Ji, H and Liu, T and Chen, C and Zhao, S and Cao, Y and Wang, N and Xiao, M and Chen, L and Cai, H}, title = {Detection of cytomegalovirus (CMV) by digital PCR in stool samples for the non-invasive diagnosis of CMV gastroenteritis.}, journal = {Virology journal}, volume = {19}, number = {1}, pages = {183}, pmid = {36369072}, issn = {1743-422X}, mesh = {Humans ; Cytomegalovirus/genetics ; Retrospective Studies ; *Cytomegalovirus Infections/diagnosis ; *Graft vs Host Disease/complications ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Polymerase Chain Reaction ; *Enteritis ; *Enterovirus Infections/complications ; *Cell-Free Nucleic Acids ; }, abstract = {BACKGROUND: CMV gastroenteritis is common in patients receiving allogeneic hematopoietic stem cell transplantation and it is difficult to distinguish from acute graft-versus-host disease (aGvHD), which has very similar symptoms but needs quite different treatment. CMV gastroenteritis is caused by local infection or reactivation of CMV in the gastrointestinal tract while aGvHD is due to immune rejection. The gold standard of diagnosis of CMV gastroenteritis and aGvHD is gastrointestinal biopsy under endoscopy, which is invasive and can potentially lead to severe side effects. Stool samples testing with quantitative polymerase chain reaction (qPCR) may be an alternative, while the application in trace level measurements and precision are not all satisfactory enough in reported research.<br><br>METHODS: In this study, we designed a novel method that extracted the cell free DNA (cfDNA) from the fecal supernatant to perform digital PCR (dPCR) for the detection of CMV, analyzed the performance and compared it with the total DNA extracted by the current procedure.<br><br>RESULTS: Twenty-two paired stool samples using two DNA extraction methods proved that the cfDNA extraction method had markedly higher DNA concentrations and control gene copy number, suggesting that cfDNA may be more informative and more useful for the detection of CMV DNA segment. The dPCR approach in detecting CMV DNA segment also exhibit good linearity (R[2]&#x2009;=&#x2009;0.997) and higher sensitivity (limit of detection at 50% was 3.534&#xa0;copies/&#x3bc;L). Eighty-two stool samples from 44 immunocompromised patients were analyzed, CMV-positive rate was 28%, indicating that more than one-quarter of the gastrointestinal symptoms within these patients may be caused by CMV infection or reactivation.<br><br>CONCLUSION: The combined results suggest that detection of CMV by dPCR in cfDNA of stool supernatant is a powerful method to identify CMV gastroenteritis and helps in clinical treatment decision making.}, }
@article {pmid36367776, year = {2023}, author = {Zhou, Y and Medik, YB and Patel, B and Zamler, DB and Chen, S and Chapman, T and Schneider, S and Park, EM and Babcock, RL and Chrisikos, TT and Kahn, LM and Dyevoich, AM and Pineda, JE and Wong, MC and Mishra, AK and Cass, SH and Cogdill, AP and Johnson, DH and Johnson, SB and Wani, K and Ledesma, DA and Hudgens, CW and Wang, J and Wadud Khan, MA and Peterson, CB and Joon, AY and Peng, W and Li, HS and Arora, R and Tang, X and Raso, MG and Zhang, X and Foo, WC and Tetzlaff, MT and Diehl, GE and Clise-Dwyer, K and Whitley, EM and Gubin, MM and Allison, JP and Hwu, P and Ajami, NJ and Diab, A and Wargo, JA and Watowich, SS}, title = {Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration.}, journal = {The Journal of experimental medicine}, volume = {220}, number = {2}, pages = {}, pmid = {36367776}, issn = {1540-9538}, support = {R01AI109294/NH/NIH HHS/United States ; HL158796/HL/NHLBI NIH HHS/United States ; P30CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Interleukin-6 ; Quality of Life ; *Colitis/pathology ; Immunotherapy ; Inflammation ; }, abstract = {Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity. We found αCTLA-4 drove increased inflammation and colonic tissue damage in mice with genetic predisposition to intestinal inflammation, acute gastrointestinal infection, transplantation with a dysbiotic fecal microbiome, or dextran sodium sulfate administration. We identified an immune signature of αCTLA-4-mediated irAEs, including colonic neutrophil accumulation and systemic interleukin-6 (IL-6) release. IL-6 blockade combined with antibiotic treatment reduced intestinal damage and improved αCTLA-4 therapeutic efficacy in inflammation-prone mice. Intestinal immune signatures were validated in biopsies from patients with ICB colitis. Our work provides new preclinical models of αCTLA-4 intestinal irAEs, mechanistic insights into irAE development, and potential approaches to enhance ICB efficacy while mitigating irAEs.}, }
@article {pmid36363516, year = {2022}, author = {Abenavoli, L and Maurizi, V and Rinninella, E and Tack, J and Di Berardino, A and Santori, P and Rasetti, C and Procopio, AC and Boccuto, L and Scarpellini, E}, title = {Fecal Microbiota Transplantation in NAFLD Treatment.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {11}, pages = {}, pmid = {36363516}, issn = {1648-9144}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/complications ; Fecal Microbiota Transplantation ; *Carcinoma, Hepatocellular ; Ecosystem ; *Liver Neoplasms ; Dysbiosis/therapy/complications ; Bile Acids and Salts ; }, abstract = {Introduction: Gut microbiota is not only a taxonomic biologic ecosystem but is also involved in human intestinal and extra-intestinal functions such as immune system modulation, nutrient absorption and digestion, as well as metabolism regulation. The latter is strictly linked to non-alcoholic fatty liver disease (NAFLD) pathophysiology. Materials and methods: We reviewed the literature on the definition of gut microbiota, the concepts of "dysbiosis" and "eubiosis", their role in NAFLD pathogenesis, and the data on fecal microbiota transplantation (FMT) in these patients. We consulted the main medical databases using the following keywords, acronyms, and their associations: gut microbiota, eubiosis, dysbiosis, bile acids, NAFLD, and FMT. Results: Gut microbiota qualitative and quantitative composition is different in healthy subjects vs. NALFD patients. This dysbiosis is associated with and involved in NAFLD pathogenesis and evolution to non-acoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). In detail, microbial-driven metabolism of bile acids (BAs) and interaction with hepatic and intestinal farnesoid nuclear X receptor (FXR) have shown a determinant role in liver fat deposition and the development of fibrosis. Over the use of pre- or probiotics, FMT has shown preclinical and initial clinical promising results in NAFLD treatment through re-modulation of microbial dysbiosis. Conclusions: Promising clinical data support a larger investigation of gut microbiota dysbiosis reversion through FMT in NAFLD using randomized clinical trials to design precision-medicine treatments for these patients at different disease stages.}, }
@article {pmid36362265, year = {2022}, author = {Nirmalkar, K and Qureshi, F and Kang, DW and Hahn, J and Adams, JB and Krajmalnik-Brown, R}, title = {Shotgun Metagenomics Study Suggests Alteration in Sulfur Metabolism and Oxidative Stress in Children with Autism and Improvement after Microbiota Transfer Therapy.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362265}, issn = {1422-0067}, mesh = {Child ; Humans ; *Autistic Disorder ; RNA, Ribosomal, 16S/genetics/metabolism ; *Autism Spectrum Disorder/genetics/therapy/metabolism ; *Microbiota ; Metagenomics ; Oxidative Stress ; Sulfur ; }, abstract = {Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including Prevotella (P. dentalis, P. enoeca, P. oris, P. meloninogenica), Bifidobacterium bifidum, and a sulfur reducer Desulfovibrio piger increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.}, }
@article {pmid36362056, year = {2022}, author = {Ustianowska, K and Ustianowski, &#x141; and Machaj, F and Gorący, A and Rosik, J and Szostak, B and Szostak, J and Pawlik, A}, title = {The Role of the Human Microbiome in the Pathogenesis of Pain.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362056}, issn = {1422-0067}, mesh = {Female ; Humans ; *Visceral Pain/pathology ; Brain/pathology ; Dysbiosis/pathology ; *Microbiota ; *Gastrointestinal Microbiome/physiology ; *Probiotics ; *Chronic Pain ; }, abstract = {Understanding of the gut microbiome's role in human physiology developed rapidly in recent years. Moreover, any alteration of this microenvironment could lead to a pathophysiological reaction of numerous organs. It results from the bidirectional communication of the gastrointestinal tract with the central nervous system, called the gut-brain axis. The signals in the gut-brain axis are mediated by immunological, hormonal, and neural pathways. However, it is also influenced by microorganisms in the gut. The disturbances in the gut-brain axis are associated with gastrointestinal syndromes, but recently their role in the development of different types of pain was reported. The gut microbiome could be the factor in the central sensitization of chronic pain by regulating microglia, astrocytes, and immune cells. Dysbiosis could lead to incorrect immune responses, resulting in the development of inflammatory pain such as endometriosis. Furthermore, chronic visceral pain, associated with functional gastrointestinal disorders, could result from a disruption in the gut microenvironment. Any alteration in the gut-brain axis could also trigger migraine attacks by affecting cytokine expression. Understanding the gut microbiome's role in pain pathophysiology leads to the development of analgetic therapies targeting microorganisms. Probiotics, FODMAP diet, and fecal microbiota transplantation are reported to be beneficial in treating visceral pain.}, }
@article {pmid36359265, year = {2022}, author = {Almeida, C and Oliveira, R and Baylina, P and Fernandes, R and Teixeira, FG and Barata, P}, title = {Current Trends and Challenges of Fecal Microbiota Transplantation-An Easy Method That Works for All?.}, journal = {Biomedicines}, volume = {10}, number = {11}, pages = {}, pmid = {36359265}, issn = {2227-9059}, abstract = {The gut microbiota refers to bacteria lodges in the gastrointestinal tract (GIT) that interact through various complex mechanisms. The disturbance of this ecosystem has been correlated with several diseases, such as neurologic, respiratory, cardiovascular, and metabolic diseases and cancer. Therefore, the modulation of the gut microbiota has emerged as a potential therapeutic tool; of the various forms of gut microbiota modulation, fecal microbiota transplantation (FMT) is the most approached. This recent technique involves introducing fecal material from a healthy donor into the patient's gastrointestinal tract, aiming to restore the gut microbiota and lead to the resolution of symptoms. This procedure implies a careful donor choice, fine collection and handling of fecal material, and a balanced preparation of the recipient and consequent administration of the prepared content. Although FMT is considered a biological therapy with promising effects, side effects such as diarrhea and abdominal pain have also been claimed, making this a significant challenge in the application of FMT. Bearing this in mind, the present review aims to summarize the recent advances in understanding FMT mechanisms, their impact across different pathological conditions, and the associated side effects, emphasizing the most recent published data.}, }
@article {pmid36358736, year = {2022}, author = {He, Y and Huang, J and Li, Q and Xia, W and Zhang, C and Liu, Z and Xiao, J and Yi, Z and Deng, H and Xiao, Z and Hu, J and Li, H and Zu, X and Quan, C and Chen, J}, title = {Gut Microbiota and Tumor Immune Escape: A New Perspective for Improving Tumor Immunotherapy.}, journal = {Cancers}, volume = {14}, number = {21}, pages = {}, pmid = {36358736}, issn = {2072-6694}, abstract = {The gut microbiota is a large symbiotic community of anaerobic and facultative aerobic bacteria inhabiting the human intestinal tract, and its activities significantly affect human health. Increasing evidence has suggested that the gut microbiome plays an important role in tumor-related immune regulation. In the tumor microenvironment (TME), the gut microbiome and its metabolites affect the differentiation and function of immune cells regulating the immune evasion of tumors. The gut microbiome can indirectly influence individual responses to various classical tumor immunotherapies, including immune checkpoint inhibitor therapy and adoptive immunotherapy. Microbial regulation through antibiotics, prebiotics, and fecal microbiota transplantation (FMT) optimize the composition of the gut microbiome, improving the efficacy of immunotherapy and bringing a new perspective and hope for tumor treatment.}, }
@article {pmid36357745, year = {2022}, author = {Zhang, YW and Cao, MM and Li, YJ and Zhang, RL and Wu, MT and Yu, Q and Rui, YF}, title = {Fecal microbiota transplantation as a promising treatment option for osteoporosis.}, journal = {Journal of bone and mineral metabolism}, volume = {40}, number = {6}, pages = {874-889}, pmid = {36357745}, issn = {1435-5604}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Osteoporosis/therapy ; }, abstract = {Osteoporosis is a systemic metabolic bone disease characterized by the descending bone mass and destruction of bone microstructure, which tends to result in the increased bone fragility and associated fractures, as well as high disability rate and mortality. The relation between gut microbiota and bone metabolism has gradually become a research hotspot, and it has been verified that gut microbiota is closely associated with reduction of bone mass and incidence of osteoporosis recently. As a novel "organ transplantation" technique, fecal microbiota transplantation (FMT) mainly refers to the transplantation of gut microbiota from healthy donors to recipients with gut microbiota imbalance, so that the gut microbiota in recipients can be reshaped and play a normal function, and further prevent or treat the diseases related to gut microbiota disorder. Herein, based on the gut-bone axis and proven regulatory effects of gut microbiota on osteoporosis, this review expounds relevant basic researches and clinical practice of FMT on osteoporosis, thus demonstrating the potentials of FMT as a therapeutic option for osteoporosis and further providing certain reference for the future researches.}, }
@article {pmid36356464, year = {2022}, author = {Brandt, A and Baumann, A and Hernández-Arriaga, A and Jung, F and Nier, A and Staltner, R and Rajcic, D and Schmeer, C and Witte, OW and Wessner, B and Franzke, B and Wagner, KH and Camarinha-Silva, A and Bergheim, I}, title = {Impairments of intestinal arginine and NO metabolisms trigger aging-associated intestinal barrier dysfunction and 'inflammaging'.}, journal = {Redox biology}, volume = {58}, number = {}, pages = {102528}, pmid = {36356464}, issn = {2213-2317}, mesh = {Mice ; Animals ; *Endotoxemia ; Arginase/metabolism ; Arginine/pharmacology ; Intestines ; Aging ; }, abstract = {Aging is considered a state of low grade inflammation, occurring in the absence of any overt infection often referred to as 'inflammaging'. Maintaining intestinal homeostasis may be a target to extend a healthier status in older adults. Here, we report that even in healthy older men low grade bacterial endotoxemia is prevalent. In addition, employing multiple mouse models, we also show that while intestinal microbiota composition changes significantly during aging, fecal microbiota transplantation to old mice does not protect against aging-associated intestinal barrier dysfunction in small intestine. Rather, intestinal NO homeostasis and arginine metabolism mediated through arginase and NO synthesis is altered in small intestine of aging mice. Treatment with the arginase inhibitor norNOHA prevented aging-associated intestinal barrier dysfunction, low grade endotoxemia and delayed the onset of senescence in peripheral tissue e.g., liver. Intestinal arginine and NO metabolisms could be a target in the prevention of aging-associated intestinal barrier dysfunction and subsequently decline and 'inflammaging'.}, }
@article {pmid36355923, year = {2022}, author = {Tang, L and Li, J and Sun, B and Bai, Y and Zhou, X and Chen, L}, title = {Transcriptomic Interaction between Young Fecal Transplantation and Perfluorobutanesulfonate in Aged Zebrafish Gonads.}, journal = {Toxics}, volume = {10}, number = {11}, pages = {}, pmid = {36355923}, issn = {2305-6304}, abstract = {The transfer of young fecal microbiota has been found to significantly refresh the reproductive endocrine system and effectively ameliorate the toxicity of perfluorobutanesulfonate (PFBS) in aged zebrafish recipients. However, the mechanisms underlying the antagonistic action of young fecal microbiota against the reproductive endocrine toxicity of PFBS remain largely unknown. In this study, the aged zebrafish were transplanted with feces from young donors and then exposed to PFBS for 14 days. After exposure, the shift in the transcriptomic fingerprint of the gonads was profiled by using high-throughput sequencing, aiming to provide mechanistic clues into the interactive mode of action between young fecal transplantation and PFBS's innate toxicity. The results showed that the gene transcription pattern associated with protein and lipid synthesis in the gonads of the aged individuals was quite different from the young counterparts. It was intriguing that the transplantation of young feces established a youth-like transcriptomic phenotype in the elderly recipients, thus attenuating the functional decline and maintaining a healthy aging state of the gonads. A sex specificity response was clearly observed. Compared to the aged females, more metabolic pathways (e.g., glycine, serine, and threonine metabolism; glyoxylate and dicarboxylate metabolism; pyrimidine metabolism) were significantly enriched in aged males receiving young feces transplants. PFBS dramatically altered the transcriptome of aged testes, while a much milder effect was observable in aged ovaries. Accordingly, a suite of biological processes related to germ cell proliferation were disrupted by PFBS in aged males, including the ECM-receptor interaction, retinol metabolism, and folate biosynthesis. In aged ovaries exposed to PFBS, mainly the fatty acid and arginine biosynthesis pathway was significantly affected. However, these transcriptomic disorders caused by PFBS were largely mitigated in aged gonads by transferring young feces. Overall, the present findings highlighted the potential of young fecal transplantation to prevent the functional compromise of gonads resulting from aging and PFBS.}, }
@article {pmid36355135, year = {2022}, author = {Yoshikawa, S and Taniguchi, K and Sawamura, H and Ikeda, Y and Tsuji, A and Matsuda, S}, title = {A New Concept of Associations between Gut Microbiota, Immunity and Central Nervous System for the Innovative Treatment of Neurodegenerative Disorders.}, journal = {Metabolites}, volume = {12}, number = {11}, pages = {}, pmid = {36355135}, issn = {2218-1989}, abstract = {Nerve cell death accounts for various neurodegenerative disorders, in which altered immunity to the integrated central nervous system (CNS) might have destructive consequences. This undesirable immune response often affects the progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, schizophrenia and/or amyotrophic lateral sclerosis (ALS). It has been shown that commensal gut microbiota could influence the brain and/or several machineries of immune function. In other words, neurodegenerative disorders may be connected to the gut-brain-immune correlational system. The engrams in the brain could retain the information of a certain inflammation in the body which might be involved in the pathogenesis of neurodegenerative disorders. Tactics involving the use of probiotics and/or fecal microbiota transplantation (FMT) are now evolving as the most promising and/or valuable for the modification of the gut-brain-immune axis. More deliberation of this concept and the roles of gut microbiota would lead to the development of stupendous treatments for the prevention of, and/or therapeutics for, various intractable diseases including several neurodegenerative disorders.}, }
@article {pmid36355122, year = {2022}, author = {Deda, O and Kachrimanidou, M and Armitage, EG and Mouskeftara, T and Loftus, NJ and Zervos, I and Taitzoglou, I and Gika, H}, title = {Metabolic Phenotyping Study of Mouse Brain Following Microbiome Disruption by C.difficile Colonization.}, journal = {Metabolites}, volume = {12}, number = {11}, pages = {}, pmid = {36355122}, issn = {2218-1989}, abstract = {Clostridioides difficile infection (CDI) is responsible for an increasing number of cases of post-antibiotic diarrhea worldwide, which has high severity and mortality among hospitalized elderly patients. The disruption of gut microbiota due to antibacterial medication facilitates the intestinal colonization of C. difficile. In the present study, a murine model was used to investigate the potential effects of antibiotic administration and subsequent colonization by C. difficile, as well as the effects of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the brain metabolome for the first time. Four different metabolomic-based methods (targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS, targeted GC-MS/MS, and untargeted GC-MS) were applied, resulting in the identification of 217 unique metabolites in the brain extracts, mainly glycerophospholipids, glycerolipids, amino acids, carbohydrates, and fatty acids. Univariate and multivariate statistical analysis revealed that CDI, as well as the subsequent treatments, altered significantly several brain metabolites, probably due to gut dysbiosis, and affected the brain through the gut-brain axis. Notably, none of the therapeutic approaches completely restored the brain metabolic profile to the original, healthy, and non-infected phenotype, even after 10 days of treatment.}, }
@article {pmid36353787, year = {2022}, author = {Gweon, TG and Lee, YJ and Yim, SK and Kim, SY and Choi, CH and Cho, YS and , }, title = {Recognition and attitudes of Korean physicians toward fecal microbiota transplantation: a survey study.}, journal = {The Korean journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.3904/kjim.2022.206}, pmid = {36353787}, issn = {2005-6648}, abstract = {BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) represents a treatment option for recurrent Clostridioides difficile infection (CDI). Recently, FMT has been investigated in various clinical settings other than CDI. This study examined Korean physicians' recognition of FMT and their attitudes toward this procedure.<br><br>METHODS: An online questionnaire included questions on indications for FMT, the FMT process, physicians' attitudes toward FMT for the treatment of CDI and non-CDI diseases, and possible concerns.<br><br>RESULTS: Finally, 107 physicians responded to this survey: 66 (61.7%) had experience of performing FMT, and 86 (80.4%) replied that they were willing to perform FMT for CDI. Two-thirds of physicians (63.6%, n = 68) would perform FMT for recurrent CDI on patients who had at least three recurrences. The most common obstacle to performing FMT for the treatment of CDI was the lack of regulations or guidelines (55.1%, n = 59). Seventy-seven (72.0%) physicians would consider FMT for non- CDI diseases when conventional treatment had failed. The most common obstacle for FMT for the treatment of non-CDI diseases was low treatment efficacy (57.0%, n = 61).<br><br>CONCLUSIONS: Two-thirds of Korean physicians had experience of performing FMT, and many performed FMT for recurrent CDI. The results of this study will prove useful to researchers and practitioners in FMT in Korea.}, }
@article {pmid36353639, year = {2022}, author = {Li, Y and Ouyang, Y and He, C}, title = {Research trends on clinical fecal microbiota transplantation: A biliometric analysis from 2001 to 2021.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {991788}, pmid = {36353639}, issn = {1664-3224}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects/methods ; *Clostridioides difficile ; Treatment Outcome ; *Clostridium Infections/therapy ; Feces ; }, abstract = {BACKGROUND: Numerous studies on fecal microbiota transplantation (FMT) have been conducted in the past two decades. We aimed to assess the research trends and hotspots in the field of FMT through a quantitative method.<br><br>MATERIALS AND METHODS: The clinical studies of FMT published from 2001 to 2021 were extracted from the Web of Science database. We analyzed the countries, institutions, authors, and keywords of these articles and visually illustrated using VOSviewer and CiteSpace software. The current application of FMT in clinical practice, including indications, efficacy, adverse events, as well as its methodology, such as donor, delivery route, were also evaluated.<br><br>RESULTS: A total of 227 records were finally identified. The number and rate of annual publications increased gradually. The USA ranked highest in the number of publications. Harvard University was the most influential institution, and Digestive Diseases and Sciences was the most productive journal. Kassam Zain published the most papers, and the high-frequency keywords were mainly related to diseases and techniques. Healthy donors were the most widely used donors, and frozen stool had the highest frequency of use. The predominant delivery route was endoscopy followed by oral capsules and enema. FMT was most frequently performed for the treatment of recurrent Clostridium Difficile Infection. The overall efficacy of FMT was 76.88%, and the incidence of minor and severe adverse events were 11.63% and 1.59%, respectively.<br><br>CONCLUSIONS: This study delineated a comprehensive landscape of the advancement in FMT field. Although in its infancy, FMT is a burgeoning option for the treatment of a variety of diseases associated with gut dysbiosis. To improve the efficacy and reduce adverse events, future studies are warranted to optimize the methodology of FMT.}, }
@article {pmid36352460, year = {2022}, author = {Wei, S and Jespersen, ML and Baunwall, SMD and Myers, PN and Smith, EM and Dahlerup, JF and Rasmussen, S and Nielsen, HB and Licht, TR and Bahl, MI and Hvas, CL}, title = {Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {193}, pmid = {36352460}, issn = {2049-2618}, mesh = {Adult ; Female ; Humans ; Infant, Newborn ; Pregnancy ; Bacteria ; *Clostridioides difficile ; *Clostridium Infections/therapy/microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment.<br><br>METHODS: A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults.<br><br>RESULTS: The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient's gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer.<br><br>CONCLUSIONS: The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. Video Abstract.}, }
@article {pmid36352455, year = {2022}, author = {Liu, Y and Zhao, Y and Qi, J and Ma, X and Qi, X and Wu, D and Xu, Y}, title = {Fecal microbiota transplantation combined with ruxolitinib as a salvage treatment for intestinal steroid-refractory acute GVHD.}, journal = {Experimental hematology &amp; oncology}, volume = {11}, number = {1}, pages = {96}, pmid = {36352455}, issn = {2162-3619}, abstract = {Acute graft-versus-host disease (aGVHD), especially intestinal aGVHD, is one of the most severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) has been applied to the treatment of intestinal steroid-refractory aGVHD (SR-aGVHD). Ruxolitinib is the first drug recommended for SR-aGVHD. Here, we reported the outcome data from 21 patients who had received the combined treatment of FMT with ruxolitinib as a salvage treatment in intestinal SR-aGVHD after HSCT. The overall response rate on day 28 was 71.4% (95% CI 50.4-92.5%), including 10 patients with complete responses. The durable overall response at day 56 in responders was 80%. GVHD relapse rate was 33.3% in responders. The levels of inflammatory cytokines as well as T cells and NK cells activation declined. The diversity of the intestinal microbiota was improved in responders. Viral reactivations and severe cytopenia were the major adverse events (61.9% and 81% respectively). The estimated 6-month overall survival was 57.1% (95% CI: 35.9-78.3%), while event-free survival was 52.4% (95% CI: 21.7%-64.1%). Collectively, FMT with ruxolitinib could be an effective treatment for intestinal SR-aGVHD after HSCT.Trial registration: ClinicalTrials.gov identifier: NCT03148743.}, }
@article {pmid36351614, year = {2022}, author = {Xie, T and Yang, R and Zhang, X and Shen, X and Yu, L and Liao, J and Bao, T and Fang, Q}, title = {Fecal Microbiota Transplantation Alleviated Cerebral Ischemia Reperfusion Injury in Obese Rats.}, journal = {The Tohoku journal of experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1620/tjem.2022.J094}, pmid = {36351614}, issn = {1349-3329}, }
@article {pmid36348361, year = {2022}, author = {Zhong, Y and Xiao, Y and Gao, J and Zheng, Z and Zhang, Z and Yao, L and Li, D}, title = {Curcumin improves insulin sensitivity in high-fat diet-fed mice through gut microbiota.}, journal = {Nutrition &amp; metabolism}, volume = {19}, number = {1}, pages = {76}, pmid = {36348361}, issn = {1743-7075}, abstract = {BACKGROUND: Insulin resistance precedes metabolic syndrome which increases the risk of type 2 diabetes and cardiovascular disease. However, there is a lack of safe and long-lasting methods for the prevention and treatment of insulin resistance. Gut microbiota dysbiosis can lead to insulin resistance and associated glucose and lipid metabolic dysfunction. Thus, the role of gut microbiota in metabolic diseases has garnered growing interest. Curcumin, the active ingredient of tropical plant Curcuma longa, has excellent prospects for the prevention and treatment of metabolic diseases. However, due to the extremely low bioavailability of curcumin, the mechanisms by which curcumin increases insulin sensitivity remains to be elucidated. This study aimed to elucidate the role of gut microbiota in mediating the effects of curcumin on improving insulin sensitivity in high-fat diet (HFD)-fed mice.<br><br>METHODS: Glucose, insulin, and pyruvate tolerance were tested and hepatic triglycerides (TGs) content was measured in HFD-fed mice treated with curcumin (100&#xa0;mg&#xa0;kg[-1] d[-1], p.o.) or vehicle for 4&#xa0;weeks and aforementioned mice after gut microbiota depletion via antibiotic treatment for 4&#xa0;weeks. Fecal microbiota transplantation (FMT) was conducted in endogenous gut microbiota-depleted HFD-fed mice. Glucose and lipid metabolic phenotypes were also measured in recipient mice colonized microbiota from vehicle- or curcumin-treated HFD-fed mice. The mechanisms underlying the effects of curcumin on increasing insulin sensitivity were testified by Western blotting, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: Curcumin ameliorated HFD-induced glucose intolerance, insulin resistance, pyruvate intolerance, and hepatic TGs accumulation, while these effects were mediated by gut microbiota. Curcumin induced insulin-stimulated Akt phosphorylation levels in insulin-regulated peripheral tissues. The inhibitory effects of curcumin on the expressions of genes involved in hepatic gluconeogenesis and de novo lipogenesis were dependent on gut microbiota. Meanwhile, curcumin upregulated the expression of fibroblast growth factor 15 (FGF15) through gut microbiota.<br><br>CONCLUSIONS: The effects of curcumin on promoting insulin sensitivity were dependent on gut microbiota in HFD-fed mice. Moreover, curcumin at least partly exerted its effects on increasing insulin sensitivity via FGF15 upregulation. This study provided new ideas on nutritional manipulations of gut microbiota for the treatment of metabolic diseases.}, }
@article {pmid36345042, year = {2022}, author = {Zhou, C and Li, J and Guo, C and Zhou, Z and Yang, Z and Zhang, Y and Jiang, J and Cai, Y and Zhou, J and Ming, Y}, title = {Comparison of intestinal flora between patients with chronic and advanced Schistosoma japonicum infection.}, journal = {Parasites &amp; vectors}, volume = {15}, number = {1}, pages = {413}, pmid = {36345042}, issn = {1756-3305}, mesh = {Humans ; Animals ; *Schistosomiasis japonica ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Feces ; Intestines ; *Schistosoma japonicum/genetics ; }, abstract = {BACKGROUND: Schistosoma japonicum infection is an important public health problem, imposing heavy social and economic burdens in 78 countries worldwide. However, the mechanism of transition from chronic to advanced S. japonicum infection remains largely unknown. Evidences suggested that gut microbiota plays a role in the pathogenesis of S. japonicum infection. However, the composition of the gut microbiota in patients with chronic and advanced S. japonicum infection is not well defined. In this study, we compared the composition of the intestinal flora in patients with chronic and advanced S. japonicum infection.<br><br>METHODS: The feces of 24 patients with chronic S. japonicum infection and five patients with advanced S. japonicum infection from the same area were collected according to standard procedures, and 16S rRNA sequencing technology was used to analyze the intestinal microbial composition of the two groups of patients.<br><br>RESULTS: We found that alteration occurs in the gut microbiota between the groups of patients with chronic and advanced S. japonicum infections. Analysis of alpha and beta diversity indicated that the diversity and abundance of intestinal flora in patients with advanced S. japonicum infection were lower than those in patients with chronic S. japonicum infection. Furthermore, Prevotella 9, Subdoligranulum, Ruminococcus torques, Megamonas and Fusicatenibacter seemed to have potential to discriminate different stages of S. japonicum infection and to act as biomarkers for diagnosis. Function prediction analysis revealed that microbiota function in the chronic group was focused on translation and cell growth and death, while that in the advanced group was concentrated on elevating metabolism-related functions.<br><br>CONCLUSIONS: Our study demonstrated that alteration in gut microbiota in different stages of S. japonicum infection plays a potential role in the pathogenesis of transition from chronic to advanced S. japonicum infection. However, further validation in the clinic is needed, and the underlying mechanism requires further study.}, }
@article {pmid36342653, year = {2022}, author = {Orenstein, R}, title = {The Role of Microbiome-Based Therapeutics in Clostridioides difficile Infection: Durable, Long-Term Results of RBX2660.}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, pmid = {36342653}, issn = {2193-8229}, abstract = {A recently published manuscript described findings from a phase 2 open label study of the microbiota-based live biotherapeutic product RBX2660 in patients with two or more previous recurrent Clostridioides difficile infection (rCDI) episodes, and described long-term safety and sustained treatment success through 24 months. As previous studies have typically focused on short-term clinical outcomes, these new data provide insight into the tolerability, safety, and efficacy of RBX2660 over the long term. When microbiota-based products were first evaluated, the long-term efficacy and safety were principal concerns of the United States Food and Drug Administration. Microbiota-based live biotherapeutic products (LBPs) represent an emerging approach to the management of CDI and perhaps other gastrointestinal and medical conditions whose pathogenesis is defined by microbial dysbiosis. RBX2660 is a human-derived, broad consortium microbiota-based LBP that consists of a population of microbes obtained from healthy stool donors and may reflect the symbiotic nature of a healthy colonic microbiome. RBX2660 is rectally administered and does not require sedation or special preparation of the recipient. Potential advantages of the rectal administration of RBX2660 include the ease of administration and lack of need for any bowel preparation, which may benefit those who are frail, have swallowing issues, or cannot take bowel laxative preparations. In this multicenter prospective trial of rCDI, patients who achieved treatment success 8 weeks after receiving RBX2660 continued to have a sustained clinical response over the course of long-term follow-up, with more than 90% of treatment responders remaining CDI-free at 6, 12, and 24 months. Following receipt of RBX2660, the gut microbiota of those with treatment success were restored from a dysbiotic state to become more diverse and similar to RBX2660 composition. The restoration of the microbiota occurred as early as 7 days after RBX2660 administration and remained stable through the 24-month analysis. No new adverse outcomes were observed during the prospective assessment, and the safety profile of RBX2660 was consistent with previous studies. Based on the clinical studies, RBX2660 will most likely benefit those with ≥ 1 rCDI episode or those who are at a high risk of subsequent rCDI, such as patients who have comorbid conditions including renal disease, heart disease, or inflammatory bowel disease, or who are immunosuppressed. The role of microbiome-based therapeutics in 47 Clostridioides difficile infection: Durable, long-term results of RBX2660 (MP4 511833 KB).}, }
@article {pmid36341987, year = {2022}, author = {Chen, G and Peng, Y and Huang, Y and Xie, M and Dai, Z and Cai, H and Dong, W and Xu, W and Xie, Z and Chen, D and Fan, X and Zhou, W and Kan, X and Yang, T and Chen, C and Sun, Y and Zeng, X and Liu, Z}, title = {Fluoride induced leaky gut and bloom of Erysipelatoclostridium ramosum mediate the exacerbation of obesity in high-fat-diet fed mice.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2022.10.010}, pmid = {36341987}, issn = {2090-1224}, abstract = {Fluoride is widely presented in drinking water and foods. A strong relation between fluoride exposure and obesity has been reported. However, the potential mechanisms on fluoride-induced obesity remain unexplored. Objectives and methods The effects of fluoride on the obesity were investigated using mice model. Furthermore, the role of gut homeostasis in exacerbation of the obesity induced by fluoride was evaluated. Results The results showed that fluoride alone did not induce obesity in normal diet (ND) fed mice, whereas, it could trigger exacerbation of obesity in high-fat diet (HFD) fed mice. Fluoride impaired intestinal barrier and activated Toll-like receptor 4 (TLR4) signaling to induce obesity, which was further verified in TLR4[-/-] mice. Furthermore, fluoride could deteriorate the gut microbiota in HFD mice. The fecal microbiota transplantation from fluoride-induced mice was sufficient to induce obesity, while the exacerbation of obesity by fluoride was blocked upon gut microbiota depletion. The fluoride-induced bloom of Erysipelatoclostridium ramosum was responsible for exacerbation of obesity. In addition, a potential strategy for prevention of fluoride-induced obesity was proposed by intervention with polysaccharides from Fuzhuan brick tea. Conclusion Overall, these results provide the first evidence of a comprehensive cross-talk mechanism between fluoride and obesity in HFD fed mice, which is mediated by gut microbiota and intestinal barrier. E. ramosum was identified as a crucial mediator of fluoride induced obesity, which could be explored as potential target for prevention and treatment of obesity with exciting translational value.}, }
@article {pmid36341838, year = {2023}, author = {Dischinger, U and Kötzner, L and Kovatcheva-Datchary, P and Kleinschmidt, H and Haas, C and Perez, J and Presek, C and Koschker, AC and Miras, AD and Hankir, MK and Vogel, J and Germer, CT and Fassnacht, M and Herrmann, MJ and Seyfried, F}, title = {Hypothalamic integrity is necessary for sustained weight loss after bariatric surgery: A prospective, cross-sectional study.}, journal = {Metabolism: clinical and experimental}, volume = {138}, number = {}, pages = {155341}, doi = {10.1016/j.metabol.2022.155341}, pmid = {36341838}, issn = {1532-8600}, mesh = {Humans ; Prospective Studies ; Cross-Sectional Studies ; *Bariatric Surgery ; Weight Loss/physiology ; Obesity/surgery ; Glucagon-Like Peptide 1 ; Hypothalamus ; *Hypothalamic Diseases ; *Gastric Bypass ; }, abstract = {OBJECTIVE: The hypothalamus is the main integrator of peripheral and central signals in the control of energy homeostasis. Its functional relevance for the effectivity of bariatric surgery is not entirely elucidated. Studying the effects of bariatric surgery in patients with hypothalamic damage might provide insight.<br><br>SUMMARY BACKGROUND DATA: Prospective study to analyze the effects of bariatric surgery in patients with hypothalamic obesity (HO) vs. matched patients with common obesity (CO) with and without bariatric surgery.<br><br>METHODS: 65 participants were included (HO-surgery: n&#xa0;=&#xa0;8, HO-control: n&#xa0;=&#xa0;10, CO-surgery: n&#xa0;=&#xa0;12, CO-control: n&#xa0;=&#xa0;12, Lean-control: n&#xa0;=&#xa0;23). Body weight, levels of anorexic hormones, gut microbiota, as well as subjective well-being/health status, eating behavior, and brain activity (via functional MRI) were evaluated.<br><br>RESULTS: Patients with HO lost significantly less weight after bariatric surgery than CO-participants (total body weight loss %: 5.5&#xa0;% vs. 26.2&#xa0;%, p&#xa0;=&#xa0;0.0004). After a mixed meal, satiety and abdominal fullness tended to be lowest in HO-surgery and did not correlate with levels of GLP-1 or PYY. Levels of PYY (11,151&#xa0;&#xb1;&#xa0;1667&#xa0;pmol/l/h vs. 8099&#xa0;&#xb1;&#xa0;1235&#xa0;pmol/l/h, p&#xa0;=&#xa0;0.028) and GLP-1 (20,975&#xa0;&#xb1;&#xa0;2893&#xa0;pmol/l/h vs. 13,060&#xa0;&#xb1;&#xa0;2357&#xa0;pmol/l/h, p&#xa0;=&#xa0;0.009) were significantly higher in the HO-surgery vs. CO-surgery group. Abundance of Enterobacteriaceae and Streptococcus was increased in feces of HO and CO after bariatric surgery. Comparing HO patients with lean-controls revealed an increased activation in insula and cerebellum to viewing high-caloric foods in left insula and cerebellum in fMRI.<br><br>CONCLUSIONS: Hypothalamic integrity is necessary for the effectiveness of bariatric surgery in humans. Peripheral changes after bariatric surgery are not sufficient to induce satiety and long-term weight loss in patients with hypothalamic damage.}, }
@article {pmid36341232, year = {2022}, author = {Tkach, S and Dorofeyev, A and Kuzenko, I and Sulaieva, O and Falalyeyeva, T and Kobyliak, N}, title = {Fecal microbiota transplantation in patients with post-infectious irritable bowel syndrome: A randomized, clinical trial.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {994911}, pmid = {36341232}, issn = {2296-858X}, abstract = {INTRODUCTION: Research in recent years has shown the potential benefits of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS). Acute infectious gastroenteritis is a well-established risk factor for developing such forms of IBS as post-infectious IBS (PI-IBS). However, the effective use of FMT in patients with IP-IBS has not yet been clarified.<br><br>AIM: The study aimed to conduct a single-center, randomized clinical trial (RCT) to assess FMT's safety, clinical and microbiological efficacy in patients with PI-IBS.<br><br>MATERIALS AND METHODS: Patients with PI-IBS were randomized into two groups: I (standard-care, n = 29) were prescribed basic therapy, namely a low FODMAP diet, as well as Otilonium Bromide (1 tablet TID) and a multi-strain probiotic (1 capsule BID) for 1 month; II (FMT group, n = 30), each patient with PI-IBS underwent a single FMT procedure with fresh material by colonoscopy. All patients underwent bacteriological examination of feces for quantitative and qualitative microbiota composition changes. The clinical efficacy of treatment was evaluated according to the dynamics of abdominal symptoms, measured using the IBS-SSS scale, fatigue reduction (FAS scale), and a change in the quality of life (IBS-QoL scale).<br><br>RESULTS: FMT was associated with rapid onset of the effect, manifested in a significant difference between IBS-SSS points after 2 weeks of intervention (p < 0.001). In other time points (after 4 and 12 weeks) IBS-SSS did not differ significantly across both groups. Only after 3 months of treatment did their QoL exceed its initial level, as well value for 2 and 4 weeks, to a significant extent. The change in the ratio of the main microbial phenotypes in the form of an increase in the relative abundance of Firmicutes and Bacteroidetes was recorded in all patients after 4 weeks. It should be noted that these changes were significant but eventually normalized only in the group of PI-IBS patients who underwent FMT. No serious adverse reactions were noted.<br><br>CONCLUSION: This comparative study of the results of FMT use in patients with PI-IBS demonstrated its effectiveness compared to traditional pharmacotherapy, as well as a high degree of safety and good tolerability.}, }
@article {pmid36340300, year = {2022}, author = {Osna, NA and Rasineni, K and Ganesan, M and Donohue, TM and Kharbanda, KK}, title = {Pathogenesis of Alcohol-Associated Liver Disease.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {6}, pages = {1492-1513}, pmid = {36340300}, issn = {0973-6883}, support = {R01 AA027189/AA/NIAAA NIH HHS/United States ; }, abstract = {Excessive alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences. While chronic, heavy alcohol consumption causes structural damage and/or disrupts normal organ function in virtually every tissue of the body, the liver sustains the greatest damage. This is primarily because the liver is the first to see alcohol absorbed from the gastrointestinal tract via the portal circulation and second, because the liver is the principal site of ethanol metabolism. Alcohol-induced damage remains one of the most prevalent disorders of the liver and a leading cause of death or transplantation from liver disease. Despite extensive research on the pathophysiology of this disease, there are still no targeted therapies available. Given the multifactorial mechanisms for alcohol-associated liver disease pathogenesis, it is conceivable that a multitherapeutic regimen is needed to treat different stages in the spectrum of this disease.}, }
@article {pmid36339629, year = {2022}, author = {Ma, C and Yuan, D and Renaud, SJ and Zhou, T and Yang, F and Liou, Y and Qiu, X and Zhou, L and Guo, Y}, title = {Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1040591}, pmid = {36339629}, issn = {1663-9812}, abstract = {Chaihu-Shugan-San (CSS) is a traditional botanical drug formula often prescribed to treat depression in oriental countries, but its pharmacotherapeutic mechanism remains unknown. It was recently reported that CSS alters the composition of intestinal microflora and related metabolites such as bile acids (BAs). Since the intestinal microflora affects physiological functions of the brain through the gut-microbiota-brain axis, herein we investigated whether CSS altered BA levels, gut microflora, and depression-like symptoms in chronic unpredictable mild stress (CUMS) mice, a well-established mouse model of depression. Furthermore, we determined whether BA manipulation and fecal microbiota transplantation altered CSS antidepressant actions. We found that the BA chelator cholestyramine impaired the antidepressant effects of CSS, which was partially rescued by dietary cholic acid. CSS increased the relative abundance of Parabacteroides distasonis in the colon of CUMS mice, and increased serum levels of various BAs including hyocholic acid (HCA) and 7-ketodeoxycholic acid (7-ketoDCA). Furthermore, gut bacteria transplantation from CSS-treated mice into untreated or cholestyramine-treated CUMS mice restored serum levels of HCA and 7-ketoDCA, alleviating depression-like symptoms. In the hippocampus, CSS-treated mice had decreased expression of genes associated with BA transport (Bsep and Fxr) and increased expression of brain-derived neurotrophic factor and its receptor, TrkB. Overall, CSS increases intestinal P. distasonis abundance, leading to elevated levels of secondary BAs in the circulation and altered expression of hippocampal genes implicated in BA transport and neurotrophic signaling. Our data strongly suggest that the gut microbiota-brain axis contributes to the potent antidepressant action of CSS by modulating BA metabolism.}, }
@article {pmid36339448, year = {2022}, author = {Cheng, Z and Zhang, L and Yang, L and Chu, H}, title = {The critical role of gut microbiota in obesity.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1025706}, pmid = {36339448}, issn = {1664-2392}, mesh = {Humans ; *Gastrointestinal Microbiome ; Obesity/metabolism ; Prebiotics ; Fecal Microbiota Transplantation/adverse effects ; Inflammation/complications ; }, abstract = {Obesity is a global epidemic characterized by energy disequilibrium, metabolic disorder, fat mass development, and chronic low-grade inflammation, which significantly affects the health state of individuals of all ages and strains the socioeconomic system. The prevalence of obesity is rising at alarming rates and its etiology involves complicated interplay of diet, genetic, and environmental factors. The gut microbiota, as an important constituent of environmental factors, has been confirmed to correlate with the onset and progression of obesity. However, the specific relationship between obesity and the gut microbiota, and its associated mechanisms, have not been fully elucidated. In this review, we have summarized that the microbial diversity was significantly decreased and the Firmicutes/Bacteroidetes ratio was significantly increased in obesity. The altered gut microbiota and associated metabolites contributed to the progression of the disease by disrupting energy homeostasis, promoting lipid synthesis and storage, modulating central appetite and feeding behavior, as well as triggering chronic inflammation, and that the intentional manipulation of gut microbiota held promise as novel therapies for obesity, including probiotics, prebiotics, and fecal microbiota transplantation.}, }
@article {pmid36339093, year = {2022}, author = {Goldsmith, R and Aburahma, A and Pachhain, S and Choudhury, SR and Phuntumart, V and Larsen, R and Ward, CS and Sprague, JE}, title = {Reversal of temperature responses to methylone mediated through bi-directional fecal microbiota transplantation between hyperthermic tolerant and naïve rats.}, journal = {Temperature (Austin, Tex.)}, volume = {9}, number = {4}, pages = {318-330}, pmid = {36339093}, issn = {2332-8940}, abstract = {The synthetic cathinone ("bath salt") methylone induces a hyperthermia response and with chronic administration tolerance to this hyperthermia has been reported. The microbiome-gut-brain axis has been implicated in multiple bodily systems and pathologies, and intentional manipulation of the gut-microbiome has yielded clinically significant results. Here, we examined the effects of bi-directional Fecal Microbiota Transplantation (FMT) between methylone-induced hyperthermic tolerant (MHT) and methylone-naïve (MN) rats. Rats treated with methylone once per week developed tolerance to methylone-induced hyperthermia by the fourth week. Once tolerant, daily bi-directional FMT between the two groups were performed for seven days prior to the next methylone treatment. The FMT abated the developed tolerance in the MHT group. When treated with methylone for the first time following FMT, recipient MN rats displayed significant tolerance to hyperthermia despite it being their initial drug treatment. Post-FMT, MHT rats displayed elevations in norepinephrine and expression of UCP1, UCP3 and TGR5 in brown adipose tissue, with reductions in expression of TGR5 and UCP3 in skeletal muscle. The pre- and post-FMT methylone tolerance phenotypes of transplant recipients are concurrent with changes in the relative abundance of several classes of Proteobacteria, most evident for Gammaproteobacteria and Alphaproteobacteria. MHT recipients demonstrated a marked increase in the relative proportion of the Firmicutes class Erysipelotrichia. These findings suggest that transplantation of gut-microbiomes can confer phenotypic responses to a drug and that the microbiome may be playing a major role in sympathomimetic-mediated hyperthermia. Abbreviations: 3,4-methylenedioxymethamphetamine (MDMA); methylone-induced hyperthermic tolerant (MHT); methylone-naïve (MN); fecal microbiota transplantation (FMT); uncoupling protein (UCP); subcutaneous (sc); intraperitoneal (ip); brown adipose tissue (BAT); skeletal muscle (SKM); sympathetic nervous system (SNS); norepinephrine (NE); quantitative PCR (qRT-PCR); quantification cycle (Cq); High Performance Liquid Chromatography-Electrochemical Detection (HPLC-EC); amplicon sequence variants (ASVs); principal coordinates analysis (PCoA); permutational multivariate analysis (PERMANOVA).}, }
@article {pmid36338232, year = {2022}, author = {Zheng, L}, title = {New insights into the interplay between intestinal flora and bile acids in inflammatory bowel disease.}, journal = {World journal of clinical cases}, volume = {10}, number = {30}, pages = {10823-10839}, pmid = {36338232}, issn = {2307-8960}, abstract = {Intestinal flora plays a key role in nutrient absorption, metabolism and immune defense, and is considered to be the cornerstone of maintaining the health of human hosts. Bile acids synthesized in the liver can not only promote the absorption of fat-soluble substances in the intestine, but also directly or indirectly affect the structure and function of intestinal flora. Under the action of intestinal flora, bile acids can be converted into secondary bile acids, which can be reabsorbed back to the liver through the enterohepatic circulation. The complex dialogue mechanism between intestinal flora and bile acids is involved in the development of intestinal inflammation such as inflammatory bowel disease (IBD). In this review, the effects of intestinal flora, bile acids and their interactions on IBD and the progress of treatment were reviewed.}, }
@article {pmid36338055, year = {2022}, author = {Yang, Z and Fu, H and Su, H and Cai, X and Wang, Y and Hong, Y and Hu, J and Xie, Z and Wang, X}, title = {Multi-omics analyses reveal the specific changes in gut metagenome and serum metabolome of patients with polycystic ovary syndrome.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1017147}, pmid = {36338055}, issn = {1664-302X}, abstract = {OBJECTIVE: The purpose of this study was to investigate the specific alterations in gut microbiome and serum metabolome and their interactions in patients with polycystic ovary syndrome (PCOS).<br><br>METHODS: The stool samples from 32 PCOS patients and 18 healthy controls underwent the intestinal microbiome analysis using shotgun metagenomics sequencing approach. Serum metabolome was analyzed by ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. An integrative network by combining metagenomics and metabolomics datasets was constructed to explore the possible interactions between gut microbiota and circulating metabolites in PCOS, which was further assessed by fecal microbiota transplantation (FMT) in a rat trial.<br><br>RESULTS: Fecal metagenomics identified 64 microbial strains significantly differing between PCOS and healthy subjects, half of which were enriched in patients. These changed species showed an ability to perturb host metabolic homeostasis (including insulin resistance and fatty acid metabolism) and inflammatory levels (such as PI3K/Akt/mTOR signaling pathways) by expressing sterol regulatory element-binding transcription factor-1, serine/threonine-protein kinase mTOR, and 3-oxoacyl-[acyl-cattier-protein] synthase III, possibly suggesting the potential mechanisms of gut microbiota underlying PCOS. By integrating multi-omics datasets, the panel comprising seven strains (Achromobacter xylosoxidans, Pseudomonas sp. M1, Aquitalea pelogenes, Porphyrobacter sp. HL-46, Vibrio fortis, Leisingera sp. ANG-Vp, and Sinorhizobium meliloti) and three metabolites [ganglioside GM3 (d18:0/16:0), ceramide (d16:2/22:0), and 3Z,6Z,9Z-pentacosatriene] showed the highest predictivity of PCOS (AUC: 1.0) with sensitivity of 0.97 and specificity of 1.0. Moreover, the intestinal microbiome modifications by FMT were demonstrated to regulate PCOS phenotypes including metabolic variables and reproductive hormones.<br><br>CONCLUSION: Our findings revealed key microbial and metabolite features and their interactions underlying PCOS by integrating multi-omics approaches, which may provide novel insights into discovering clinical diagnostic biomarkers and developing efficient therapeutic strategies for PCOS.}, }
@article {pmid36336379, year = {2022}, author = {Aira, A and Rubio, E and Fehér, C and González-Suárez, B and Casals-Pascual, C and Soriano, &#xc1;}, title = {Stool donor recruitment - A one-year experience.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {40}, number = {9}, pages = {495-498}, doi = {10.1016/j.eimce.2021.01.010}, pmid = {36336379}, issn = {2529-993X}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Clostridium Infections ; Feces ; Tissue Donors ; *Microbiota ; }, abstract = {Stool donors for fecal microbiota transference (FMT) should be rigorously screened to identify any disorder in health status. The success of our screening protocol to identify eligible donors in the last year and a half was evaluated and compared with the published literature. The target population was medical students who responded to 3 public calls to donate stools. Qualified donors brought stool samples to our lab. Out of the 110 students who responded to the call, 26 were enrolled as study donors and delivered at least one stool sample. The main reason for volunteer exclusion was body mass index (BMI) <18.5kg/m[2] or >25kg/m[2] (n=11) and for the identification of ESBL Escherichia coli in feces (n=3). Our success rate after the screening protocol was considered high. Understanding the incentives to participate is critical to the success of recruitment strategies as FMT is still a little-known practice for general population.}, }
@article {pmid36329546, year = {2022}, author = {Terry, SM and Barnett, JA and Gibson, DL}, title = {A critical analysis of eating disorders and the gut microbiome.}, journal = {Journal of eating disorders}, volume = {10}, number = {1}, pages = {154}, pmid = {36329546}, issn = {2050-2974}, abstract = {The gut microbiota, also known as our "second brain" is an exciting frontier of research across a multitude of health domains. Gut microbes have been implicated in feeding behaviour and obesity, as well as mental health disorders including anxiety and depression, however their role in the development and maintenance of eating disorders (EDs) has only recently been considered. EDs are complex mental health conditions, shaped by a complicated interplay of factors. Perhaps due to an incomplete understanding of the etiology of EDs, treatment remains inadequate with affected individuals likely to face many relapses. The gut microbiota may be a missing piece in understanding the etiology of eating disorders, however more robust scientific inquiry is needed in the field before concrete conclusions can be made. In this spotlight paper, we critically evaluate what is known about the bi-directional relationship between gut microbes and biological processes that are implicated in the development and maintenance of EDs, including physiological functioning, hormones, neurotransmitters, the central nervous system, and the immune system. We outline limitations of current research, propose concrete steps to move the field forward and, hypothesize potential clinical implications of this research. Our gut is inhabited by millions of bacteria which have more recently been referred to as "our second brain". In fact, these microbes are thought to play a role in ED behaviour, associated anxiety and depression, and even affect our weight. Recent research has dove into this field with promising findings that have the potential to be applied clinically to improve ED recovery. The present paper discusses what is known about the gut microbiome in relation to EDs and the promising implications that leveraging this knowledge, through fecal microbiome transplants, probiotics, and microbiome-directed supplemental foods, could have on ED treatment.}, }
@article {pmid36328641, year = {2022}, author = {Rimawi, RH and Busby, S and Greene, WR}, title = {Severe Clostridioides difficile Infection in the Intensive Care Unit-Medical and Surgical Management.}, journal = {Infectious disease clinics of North America}, volume = {36}, number = {4}, pages = {889-895}, doi = {10.1016/j.idc.2022.07.006}, pmid = {36328641}, issn = {1557-9824}, mesh = {Humans ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy ; Fidaxomicin ; Intensive Care Units ; }, abstract = {Clostridioides difficile remains a major cause of morbidity and mortality in the intensive care unit, and therefore, C difficile guidelines are frequently being updated. Currently, fidaxomicin is the suggested treatment of initial and recurrent infection. Oral vancomycin is an acceptable alternative, followed by rifaximin and fecal microbiota transplantation. Bezlotoxumab is suggested in recurrent cases within 6 months. If patients fail to improve within 3 to 5 days of therapy, especially in patients who have had nasogastric tubes or emergent surgery, fulminant colitis is possible and surgical consultation should be considered for total colectomy.}, }
@article {pmid36326575, year = {2022}, author = {Hu, L and Zhao, Y and Liu, S and Zhang, J and Yuan, H and Xu, H}, title = {High-fat diet in mice led to increased severity of spermatogenesis impairment by lead exposure: perspective from gut microbiota and the efficacy of probiotics.}, journal = {Journal of the science of food and agriculture}, volume = {}, number = {}, pages = {}, doi = {10.1002/jsfa.12309}, pmid = {36326575}, issn = {1097-0010}, abstract = {BACKGROUND: The mechanism of multifactorial spermatogenesis impairment is unclear. This study aimed to investigate the reproductive toxicity of lead (Pb) in mice fed a high-fat diet (HFD) and to delineate the important role of gut microbiota.<br><br>RESULTS: Results showed that, compared with mice fed a normal diet (ND), Pb exposure caused more severe spermatogenesis impairment in HFD-fed mice, including decreased sperm count and motility, seminiferous tubule injury, serum and intratesticular testosterone decline, and downregulated expression level of spermatogenesis-related genes. Besides, 16S sequencing indicated that HFD-fed mice had increased severity of gut microbiota dysbiosis by Pb exposure compared to ND-fed mice. With fecal microbiota transplantation, the same trend of spermatogenesis impairment occurred in recipient mice, which confirmed the important role of gut microbiota. Moreover, probiotics supplementation restored the gut microbial ecosystem, and thus improved spermatogenic function.<br><br>CONCLUSION: Our work suggested that a population with HFD might face more reproductive health risks upon Pb exposure, and revealed an intimate linkage between microbiota dysbiosis and spermatogenesis impairment, accompanied by the potential usefulness of probiotics as prophylactic and therapeutic. &#xa9; 2022 Society of Chemical Industry.}, }
@article {pmid36326009, year = {2022}, author = {Gu, Y and Qin, X and Zhou, G and Wang, C and Mu, C and Liu, X and Zhong, W and Xu, X and Wang, B and Jiang, K and Liu, J and Cao, H}, title = {Lactobacillus rhamnosus GG supernatant promotes intestinal mucin production through regulating 5-HT4R and gut microbiota.}, journal = {Food &amp; function}, volume = {13}, number = {23}, pages = {12144-12155}, doi = {10.1039/d2fo01900k}, pmid = {36326009}, issn = {2042-650X}, mesh = {Mice ; Animals ; *Lactobacillus rhamnosus/metabolism ; *Gastrointestinal Microbiome ; Mucins/metabolism ; Intestinal Mucosa/metabolism ; Mice, Inbred C57BL ; Mucin-2/genetics/metabolism ; *Probiotics/therapeutic use ; *Intestinal Diseases/metabolism ; Constipation ; }, abstract = {Lactobacillus rhamnosus GG (LGG) is a well-known probiotic widely used in foods and drugs. It has been reported that LGG can improve bowel dysfunction in gastrointestinal motility disorders, such as constipation; however, the specific mechanisms remain unclear. The colonic mucus layer is mainly composed of mucin secreted by goblet cells, which plays important roles in lubricating colonic contents and maintaining normal defecation function. It has been reported that increased mucin production is beneficial for relieving constipation symptoms. In this study, we aimed to investigate the role of LGG in regulating intestinal mucin production and the associated mechanisms. Six-week-old C57BL/6J mice were randomized into 3 groups, and were treated with De-Man Rogosa and Sharpe broth (MRS group), tegaserod maleate (tegaserod group) and LGG supernatant (LGGs group) by gavage, respectively. After treatments, defecation parameters, intestinal mucin-2 (MUC2) and serotonin 4 receptor (5-HT4R), goblet cells, and microbiota composition of the mice in each group were assessed. In comparison with the MRS group, higher fecal water content and increased fecal pellet number were found in the tegaserod group and LGGs group. Moreover, LGGs increased the number of goblet cells and upregulated the expression of 5-HT4R and MUC2 in the mouse colon. In addition, Alcian Blue Periodic acid Schiff staining showed that activated 5-HT4R enhanced intestinal MUC2 secretion. Further exploration of the mechanism discovered that LGGs upregulated intestinal S100A10, which was found to be involved in regulating 5-HT4R expression. Furthermore, gut microbiota analysis showed the higher abundance of Alistipes, Allobaculum, Desulfovibrio, and Clostridium XlVa in the LGGs group, which have been reported to be involved in regulating gut motility and the intestinal barrier, and alleviating bowel dysfunction. Interestingly, gut dysbiosis was present in the tegaserod group. It is noteworthy that the fecal microbiota transplanted from LGGs-treated mice significantly improved the gut dysmotility in a constipation mouse model. Our results suggested that LGGs could upregulate 5-HT4R to promote MUC2 production, as well as modulate the gut microbiota, thus improving the defecation function in mice. This finding might provide evidence for the application of diet supplementary LGG in relieving gastrointestinal motility disorders.}, }
@article {pmid36325000, year = {2022}, author = {Favero, C and Ortiz, A and Sanchez-Niño, MD}, title = {Probiotics for kidney disease.}, journal = {Clinical kidney journal}, volume = {15}, number = {11}, pages = {1981-1986}, pmid = {36325000}, issn = {2048-8505}, abstract = {Diet has long been known to influence the course of chronic kidney disease (CKD) and may even result in acute kidney injury (AKI). Diet may influence kidney disease through a direct impact of specific nutrients on the human body through modulation of the gut microbiota composition or through metabolites generated by the gut microbiota from ingested nutrients. The potential for interaction between diet, microbiota and CKD has fueled research into interventions aimed at modifying the microbiota to treat CKD. These interventions may include diet, probiotics, prebiotics, fecal microbiota transplant and other interventions that modulate the microbiota and its metabolome. A recent report identified Lactobacillus casei Zhang from traditional Chinese koumiss as a probiotic that may protect mice from AKI and CKD and slow CKD progression in humans. Potential mechanisms of action include modulation of the gut microbiota and increased availability of short-chain fatty acids with anti-inflammatory properties and of nicotinamide. However, the clinical relevance needs validation in large well-designed clinical trials.}, }
@article {pmid36324251, year = {2022}, author = {Bogatic, D and Bryant, RV and Lynch, KD and Costello, SP}, title = {Microbial manipulation as therapy for primary sclerosing cholangitis.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.17251}, pmid = {36324251}, issn = {1365-2036}, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested.<br><br>AIM: To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis.<br><br>METHODS: We conducted a&#xa0;comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC.<br><br>RESULTS: A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking.<br><br>CONCLUSIONS: The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease.}, }
@article {pmid36321732, year = {2022}, author = {Liu, LW and Xie, Y and Li, GQ and Zhang, T and Sui, YH and Zhao, ZJ and Zhang, YY and Yang, WB and Geng, XL and Xue, DB and Chen, H and Wang, YW and Lu, TQ and Shang, LR and Li, ZB and Li, L and Sun, B}, title = {Gut microbiota-derived nicotinamide mononucleotide alleviates acute pancreatitis by activating pancreatic SIRT3 signalling.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.15980}, pmid = {36321732}, issn = {1476-5381}, abstract = {BACKGROUND AND PURPOSE: Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory responses. The alleviation of gut microbiota dysbiosis through faecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota-derived metabolites on AP and further clarify the mechanisms associated with pancreatic damage and inflammation.<br><br>EXPERIMENTAL APPROACH: AP rat and mouse models were established by administration of caerulein or sodium taurocholate in vivo. Pancreatic acinar cells were exposed to caerulein and lipopolysaccharide in vitro to simulate AP.<br><br>KEY RESULTS: Normobiotic FMT alleviated AP-induced gut microbiota dysbiosis and ameliorated the severity of AP, including mitochondrial dysfunction, oxidative damage and inflammation. Normobiotic FMT induced higher levels of NAD[+] (nicotinamide adenine dinucleotide)-associated metabolites, particularly nicotinamide mononucleotide (NMN). NMN administration mitigated AP-mediated mitochondrial dysfunction, oxidative damage and inflammation by increasing pancreatic NAD[+] levels. Similarly, overexpression of the NAD[+] -dependent mitochondrial deacetylase sirtuin 3 (SIRT3) alleviated the severity of AP. Furthermore, SIRT3 deacetylated peroxiredoxin 5 (PRDX5) and enhanced PRDX5 protein expression, thereby promoting its antioxidant and anti-inflammatory activities in AP. Importantly, normobiotic FMT-mediated NMN metabolism induced SIRT3-PRDX5 pathway activation during AP.<br><br>CONCLUSION AND IMPLICATIONS: Gut microbiota-derived NMN alleviates the severity of AP by activating the SIRT3-PRDX5 pathway. Normobiotic FMT could be served as a potential strategy for AP treatment.}, }
@article {pmid36321440, year = {2022}, author = {Losurdo, G and Pricci, M and De Bellis, M and Celiberto, F and Russo, F and Riezzo, G and D'Attoma, B and Iannone, A and Rendina, M and Ierardi, E and di Leo, A}, title = {Effect of metronidazole resistance on Helicobacter pylori eradication regimens.}, journal = {Journal of digestive diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-2980.13142}, pmid = {36321440}, issn = {1751-2980}, abstract = {AIMS: Guidelines suggest bismuth-containing quadruple (BQT) or concomitant regimens (CT) as first line therapy in our geographic area. Both schedules contain metronidazole.<br><br>METHODS: We recruited na&#xef;ve subjects with H. pylori infection in the period January 2020-December 2021, receiving either CT or BQT. Before therapy, patients collected a fecal sample using the THD fecal test device. H. pylori DNA was extracted and mutations rdxA/frxA and A2143G in genes for metronidazole and clarithromycin resistance were respectively investigated using RT-PCR with high resolution melting curve.<br><br>RESULTS: Ninety-six patients were enrolled: 29 received BQT and 67 CT. The overall eradication rate was 94.8%, in detail 100% for BQT and 92.5% for CT, respectively. Metronidazole resistance was found in 18 subjects (18.8%), while clarithromycin resistance in 19 (19.8%). All 18 patients with metronidazole resistance experienced eradication. Five had assumed BQT and 13 CT. The eradication rate in metronidazole-sensitive strains was 93.6%. Of these, 24 received BQT with 100% success, and 54 had CT with 5 failures (success 90.7%). Two failing patients were resistant to clarithromycin, and the remaining 3 were susceptible to both clarithromycin and metronidazole. We did not observe any statistical significance in the eradication rate between metronidazole-resistant and sensitive strains (100% versus 93.6%, respectively, p&#xa0;=&#xa0;0.58).<br><br>CONCLUSIONS: Our results suggest that metronidazole resistance does not influence the eradication rate of BQT and CT regimens in our geographical area, even if such result needs to confirmed in a larger sample.}, }
@article {pmid36318049, year = {2022}, author = {Wang, J and Chen, J and Li, L and Zhang, H and Pang, D and Ouyang, H and Jin, X and Tang, X}, title = {Clostridium butyricum and Bifidobacterium pseudolongum Attenuate the Development of Cardiac Fibrosis in Mice.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0252422}, doi = {10.1128/spectrum.02524-22}, pmid = {36318049}, issn = {2165-0497}, abstract = {Cardiac fibrosis is an integral aspect of every form of cardiovascular diseases, which is one of the leading causes of death worldwide. It is urgent to explore new effective drugs and treatments. In this paper, transverse aortic constriction (TAC)-induced cardiac fibrosis was significantly alleviated by a cocktail of antibiotics to clear the intestinal flora, indicating that the gut microbiota was associated with the disease process of cardiac fibrosis. We transplanted feces from sham-operated and TAC-treated mice to mice treated with a cocktail of antibiotics. We found that TAC-treated gut microbiota dysbiosis cannot cause cardiac fibrosis on its own. Interestingly, healthy fecal microbiota transplantation could alleviate cardiac fibrosis, indicating that targeted probiotics and related metabolite intervention may restore a normal microenvironment for the treatment or prevention of cardiac fibrosis. We used 16S rRNA sequencing of fecal samples and discovered that butyric acid-producing bacteria and Bifidobacterium pseudolongum were the dominant bacteria in the group with the lowest degree of cardiac fibrosis. Moreover, we demonstrated that sodium butyrate prevented the development of cardiac fibrosis. The effect of Clostridium butyricum (butyric acid-producing bacteria) was better than that of B. pseudolongum on cardiac fibrosis. Surprisingly, the cocktail of two probiotics had a stronger ability than a single probiotic. In conclusion, therapies targeting the gut microbiota and metabolites such as probiotics present new strategies for treating cardiovascular disease. IMPORTANCE Cardiac fibrosis is a basic process in cardiac remodeling. It is related to almost all types of cardiovascular diseases (CVD) and has become an important global health problem. Basic research and a number of clinical studies have shown that myocardial fibrosis can be prevented and reversed to a certain extent. It is urgent to explore new effective drugs and treatments. We indicated a causal relationship between cardiac fibrosis and gut microbiota. Gut microbiota dysbiosis cannot cause cardiac fibrosis on its own. Interestingly, healthy fecal microbiota transplantation could alleviate cardiac fibrosis. According to our findings, the combined use of butyric acid-producing bacteria and B. pseudolongum can help prevent cardiac fibrosis. Therapies targeting the gut microbiota and metabolites, such as probiotics, represent new strategies for treating cardiovascular disease.}, }
@article {pmid36316361, year = {2022}, author = {Li, Y and Chen, M and Ma, Y and Yang, Y and Cheng, Y and Ma, H and Ren, D and Chen, P}, title = {Regulation of viable/inactivated/lysed probiotic Lactobacillus plantarum H6 on intestinal microbiota and metabolites in hypercholesterolemic mice.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {50}, pmid = {36316361}, issn = {2396-8370}, abstract = {Evidence suggests that probiotic interventions reduce non-communicable diseases (NCDs) risk. However, its therapeutic effect and mechanism are still unclear. To evaluate the hypocholesterolemic effect of Lactobacillus plantarum H6 (L.p H6), a new commercial patent strain capable of preventing hypercholesterolemia, and its mechanism in depth, three states of the strain were prepared, namely, viable (vH6), heat-inactivated (iH6), and ultrasonically-lysed (uH6) bacteria cells. The results showed that v/i/uH6 cells could lower serum and liver blood lipid levels, alleviate liver damage and improve glucose tolerance test (GTT) and insulin tolerance test (ITT) indexes. v/i/uH6 cells improved the gut microbial composition and significantly reduced the Firmicutes to Bacteroidetes ratio (F/B ratio) in feces. In particular, Muribaculaceae may be a potential biomarker for effective cholesterol reduction. Also, the recovery of these biochemical indices and gut microbiome was found following fecal microbiota transplantation (FMT) using stool from vH6 treated mice. The v/i/uH6 cells increased the intestinal flora metabolism of vitamins-cofactors, as well as amino acids, while decreasing the relative content of primary bile acids. The Pearson correlation analysis showed that norank_f__Muribaculaceae and Lactobacillus had a negative correlation with blood lipid levels. Overall, v/i/uH6 cells were effective in improving hypercholesterolemia in mice, and this effect was attributed partly to the regulation of intestinal microbiota and metabolites related to lipid metabolism. Our findings provided a theoretical basis for the industrial development of probiotics and postbiotics and the treatment of cholesterol diseases.}, }
@article {pmid36315335, year = {2022}, author = {Mi, F and Wang, X and Zheng, W and Wang, J and Lin, T and Sun, M and Su, M and Li, H and Ye, H}, title = {Effects of Different Preparation Methods on Microbiota Composition of Fecal Suspension.}, journal = {Molecular biotechnology}, volume = {}, number = {}, pages = {}, pmid = {36315335}, issn = {1559-0305}, abstract = {Fecal microbiota transplantation is an emerging disease-modifying therapy. The viability of the microbiome in feces and its successful transfer depends on the preparation of fecal microbiota suspension. However, currently, no standard operation procedure is proposed for fecal suspension preparation. This study aims to compare the effect of different preparation methods on the composition of fecal microbiota composition in the rat. Four methods were used to collect the fecal suspension from fresh rat fecal (Group A), including stirring with normal saline (Group B), stirring with normal saline and then standing (Group C), stirring with normal saline and filtered with gauze (Group D), and stirring with normal saline and centrifuged (Group E). 16S ribosomal RNA gene (16S rDNA) sequencing technology was used to analyze the microbiota diversity and composition of each group of samples. Compared with fresh feces, the bacterial richness of the fecal suspension obtained by the four methods was significantly decreased (P < 0.05). The structural similarity with fresh fecal microbiota from high to low is groups B, D, C, and E. All four methods changed the microbiota structure to varying degrees, thus may affect the effect of FMT. In conclusion, choosing different methods to prepare fecal suspensions may help to better optimize the application of FMT.}, }
@article {pmid36313072, year = {2022}, author = {Sarmiento-Andrade, Y and Suárez, R and Quintero, B and Garrochamba, K and Chapela, SP}, title = {Gut microbiota and obesity: New insights.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {1018212}, pmid = {36313072}, issn = {2296-861X}, abstract = {Obesity is a pathology whose incidence is increasing throughout the world. There are many pathologies associated with obesity. In recent years, the influence of the microbiota on both health and pathological states has been known. There is growing information related to changes in the microbiome and obesity, as well as its associated pathologies. Changes associated with age, exercise, and weight changes have been described. In addition, metabolic changes associated with the microbiota, bariatric surgery, and fecal matter transplantation are described. In this review, we summarize the biology and physiology of microbiota in obese patients, its role in the pathophysiology of several disorders associated, and the emerging therapeutic applications of prebiotics, probiotics, and fecal microbiota transplantation.}, }
@article {pmid36312938, year = {2022}, author = {Cui, X and Chen, J and Yang, Y}, title = {Administration of selenomethionine in combination with serine benefits diabetes via gut microbiota.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1007814}, pmid = {36312938}, issn = {1664-302X}, abstract = {Either selenium or serine could modulate glucose homeostasis, however, whether there are synergistic effects of selenium with serine on diabetes remains to be unknown. In the present study, eight male db/m mice were used as a control, and 24 male diabetic db/db mice were either orally gavaged with PBS, or with selenomethionine alone, or with both selenomethionine and serine, to investigate the effects of selenomethionine and serine on body weight and glucose level. Furthermore, intestinal microbiota composition was analyzed and fecal microbiota transplantation (FMT) was performed to explore whether microbes mediate the beneficial effects of selenomethionine and serine. The results showed that administration of selenomethionine decreased body weight, adipose tissue weight and serum glucose level in db/db diabetic mice. Importantly, administration of selenomethionine in combination with serine exerted better effects than selenomethionine alone did. Furthermore, a combined administration of selenomethionine and serine restored the microbial composition in diabetic mice. Corynebacterium glutamicum, Bifidobacterium pseudolongum, and Aerococcus urinaeequi were significantly decreased, whereas Lactobacillus murinus was increased in mice in the selenomethionine group and selenomethionine in combination with serine group, when compared with those in the db/db group. FMT decreased body weight and glucose level in db/db mice, further indicating that microbes play critical roles in the beneficial effects of selenomethionine and serine. Thus, we concluded that administration of selenomethionine in combination with serine benefits diabetes via gut microbes. Our results suggested that the synergic application of selenomethionine and serine could be potentially used for the treatment of diabetes.}, }
@article {pmid36312936, year = {2022}, author = {Pan, T and Zheng, S and Zheng, W and Shi, C and Ning, K and Zhang, Q and Xie, Y and Xiang, H and Xie, Q}, title = {Christensenella regulated by Huang-Qi-Ling-Hua-San is a key factor by which to improve type 2 diabetes.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1022403}, pmid = {36312936}, issn = {1664-302X}, abstract = {There is a lot of evidence that oral hypoglycemic drugs work by affecting gut microbes, but the key strains responsible for this effect are not well known. Huang-Qi-Ling-Hua-San (HQLHS), composed of Astragalus Membranaceus, Ganoderma lucidum, Inonotus obliquus, and Momordica charantia L., is a specially designed Chinese medicine formula to treat type 2 diabetes (T2D). In this study, a mouse model of T2D induced by high-fat diet and streptozotocin was used to explore the mechanism of HQLHS in improving hyperglycemia and hyperlipidemia through multiple rounds of animal experiments, such as HQLHS feeding, fecal microbiota transplantation (FMT), and live bacteria feeding, so as to explore the potential target intestinal flora in its hypoglycemic effect. Results show that such specific taxa as Bifidobacterium, Turicibacter, Alistipes, Romboutsia, and Christensenella were identified to be preferably enriched by HQLHS and then assumed to be the target microbes. Herein, FMT was used to test if the upregulated beneficial bacteria by HQLHS play a therapeutic role. The strain Christensenella minuta DSM 22607 and the strain Christensenella timonensis DSM 102800 were selected to test the beneficial effect of Christensenella taxa on T2D. Diabetic animals supplemented with these strains showed the improvement in blood glucose and lipid metabolism, the promotion of GLP-1 secretion, the increase in antioxidant capacity, the inhibition of hepatic gluconeogenesis, the suppression of intestinal glucose absorption, the enhancement of intestinal barrier, reduced LPS-induced inflammation, and the reduction of branched amino acids (BCAAs) content in the liver. Overall, these data demonstrate that Christensenella plays a beneficial role in T2D and is a target for the action of HQLHS therapy.}, }
@article {pmid36312920, year = {2022}, author = {Yang, JY and Liu, MJ and Lv, L and Guo, JR and He, KY and Zhang, H and Wang, KK and Cui, CY and Yan, BZ and Du, DD and Wang, JH and Ding, Q and Liu, GL and Xu, ZX and Jian, YP}, title = {Metformin alleviates irradiation-induced intestinal injury by activation of FXR in intestinal epithelia.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {932294}, pmid = {36312920}, issn = {1664-302X}, abstract = {Abdominal irradiation (IR) destroys the intestinal mucosal barrier, leading to severe intestinal infection. There is an urgent need to find safe and effective treatments to reduce IR-induced intestinal injury. In this study, we reported that metformin protected mice from abdominal IR-induced intestinal injury by improving the composition and diversity of intestinal flora. The elimination of intestinal microbiota (Abx) abrogated the protective effects of metformin on irradiated mice. We further characterized that treatment of metformin increased the murine intestinal abundance of Lactobacillus, which mediated the radioprotective effect. The administration of Lactobacillus or fecal microbiota transplantation (FMT) into Abx mice considerably lessened IR-induced intestinal damage and restored the radioprotective function of metformin in Abx mice. In addition, applying the murine intestinal organoid model, we demonstrated that IR inhibited the formation of intestinal organoids, and metformin alone bore no protective effect on organoids after IR. However, a combination of metformin and Lactobacillus or Lactobacillus alone displayed a strong radioprotection on the organoid formation. We demonstrated that metformin/Lactobacillus activated the farnesoid X receptor (FXR) signaling in intestinal epithelial cells and hence upregulated tight junction proteins and mucins in intestinal epithelia, increased the number of goblet cells, and augmented the mucus layer thickness to maintain the integrity of intestinal epithelial barrier, which eventually contributed to reduced radiation intestinal injury. In addition, we found that Lactobacillus abundance was significantly increased in the intestine of patients receiving metformin while undergoing abdominal radiotherapy and the abundance was negatively correlated with the diarrhea duration of patients. In conclusion, our results demonstrate that metformin possesses a protective effect on IR-induced intestinal injury by upregulating the abundance of Lactobacillus in the intestine.}, }
@article {pmid36309938, year = {2022}, author = {Wu, Y and Hang, Z and Lei, T and Du, H}, title = {Intestinal Flora Affect Alzheimer's Disease by Regulating Endogenous Hormones.}, journal = {Neurochemical research}, volume = {47}, number = {12}, pages = {3565-3582}, pmid = {36309938}, issn = {1573-6903}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Alzheimer Disease/metabolism ; Intestines ; Brain/metabolism ; Hormones/metabolism ; }, abstract = {Alzheimer's disease (AD) is a central nervous system disease that can lead to cognitive impairment and progressive memory loss. An increasing number of studies have shown that intestinal flora play a crucial role in regulating the brain-gut axis. Short-chain fatty acids are metabolites of intestinal flora that regulate hormone synthesis and play an essential role in microbial-intestinal-brain communication. An imbalance of intestinal flora can promote microglia to secrete proinflammatory factors, cause nerve inflammation, and then affect cognitive and learning ability. However, the mechanism is not clear. From this, we infer that endogenous hormones may be the medium for intestinal flora to affect the process of AD. This review of the relationships among AD, endogenous hormones, and intestinal flora expounds on the critical role of various hormones in the brain-gut axis. It discusses intervention measures aimed at intestinal flora to prevent or delay AD occurrence. Finally, the potential development prospects of fecal microbiota transplantation in treating AD are put forward, which provide potential ideas for future AD research.}, }
@article {pmid36309716, year = {2022}, author = {Ma, J and Chen, T and Ma, X and Zhang, B and Zhang, J and Xu, L and Wang, Y and Huang, J and Liu, Z and Wang, F and Tang, X}, title = {Comprehensive bibliometric and visualized analysis of research on fecal microbial transplantation published from 2000 to 2021.}, journal = {Biomedical engineering online}, volume = {21}, number = {1}, pages = {78}, pmid = {36309716}, issn = {1475-925X}, mesh = {*Biomedical Research ; Publications ; Bibliometrics ; China ; }, abstract = {BACKGROUND: Fecal microbial transplantation has emerged in recent years as a method of treating disease by rebuilding the intestinal flora. However, few bibliometric analyses have systematically studied this area of research. We aimed to use bibliometric analysis to visualize trends and topical research in fecal microbial transplantation to help provide insight into future trends in clinical and basic research.<br><br>MATERIALS AND METHODS: Articles and reviews related to fecal microbial transplantation were collected from the Web of Science Core Collection. Significant information associated with this field was visually analyzed by using Biblioshiny and CtieSpace software.<br><br>RESULTS: A total of 3144 articles and overviews were included. The number of publications related to fecal microbial transplantation significantly increased yearly. These publications mainly came from 100 countries, led by the US and China, and 521 institutions. The most prolific and influential author is KHORUTS A. The main disciplines and application fields of fecal microbial transplantation included molecular /biology/immunology and medicine/clinical medicine, and the research foundation of fecal microbial transplantation was molecular /biology/genetics and health/nursing/medicine. An alluvial flow visualization showed several landmark articles. New developments were identified in terms of reference and keyword citation bursts. Data analysis showed that different FMT preparation and delivery methods gradually appeared as research hotspots. The main research keywords in the last 3&#xa0;years were chain fatty acids, Akkermansia muciniphila, and insulin sensitivity, other keywords were current and developing research fields.<br><br>CONCLUSION: Research on fecal microbial transplantation is flourishing and many new applications of fecal microbial transplantation are emerging. Microbial metabolites such as short-chain fatty acids and the microbiota-gut-brain axis have become the focus of current research and are future research trends.}, }
@article {pmid36309224, year = {2022}, author = {Najafi, S and Majidpoor, J and Mortezaee, K}, title = {The impact of microbiota on PD-1/PD-L1 inhibitor therapy outcomes: A focus on solid tumors.}, journal = {Life sciences}, volume = {310}, number = {}, pages = {121138}, doi = {10.1016/j.lfs.2022.121138}, pmid = {36309224}, issn = {1879-0631}, mesh = {Humans ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy/methods ; *Neoplasms/drug therapy ; *Gastrointestinal Microbiome ; }, abstract = {Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in the last decade. Among various checkpoints identified so far, interaction between programmed death-1 (PD-1) with programmed death ligand 1 (PD-L1) and their targeting using human monoclonal antibodies has attracted the most attention and is considered as the most prominent treatment with the best clinical outcomes. Accumulating evidence is the witness for the impact of gut microbiota on clinical responses and ICI efficacy. Specific bacterial species are identified in fecal specimens of cancer patients responding to the anti-PD-(L)1 immunotherapy, while non-responders demonstrate high abundance of other bacterial sources. Thus, the composition of gut microbiota may suggest potential biomarker in identification of patients with the best responses to immunotherapy. Notably, fecal microbial transplantation (FMT) from responders to non-responders has shown hopeful results in improving clinical outcomes and overcoming resistance to ICIs. Additionally, some bacterial components, such as the use of antibiotics and probiotic supplements have been shown to affect the efficacy of ICIs treatment. However, employment of these findings requires further investigations and precise understanding of the impact of gut microbiota on the host's immune responses. In the current review, we aim to discuss the roles of PD-1/PD-L1 checkpoint pathway, their therapeutic significance, and the impact of gut microbiota/products on the PD-1/PD-L1 immunotherapy outcomes.}, }
@article {pmid36309048, year = {2022}, author = {Xu, H and Yang, F and Bao, Z}, title = {Gut microbiota and myocardial fibrosis.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {175355}, doi = {10.1016/j.ejphar.2022.175355}, pmid = {36309048}, issn = {1879-0712}, abstract = {Myocardial fibrosis (MF) is a pathophysiological condition that accompanies various myocardial diseases and comprises a damaged myocardial matrix repair process. Although fibrosis plays a vital role in repair, it ultimately alters cardiac systolic and diastolic functions. The gut microbiota is a complex and dynamic ecosystem with billions of microorganisms that produce bioactive compounds that influence host health and disease progression. Intestinal microbiota has been shown to correlate with cardiovascular disease, and dysbiosis of the intestinal microbiota is involved in the development of MF. In this review, we discuss the role of intestinal microbiota in the process of MF, including alterations in microbiota composition and the effects of metabolites. We also discuss how diet and medicines can affect cardiac fibrosis by influencing the gut microbiota, and potential future therapies targeting the gut-heart axis. A healthy gut microbiota can prevent disease, but dysbiosis can lead to various symptoms, including the induction of heart disease. In this review, we discuss the relevance of the gut-heart axis and the multiple pathways by which gut microbiota may affect cardiac fibrosis, including inflammatory factors, immune cells, and gut microbiota metabolites, such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs). Finally, we discuss the involvement of gut microbiota in the treatment of cardiac fibrosis, including drugs, fecal microbiota transplantation, and oral probiotics or prebiotics. With future studies on the relationship between the heart and gut microbiota, we hope to find better ways to improve MF through the gut-heart axis.}, }
@article {pmid36305395, year = {2022}, author = {Ju, Y and Wang, X and Wang, Y and Li, C and Yue, L and Chen, F}, title = {[Application of metagenomic and culturomic technologies in fecal microbiota transplantation: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {38}, number = {10}, pages = {3594-3605}, doi = {10.13345/j.cjb.220573}, pmid = {36305395}, issn = {1872-2075}, mesh = {Humans ; *Fecal Microbiota Transplantation ; Metagenomics ; Feces/microbiology ; *Gastrointestinal Microbiome ; Bacteria ; }, abstract = {Fecal microbiota transplantation (FMT) refers to using the intestinal microorganisms present in the feces or processed feces from healthy people for treating various types of diseases, such as digestive and metabolic diseases. The rapid development of metagenomic and culturomic technologies in gut microbiome analysis provides powerful tools for the FMT research and its clinical applications. Metagenomics technologies comprehensively revealed the diversity and functions of gut microbiota under health and disease conditions, while culturomics technologies helped isolation and identification of "unculturable" bacteria in the human gut under conventional culture conditions. The combination of these two technologies not only enabled us better understand the FMT regularities of cause and effect in clinical practices, but also effectively promoted its applications. Considering the above advantages, this article summarized the applications of metagenomics and culturomics technologies in FMT and prospected its future development trend.}, }
@article {pmid36304525, year = {2022}, author = {Zou, B and Liu, SX and Li, XS and He, JY and Dong, C and Ruan, ML and Xu, L and Bai, T and Huang, ZH and Shu, SN}, title = {Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {964154}, pmid = {36304525}, issn = {2296-2360}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for intestinal and extra-intestinal disorders. Nonetheless, long-term safety and efficacy remain major challenges for FMT applications. To date, few long-term follow-up studies have been published on FMT in children.<br><br>METHODS: Retrospective reviewed the medical charts of 74 patients who underwent 508 FMT courses between August 2014 and July 2019 at our medical center. All the FMT procedures followed uniform standards. Baseline characteristics pre-FMT and follow-up data were collected at 1, 3, 6, 12, 36, 60, and 84 months after FMT. All potential influencing factors for adverse events (AEs) were analyzed and assessed using regression analyses.<br><br>RESULTS: A total of 70 (13.7%) short-term AEs occurred in twenty-six patients (35.1%). Most AEs (88.5%) occurred within 2 days post-FMT. A total of 91.4% of the AEs were self-limiting. Ulcerative colitis (UC) and within four times of FMT were associated with a higher rate of AEs (p = 0.028 and p = 0.021, respectively). The primary clinical remission rate after FMT was as high as 72.9%. Twenty-five children were followed for more than 5 years after FMT. The clinical remission rates gradually decreased over time after FMT. During follow-up, none of the patients developed autoimmune, metabolic, or rheumatologic disorders or tumor-related diseases. However, nine children developed rhinitis, five developed rhinitis, were underweight, and six developed constipation.<br><br>CONCLUSIONS: FMT is a safe and effective treatment for dysbiosis in children. The long-term efficacy of FMT for each disease decreased over time. Moreover, multiple FMTs are recommended 3 months post-FMT for recurrent diseases.}, }
@article {pmid36302811, year = {2022}, author = {Aalam, SMM and Crasta, DN and Roy, P and Miller, AL and Gamb, SI and Johnson, S and Till, LM and Chen, J and Kashyap, P and Kannan, N}, title = {Genesis of fecal floatation is causally linked to gut microbial colonization in mice.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {18109}, pmid = {36302811}, issn = {2045-2322}, mesh = {Mice ; Humans ; Animals ; *Gastrointestinal Microbiome ; Feces/microbiology ; Fecal Microbiota Transplantation ; Metagenomics ; Bacteria/genetics ; }, abstract = {The origin of fecal floatation phenomenon remains poorly understood. Following our serendipitous discovery of differences in buoyancy of feces from germ-free and conventional mice, we characterized microbial and physical properties of feces from germ-free and gut-colonized (conventional and conventionalized) mice. The gut-colonization associated differences were assessed in feces using DNA, bacterial-PCR, scanning electron microscopy, FACS, thermogravimetry and pycnometry. Based on the differences in buoyancy of feces, we developed levô in fimo test (LIFT) to distinguish sinking feces (sinkers) of germ-free mice from floating feces (floaters) of gut-colonized mice. By simultaneous tracking of microbiota densities and gut colonization kinetics in fecal transplanted mice, we provide first direct evidence of causal relationship between gut microbial colonization and fecal floatation. Rare discordance in LIFT and microbiota density indicated that enrichment of gasogenic gut colonizers may be necessary for fecal floatation. Finally, fecal metagenomics analysis of 'floaters' from conventional and syngeneic fecal transplanted mice identified colonization of > 10 gasogenic bacterial species including highly prevalent B. ovatus, an anaerobic commensal bacteria linked with flatulence and intestinal bowel diseases. The findings reported here will improve our understanding of food microbial biotransformation and gut microbial regulators of fecal floatation in human health and disease.}, }
@article {pmid36301100, year = {2022}, author = {Bai, X and Liu, G and Yang, J and Zhu, J and Wang, Q and Zhou, Y and Gu, W and La, L and Li, X}, title = {Changes in the Gut Microbiota of Rats in High-Altitude Hypoxic Environments.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0162622}, doi = {10.1128/spectrum.01626-22}, pmid = {36301100}, issn = {2165-0497}, abstract = {This study was conducted to investigate the effects of high-altitude hypoxic environments on the gut microbiota. Male Sprague-Dawley rats were randomly divided into three groups, namely, the plain, moderate-altitude hypoxic, and high-altitude hypoxic groups. On the 3rd, 7th, 15th, and 30th days of exposure, fecal samples were collected and analyzed via 16S rRNA gene sequencing technology. Fecal microbiota transplantation (FMT) experiments were also performed. The results showed significant differences between the gut microbiota structure and diversity of rats in the high-altitude hypoxic group and those of rats in the other groups. Further, compared with that of rats in the plain group, the gut microbiota of rats in the two hypoxic groups showed the most significant changes on day 7. Furthermore, the gut microbiota of the rats in the FMT groups exhibited changes and became increasingly similar to those of the rats in the hypoxic groups. We also identified the phylum Firmicutes, genus Akkermansia, and genus Lactobacillus as the core microbiota under hypoxic conditions. Phenotypic analysis indicated a decrease in the proportion of aerobic bacteria and an increase in that of anaerobic bacteria, possibly owing to the high-altitude hypoxic environment. Additionally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including carbohydrate metabolism, energy metabolism, glycan biosynthesis, and metabolism. These findings indicated significant changes in gut microbiota structure and diversity under high-altitude hypoxia, establishing a foundation for further research on the pathogenesis and development of diseases, as well as drug metabolism, under high-altitude hypoxia. IMPORTANCE In this study, we investigated the effects of high-altitude hypoxic environments with low oxygen levels on the gut microbiota characteristics of rats. We observed that high-altitude hypoxia is an important environmental factor that can affect gut microbiota structure and diversity, thereby affecting homeostasis in the host intestinal environment. These findings provide a basis for further studies on disease initiation and development, as well as drug metabolism, in high-altitude hypoxic environments.}, }
@article {pmid36300959, year = {2022}, author = {Patwa, SA and Ward, C and Kelly, CR}, title = {FMT: What's Next? A Narrative Review of Fecal Microbiota Transplantation in Clostridioides difficile Infection and Inflammatory Bowel Disease.}, journal = {Rhode Island medical journal (2013)}, volume = {105}, number = {9}, pages = {20-24}, pmid = {36300959}, issn = {2327-2228}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; Treatment Outcome ; *Clostridium Infections/therapy/complications ; *Inflammatory Bowel Diseases/therapy/complications ; Chronic Disease ; }, abstract = {Fecal microbiota transplantation (FMT) is an increasingly employed treatment option for Clostridioides difficile infection (CDI), with growing data supporting its safety and effectiveness in patients with concurrent inflammatory bowel disease (IBD). Given that alterations in the gut microbiome are associated with both ulcerative colitis (UC) and Crohn's disease (CD), the use of FMT for the treatment of IBD itself is another area of active investigation. In this narrative review, we highlight the evidence for use of FMT in the treatment of CDI in patients with IBD, as well as for IBD alone, and provide insight into the future of microbiome therapeutics.}, }
@article {pmid36300928, year = {2022}, author = {Chen, J and Zeng, P and Gong, L and Zhang, X and Ling, Z and Bi, K and Shi, F and Wang, K and Zhang, Q and Jiang, J and Zhang, Y and Uede, T and El-Omar, EM and Diao, H}, title = {Osteopontin Exacerbates High-Fat Diet-Induced Metabolic Disorders in a Microbiome-Dependent Manner.}, journal = {mBio}, volume = {}, number = {}, pages = {e0253122}, doi = {10.1128/mbio.02531-22}, pmid = {36300928}, issn = {2150-7511}, abstract = {The gut microbiome is involved in metabolic disorders. Osteopontin (OPN), as a key cytokine, contributes to various inflammation-related diseases. The underlying role of OPN in the microbiome remains poorly understood. Here, we investigated whether OPN could modulate metabolic disorders by affecting gut microbiota. In our present study, we found that the expression of OPN was elevated in individuals with obesity compared to that observed in healthy controls. There was a positive correlation between plasma OPN levels and body mass index (BMI) in humans. Moreover, OPN significantly exacerbated lipid accumulation and metabolic disorders in high-fat diet (HFD)-fed mice. Importantly, OPN significantly aggravated HFD-induced gut dysbiosis with a key signature profile. Fecal microbiota transplantation also supported the role of OPN in HFD-induced metabolic disorders in a microbiota-dependent manner. Moreover, the microbiome shift of OPN-deficient mice would be compensated to resemble those of wild-type mice by feeding with either OPN-containing milk or recombinant OPN protein in vivo. Furthermore, metagenomic analysis showed that OPN induced a higher abundance of Dorea and a lower abundance of Lactobacillus, which were positively and negatively correlated with body weight, respectively. Indeed, the abundance of Dorea was significantly decreased after Lactobacillus administration, suggesting that OPN may regulate the intestinal abundance of Dorea by reducing the colonization of Lactobacillus. We further confirmed that OPN decreased the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. This study suggested that OPN could exacerbate HFD-induced metabolic dysfunctions through the OPN-induced alteration of the gut microbiome. Therefore, OPN could be a potential therapeutic target for metabolic syndrome. IMPORTANCE Gut microbiota are involved in metabolic disorders. However, microbiome-based therapeutic interventions are not always effective, which might be due to interference of the host factors. Here, we identified a strong positive correlation between OPN levels and BMI in humans. Next, we confirmed that OPN could aggravate high-fat diet-induced metabolic disorders in mice. Importantly, we found that fecal microbiota transplantation from OPN-deficient mice significantly alleviated metabolic disorders in WT mice. OPN directly induces the remodeling of the gut microbiota both in vitro and in vivo. These findings indicate that OPN could contribute to metabolic disorders by inducing an alteration of gut microbiota. OPN regulated the relative abundance of Lactobacillus by decreasing the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. These data identify OPN as a potential pharmaceutical target for weight control and for the treatment of metabolic disorders.}, }
@article {pmid36297012, year = {2022}, author = {Kaczynska, A and Klosinska, M and Chmiel, P and Janeczek, K and Emeryk, A}, title = {The Crosstalk between the Gut Microbiota Composition and the Clinical Course of Allergic Rhinitis: The Use of Probiotics, Prebiotics and Bacterial Lysates in the Treatment of Allergic Rhinitis.}, journal = {Nutrients}, volume = {14}, number = {20}, pages = {}, pmid = {36297012}, issn = {2072-6643}, mesh = {Humans ; Prebiotics ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Rhinitis, Allergic/therapy ; }, abstract = {Although massive progress in discovering allergic rhinitis (AR) aetiology has been made in recent years, its prevalence is still rising and it significantly impacts patients' lives. That is why further and non-conventional research elucidating the role of new factors in AR pathogenesis is needed, facilitating discoveries of new treatment approaches. One of these factors is the gut microbiota, with its specific roles in health and disease. This review presents the process of gut microbiota development, especially in early life, focusing on its impact on the immune system. It emphasizes the link between the gut microbiota composition and immune changes involved in AR development. Specifically, it elucidates the significant link between bacteria colonizing the gut and the Th1/Th2 imbalance. Probiotics, prebiotics and bacterial lysates, which are medications that restore the composition of intestinal bacteria and indirectly affect the clinical course of AR, are also discussed.}, }
@article {pmid36296961, year = {2022}, author = {Chen, YH and Yuan, W and Meng, LK and Zhong, JC and Liu, XY}, title = {The Role and Mechanism of Gut Microbiota in Pulmonary Arterial Hypertension.}, journal = {Nutrients}, volume = {14}, number = {20}, pages = {}, pmid = {36296961}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Pulmonary Arterial Hypertension ; Lipopolysaccharides ; Serotonin ; Dysbiosis/microbiology ; Fatty Acids, Volatile ; Inflammation ; *Probiotics ; }, abstract = {Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease characterized by increased pulmonary vascular resistance, pulmonary vasoconstriction, and right ventricular hypertrophy. Recent developments in genomics and metabolomics have gradually revealed the roles of the gut microbiota (GM) and its metabolites in cardiovascular diseases. Accumulating evidence reveals that the GM plays important roles in the occurrence and development of PAH. Gut microbiota dysbiosis directly increases the gut permeability, thereby facilitating pathological bacterial translocation and allowing translocation of bacterial products such as lipopolysaccharides from the gut into circulation. This process aggravates pulmonary perivascular inflammation and exacerbates PAH development through the endothelial-mesenchymal transition. Additionally, a shift in the composition of PAH also affects the gut metabolites. Changes in gut metabolites, such as decreased short-chain fatty acids, increased trimethylamine N-oxide, and elevated serotonin, contribute to pulmonary perivascular inflammation and pulmonary vascular remodeling by activating several signaling pathways. Studies of the intestinal microbiota in treating pulmonary hypertension have strengthened linkages between the GM and PAH. Probiotic therapy and fecal microbiota transplantation may supplement existing PAH treatments. In this article, we provide new insight for diagnosing, preventing and treating PAH by adding to the current knowledge of the intestinal flora mechanisms and its metabolites efficacy involved in PAH.}, }
@article {pmid36296186, year = {2022}, author = {Guzzo, GL and Mittinty, MN and Llamas, B and Andrews, JM and Weyrich, LS}, title = {Individuals with Inflammatory Bowel Disease Have an Altered Gut Microbiome Composition of Fungi and Protozoa.}, journal = {Microorganisms}, volume = {10}, number = {10}, pages = {}, pmid = {36296186}, issn = {2076-2607}, abstract = {It is known that the bacterial gut microbiome is altered in inflammatory bowel disease (IBD), but far less is known about the role of eukaryotic microorganisms in IBD. While eukaryotes are rarer than bacteria within the gastrointestinal environment, the current literature suggests that they may also be implicated in IBD. In our study, we characterized these often-neglected eukaryotic microbial communities by identifying fungi and protozoa in published shotgun stool metagenomes from 355 people with IBD (206 with Crohn's disease, 126 with ulcerative colitis, and 23 with IBD-unclassified) and 471 unaffected healthy individuals. The individuals with IBD had a higher prevalence of fungi, particularly Saccharomyces cerevisiae, and a lower prevalence of protozoa, particularly Blastocystis species (subtypes 1, 2, 3, and 4). Regression analysis showed that disease state, age, and BMI were associated with the prevalence and abundance of these two genera. We also characterized the eukaryotic gut microbiome in a shotgun stool metagenomic dataset from people with IBD who received fecal transplants, with samples pre- and post-transplantation, and from their donors. We found that in some FMT recipients, a single eukaryotic species remained stable over time, while in other recipients, the eukaryotic composition varied. We conclude that the eukaryotic gut microbiome is altered and varies over time in IBD, and future studies should aim to include these microbes when characterizing the gut microbiome in IBD.}, }
@article {pmid36296181, year = {2022}, author = {Jensen, C and Antonsen, MF and Lied, GA}, title = {Gut Microbiota and Fecal Microbiota Transplantation in Patients with Food Allergies: A Systematic Review.}, journal = {Microorganisms}, volume = {10}, number = {10}, pages = {}, pmid = {36296181}, issn = {2076-2607}, abstract = {The prevalence of food allergies (FAs) has increased considerably in recent decades, with the only available treatment being the avoidance of the specific food items causing the allergy. FAs may have a major impact on quality of life, and it is of great interest to explore new strategies to prevent and treat FAs. Some studies show an altered gut microbiota profile in individuals with FAs, and the modulation of gut microbiota is therefore proposed as a potential strategy for prevention and treatment. This systematic review aimed to investigate: (1) the gut microbiota profile in individuals with FAs compared to healthy individuals and (2) the effect of fecal microbiota transplantation (FMT) on gut microbiota profiles and/or allergy symptoms. A literature search was conducted in PubMed (Medline) on 5 April 2022. Of the 236 publications identified, 12 studies were included based on inclusion and exclusion criteria. Eleven of these studies reported results on the gut microbiota in children with FAs compared to healthy controls (HCs). The majority of studies (six studies) observed no difference in alpha diversity when comparing children with FAs to HCs; however, a difference in beta diversity was observed in five studies. At the phylum level, we observed a high abundance of Firmicutes (six studies) and Proteobacteria (five studies), whereas a low abundance of Bacteroidetes (5 studies) was observed in children with FAs compared to HCs. Of the 12 included studies, four explored the effect of FMT on gut microbiota and/or allergy symptoms. Three studies reported that transferring gut microbiota from children without FAs to germ-free mice, protected the mice against allergic reactions, whereas one study did not report findings on the allergic symptoms. The results on gut microbiota after FMT varied and were too divergent to draw any conclusions. Overall, our results suggest that there are differences in the gut microbiota profile in individuals with FAs compared to individuals without FAs. FMT seems to be a promising strategy to prevent allergic symptoms but needs to be further explored in animal and human models. As the findings in this review are based on a small number of studies (12 studies), further studies are warranted before any clear conclusions can be drawn regarding gut microbiota profiles and the effect of FMT on individuals with FAs.}, }
@article {pmid36293176, year = {2022}, author = {Varesi, A and Campagnoli, LIM and Fahmideh, F and Pierella, E and Romeo, M and Ricevuti, G and Nicoletta, M and Chirumbolo, S and Pascale, A}, title = {The Interplay between Gut Microbiota and Parkinson's Disease: Implications on Diagnosis and Treatment.}, journal = {International journal of molecular sciences}, volume = {23}, number = {20}, pages = {}, pmid = {36293176}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Parkinson Disease/diagnosis/therapy/pathology ; Dysbiosis/therapy ; Anti-Bacterial Agents ; Biomarkers ; }, abstract = {The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson's disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment.}, }
@article {pmid36291139, year = {2022}, author = {Svensson, CK and Cold, F and Ribberholt, I and Zangenberg, M and Mirsepasi-Lauridsen, HC and Petersen, AM and Helms, M}, title = {The Efficacy of Faecal Microbiota Transplant and Rectal Bacteriotherapy in Patients with Recurrent Clostridioides difficile Infection: A Retrospective Cohort Study.}, journal = {Cells}, volume = {11}, number = {20}, pages = {}, pmid = {36291139}, issn = {2073-4409}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; Retrospective Studies ; *Clostridium Infections/therapy ; Treatment Outcome ; }, abstract = {The most effective treatment for recurrent Clostridioides difficile infection (CDI) is faecal microbiota transplantation (FMT); however, the optimal route of administration is thus far unknown. This retrospective cohort study of 343 patients sought to evaluate the efficacy of treatment with FMT capsules, FMT enema, and rectal bacteriotherapy (RBT) during a five-year period. The primary endpoint was clinical resolution from CDI after eight weeks, and secondary endpoints were time to recurrence and death during the follow-up period. The proportion of patients with clinical resolution was 79.9% in the FMT capsule group, 53.3% in the FMT enema group, and 61.8% in the RBT group, corresponding to an adjusted odds ratio of 3.79 (CI: 1.82 to 8.26) in the FMT capsule group compared with FMT enema, and 2.92 (CI: 1.49 to 6.03) compared with RBT. The hazards ratio for recurrence within the first 12 months of follow-up was 0.24 (CI: 0.06 to 0.89) in the FMT capsule group compared with FMT enema, and 0.26 (CI: 0.08 to 0.91) compared with RBT. There was no difference in mortality. In conclusion, FMT capsules were more effective than both FMT enema and RBT as treatment of recurrent CDI and reduced the risk of further recurrences.}, }
@article {pmid36289668, year = {2022}, author = {Shin, J and Lee, JH and Park, SH and Cha, B and Kwon, KS and Kim, H and Shin, YW}, title = {Efficacy and Safety of Fecal Microbiota Transplantation for Clearance of Multidrug-Resistant Organisms under Multiple Comorbidities: A Prospective Comparative Trial.}, journal = {Biomedicines}, volume = {10}, number = {10}, pages = {}, pmid = {36289668}, issn = {2227-9059}, abstract = {Fecal microbiota transplantation (FMT) could decolonize multidrug-resistant organisms. We investigated FMT effectiveness and safety in the eradication of carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant enterococci (VRE) intestinal colonization. A prospective non-randomized comparative study was performed with 48 patients. FMT material (60 g) was obtained from a healthy donor, frozen, and administered via endoscopy. The primary endpoint was 1-month decolonization, and secondary endpoints were 3-month decolonization and adverse events. Microbiota analysis of fecal samples was performed using 16S rRNA sequencing. Intention-to-treat analysis revealed overall negative conversion between the FMT and control groups at 1 (26% vs. 10%, p = 0.264) and 3 (52% vs. 24%, p = 0.049) months. The 1-month and 3-month CRE clearance did not differ significantly by group (36% vs. 10%, p = 0.341; and 71% vs. 30%, p = 0.095, respectively). Among patients with VRE, FMT was ineffective for 1-month or 3-month negative conversion (13% vs. 9%, p > 0.999; and 36% vs. 18%, p = 0.658, respectively) However, cumulative overall negative-conversion rate was significantly higher in the FMT group (p = 0.037). Enterococcus abundance in patients with VRE significantly decreased following FMT. FMT may be effective at decolonizing multidrug-resistant organisms in the intestinal tract.}, }
@article {pmid36289064, year = {2022}, author = {Nzabarushimana, E and Tang, H}, title = {Functional profile of host microbiome indicates Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2135963}, pmid = {36289064}, issn = {1949-0984}, support = {R01 AI143254/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Clostridioides difficile/genetics ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/methods ; *Microbiota ; Anti-Bacterial Agents/therapeutic use ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) is a gastro-intestinal (GI) infection that illustrates how perturbations in symbiotic host-microbiome interactions render the GI tract vulnerable to the opportunistic pathogens. CDI also serves as an example of how such perturbations could be reversed via gut microbiota modulation mechanisms, especially fecal microbiota transplantation (FMT). However, microbiome-mediated diagnosis of CDI remains understudied. Here, we evaluated the diagnostic capabilities of the fecal microbiome on the prediction of CDI. We used the metagenomic sequencing data from ten previous studies, encompassing those acquired from CDI patients treated by FMT, CDI-negative patients presenting other intestinal health conditions, and healthy volunteers taking antibiotics. We designed a hybrid species/function profiling approach that determines the abundances of microbial species in the community contributing to its functional profile. These functionally informed taxonomic profiles were then used for classification of the microbial samples. We used logistic regression (LR) models using these features, which showed high prediction accuracy (with an average <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>A</mml:mi><mml:mi>U</mml:mi><mml:mi>C</mml:mi><mml:mo>≥</mml:mo><mml:mn>0.91</mml:mn></mml:math>), substantiating that the species/function composition of the gut microbiome has a robust diagnostic prediction of CDI. We further assessed the confounding impact of antibiotic therapy on CDI prediction and found that it is distinguishable from the CDI impact. Finally, we devised a log-odds score computed from the output of the LR models to quantify the likelihood of CDI in a gut microbiome sample and applied it to evaluating the effectiveness of FMT based on post-FMT microbiome samples. The results showed that the gut microbiome of patients exhibited a gradual but steady improvement after receiving successful FMT, indicating the restoration of the normal microbiome functions.}, }
@article {pmid36287379, year = {2022}, author = {Khanna, S and Assi, M and Lee, C and Yoho, D and Louie, T and Knapple, W and Aguilar, H and Garcia-Diaz, J and Wang, GP and Berry, SM and Marion, J and Su, X and Braun, T and Bancke, L and Feuerstadt, P}, title = {Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection.}, journal = {Drugs}, volume = {82}, number = {15}, pages = {1527-1538}, pmid = {36287379}, issn = {1179-1950}, mesh = {Adult ; Humans ; *Clostridioides difficile ; Bayes Theorem ; Diarrhea/drug therapy/prevention &amp; control ; *Clostridium Infections/drug therapy/prevention &amp; control ; Anti-Bacterial Agents/adverse effects ; Treatment Outcome ; Recurrence ; Fecal Microbiota Transplantation/adverse effects ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection, associated with dysbiosis of gut microbiota, has substantial disease burden in the USA. RBX2660 is a live biotherapeutic product consisting of a broad consortium of microbes prepared from human stool that is under investigation for the reduction of recurrent C. difficile infection.<br><br>METHODS: A randomized, double-blind, placebo-controlled, phase III study, with a Bayesian primary analysis integrating data from a previous phase IIb study, was conducted. Adults who had one or more C. difficile infection recurrences with a positive stool assay for C. difficile and who were previously treated with standard-of-care antibiotics were randomly assigned 2:1 to receive a subsequent blinded, single-dose enema of RBX2660 or placebo. The primary endpoint was treatment success, defined as the absence of C. difficile infection diarrhea within 8 weeks of study treatment.<br><br>RESULTS: Of the 320 patients screened, 289 were randomly assigned and 267 received blinded treatment (n = 180, RBX2660; n = 87, placebo). Original model estimates of treatment success were 70.4% versus 58.1% with RBX2660 and placebo, respectively. However, after aligning the data to improve the exchangeability and interpretability of the Bayesian analysis, the model-estimated treatment success rate was 70.6% with RBX2660 versus 57.5% with placebo, with an estimated treatment effect of 13.1% and a posterior probability of superiority of 0.991. More than 90% of the participants who achieved treatment success at 8 weeks had sustained response through 6 months in both the RBX2660 and the placebo groups. Overall, RBX2660 was well tolerated, with manageable adverse events. The incidence of treatment-emergent adverse events was higher in RBX2660 recipients compared with placebo and was mostly driven by a higher incidence of mild gastrointestinal events.<br><br>CONCLUSIONS: RBX2660 is a safe and effective treatment to reduce recurrent C. difficile infection following standard-of-care antibiotics with a sustained response through 6 months.<br><br>CLINICAL TRIAL REGISTRATION: NCT03244644; 9 August, 2017.}, }
@article {pmid36284437, year = {2022}, author = {Li, Z and Liang, H and Hu, Y and Lu, L and Zheng, C and Fan, Y and Wu, B and Zou, T and Luo, X and Zhang, X and Zeng, Y and Liu, Z and Zhou, Z and Yue, Z and Ren, Y and Li, Z and Su, Q and Xu, P}, title = {Gut bacterial profiles in Parkinson's disease: A systematic review.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/cns.13990}, pmid = {36284437}, issn = {1755-5949}, abstract = {INTRODUCTION: Recent advances have highlighted the relationships between gut dysbiosis and Parkinson's disease (PD). Microbiota transplantation from PD patients to mice can induce increased alpha-synuclein-mediated motor deficits. Human studies have identified differences in the gut microbiota of PD patients compared to healthy controls. We undertook a systematic review to evaluate the available evidence for the involvement of gut bacteria in the etiology of PD.<br><br>METHODS: The PubMed databank, the China National Knowledge Infrastructure databank, and Wanfang Data were searched from inception until June 2021 to identify human case-control studies that investigated relationships between PD and microbiota quantified from feces. We evaluated the resulting studies focusing on bacterial taxa that were different between PD patients and healthy controls.<br><br>RESULTS: Twenty-six studies were found in which 53 microbial families and 98 genera exhibited differences between patients with PD and healthy controls. The genera identified by more than two studies as increased in PD were Bifidobacterium, Alistipes, Christensenella, Enterococcus, Oscillospira, Bilophila, Desulfovibrio, Escherichia/Shigella, and Akkermansia, while Prevotella, Blautia, Faecalibacterium, Fusicatenibacter, and Haemophilus had three or more reports of being lower in PD patients. More than one report demonstrated that Bacteroides, Odoribacter, Parabacteroides, Butyricicoccus, Butyrivibrio, Clostridium, Coprococcus, Lachnospira, Lactobacillus, Megasphaera, Phascolarctobacterium, Roseburia, Ruminococcus, Streptococcus, and Klebsiella were altered in both directions.<br><br>CONCLUSION: Our review shows that the involvement of the gut microbiome in the etiology of PD may involve alterations of short-chain fatty acids (SCFAs)-producing bacteria and an increase in putative gut pathobionts. SCFAs-producing bacteria may vary above or below an "optimal range," causing imbalances. Considering that Bifidobacterium, Lactobacillus, and Akkermansia are beneficial for human health, increased Bifidobacterium and Lactobacillus in the PD gut microbiome may be associated with PD medications, especially COMT inhibitors, while a high level of Akkermansia may be associated with aging.}, }
@article {pmid36281730, year = {2022}, author = {Li, P and Liu, Y and Zhao, J and Pan, W and He, Y and Fu, S and Liu, Y and Xu, YJ}, title = {Salecan ameliorates liver injury by regulating gut microbiota and its metabolites.}, journal = {Food &amp; function}, volume = {13}, number = {22}, pages = {11744-11757}, doi = {10.1039/d2fo02210a}, pmid = {36281730}, issn = {2042-650X}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *beta-Glucans/chemistry ; Liver/metabolism ; Oxidative Stress ; Mice, Inbred C57BL ; }, abstract = {Salecan, a natural β-glucan consisting of seven residues linked by β-(1→3)/α-(1→3) glycosidic bonds, is one of the novel food ingredients approved in China. β-Glucan has a variety of health-improving effects, yet its mechanism against liver injury remains poorly understood. β-Glucan can induce shifts in the gut microbiota and show health benefits; however, whether modulation of the gut microbiota by β-glucan is associated with its benefits remains unclear. Here, the hepatoprotective effect and potential mechanism of salecan supplementation using a model of CCl4-induced liver injury were investigated. After 8 weeks of treatment, salecan alleviated liver injury by regulating oxidative stress and activating the Nrf2 signaling pathway. In addition, salecan treatment modulated the composition of the gut microbiota, and the antibiotic cocktail treatment indicated that the hepatoprotective effect of salecan was dependent on the gut microbiota. Fecal microbiota transplantation was used to further verify this mechanism, and we confirmed that microbial colonization partially alleviated liver injury. Besides, microbiota-derived metabolites of salecan also contributed to the hepatoprotective effect of salecan against liver injury and inhibited oxidative stress. These findings supported that salecan intervention attenuated liver injury by regulating the gut microbiota and its metabolites.}, }
@article {pmid36280756, year = {2022}, author = {Yao, H and Zhang, D and Yu, H and Yuan, H and Shen, H and Lan, X and Liu, H and Chen, X and Meng, F and Wu, X and Zhang, G and Wang, X}, title = {Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {36280756}, issn = {1476-5578}, abstract = {Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.}, }
@article {pmid36280324, year = {2022}, author = {Gupta, A and Singh, V and Mani, I}, title = {Dysbiosis of human microbiome and infectious diseases.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {33-51}, doi = {10.1016/bs.pmbts.2022.06.016}, pmid = {36280324}, issn = {1878-0814}, mesh = {Humans ; Dysbiosis ; Prebiotics ; *Gastrointestinal Microbiome ; *Microbiota ; *Probiotics ; Bacteria ; *Communicable Diseases ; }, abstract = {Since birth, the human body gets colonized by various communities of symbiotic or commensal microorganisms and they persist till the death of an individual. The human microbiome is comprised of the genomes of microorganisms such as viruses, archaea, eukaryotes, protozoa, and, most remarkably, bacteria. The development of "omics" technologies gave way to the Human Microbiome Project (HMP) which aimed at exploring the collection of microbial genes and genomes inhabiting the human body. Eubiosis, i.e., a healthy and balanced composition of such microbes contributes to the metabolic function, protection against pathogens and provides nutrients and energy to the host. Whereas, an imbalance in the diversity of microorganisms, termed dysbiosis, greatly influences the state of health and disease. This chapter summarizes the impact of gut bacteria on the well-being of humans and highlights the protective role played by the human microbiota during bacterial and viral infections. The condition of dysbiosis and how it plays a role in the establishment of various infections and metabolic disorders such as Clostridioides difficile infection (CFI), inflammatory bowel disease (IBD), cancer, periodontitis, and obesity are described in detail. Further, treatments such as fecal transplantation, probiotics, prebiotics, phage therapy, and CRISPR/Cas system, which target gut microbiota during digestive diseases are also discussed.}, }
@article {pmid36280104, year = {2022}, author = {van Lier, YF and Rolling, T and Armijo, GK and Zhai, B and Haverkate, NJE and Meijer, E and Nur, E and Blom, B and Peled, JU and van den Brink, MRM and Hohl, TM and Hazenberg, MD and Markey, KA}, title = {Profiling the Fungal Microbiome after Fecal Microbiota Transplantation for Graft-versus-Host Disease: Insights from a Phase 1 Interventional Study.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2022.10.011}, pmid = {36280104}, issn = {2666-6367}, abstract = {Disruption of the intestinal bacterial microbiota is frequently observed in the context of allogeneic hematopoietic cell transplantation (HCT) and is particularly pronounced in patients who develop graft-versus-host disease (GVHD). Donor fecal microbiota transplantation (FMT) restores gut microbial diversity and reduces GVHD in HCT recipients. The composition of the intestinal fungal community in patients with GVHD, and whether fungal taxa are transferred during FMT are currently unknown. We performed a secondary analysis of our clinical trial of FMT in patients with steroid-refractory GVHD with a focus on the mycobiota. We characterized the fecal mycobiota of 17 patients and healthy FMT donors using internal transcribed spacer amplicon sequencing. The donor who provided the majority of FMT material in our study represents an n-of-one study of the intestinal flora over time. In this donor, mycobiota composition fluctuated over time while the bacterial microbiota remained stable over 16 months. Fungal DNA was detected more frequently in baseline stool samples from patients with steroid-refractory GVHD than in patients with steroid-dependent GVHD. We could detect fungal taxa in the majority of samples but did not see evidence of mycobiota transfer from donor to recipient. Our study demonstrates the feasibility of profiling the mycobiota alongside the more traditional bacterial microbiota, establishes the methodology, and provides a first insight into the mycobiota composition of patients with GVHD.}, }
@article {pmid36279081, year = {2022}, author = {Zhang, J and Wu, K and Shi, C and Li, G}, title = {Cancer Immunotherapy: Fecal Microbiota Transplantation Brings Light.}, journal = {Current treatment options in oncology}, volume = {}, number = {}, pages = {1-16}, pmid = {36279081}, issn = {1534-6277}, abstract = {Immunotherapy is revolutionizing tumor treatment by activating the immune response to tumors. Among them, immunotherapy represented by immune checkpoint inhibitors is considered to be a milestone in tumor treatment. It has revolutionized the management of advanced malignant tumors by activating T cells, promoting cytotoxic signaling pathways, and killing tumor cells, effectively improving the overall survival of patients. However, resistance to immunotherapy and immune-related adverse events remain challenges for immunotherapy. It has been demonstrated in previous studies that modulating intestinal microbiota can enhance immunotherapy response and reduce complications. Currently, the more mature method for microbiota regulation is fecal microbiota transplantation, which involves transfering a donor's microbiome to the recipient in the form of capsules or fecal microbiota suspension to restore the richness of the recipient's intestinal microbiota. In terms of cancer immunotherapy, fecal microbiota transplantation in patients who fail to respond to immune checkpoint inhibitors is expected to produce better prognosis for patients.}, }
@article {pmid36278360, year = {2022}, author = {Chan, DG and Ventura, K and Villeneuve, A and Du Bois, P and Holahan, MR}, title = {Exploring the Connection Between the Gut Microbiome and Parkinson's Disease Symptom Progression and Pathology: Implications for Supplementary Treatment Options.}, journal = {Journal of Parkinson's disease}, volume = {}, number = {}, pages = {}, doi = {10.3233/JPD-223461}, pmid = {36278360}, issn = {1877-718X}, abstract = {The contribution of the microbiota to induce gastrointestinal inflammation is hypothesized to be a key component of alpha-synuclein (aSyn) aggregation within the gastrointestinal (GI) tract in the pathological progression of Parkinson's disease (PD). The function of the GI tract is governed by a system of neurons that form part of the enteric nervous system (ENS). The ENS hosts 100-500 million nerve cells within two thin layers lining the GI tract. The gut-brain axis (GBA) is the major communication pathway between the ENS and the central nervous system. It has become increasingly clear that the microbiota in the gut are key regulators of GBA function and help to maintain homeostasis in the immune and endocrine systems. The GBA may act as a possible etiological launching pad for the pathogenesis of age-related neurodegenerative diseases, such as PD, because of an imbalance in the gut microbiota. PD is a multi-faceted illness with multiple biological, immunological, and environmental factors contributing to its pathological progression. Interestingly, individuals with PD have an altered gut microbiota compared to healthy individuals. However, there is a lack of literature describing the relationship between microbiota composition in the gut and symptom progression in PD patients. This review article examines how the pathology and symptomology of PD may originate from dysregulated signaling in the ENS. We then discuss by targeting the imbalance within the gut microbiota such as prebiotics and probiotics, some of the prodromal symptoms might be alleviated, possibly curtailing the pathological spread of aSyn and ensuing debilitating motor symptoms.}, }
@article {pmid36275423, year = {2022}, author = {Hamblin, H and Gunaratne, AW and Clancy, A and Pilarinos, D and LeBusque, A and Dawson, MVM and Borody, TJ}, title = {Pre-Antibiotic Treatment Followed by Prolonged Repeated Faecal Microbiota Transplantation Improves Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome: An Observational Australian Clinical Experience.}, journal = {Gastroenterology research and practice}, volume = {2022}, number = {}, pages = {6083896}, pmid = {36275423}, issn = {1687-6121}, abstract = {BACKGROUND: The use of faecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) has frequently failed to induce long-term symptomatic improvement. The use of multiple FMT infusions is one proposed mechanism through which the efficacy of FMT can be amplified.<br><br>AIMS: To evaluate the safety and efficacy of a novel six-month FMT treatment protocol in IBS.<br><br>METHODS: Patients diagnosed with IBS confirmed by Rome IV Criteria were recruited for single-centre, single-arm, prospective clinical observational study. Participants received one colonoscopically delivered FMT followed by 36 rectal enemas across a six-month period. Validated abdominal symptoms and Short-Form (SF-36) Quality of Life (QOL) questionnaires were collected at baseline, week-12, week-24, and week-56, respectively. Wilcoxon matched-pairs signed-rank tests were conducted to compare differences in abdominal symptom and SF-36 QOL scores over the follow-up timepoints. Statistical significance was set at 5%.<br><br>RESULTS: Sixty participants diagnosed with IBS [IBS-constipation (n = 27), IBS-diarrhoea (n = 18), and IBS-mixed (n = 15)] received the six-month FMT treatment. IBS symptom severity reduction was achieved in up to 61% of respondents at week-12, 64% of respondents at week-24, and maintained in up to 75% of respondents at week-52. Long-term reduction in symptom severity was associated with an increase in QOL, achieved in up to 64% of respondents at week-52 when compared to baseline. Adverse events were experienced in 28% of participants, though they were both transient and mild in nature.<br><br>CONCLUSIONS: Six-month sustained FMT appears to be both safe and effective in the short- and long-term alleviation of IBS associated symptoms as well as improving participant QOL.}, }
@article {pmid36270679, year = {2022}, author = {Mehrotra, T and Maulik, SK}, title = {Hepatic drug metabolism and gut microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {207-228}, doi = {10.1016/bs.pmbts.2022.07.005}, pmid = {36270679}, issn = {1878-0814}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; *Diabetes Mellitus, Type 2 ; Fecal Microbiota Transplantation ; *Probiotics ; }, abstract = {This chapter focuses on intestinal microbiota and its effect on drug metabolism. Here, we discussed about different drugs which are metabolized either by some enzymes or gut microbiota and their mechanism. Nowadays, consuming drugs without a doctor's prescription is common. This chapter will make people aware about its negative consequences and how it is related to gut microbiota dysbiosis. Intestinal disorders like inflammatory bowel disease (IBD), colorectal cancer (CRC) and metabolic disorders such as obesity and type 2 diabetes mellitus (T2D) are found to be affected with gut microbiota dysbiosis. To address this issue, we discussed a variety of strategies such as fecal microbiota transplantation (FMT), probiotics and antibiotic stewardship programs which are commonly used to tackle this problem.}, }
@article {pmid36270678, year = {2022}, author = {Purohit, A and Alam, MJ and Kandiyal, B and Shalimar,  and Das, B and Banerjee, SK}, title = {Gut microbiome and non-alcoholic fatty liver disease.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {187-206}, doi = {10.1016/bs.pmbts.2022.07.004}, pmid = {36270678}, issn = {1878-0814}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease/therapy/complications/microbiology ; Prebiotics ; Dysbiosis ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; }, abstract = {The human gastrointestinal tract (GIT) contains a dynamic and diverse collection of bacteria, archaea, and fungi termed the "gut microbiome." The gut microbiome has a major impact on the host during homeostasis and disease. The connection between both the host and the microbiome is complex, although its manipulation may assist prevent or treating a multitude of morbidities. These microorganisms play a critical role in the host's energy metabolism and homeostasis. According to new research, the microbes in the gastrointestinal tract play a substantial role in host health, and alterations in its composition and function might lead to the emergence of metabolic disorders like non-alcoholic fatty liver disease (NAFLD). The resilience of the GIT microbial ecology and its tolerance to perturbation are robust but not ideal. Several factors may disrupt the GIT microbiome's homeostasis leading to dysbiosis, characterized by an imbalanced equilibrium and perturbations in gut homeostasis. Irritable bowel disease (IBD), malnutrition, and metabolic disorders, such as NAFLD, have been associated with the dysbiotic gut microbiome. Recent evidence suggests that utilizing medications, prebiotics, probiotics, and fecal microbiota transplantation (FMT) to manipulate the microbiome could be a viable method for treating NAFLD.}, }
@article {pmid36270677, year = {2022}, author = {Patel, S and Seshadri, S and Dalai, S}, title = {Gut microbiome and type 2 diabetes.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {175-185}, doi = {10.1016/bs.pmbts.2022.06.029}, pmid = {36270677}, issn = {1878-0814}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2/metabolism/microbiology ; Bacteria/metabolism ; Bile Acids and Salts/metabolism ; Anti-Bacterial Agents ; Glucose/metabolism ; Lipids ; }, abstract = {Dietary patterns with excess caloric have shaped a complex metabolic disorders like type 2 diabetes (T2D). T2D involves complications in the metabolism of glucose, lipid, cholesterol and their storage. Along with the metabolic dysregulation, systemic inflammation is also the reason for Insulin Resistance and T2D. The importance of gut microbiota has recently been highlighted. It establishes a link between dietary patterns and the types of bacteria that overgrow and modify fermentation bi-products such as SCFA, secondary bile acids, and mucosal immune cells. These changes have a direct impact on the liver's metabolism and immune system. As a result, using Pre-Pro-biotics to manage microbiota can assist overcome or lessening disease symptoms. Antibiotics are currently employed to produce a germ-free environment or to eradicate specific types of bacteria in order to better understand the role of microflora. This chapter covers the basics of good bacteria, as well as the mechanisms that they work on.}, }
@article {pmid36269743, year = {2022}, author = {Slanzon, GS and Ridenhour, BJ and Parrish, LM and Trombetta, SC and Moore, DA and Sischo, WM and McConnel, CS}, title = {Effects of a farm-specific fecal microbial transplant (FMT) product on clinical outcomes and fecal microbiome composition in preweaned dairy calves.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276638}, pmid = {36269743}, issn = {1932-6203}, mesh = {Cattle ; Animals ; Farms ; *Fecal Microbiota Transplantation/methods ; Feces ; *Microbiota ; Anti-Bacterial Agents ; }, abstract = {Gastrointestinal disease (GI) is the most common illness in pre-weaned dairy calves. Therefore, effective strategies to manipulate the microbiome of dairy calves under commercial dairy operations are of great importance to improve animal health and reduce antimicrobial usage. The objective of this study was to develop a farm-specific FMT product and to investigate its effects on clinical outcomes and fecal microbial composition of dairy calves. The FMT product was derived from feces from healthy donors (5-24 days of age) raised in the same calf ranch facility as the FMT recipients. Healthy and diarrheic calves were randomly enrolled to a control (n = 115) or FMT (n = 112) treatment group (~36 g of processed fecal matter once daily for 3 days). Fecal samples were collected at enrollment and again 9 days later after the first FMT dose. Although the FMT product was rich in organisms typically known for their beneficial probiotic properties, the FMT therapy did not prevent or ameliorate GI disease in dairy calves. In fact, calves that received FMT were less likely to recover from GI disease, and more likely to die due to GI disease complications. Fecal microbial community analysis revealed an increase in the alpha-diversity in FMT calves; however, no major differences across treatment groups were observed in the beta-diversity analysis. Calves that received FMT had higher relative abundance of an uncultured organism of the genus Lactobacillus and Lactobacillus reuteri on day 10. Moreover, FMT calves had lower relative abundance of Clostridium nexile and Bacteroides vulgatus on day 10. Our results indicate the need to have an established protocol when developing FMT products, based on rigorous inclusion and exclusion criteria for the selection of FMT donors free of potential pathogens, no history of disease or antibiotic treatment.}, }
@article {pmid36268259, year = {2022}, author = {Willman, J and Willman, M and Reddy, R and Fusco, A and Sriram, S and Mehkri, Y and Charles, J and Goeckeritz, J and Lucke-Wold, B}, title = {Gut microbiome and neurosurgery: Implications for treatment.}, journal = {Clinical and translational discovery}, volume = {2}, number = {4}, pages = {}, pmid = {36268259}, issn = {2768-0622}, support = {R25 NS108939/NS/NINDS NIH HHS/United States ; }, abstract = {INTRODUCTION: The aim of this review is to summarize the current understanding of the gut-brain axis (GBA), its impact on neurosurgery, and its implications for future treatment.<br><br>BACKGROUND: An abundance of research has established the existence of a collection of pathways between the gut microbiome and the central nervous system (CNS), commonly known as the GBA. Complicating this relationship, the gut microbiome bacterial diversity appears to change with age, antibiotic exposure and a number of external and internal factors.<br><br>METHODS: In this paper, we present the current understanding of the key protective and deleterious roles the gut microbiome plays in the pathogenesis of several common neurosurgical concerns.<br><br>RESULTS: Specifically, we examine how spinal cord injury, traumatic brain injury and stroke may cause gut microbial dysbiosis. Furthermore, this link appears to be bidirectional as gut dysbiosis contributes to secondary CNS injury in each of these ailment settings. This toxic cycle may be broken, and the future secondary damage rescued by timely, therapeutic, gut microbiome modification. In addition, a robust gut microbiome appears to improve outcomes in brain tumour treatment. There are several primary routes by which microbiome dysbiosis may be ameliorated, including faecal microbiota transplant, oral probiotics, bacteriophages, genetic modification of gut microbiota and vagus nerve stimulation.<br><br>CONCLUSION: The GBA represents an important component of patient care in the field of neurosurgery. Future research may illuminate ideal methods of therapeutic microbiome modulation in distinct pathogenic settings.}, }
@article {pmid36267243, year = {2022}, author = {Huang, W and Zhu, L and Song, W and Zhang, M and Teng, L and Wu, M}, title = {Crosstalk between the Gut and Brain in Ischemic Stroke: Mechanistic Insights and Therapeutic Options.}, journal = {Mediators of inflammation}, volume = {2022}, number = {}, pages = {6508046}, pmid = {36267243}, issn = {1466-1861}, mesh = {Humans ; Prebiotics ; *Ischemic Stroke ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Brain/metabolism ; *Stroke/therapy/metabolism ; }, abstract = {There has been a significant amount of interest in the past two decades in the study of the evolution of the gut microbiota, its internal and external impacts on the gut, and risk factors for cerebrovascular disorders such as cerebral ischemic stroke. The network of bidirectional communication between gut microorganisms and their host is known as the microbiota-gut-brain axis (MGBA). There is mounting evidence that maintaining gut microbiota homeostasis can frequently enhance the effectiveness of ischemic stroke treatment by modulating immune, metabolic, and inflammatory responses through MGBA. To effectively monitor and cure ischemic stroke, restoring a healthy microbial ecology in the gut may be a critical therapeutic focus. This review highlights mechanistic insights on the MGBA in disease pathophysiology. This review summarizes the role of MGBA signaling in the development of stroke risk factors such as aging, hypertension, obesity, diabetes, and atherosclerosis, as well as changes in the microbiota in experimental or clinical populations. In addition, this review also examines dietary changes, the administration of probiotics and prebiotics, and fecal microbiota transplantation as treatment options for ischemic stroke as potential health benefits. It will become more apparent how the MGBA affects human health and disease with continuing advancements in this emerging field of biomedical sciences.}, }
@article {pmid36266965, year = {2022}, author = {Zhou, LJ and Lin, WZ and Liu, T and Chen, BY and Meng, XQ and Li, YL and Du, LJ and Liu, Y and Qian, YC and Zhu, YQ and Duan, SZ}, title = {Oral Pathobionts Promote MS-like Symptoms in Mice.}, journal = {Journal of dental research}, volume = {}, number = {}, pages = {220345221128202}, doi = {10.1177/00220345221128202}, pmid = {36266965}, issn = {1544-0591}, abstract = {Dysbiotic oral microbiota has been associated with multiple sclerosis. However, the role and mechanism of oral microbiota in the development of multiple sclerosis are still elusive. Here, we demonstrated that ligature-induced periodontitis (LIP) aggravated experimental autoimmune encephalomyelitis (EAE) in mice, and this was likely dependent on the expansion of T helper 17 (Th17) cells. LIP increased the splenic richness of Enterobacter sp., which was able to induce the expansion of splenic Th17 cells and aggravate EAE in mice. LIP also led to enrichment of Erysipelotrichaceae sp. in the gut and increased Th17 cells in the large intestinal lamina propria of EAE mice. Fecal microbiota transplantation from EAE mice with LIP also promoted EAE symptoms. In conclusion, periodontitis exacerbates EAE, likely through ectopic colonization of oral pathobionts and expansion of Th17 cells.}, }
@article {pmid36264933, year = {2022}, author = {Bénard, MV and de Bruijn, CMA and Fenneman, AC and Wortelboer, K and Zeevenhoven, J and Rethans, B and Herrema, HJ and van Gool, T and Nieuwdorp, M and Benninga, MA and Ponsioen, CY}, title = {Challenges and costs of donor screening for fecal microbiota transplantations.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276323}, pmid = {36264933}, issn = {1932-6203}, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Fecal Microbiota Transplantation ; Donor Selection ; SARS-CoV-2 ; *COVID-19 ; Feces ; *Clostridium Infections ; }, abstract = {BACKGROUND: The increasing interest to perform and investigate the efficacy of fecal microbiota transplantation (FMT) has generated an urge for feasible donor screening. We report our experience with stool donor recruitment, screening, follow-up, and associated costs in the context of clinical FMT trials.<br><br>METHODS: Potential stool donors, aged between 18-65 years, underwent a stepwise screening process starting with an extensive questionnaire followed by feces and blood investigations. When eligible, donors were rescreened for MDROs and SARS-CoV-2 every 60-days, and full rescreening every 4-6 months. The costs to find and retain a stool donor were calculated.<br><br>RESULTS: From January 2018 to August 2021, 393 potential donors underwent prescreening, of which 202 (51.4%) did not proceed primarily due to loss to follow-up, medication use, or logistic reasons (e.g. COVID-19 measures). 191 potential donors filled in the questionnaire, of which 43 (22.5%) were excluded. The remaining 148 candidates underwent parasitology screening: 91 (61.5%) were excluded, mostly due to Dientamoeba fragilis and/or high amounts of Blastocystis spp. After additional feces investigations 18/57 (31.6%) potential donors were excluded (mainly for presence of Helicobacter Pylori and ESBL-producing organisms). One donor failed serum testing. Overall, 38 out of 393 (10%) potential donors were enrolled. The median participation time of active stool donors was 13 months. To recruit 38 stool donors, &#x20ac;64.112 was spent.<br><br>CONCLUSION: Recruitment of stool donors for FMT is challenging. In our Dutch cohort, failed eligibility of potential donors was often caused by the presence of the protozoa Dientamoeba fragilis and Blastocystis spp.. The exclusion of potential donors that carry these protozoa, especially Blastocystis spp., is questionable and deserves reconsideration. High-quality donor screening is associated with substantial costs.}, }
@article {pmid36264425, year = {2022}, author = {Kelly-Goss, MR and Badran, YR and Dougan, M}, title = {Update on Immune Checkpoint Inhibitor Enterocolitis.}, journal = {Current gastroenterology reports}, volume = {}, number = {}, pages = {1-11}, pmid = {36264425}, issn = {1534-312X}, support = {1K08DK114563/DK/NIDDK NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Immune checkpoint inhibitor (ICI) therapy revolutionized the treatment of multiple solid and hematologic malignancies. Yet, with it came profound inflammatory toxicities that mimic autoimmune diseases, termed immune-related adverse events (irAEs). Prominent among these is gastrointestinal inflammation, including a spectrum of gastritis, enteritis, and colitis. Here we synthesize an approach to immune checkpoint related enterocolitis (irEC) - including diagnostics and therapeutics - underpinned by new insights into the mechanism behind these phenomena.<br><br>RECENT FINDINGS: This review presents updated insights on how to approach irEC, including novel approaches to selective immunosuppressive therapy, the role of fecal microbiota transplant, and the underlying cellular mechanisms of irEC. This review provides an update on irEC diagnosis and therapy, with considerations of new therapies and special patient populations. The field of gastrointestinal irAEs requires additional investigation, which will ultimately provide the tools required for patients to continue to receive life-saving ICI therapy.}, }
@article {pmid36264385, year = {2022}, author = {Hu, L and Zhao, Y and Liu, S and Zhang, J and You, T and Gan, B and Xu, H}, title = {Lead exposure exacerbates adverse effects of HFD on metabolic function via disruption of gut microbiome, leading to compromised barrier function and inflammation.}, journal = {European journal of nutrition}, volume = {}, number = {}, pages = {}, pmid = {36264385}, issn = {1436-6215}, abstract = {PURPOSE: The toxicity of lead (Pb) has been intensively studied, while the adverse effects in the population on a high-fat diet (HFD) remain unclear. This study compared the different biologic effects of Pb in CHOW and HFD-fed mice and investigated the important role that gut microbiota may play.<br><br>METHODS: C57BL/6 mice were fed a CHOW diet and HFD with or without 1&#xa0;g/L Pb exposure through drinking water for 8&#xa0;weeks. Using oral glucose tolerance test, histopathological observation, real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay, and 16S high-throughput sequencing to compare the Pb toxicity, fecal microbiota transplantation was conducted to investigate the key role of gut microbiota.<br><br>RESULTS: The metabolic disorders induced by HFD were aggravated by chronic Pb intake, and HFD exacerbated the Pb accumulation in the colon by 96%, 32% in blood, 27% in the liver, and 142% in tibiae. Concomitantly, Pb induced more serious colonic injury, further disturbing the composition of gut microbiota in the HFD-fed mice. Moreover, altered fecal microbiota by HFD and Pb directly mediated metabolic disorders and colonic damage in recipient mice, which emphasized the importance of gut microbiota.<br><br>CONCLUSION: These findings indicated that the population with HFD has lower resistance and would face more security risks under Pb pollution, and pointed out the importance of assessing the health impacts of food contaminants in people with different dietary patterns.}, }
@article {pmid36264038, year = {2022}, author = {Du, H and Shi, L and Wang, Q and Yan, T and Wang, Y and Zhang, X and Yang, C and Zhao, Y and Yang, X}, title = {Fu Brick Tea Polysaccharides Prevent Obesity via Gut Microbiota-Controlled Promotion of Adipocyte Browning and Thermogenesis.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {43}, pages = {13893-13903}, doi = {10.1021/acs.jafc.2c04888}, pmid = {36264038}, issn = {1520-5118}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Tea/metabolism ; Thermogenesis ; Obesity/metabolism ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/metabolism ; Diet, High-Fat ; Mice, Obese ; Adipocytes/metabolism ; Polysaccharides/metabolism ; Mice, Inbred C57BL ; }, abstract = {The antiobesity efficacy and underlying mechanisms of polysaccharides extracted from Fu brick tea (FBTP) were investigated. An 8-week administration of FBTP dose-dependently inhibited increases in body weight and weights of the epididymal-, retroperitoneal- and inguinal-white adipose tissues and stimulated beige-fat development and brown adipose tissue-derived nonshivering thermogenesis in high-fat diet-induced obese mice. FBTP protected against obesity-associated abnormality in serum adiponectin and leptin, indicating its positive regulation of energy metabolism. FBTP reversed gut dysbiosis by enriching beneficial bacteria, for example, Lactobacillus, Parabacteroides, Akkermansia, Bifidobacterium, and Roseburia. Results from the fecal microbiota transplantation further confirmed that FBTP-induced microbial shifts contributed to adipose browning and thermogenesis, thereby alleviating host adiposity, glucose homeostasis, dyslipidemia, and its related hepatic steatosis. Our study demonstrates the great potential of FBTP with prebiotic-like activities in preventing diet-induced obesity and its related metabolic complications via gut microbiota-derived enhancement of fat burning and energy expenditures.}, }
@article {pmid36263410, year = {2022}, author = {Liu, B and Yu, D and Sun, J and Wu, X and Xin, Z and Deng, B and Fan, L and Fu, J and Ge, L and Ren, W}, title = {Characterizing the influence of gut microbiota on host tryptophan metabolism with germ-free pigs.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {11}, number = {}, pages = {190-200}, pmid = {36263410}, issn = {2405-6383}, abstract = {Intestinal microbes are closely associated with host health, depending on metabolic crosstalk between the microbiota and host. Tryptophan metabolism is one of the best examples of metabolic crosstalk between intestinal microbiota and host; however, our understanding about the influence of intestinal microbiota on host tryptophan metabolism is limited. Thus, we established germ-free (GF) pig models to systemically explore the influence of intestinal microbiota on tryptophan metabolism. Five GF pigs were kept in GF conditions throughout the experiment (GF group). Six GF pigs were transplanted with fecal microbiota from donor sows to act as control pigs. Compared with control pigs, the GF pigs had remarkable alterations in tryptophan metabolism. The differential metabolites (P < 0.05) were mainly found in the liver, circulation system and large intestine. Notably, the alteration of metabolites in tryptophan metabolism varied among organs, especially for the serotonin pathway. In GF pigs, tryptophan and kynurenine in the large intestine and 5-hydroxytryptophan in most organs were increased (P < 0.05), while metabolites in the indole pathway in most organs were decreased (P < 0.05). Collectively, our study reveals changes in tryptophan metabolism in GF pigs, highlighting the critical role of gut microbes in shaping host tryptophan metabolism.}, }
@article {pmid36262889, year = {2022}, author = {Zhang, N and Zhang, Y and Wang, Z and Pan, F and Ren, R and Li, Z and Zhao, H and Luo, X and Li, Z and Wang, L and Mo, R and Sun, G and Peng, L and Ni, M and Yang, Y}, title = {Regular fecal microbiota transplantation to Senescence Accelerated Mouse-Prone 8 (SAMP8) mice delayed the aging of locomotor and exploration ability by rejuvenating the gut microbiota.}, journal = {Frontiers in aging neuroscience}, volume = {14}, number = {}, pages = {991157}, pmid = {36262889}, issn = {1663-4365}, abstract = {Recent evidence points out the role of the gut microbiota in the aging process. However, the specific changes and relevant interventions remain unclear. In this study, Senescence Accelerated Mouse-Prone 8 (SAMP8) mice were divided into four groups; young-FMT-group transplanted fecal microbiota from young donors (2-3°months old) and old-FMT-group transplanted from old donors (10-11°months old); additionally, other two groups either adult mice injected with saline solution or untreated mice served as the saline and blank control groups, respectively. All mice were intervened from their 7-months-old until 13-months-old. The open field test at 9 and 11°months of age showed that the mice transplanted with gut microbiota from young donors had significantly better locomotor and exploration ability than those of transplanted with old-donors gut microbiota and those of saline control while was comparable with the blank control. 16S rRNA gene sequencing showed that the gut microbiome of recipient mice of young donors was altered at 11°months of age, whereas the alternation of the gut microbiome of old-donor recipient mice was at 9°months. For comparison, the recipient mice in the blank and saline control groups exhibited changes in the gut microbiome at 10°months of age. The hallmark of aging-related gut microbiome change was an increase in the relative abundance of Akkermansia, which was significantly higher in the recipients transplanted with feces from older donors than younger donors at 9°months of age. This study shows that fecal microbiota transplantation from younger donors can delay aging-related declines in locomotor and exploration ability in mice by changing the gut microbiome.}, }
@article {pmid36261653, year = {2022}, author = {Sophocleous, A and Azfer, A and Huesa, C and Stylianou, E and Ralston, SH}, title = {Probiotics Inhibit Cartilage Damage and Progression of Osteoarthritis in Mice.}, journal = {Calcified tissue international}, volume = {}, number = {}, pages = {}, pmid = {36261653}, issn = {1432-0827}, abstract = {Increasing interest has focussed on the possible role of alterations in the microbiome in the pathogenesis of metabolic disease, inflammatory disease, and osteoporosis. Here we examined the role of the microbiome in a preclinical model of osteoarthritis in mice subjected to destabilisation of medical meniscus (DMM). The intestinal microbiome was depleted by broad-spectrum antibiotics from 1 week before birth until the age of 6 weeks when mice were subjected reconstitution of the microbiome with faecal microbial transplant (FMT) followed by the administration of a mixture of probiotic strains Lacticaseibacillus paracasei 8700:2, Lactiplantibacillus plantarum HEAL9 and L. plantarum HEAL19 or vehicle. All mice were subjected to DMM at the age of 8 weeks. The severity of osteoarthritis was evaluated by histological analysis and effects on subchondral bone were investigated by microCT analyses. The combination of FMT and probiotics significantly inhibited cartilage damage at the medial femoral condyle such that the OARSI score was 4.64 ± 0.32 (mean ± sem) in the FMT and probiotic group compared with 6.48 ± 0.53 in the FMT and vehicle group (p = 0.007). MicroCT analysis of epiphyseal bone from the femoral condyle showed that the probiotic group had higher BV/TV, increased Tb.Th, and moderately thicker subchondral bone plates than the control group. There was no difference between groups in joint inflammation or in serum concentrations of inflammatory cytokines and chemokines. We conclude that treatment with probiotics following FMT in mice where the microbiome has been depleted inhibits DMM-induced cartilage damage and impacts on the structure of subchondral bone particularly at the femoral condyle. While further studies are required to elucidate the mechanism of action, our research suggests that these probiotics may represent a novel intervention for the treatment of osteoarthritis.}, }
@article {pmid36261423, year = {2022}, author = {Wolstenholme, JT and Saunders, JM and Smith, M and Kang, JD and Hylemon, PB and González-Maeso, J and Fagan, A and Zhao, D and Sikaroodi, M and Herzog, J and Shamsaddini, A and Peña-Rodríguez, M and Su, L and Tai, YL and Zheng, J and Cheng, PC and Sartor, RB and Gillevet, PM and Zhou, H and Bajaj, JS}, title = {Reduced alcohol preference and intake after fecal transplant in patients with alcohol use disorder is transmissible to germ-free mice.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6198}, pmid = {36261423}, issn = {2041-1723}, mesh = {Humans ; Mice ; Animals ; Male ; *Fecal Microbiota Transplantation ; *Alcoholism/therapy ; Mice, Inbred C57BL ; Alcohol Drinking ; Ethanol ; }, abstract = {Alcohol use disorder is a major cause of morbidity, which requires newer treatment approaches. We previously showed in a randomized clinical trial that alcohol craving and consumption reduces after fecal transplantation. Here, to determine if this could be transmitted through microbial transfer, germ-free male C57BL/6 mice received stool or sterile supernatants collected from the trial participants pre-/post-fecal transplant. We found that mice colonized with post-fecal transplant stool but not supernatants reduced ethanol acceptance, intake and preference versus pre-fecal transplant colonized mice. Microbial taxa that were higher in post-fecal transplant humans were also associated with lower murine alcohol intake and preference. A majority of the differentially expressed genes (immune response, inflammation, oxidative stress response, and epithelial cell proliferation) occurred in the intestine rather than the liver and prefrontal cortex. These findings suggest a potential for therapeutically targeting gut microbiota and the microbial-intestinal interface to alter gut-liver-brain axis and reduce alcohol consumption in humans.}, }
@article {pmid36259455, year = {2022}, author = {Celorrio Navarro, M and Shumilov, K and Rodgers, R and Schriefer, L and Li, Y and Baldridge, MT and Friess, S}, title = {Innate and peripheral immune alterations after TBI are regulated in a gut microbiota-dependent manner in mice.}, journal = {Journal of neurotrauma}, volume = {}, number = {}, pages = {}, doi = {10.1089/neu.2022.0356}, pmid = {36259455}, issn = {1557-9042}, abstract = {Traumatic brain injury (TBI) patients are at high risk for disruption of the gut microbiome. Previously, we have demonstrated that broad-spectrum antibiotic exposure after TBI drastically alters the gut microbiota and modulates neuroinflammation, neurogenesis, and long-term fear memory. However, these data did not determine if the impact of antibiotic exposure on the brain's response to injury was mediated directly by antibiotics or indirectly via modulation of the gut microbiota. We designed two different approaches to address this knowledge gap utilizing fecal microbiota transplantation (FMT) from control and antibiotic-treated mice (VNAM: vancomycin, neomycin, ampicillin and metronidazole) into germ free (GF) mice prior to injury and exposing single pathogen free (SPF) mice to a 2-week period of antibiotics prior to injury but discontinuing antibiotics 72 hours prior to injury. GF mice receiving FMT from VNAM exposed mice (GF-VNAM) demonstrated reduced gut bacterial alpha diversity and richness compared with GF mice receiving FMT from control. At 7 days post injury, GF-VNAM had increased microglial activation, reduced infiltration of T cells, and decreased neurogenesis 7 days after injury. Similarly, SPF mice exposed to antibiotics prior to but not after injury demonstrated similar alterations in neuroinflammation and neurogenesis compared to control mice. These data support our hypothesis implicating the gut microbiota as an important modulator of the neuroinflammatory process and neurogenesis after TBI and provide an exciting new approach for neuroprotective therapeutics for TBI.}, }
@article {pmid36257564, year = {2022}, author = {Li, P and Ma, X and Liu, D and Wei, Y and Li, P and Hou, H and Yao, J and Chen, A and Liang, Y and Zhou, Z and Wang, P}, title = {A microbiome abundant environment remodels the intestinal microbiota and improves resistance to obesity induced by chlorpyrifos in mice.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {315}, number = {}, pages = {120415}, doi = {10.1016/j.envpol.2022.120415}, pmid = {36257564}, issn = {1873-6424}, mesh = {Animals ; Mice ; Humans ; *Chlorpyrifos/toxicity ; *Gastrointestinal Microbiome ; Ecosystem ; Obesity ; Intestines ; Mice, Inbred C57BL ; }, abstract = {There is a growing consensus that the appropriate microbiome abundant environment actuates microbiota changes to influence human health. Whether living environment reacts on the threat of contaminants and the underlying mechanism remain largely unknown. Therefore, we constructed microbiome abundant environment models, focusing on their regulatory effects on the obesity induced by the exogenous chemical chlorpyrifos (CPF) and the related mechanisms. The results uncovered that the constructed farm and woodland microbiome abundant environment could protect mice against CPF-induced obesity effectively. The microbiome abundant environment regulated CPF-induced microbiota imbalance, characterized by an increase in Lactobacillus abundance. These altered microbiotas modified the intestinal immune system by increasing the expression of Foxp3 and IL-10, and mitigated intestinal barrier injury by upregulating the expression of IL-22 and intestinal tight junction proteins. Fecal microbiota transplantation could receive similar phenotypes on alleviating CPF-induced obesity development. Our results demonstrate that the microbiome abundant environment attenuates exogenous chemical-induced health risks by remodeling the intestinal microbiota, improving the intestinal ecosystem, and preventing intestinal epithelial leakage.}, }
@article {pmid36256653, year = {2022}, author = {Collier, AJ and Gomez, DE and Monteith, G and Plattner, BL and Verbrugghe, A and Webb, J and Weese, JS and Blois, SL}, title = {Investigating fecal microbial transplant as a novel therapy in dogs with inflammatory bowel disease: A preliminary study.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276295}, pmid = {36256653}, issn = {1932-6203}, mesh = {Dogs ; Animals ; Fecal Microbiota Transplantation/methods ; *Inflammatory Bowel Diseases/therapy/veterinary/etiology ; Feces ; *Microbiota ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: There are limited studies investigating the use of fecal microbial transplant (FMT) in dogs with inflammatory bowel disease (IBD). The aim of this preliminary study was to assess the feasibility of adding FMT to standard therapy (corticosteroids and a hypoallergenic diet) for dogs with IBD and to and to describe the changes in measured outcomes after 30 days of treatment.<br><br>METHODS: Thirteen client-owned dogs with IBD were enrolled in this double blinded, randomized clinical trial. All dogs received corticosteroid therapy and a hypoallergenic diet; dogs were randomized to receive either placebo or FMT. Measured outcomes included the canine chronic enteropathy clinical activity index (CCECAI) at 1 week and 1 month after enrolment. Fecal microbiota were analyzed after extracting DNA from fecal samples and profiling using 16S amplicon sequencing. Dogs in the placebo group not responding to treatment after 1 month were offered FMT.<br><br>RESULTS: The CCECAI significantly decreased over time in both groups (p = 0.001). There were no significant differences between the CCECAI of the placebo and FMT group at each time point (F test from ANOVA, p = 0.40). No adverse effects were reported in the 30 days following FMT.<br><br>CONCLUSIONS: The addition of FMT to standard therapy for IBD was feasible. No significant differences were observed in the CCECAI between groups at each time point. Large scale clinical trials can be performed using these methods to evaluate the longer term effect of FMT on clinical signs, microbial diversity, and other outcomes.}, }
@article {pmid36256625, year = {2022}, author = {Davis, BT and Chen, Z and Islam, MBAR and Timken, ME and Procissi, D and Schwulst, SJ}, title = {POSTINJURY FECAL MICROBIOME TRANSPLANT DECREASES LESION SIZE AND NEUROINFLAMMATION IN TRAUMATIC BRAIN INJURY.}, journal = {Shock (Augusta, Ga.)}, volume = {58}, number = {4}, pages = {287-294}, pmid = {36256625}, issn = {1540-0514}, support = {R01 GM130662/GM/NIGMS NIH HHS/United States ; R21 NS116638/NS/NINDS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation ; Neuroinflammatory Diseases ; *Neurodegenerative Diseases/complications/metabolism ; *Brain Injuries, Traumatic/microbiology ; Mice, Inbred C57BL ; Microglia/metabolism ; *Microbiota ; Chromium/metabolism ; }, abstract = {Background: Traumatic brain injury (TBI) is an underrecognized public health threat. The constitutive activation of microglia after TBI has been linked to long-term neurocognitive deficits and the progression of neurodegenerative disease. Evolving evidence indicates a critical role for the gut-brain axis in this process. Specifically, TBI has been shown to induce the depletion of commensal gut bacteria. The resulting gut dysbiosis is associated with neuroinflammation and disease. Hypothesis: We hypothesized that fecal microbiota transplantation would attenuate microglial activation and improve neuropathology after TBI. Methods: C57Bl/6 mice were subjected to severe TBI (n = 10) or sham injury (n = 10) via an open-head controlled cortical impact. The mice underwent fecal microbiota transplantation (FMT) or vehicle alone via oral gavage once weekly for 4 weeks after injury. At 59 days after TBI, mice underwent three-dimensional, contrast-enhanced magnetic resonance imaging. Following imaging, mice were killed, brains harvested at 60 DPI, and CD45+ cells isolated via florescence-activated cell sorting. cDNA libraries were prepared using the 10x Genomics Chromium Single Cell 3' Reagent kit followed by sequencing on a HiSeq4000 instrument, and computational analysis was performed. Results: Fecal microbiota transplantation resulted in a >marked reduction of ventriculomegaly (P < 0.002) and preservation of white matter connectivity at 59 days after TBI (P < 0.0001). In addition, microglia from FMT-treated mice significantly reduced inflammatory gene expression and enriched pathways involving the heat-shock response compared with mice treated with vehicle alone. Conclusions: We hypothesized that restoring gut microbial community structure via FMT would attenuate microglial activation and reduce neuropathology after TBI. Our data demonstrated significant preservation of cortical volume and white matter connectivity after an injury compared with mice treated with vehicle alone. This preservation of neuroanatomy after TBI was associated with a marked reduction in inflammatory gene expression within the microglia of FMT-treated mice. Microglia from FMT-treated mice enriched pathways in the heat-shock response, which is known to play a neuroprotective role in TBI and other neurodegenerative disease processes.}, }
@article {pmid36255205, year = {2022}, author = {Hu, B and Das, P and Lv, X and Shi, M and Aa, J and Wang, K and Duan, L and Gilbert, JA and Nie, Y and Wu, XL}, title = {Erratum for Hu et al., "Effects of 'Healthy' Fecal Microbiota Transplantation against the Deterioration of Depression in Fawn-Hooded Rats".}, journal = {mSystems}, volume = {}, number = {}, pages = {e0095322}, doi = {10.1128/msystems.00953-22}, pmid = {36255205}, issn = {2379-5077}, }
@article {pmid36254996, year = {2023}, author = {Kang, JN and Sun, ZF and Li, XY and Zhang, XD and Jin, ZX and Zhang, C and Zhang, Y and Wang, HY and Huang, NN and Jiang, JH and Ning, B}, title = {Alterations in gut microbiota are related to metabolite profiles in spinal cord injury.}, journal = {Neural regeneration research}, volume = {18}, number = {5}, pages = {1076-1083}, doi = {10.4103/1673-5374.355769}, pmid = {36254996}, issn = {1673-5374}, abstract = {Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8-T10 traumatic spinal cord injury. We used 16S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids (L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.}, }
@article {pmid36253536, year = {2022}, author = {Fernandes, MR and Aggarwal, P and Costa, RGF and Cole, AM and Trinchieri, G}, title = {Targeting the gut microbiota for cancer therapy.}, journal = {Nature reviews. Cancer}, volume = {22}, number = {12}, pages = {703-722}, pmid = {36253536}, issn = {1474-1768}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Immunotherapy/methods ; Fecal Microbiota Transplantation/methods ; *Neoplasms/drug therapy ; *Microbiota ; }, abstract = {Growing evidence suggests that the gut microbiota modulates the efficacy and toxicity of cancer therapy, most notably immunotherapy and its immune-related adverse effects. The poor response to immunotherapy in patients treated with antibiotics supports this influential role of the microbiota. Until recently, results pertaining to the identification of the microbial species responsible for these effects were incongruent, and relatively few studies analysed the underlying mechanisms. A better understanding of the taxonomy of the species involved and of the mechanisms of action has since been achieved. Defined bacterial species have been shown to promote an improved response to immune-checkpoint inhibitors by producing different products or metabolites. However, a suppressive effect of Gram-negative bacteria may be dominant in some unresponsive patients. Machine learning approaches trained on the microbiota composition of patients can predict the ability of patients to respond to immunotherapy with some accuracy. Thus, interest in modulating the microbiota composition to improve patient responsiveness to therapy has been mounting. Clinical proof-of-concept studies have demonstrated that faecal microbiota transplantation or dietary interventions might be utilized clinically to improve the success rate of immunotherapy in patients with cancer. Here, we review recent advances and discuss emerging strategies for microbiota-based cancer therapies.}, }
@article {pmid36253108, year = {2022}, author = {Zhu, T and Wang, Z and He, J and Zhang, X and Zhu, C and Zhang, S and Li, Y and Fan, S}, title = {D-galactose protects the intestine from ionizing radiation-induced injury by altering the gut microbiome.}, journal = {Journal of radiation research}, volume = {63}, number = {6}, pages = {805-816}, doi = {10.1093/jrr/rrac059}, pmid = {36253108}, issn = {1349-9157}, abstract = {This article aims to investigate the protection of the intestine from ionizing radiation-induced injury by using D-galactose (D-gal) to alter the gut microbiome. In addition, this observation opens up further lines of research to further increase therapeutic potentials. Male C57BL/6 mice were exposed to 7.5 Gy of total body irradiation (TBI) or 13 Gy of total abdominal irradiation (TAI) in this study. After adjustment, D-gal was intraperitoneally injected into mice at a dose of 750 mg/kg/day. Survival rates, body weights, histological experiments and the level of the inflammatory factor IL-1β were observed after TBI to investigate radiation injury in mice. Feces were collected from mice for 16S high-throughput sequencing after TAI. Furthermore, fecal microorganism transplantation (FMT) was performed to confirm the effect of D-gal on radiation injury recovery. Intraperitoneally administered D-gal significantly increased the survival of irradiated mice by altering the gut microbiota structure. Furthermore, the fecal microbiota transplanted from D-gal-treated mice protected against radiation injury and improved the survival rate of recipient mice. Taken together, D-gal accelerates gut recovery following radiation injury by promoting the growth of specific microorganisms, especially those in the class Erysipelotrichia. The study discovered that D-gal-induced changes in the microbiota protect against radiation-induced intestinal injury. Erysipelotrichia and its metabolites are a promising therapeutic option for post-radiation intestinal regeneration.}, }
@article {pmid36252894, year = {2022}, author = {Li, D and Cui, L and Gao, Y and Li, Y and Tan, X and Xu, H}, title = {Fecal microbiota transplantation improves intestinal inflammation in mice with ulcerative colitis by modulating intestinal flora composition and down-regulating NF-kB signaling pathway.}, journal = {Microbial pathogenesis}, volume = {173}, number = {Pt A}, pages = {105803}, doi = {10.1016/j.micpath.2022.105803}, pmid = {36252894}, issn = {1096-1208}, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy ; *Gastrointestinal Microbiome ; NF-kappa B ; Dextran Sulfate/pharmacology ; Interleukin-6 ; *Colitis ; Signal Transduction ; Inflammation/therapy/pathology ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/pathology ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine. It is characterized with recurrent. The pathogenesis is mainly associated with environmental factors, genetic susceptibility, dysbiosis of the intestinal flora and autoimmunity. The role of intestinal flora disorders in the pathogenesis and progression of UC is becoming increasingly prominent. More and more studies have confirmed that fecal microbiota transplantation (FMT) could reshape the composition of UC intestinal flora and it is expected to be a new strategy for UC treatment. In this study, we used 2% Dextran sulfate sodium (DSS) for 7 days to induce acute colitis model in mice, and interfere with FMT and Enterotoxigenic Escherichia coli (ETEC). ELISA and immunohistochemistry were applied to detect the concentration and expression of NF-κB p65, STAT3 and IL-6. 16SrRNA high-throughput sequencing was performed to explore the composition of intestinal flora. The aim was to study the treatment effect of FMT on UC mice and explore its potential mechanism by observing the changes of intestinal flora composition and diversity, and its relationship with NF-κB p65, STAT3 and IL-6 expression. We conclude that FMT could improve intestinal flora disorder in mice with ulcerative colitis, regulate NF-κB signaling pathway, and significantly reduce intestinal inflammation in UC mice.}, }
@article {pmid36250045, year = {2022}, author = {Lv, L and Ruan, G and Ping, Y and Cheng, Y and Tian, Y and Xiao, Z and Zhao, X and Chen, D and Wei, Y}, title = {Clinical study on sequential treatment of severe diarrhea irritable bowel syndrome with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1025889}, pmid = {36250045}, issn = {2235-2988}, mesh = {Abdominal Pain ; Bacillus subtilis ; Diarrhea/therapy ; *Enterococcus faecium ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome/therapy ; *Probiotics/therapeutic use ; Quality of Life ; Treatment Outcome ; }, abstract = {OBJECTIVE: To study the effect of precision probiotic strains transplantation capsules on diarrhea irritable bowel syndrome compared with fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules.<br><br>METHODS: Two patients with severe irritable bowel syndrome were treated with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules in sequence. IBS-SSS, IBS-QoL, GSRS, stool frequency, stool character, degree of abdominal pain, GAD-7, and PHQ9 scores of patients at 0, 2, 4, 6, 8, 10, and 12 weeks of treatment were monitored and recorded, and stool samples were collected for metagenomics and metabolomics.<br><br>RESULTS: It was found that the IBS-SSS score of patient case 1 decreased by 175 points and that of patient case 2 decreased by 100 points after treatment of precision probiotic strains transplantation capsules. There was no significant decrease after fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules were used. At the same time, compared with fecal microbiota transplantation and live combined bacillus subtilis and enterococcus faecium capsules, the IBS QoL, stool frequency, stool character, degree of abdominal pain and GAD-7 score of patient case 1 improved more significantly by the precision probiotic strains transplantation capsules. And the stool frequency and stool character score of patient case 2 decreased more significantly. Intestinal microbiota also improved more significantly after the precise capsule transplantation treatment. And we found Eubacterium_ Eligens showed the same change trend in the treatment of two patients, which may play a role in the treatment.<br><br>CONCLUSION: precision probiotic strains transplantation capsules is more beneficial to improve the intestinal microbiota of patients than microbiota transplantation capsule and live combined bacillus subtilis and enterococcus faecium capsules, so as to better alleviate clinical symptoms. This study provides a more perfect and convenient therapeutic drugs for the treatment of IBS.}, }
@article {pmid36249307, year = {2022}, author = {Owais, R and Iqbal, M}, title = {Monkeypox and fecal microbiota for transplantation(FMT): An unprecedented risk?.}, journal = {Annals of medicine and surgery (2012)}, volume = {82}, number = {}, pages = {104779}, pmid = {36249307}, issn = {2049-0801}, }
@article {pmid36248877, year = {2022}, author = {Zeng, L and Deng, Y and Yang, K and Chen, J and He, Q and Chen, H}, title = {Safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases: A systematic review and meta-analysis.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {944387}, pmid = {36248877}, issn = {1664-3224}, mesh = {*Autoimmune Diseases/etiology/therapy ; C-Peptide ; Child ; *Colitis, Ulcerative/therapy ; *Crohn Disease/etiology ; Fecal Microbiota Transplantation/adverse effects/methods ; *Hereditary Autoinflammatory Diseases/etiology ; Humans ; }, abstract = {OBJECTIVE: To evaluate the safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases.<br><br>METHODS: Relevant literature was retrieved from the PubMed database, Embase database, Cochrane Library database, etc. The search period is from the establishment of the database to January 2022. The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events. Literature screening and data extraction were independently carried out by two researchers according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for statistics and analysis.<br><br>RESULTS: Overall, a total of 14 randomized controlled trials (RCTs) involving six types of autoimmune diseases were included. The results showed the following. 1) Type 1 diabetes mellitus (T1DM): compared with the autologous fecal microbiota transplantation (FMT) group (control group), the fasting plasma C peptide in the allogenic FMT group at 12 months was lower. 2) Systemic sclerosis: at week 4, compared with one of two placebo controls, three patients in the experimental group reported a major improvement in fecal incontinence. 3) Ulcerative colitis, pediatric ulcerative colitis, and Crohn's disease: FMT may increase clinical remission, clinical response, and endoscopic remission for patients with ulcerative colitis and increase clinical remission for patients with Crohn's disease. 4) Psoriatic arthritis: there was no difference in the ratio of ACR20 between the two groups.<br><br>CONCLUSION: Based on current evidence, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases.<br><br>https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235055, identifier CRD42021235055.}, }
@article {pmid36247756, year = {2022}, author = {Barlow, B and Ponnaluri, S and Barlow, A and Roth, W}, title = {Targeting the gut microbiome in the management of sepsis-associated encephalopathy.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {999035}, pmid = {36247756}, issn = {1664-2295}, abstract = {Brain injury resulting from sepsis, or sepsis-associated encephalopathy (SAE), occurs due to impaired end-organ perfusion, dysregulated inflammation affecting the central nervous system (CNS), blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, accumulation of toxic neuropeptides and impaired toxin clearance secondary to sepsis-induced hepatic and renal dysfunction. The gut microbiome becomes pathologically altered in sepsis, which likely contributes to the pathogenesis of SAE. Herein, we review the literature detailing dysregulation of microbiota-gut-brain axis (MGBA) in SAE and highlight potential therapeutic strategies to modulate the gut microbiome to mitigate sepsis-induced brain injury.}, }
@article {pmid36246150, year = {2021}, author = {Li, H and Fu, ZY and Arslan, ME and Cho, D and Lee, H}, title = {Differential diagnosis and management of immune checkpoint inhibitor-induced colitis: A comprehensive review.}, journal = {World journal of experimental medicine}, volume = {11}, number = {6}, pages = {79-92}, pmid = {36246150}, issn = {2220-315X}, abstract = {Immune checkpoint inhibitors (ICIs) are a new class of cancer pharmacotherapy consisting of antibodies that block inhibitory immune regulators such as cytotoxic T lymphocyte antigen 4, programmed cell death 1 and programmed death-ligand 1. Checkpoint blockade by ICIs reactivates a tumor-specific T cell response. Immune-related adverse events can occur in various organs including skin, liver, and gastrointestinal tract. Mild to severe colitis is the most common side effect with some experiencing rapid progression to more serious complications including bowel perforation and even death. Prompt diagnosis and management of ICI-induced colitis is crucial for optimal outcome. Unfortunately, its clinical, endoscopic and histopathologic presentations are non-specific and overlap with those of colitis caused by other etiologies, such as infection, medication, graft-versus-host disease and inflammatory bowel disease. Thus, a definitive diagnosis can only be rendered after these other possible etiologies are excluded. Sometimes an extensive clinical, laboratory and radiologic workup is required, making it challenging to arrive at a prompt diagnosis. Most patients experience full resolution of symptoms with corticosteroids and/or infliximab. For ICI-induced colitis that is treatment-refractory, small scale studies offer alternative strategies, such as vedolizumab and fecal microbiota transplantation. In this review, we focus on the clinical features, differential diagnosis, and management of ICI-induced colitis with special attention to emerging treatment options for treatment-refractory ICI-induced colitis.}, }
@article {pmid36246106, year = {2022}, author = {Dardi, P and Dos Santos-Eichler, RA and de Oliveira, S and Vinolo, MAR and Câmara, NOS and Rossoni, LV}, title = {Reduced intestinal butyrate availability is associated with the vascular remodeling in resistance arteries of hypertensive rats.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {998362}, pmid = {36246106}, issn = {1664-042X}, abstract = {During hypertension an unbalance of short-chain fatty acids (SCFAs) production by intestinal bacteria is described. However, no data evaluate the association of SCFAs and vascular remodeling in hypertension, which is an important hallmark of this disease. Thus, the present study aims to evaluate the correlations between SCFAs availability and the resistance arteries remodeling in hypertension, as well as to identify the possible pathway by which the SCFAs could exert a structural and mechanical influence. Hence, male spontaneously hypertensive rats (SHR) and normotensive Wistar rats had blood pressure measured by tail-cuff plethysmography; fecal SCFAs content assessed by gas chromatography; gene expression of SCFAs-transporters in gut epithelium and SCFAs-sensing receptors on mesenteric resistance arteries (MRA) quantified by PCR; and MRA structural and mechanical parameters analyzed by pressure myograph. Reduced butyrate fecal content was found in SHR, with no changes in propionate and acetate, as well as decreased mRNA levels of SCFAs-transporters (MCT1, MCT4, and SMCT1) in the intestinal epithelium. In addition, lower gene expression of SCFAs-sensing receptors (GPR41, GPR43, and GPR109a, but not Olfr78) was identified in MRAs of SHR, which also shows inward eutrophic remodeling with stiffness. Butyrate content presented a negative correlation with systolic blood pressure and with the structural alterations found on MRAs, while a positive correlation between butyrate content and mechanical parameters was detected. Altogether the present study suggests that lower butyrate content due to ineffective SCFA bioavailability, associated with lower SCFAs-sensing receptors expression, could favor MRA remodeling, increasing peripheral vascular resistance and worsening hypertension prognosis.}, }
@article {pmid36239349, year = {2022}, author = {Ni, Y and Zheng, L and Nan, S and Ke, L and Fu, Z and Jin, J}, title = {Enterorenal crosstalks in diabetic nephropathy and novel therapeutics targeting the gut microbiota.}, journal = {Acta biochimica et biophysica Sinica}, volume = {}, number = {}, pages = {}, doi = {10.3724/abbs.2022140}, pmid = {36239349}, issn = {1745-7270}, abstract = {The role of gut-kidney crosstalk in the progression of diabetic nephropathy (DN) is receiving increasing concern. On one hand, the decline in renal function increases circulating uremic toxins and affects the composition and function of gut microbiota. On the other hand, intestinal dysbiosis destroys the epithelial barrier, leading to increased exposure to endotoxins, thereby exacerbating kidney damage by inducing systemic inflammation. Dietary inventions, such as higher fiber intake, prebiotics, probiotics, postbiotics, fecal microbial transplantation (FMT), and engineering bacteria and phages, are potential microbiota-based therapies for DN. Furthermore, novel diabetic agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, may affect the progression of DN partly through gut microbiota. In the current review, we mainly summarize the evidence concerning the gut-kidney axis in the advancement of DN and discuss therapies targeting the gut microbiota, expecting to provide new insight into the clinical treatment of DN.}, }
@article {pmid36239189, year = {2022}, author = {Ghorbani, Y and Schwenger, KJP and Sharma, D and Jung, H and Yadav, J and Xu, W and Lou, W and Poutanen, S and Hota, SS and Comelli, EM and Philpott, D and Jackson, TD and Okrainec, A and Gaisano, HY and Allard, JP}, title = {Effect of faecal microbial transplant via colonoscopy in patients with severe obesity and insulin resistance: A randomized double-blind, placebo-controlled Phase 2 trial.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.14891}, pmid = {36239189}, issn = {1463-1326}, support = {TB2-138775/CAPMC/CIHR/Canada ; TB2-138775/CAPMC/CIHR/Canada ; }, abstract = {AIM: To assess the effects of faecal microbial transplant (FMT) from lean people to subjects with obesity via colonoscopy.<br><br>MATERIAL AND METHODS: In a double-blind, randomized controlled trial, subjects with a body mass index &#x2265;&#x2009;35&#x2009;kg/m[2] and insulin resistance were randomized, in a 1:1 ratio in blocks of four, to either allogenic (from healthy lean donor; n&#xa0;=&#xa0;15) or autologous FMT (their own stool; n&#xa0;=&#xa0;13) delivered in the caecum and were followed for 3&#xa0;months. The main outcome was homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes were glycated haemoglobin levels, lipid profile, weight, gut hormones, endotoxin, appetite measures, intestinal microbiome (IM), metagenome, serum/faecal metabolites, quality of life, anxiety and depression scores.<br><br>RESULTS: In the allogenic versus autologous groups, HOMA-IR and clinical variables did not change significantly, but IM and metabolites changed favourably (P&#xa0;<&#x2009;0.05): at 1 month, Coprococcus, Bifidobacterium, Bacteroides and Roseburia increased, and Streptococcus decreased; at 3 months, Bacteroides and Blautia increased. Several species also changed significantly. For metabolites, at 1 month, serum kynurenine decreased and faecal indole acetic acid and butenylcarnitine increased, while at 3 months, serum isoleucine, leucine, decenoylcarnitine and faecal phenylacetic acid decreased. Metagenomic pathway representations and network analyses assessing relationships with clinical variables, metabolites and IM were significantly enhanced in the allogenic versus autologous groups. LDL and appetite measures improved in the allogenic (P&#xa0;<&#x2009;0.05) but not in the autologous group.<br><br>CONCLUSIONS: Overall, in those with obeisty, allogenic FMT via colonoscopy induced favourable changes in IM, metabolites, pathway representations and networks even though other metabolic variables did not change. LDL and appetite variables may also benefit.}, }
@article {pmid36237764, year = {2022}, author = {Jayasinghe, M and Prathiraja, O and Kayani, AMA and Jena, R and Caldera, D and Silva, MS and Singhal, M and Pierre, J}, title = {The Role of Diet and Gut Microbiome in Multiple Sclerosis.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e28975}, pmid = {36237764}, issn = {2168-8184}, abstract = {Multiple sclerosis (MS) is a chronic demyelinating condition of the central nervous system (CNS) characterized by immune-mediated damage to the myelin sheath of nerve cells. Genetic and environmental factors are believed to play a significant role. Unfortunately, the knowledge of therapeutic modalities in MS remains very limited, necessitating the need for novel therapeutic strategies. In the previous decade, there has been an influx of studies on the gut microbiome and its link to various neurological conditions, including MS. Various diets may have favorable effects on the gut microflora and may significantly alter the progression and outcomes of MS. Thus, identifying the merits of various diets and modulating them according to the specific nutritional requirements of MS patients can go a long way toward slowing the progression of the disease. Nutritional interventions and the use of the gut microbiome as diagnostic and therapeutic modalities open a host of new possibilities regarding the disease. In this review, we investigate the role of diet and the gut microbiome in the progression of MS. The functions of the gut-brain axis, antioxidants, vitamins, obesity, and various diets are also covered in this article.}, }
@article {pmid36233289, year = {2022}, author = {Guardamagna, M and Berciano-Guerrero, MA and Villaescusa-González, B and Perez-Ruiz, E and Oliver, J and Lavado-Valenzuela, R and Rueda-Dominguez, A and Barragán, I and Queipo-Ortuño, MI}, title = {Gut Microbiota and Therapy in Metastatic Melanoma: Focus on MAPK Pathway Inhibition.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36233289}, issn = {1422-0067}, mesh = {Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy ; *Melanoma/drug therapy ; Mitogen-Activated Protein Kinase Kinases ; *Neoplasms, Second Primary/drug therapy ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Proto-Oncogene Proteins B-raf/genetics ; Tumor Microenvironment ; }, abstract = {Gut microbiome (GM) and its either pro-tumorigenic or anti-tumorigenic role is intriguing and constitutes an evolving landscape in translational oncology. It has been suggested that these microorganisms may be involved in carcinogenesis, cancer treatment response and resistance, as well as predisposition to adverse effects. In melanoma patients, one of the most immunogenic cancers, immune checkpoint inhibitors (ICI) and MAPK-targeted therapy-BRAF/MEK inhibitors-have revolutionized prognosis, and the study of the microbiome as a modulating factor is thus appealing. Although BRAF/MEK inhibitors constitute one of the main backbones of treatment in melanoma, little is known about their impact on GM and how this might correlate with immune re-induction. On the contrary, ICI and their relationship to GM has become an interesting field of research due to the already-known impact of immunotherapy in modulating the immune system. Immune reprogramming in the tumor microenvironment has been established as one of the main targets of microbiome, since it can induce immunosuppressive phenotypes, promote inflammatory responses or conduct anti-tumor responses. As a result, ongoing clinical trials are evaluating the role of fecal microbiota transplant (FMT), as well as the impact of using dietary supplements, antibiotics and probiotics in the prediction of response to therapy. In this review, we provide an overview of GM's link to cancer, its relationship with the immune system and how this may impact response to treatments in melanoma patients. We also discuss insights about novel therapeutic approaches including FMT, changes in diet and use of probiotics, prebiotics and symbiotics. Finally, we hypothesize on the possible pathways through which GM may impact anti-tumor efficacy in melanoma patients treated with targeted therapy, an appealing subject of which little is known.}, }
@article {pmid36232336, year = {2022}, author = {Huynh, QS and Elangovan, S and Holsinger, RMD}, title = {Non-Pharmacological Therapeutic Options for the Treatment of Alzheimer's Disease.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232336}, issn = {1422-0067}, mesh = {*Alzheimer Disease/metabolism ; Humans ; }, abstract = {Alzheimer's disease is a growing global crisis in need of urgent diagnostic and therapeutic strategies. The current treatment strategy mostly involves immunotherapeutic medications that have had little success in halting disease progress. Hypotheses for pathogenesis and development of AD have been expanded to implicate both organ systems as well as cellular reactions. Non-pharmacologic interventions ranging from minimally to deeply invasive have attempted to address these diverse contributors to AD. In this review, we aim to delineate mechanisms underlying such interventions while attempting to provide explanatory links between the observed differences in disease states and postulated metabolic or structural mechanisms of change. The techniques discussed are not an exhaustive list of non-pharmacological interventions against AD but provide a foundation to facilitate a deeper understanding of the area of study.}, }
@article {pmid36230772, year = {2022}, author = {Bawaneh, A and Wilson, AS and Levi, N and Howard-McNatt, MM and Chiba, A and Soto-Pantoja, DR and Cook, KL}, title = {Intestinal Microbiota Influence Doxorubicin Responsiveness in Triple-Negative Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {19}, pages = {}, pmid = {36230772}, issn = {2072-6694}, support = {P30CA012197/NH/NIH HHS/United States ; }, abstract = {Triple-negative breast cancer (TNBC) is highly aggressive with a poor 5-year survival rate. Targeted therapy options are limited and most TNBC patients are treated with chemotherapy. This study aimed to determine whether doxorubicin (Dox) shifts the gut microbiome and whether gut microbiome populations influence chemotherapeutic responsiveness. Female BALB/c mice (n = 115) were injected with 4T1-luciferase cells (a murine syngeneic TNBC model) and treated with Dox and/or antibiotics, high-fat diet-derived fecal microbiota transplant (HFD-FMT), or exogenous lipopolysaccharide (LPS). Metagenomic sequencing was performed on fecal DNA samples. Mice that received Dox were stratified into Dox responders or Dox nonresponders. Mice from the Dox responders and antibiotics + Dox groups displayed reduced tumor weight and metastatic burden. Metagenomic analysis showed that Dox was associated with increased Akkermansia muciniphila proportional abundance. Moreover, Dox responders showed an elevated proportional abundance of Akkermansia muciniphila prior to Dox treatment. HFD-FMT potentiated tumor growth and decreased Dox responsiveness. Indeed, lipopolysaccharide, a structural component of Gram-negative bacteria, was increased in the plasma of Dox nonresponders and FMT + Dox mice. Treatment with exogenous LPS increases intestinal inflammation, reduces Dox responsiveness, and increases lung metastasis. Taken together, we show that modulating the gut microbiota through antibiotics, HFD-FMT, or by administering LPS influenced TNBC chemotherapy responsiveness, lung metastasis, and intestinal inflammation.}, }
@article {pmid36230563, year = {2022}, author = {Tojjari, A and Abushukair, H and Saeed, A}, title = {The Crosstalk between Microbiome and Immunotherapeutics: Myth or Reality.}, journal = {Cancers}, volume = {14}, number = {19}, pages = {}, pmid = {36230563}, issn = {2072-6694}, abstract = {The gut microbiome refers to microorganisms and their genetic material influencing local and systemic inflammation. Inflammation is known to contribute to cancer development, progression, and treatment. Evidence suggests that modulating the gut microbiome may affect responses to various cancer therapies. The gut microbiota has been suggested to have an impact on immunotherapy efficacy, especially the currently widely used immune checkpoint inhibitors in various malignancies. Microbial interventions like fecal microbiota transplantation, various probiotics, or even antibiotics can increase or decrease the tumor's sensitivity to immunotherapy. However, not all tumors react in the same manner, highlighting the tumor microenvironment heterogeneity across tumor types and the influence this has on the crosstalk between the microbiome and therapy outcomes. In this study, we intend to review the association between the gut microbiota and immunotherapy response in cancer patients and the factors regulating this interaction.}, }
@article {pmid36230076, year = {2022}, author = {Li, HY and Huang, SY and Xiong, RG and Wu, SX and Zhou, DD and Saimaiti, A and Luo, M and Zhu, HL and Li, HB}, title = {Anti-Obesity Effect of Theabrownin from Dark Tea in C57BL/6J Mice Fed a High-Fat Diet by Metabolic Profiles through Gut Microbiota Using Untargeted Metabolomics.}, journal = {Foods (Basel, Switzerland)}, volume = {11}, number = {19}, pages = {}, pmid = {36230076}, issn = {2304-8158}, abstract = {The epidemic of obesity is a serious public health problem. In this study, the effect of theabrownin from dark tea on obesity was evaluated by biochemical tests and nuclear magnetic resonance in C57BL/6J mice fed a high-fat diet. A mixture of antibiotics was used to deplete gut microbiota and then fecal microbiota transplant was used to restore gut microbiota. Untargeted metabolomics was used to reveal the effects of theabrownin on metabolic profiles through gut microbiota. The results showed that theabrownin significantly reduced body weight gain (83.0%) and body fat accumulation (30.29%) without affecting appetite. Also, theabrownin promoted lipid clearance with a hepatoprotective effect. The extra antibiotics disrupted the regulation of theabrownin on weight control while fecal microbiota transplant restored the beneficial regulation. That is, gut microbiota was important for theabrownin to reduce body weight gain. The untargeted metabolomics indicated that 18 metabolites were related to the anti-obesity effect of theabrownin mediated by gut microbiota. Furthermore, phenylalanine metabolism, histidine metabolism, as well as protein digestion and absorption pathway played a role in the anti-obesity of theabrownin. Our findings suggested that theabrownin significantly alleviated obesity via gut microbiota-related metabolic pathways, and theabrownin could be used for the prevention and treatment of obesity.}, }
@article {pmid36227005, year = {2022}, author = {Dogra, S and Oneto, C and Sherman, A and Varughese, R and Yuen, A and Sherman, I and Cohen, A and Luo, Y and Chen, LA}, title = {Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for C. difficile Infections Across Academic and Private Clinical Settings.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001778}, pmid = {36227005}, issn = {1539-2031}, abstract = {PURPOSE: Fecal microbiota transplant (FMT) is increasingly performed for Clostridioides difficile infection (CDI), although long-term efficacy and safety data are limited and are focused on results from academic medical centers rather than private settings where most patients receive care.<br><br>METHODS: Medical records of 165 patients who received FMTs for CDI were reviewed from an academic medical center and an adjacent, unaffiliated private practice. Of these patients, 68 also completed a survey regarding their long-term disease course and interval health.<br><br>RESULTS: CDI resolution occurred in 81.3% (100/123) at the academic center and 95.2% (40/42) in the private setting. Private practice patients were more likely to present with recurrent, rather than refractory, CDI (92.9% vs. 66.7% P<0.001). Those from the academic center were more likely to have comorbid IBD, recent hospitalization, recent proton pump inhibitor use, ongoing immunosuppression, and inpatient FMT (all P values <0.05).Among surveyed patients, 29.4% developed interval comorbidities or changes to pre-existing conditions after a median follow-up of 33.7 months (IQR 13.2 to 44.3&#xa0;mo). Of 30 patients requiring subsequent antibiotics, 13.3% suffered CDI relapse. All subjects who had initially responded to FMT but had a subsequent CDI (17.9%, 10/56) responded to another FMT.<br><br>CONCLUSIONS: In a real-world setting, patients who underwent FMT at academic centers differed significantly in clinical characteristics from those treated at a private practice. In both settings, FMT is an effective treatment for CDI not responding to standard therapies, even after subsequent antibiotic use. New diagnoses following FMT, however, are common and merit further exploration.}, }
@article {pmid36226734, year = {2022}, author = {Sangiuolo, K and Cheng, E and Terala, A and Dubrosa, F and Milanaik, RL}, title = {The gut microbiome: an overview of current trends and risks for paediatric populations.}, journal = {Current opinion in pediatrics}, volume = {34}, number = {6}, pages = {634-642}, doi = {10.1097/MOP.0000000000001186}, pmid = {36226734}, issn = {1531-698X}, mesh = {Adolescent ; Humans ; Child ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Microbiota ; Diet ; *Malnutrition ; }, abstract = {PURPOSE OF REVIEW: Gut health is an increasingly popular topic of discussion among scientists and the general population alike. As interest surrounding the gut microbiome grows, the accessibility to misinformation and unfounded gut health trends to youth is likely to emerge as a public health concern. The purpose of this review is to provide paediatricians with current information about the gut microbiome, as well as explanations and possible risks of the multitude of gut health trends that adolescents may be exposed to.<br><br>RECENT FINDINGS: The gut microbiome is implicated in overall health by playing roles in digestion, immunity and mental health. Novel microbiome-related therapies, such as faecal microbiota transplants, and the gut-brain link show the therapeutic potential of the gut microbiome. However, unproven dietary fads and trends on social media are rampant as well, such as ginger juice shots. In addition, paediatric supplements meant to target gut health are unregulated, yet are highly marketed. Improperly applying these trends and diets may result in risks of malnutrition and body image issues for impressionable children.<br><br>SUMMARY: Increased familiarity regarding the types of gut health trends and diets among young people will allow paediatricians to more effectively advise their patients about potential risks and good gut health practices. Paediatricians and caregivers serve as role models and educators with regard to children's perceptions and management of their gut and overall health.}, }
@article {pmid36222487, year = {2022}, author = {Cuomo, M and Carobbio, A and Aloi, M and Alvisi, P and Banzato, C and Bosa, L and Bramuzzo, M and Campanozzi, A and Catassi, G and D'Antiga, L and Di Paola, M and Felici, E and Fioretti, MT and Gatti, S and Graziano, F and Lega, S and Lionetti, P and Marseglia, A and Martinelli, M and Musto, F and Sansotta, N and Scarallo, L and Zuin, G and Norsa, L}, title = {Induction of Remission With Exclusive Enteral Nutrition in Children With Crohn's Disease: Determinants of Higher Adherence and Response.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izac215}, pmid = {36222487}, issn = {1536-4844}, abstract = {BACKGROUND: Exclusive enteral nutrition (EEN) is the first choice to induce remission and promote mucosal healing in pediatric Crohn's disease (CD). However, full adherence to EEN treatment may be problematic for children with CD.<br><br>METHODS: The goal of the current multicenter retrospective study was to define predictive factors of nonadherence to treatment and nonremission at the end of induction treatment. Those data together were analyzed with the ultimate goal of trying to define an individualized induction treatment for children with CD.<br><br>RESULTS: Three hundred seventy-six children with CD from 14 IBD pediatric referral centers were enrolled in the study. The rate of EEN adherence was 89%. Colonic involvement and fecal calprotectin&#x2005;>600 &#x3bc;g/g at diagnosis were found to be associated with a reduced EEN adherence. Exclusive enteral nutrition administered for 8 weeks was effective for inducing clinical remission in 67% of the total cohort. Factors determining lower remission rates were age&#x2005;>15 years and Pediatric Crohn's Disease Activity Index >50.<br><br>CONCLUSION: Although EEN is extremely effective in promoting disease remission, several patients' related factors may adversely impact EEN adherence and response. Personalized treatments should be proposed that weigh benefits and risks based on the patient's disease location, phenotype, and disease activity and aim to promote a rapid control of inflammation to reduce long-term bowel damage.}, }
@article {pmid36216056, year = {2023}, author = {Yi, W and Ji, Y and Gao, H and Luo, S and Pan, R and Song, J and He, Y and Li, Y and Wu, Y and Yan, S and Liang, Y and Sun, X and Jin, X and Mei, L and Cheng, J and Su, H}, title = {Effects of urban particulate matter on gut microbiome and partial schizophrenia-like symptoms in mice: Evidence from shotgun metagenomic and metabolomic profiling.}, journal = {The Science of the total environment}, volume = {857}, number = {Pt 1}, pages = {159305}, doi = {10.1016/j.scitotenv.2022.159305}, pmid = {36216056}, issn = {1879-1026}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Particulate Matter/toxicity ; *Schizophrenia ; Dizocilpine Maleate/pharmacology ; Phosphorylcholine/pharmacology ; Feces ; Estriol ; Estrogens ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Epidemiological evidence reported that particulate matter (PM) was associated with increased schizophrenia (SCZ) risk. Disturbance of gut microbiome was involved in SCZ. However, it remains unclear whether PM induces SCZ-like symptoms and how gut microbiome regulates them. Therefore, a multi-omics animal experiment was conducted to verify how urban PM induces SCZ-like behavior and altered gut microbiota and metabolic pathways.<br><br>METHODS: Using a completely random design, mice were divided into three groups: PM group, control group and MK801 group, which received daily tracheal instillation of PM solution, sterile PBS solution and intraperitoneal injection of MK801 (establish SCZ model), respectively. After a 14-day intervention, feces were collected for multi-omics testing (shotgun metagenomic sequencing and untargeted metabolomic profiling), followed by open field test, tail suspension test, and passive avoidance test. Besides, fecal microbiome of PM group and control group were transplanted into "pseudo-sterile" mice, then behavioral tests were conducted.<br><br>RESULTS: Similar to MK801 group, mice in PM group showed SCZ-like symptoms, including increased spontaneous activity, excitability, anxiety and decreased learning and spatial memory. PM exposure significantly increased the relative abundance of Verrucomicrobia and decreased that of Fibrobacteres et al. The metabolism pathways of estrogen signaling (estriol, 16-glucuronide-estriol and 21-desoxycortisol) and choline metabolism (phosphocholine) were significantly altered by PM exposure. Verrucomicrobia was negatively correlated with the level of estriol, which was correlated with decreased learning and spatial memory. Fibrobacteres and Deinococcus-Thermus were positively correlated with the level of phosphocholine, which was correlated with increased spontaneous activity, excitability and anxiety. Fecal microbiome transplantation from PM group mice reproduced excitability and anxiety symptoms.<br><br>CONCLUSIONS: Exposure to PM may affect composition of gut microbiome and alterations of estrogen signaling pathway and choline metabolism pathway, which were associated with partial SCZ-like behaviors. But whether gut microbiome regulates these metabolic pathways and behaviors remains to be determined.}, }
@article {pmid36214691, year = {2022}, author = {Yan, X and Feng, Y and Hao, Y and Zhong, R and Jiang, Y and Tang, X and Lu, D and Fang, H and Agarwal, M and Chen, L and Zhao, Y and Zhang, H}, title = {Gut-Testis Axis: Microbiota Prime Metabolome To Increase Sperm Quality in Young Type 2 Diabetes.}, journal = {Microbiology spectrum}, volume = {10}, number = {5}, pages = {e0142322}, pmid = {36214691}, issn = {2165-0497}, mesh = {Male ; Mice ; Animals ; Testis ; *Diabetes Mellitus, Type 2/therapy ; Semen Analysis ; Butyric Acid ; Blood Glucose ; Eicosapentaenoic Acid ; Docosahexaenoic Acids ; Antioxidants ; Semen ; *Gastrointestinal Microbiome ; Spermatozoa ; Metabolome ; Testosterone ; Alginates ; }, abstract = {Young type 2 diabetes (T2D) affects 15% of the population, with a noted increase in cases, and T2D-related male infertility has become a serious issue in recent years. The current study aimed to explore the improvements of alginate oligosaccharide (AOS)-modified gut microbiota on semen quality in T2D. The T2D was established in young mice of 5 weeks of age with a blood glucose level of 21.2 ± 2.2 mmol/L, while blood glucose was 8.7 ± 1.1 mM in control animals. We discovered that fecal microbiota transplantation (FMT) of AOS-improved microbiota (A10-FMT) significantly decreased blood glucose, while FMT of gut microbiota from control animals (Con-FMT) did not. Sperm concentration and motility were decreased in T2D to 10% to 20% of those in the control group, while A10-FMT brought about a recovery of around 5- to 10-fold. A10-FMT significantly increased small intestinal Allobaculum, while it elevated small intestinal and cecal Lactobacillus in some extent, blood butyric acid and derivatives and eicosapentaenoic acid (EPA), and testicular docosahexaenoic acid (DHA), EPA, and testosterone and its derivatives. Furthermore, A10-FMT improved liver functions and systemic antioxidant environments. Most importantly, A10-FMT promoted spermatogenesis through the improvement in the expression of proteins important for spermatogenesis to increase sperm concentration and motility. The underlying mechanisms may be that A10-FMT increased gut-beneficial microbes Lactobacillus and Allobaculum to elevate blood and/or testicular butyric acid, DHA, EPA, and testosterone to promote spermatogenesis and thus to ameliorate sperm concentration and motility. AOS-improved gut microbes could emerge as attractive candidates to treat T2D-diminished semen quality. IMPORTANCE A10-FMT benefits gut microbiota, liver function, and systemic environment via improvement in blood metabolome, consequently to favor the testicular microenvironment to improve spermatogenesis process and to boost T2D-diminished semen quality. We established that AOS-improved gut microbiota may be used to boost T2D-decreased semen quality and metabolic disease-related male subfertility.}, }
@article {pmid36213281, year = {2022}, author = {Wu, L and Li, MQ and Xie, YT and Zhang, Q and Lu, XJ and Liu, T and Lin, WY and Xu, JT and Wu, QP and He, XX}, title = {Washed microbiota transplantation improves patients with high blood glucose in South China.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {985636}, pmid = {36213281}, issn = {1664-2392}, mesh = {Animals ; Blood Glucose/metabolism ; Cholesterol ; *Gastrointestinal Microbiome ; Glycated Hemoglobin A ; *Hyperglycemia/prevention &amp; control ; Hypoglycemic Agents ; Lipids ; Retrospective Studies ; Triglycerides ; }, abstract = {BACKGROUND AND AIMS: Although fecal microbiota transplantation (FMT) from healthy donors has been shown to have hypoglycemic effects in animal models of diabetes, its clinical impact in patients with abnormal blood glucose metabolism is unclear, especially in southern Chinese populations. The aim of this study was to investigate the feasibility and efficacy of washed microbiota transplantation (WMT) in the treatment of abnormal blood glucose metabolism in a population in southern China.<br><br>METHODS: The clinical data of patients with different indications who received 1-3 treatments of WMT were retrospectively collected. The changes of blood glucose, blood lipids, blood pressure, liver function and blood routine before and after WMT were compared, such as fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), systolic blood pressure (SBP), white blood cells (WBC), lymphocytes (LY) and platelets (PLT), etc.<br><br>RESULTS: A total of 195 patients were included in the First Affiliated Hospital of Guangdong Pharmaceutical University, including 20 patients with high blood glucose and 175 patients with normal blood glucose. WMT has a significant effect in reducing short term blood glucose level (FBG) in patients with high blood glucose (p < 0.05). The fasting blood glucose (FBG) of 72.22% of patients with high blood glucose decreased to normal in a short term (about 1 month) (p < 0.001); In the medium term (about 2 months), there was a significant hypolipidemic (TG) (p = 0.043) effect, long term (about 6 months) significant blood pressure lowering (SBP, p = 0.048) effect. Overall, WMT significantly reduced the risk of high risk classes of Atherosclerotic Cardiovascular Disease (ASCVD) in the short term (p = 0.029) and medium term (p = 0.050).<br><br>CONCLUSION: WMT can significantly improve blood glucose in patients with high blood glucose, and there is no long-term elevated risk of blood glucose and ASCVD. FBG levels were significantly reduced in both the short and medium term in patients with high blood glucose treated with WMT. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of abnormal blood glucose metabolism.}, }
@article {pmid36212891, year = {2022}, author = {Luo, D and Yang, L and Pang, H and Zhao, Y and Li, K and Rong, X and Guo, J}, title = {Tianhuang formula reduces the oxidative stress response of NAFLD by regulating the gut microbiome in mice.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {984019}, pmid = {36212891}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiome affects the occurrence and development of NAFLD, but its mechanism has not yet been fully elucidated. Chinese medicine is a new treatment strategy to improve NAFLD by regulating the gut microbiome. Tianhuang formula (TH) has been proved to have a lipid-lowering effect in which constituents of ginsenoside Rb1, ginsenoside Rg1, ginsenoside Rb, ginsenoside Re, and ginsenoside R1 from Panax notoginseng and berberine, palmatine, and coptisine from Coptis chinensis have low drug permeability, which results in poor intestinal absorption into the human body, and are thus able to come into contact with the gut microflora for a longer time. Therefore, it might be able to influence the gut microbial ecosystem, but it still needs to be investigated.<br><br>METHOD: The characteristics of the gut microbiome were represented by 16S rRNA sequencing, and the metabolites in intestinal contents and liver were discovered by non-targeted metabolomics. Correlation analysis and fermentation experiments revealed the relationship between the gut microbiome and metabolites. Blood biochemical indicators, liver function indicators, and oxidation-related indicators were assayed. H&amp;E staining and Oil Red O staining were used to analyze the characteristics of hepatic steatosis. RT-qPCR and western blotting were used to detect the expression of genes and proteins in liver tissues, and fecal microbial transplantation (FMT) was performed to verify the role of the gut microbiome.<br><br>RESULTS: Gut microbiome especially Lactobacillus reduced, metabolites such as 5-Methoxyindoleacetate (5-MIAA) significantly reduced in the liver and intestinal contents, the level of hepatic GSH and SOD reduced, MDA increased, and the protein expression of Nrf2 also reduced in NAFLD mice induced by high-fat diet (HFD). The normal diet mice transplanted with NAFLD mice feces showed oxidative liver injury, indicating that the NAFLD was closely related to the gut microbiome. TH and TH-treated mice feces both can reshape the gut microbiome, increase the abundance of Lactobacillus and the content of 5-MIAA in intestinal contents and liver, and improve oxidative liver injury. This indicated that the effect of TH improving NAFLD was related to the gut microbiome, especially Lactobacillus. 5-MIAA, produced by Lactobacillus, was proved with fermentation experiments in vitro. Further experiments proved that 5-MIAA activated the Nrf2 pathway to improve oxidative stress in NAFLD mice induced by HFD. TH reshaped the gut microbiome, increased the abundance of Lactobacillus and its metabolite 5-MIAA to alleviate oxidative stress, and improved NAFLD.<br><br>CONCLUSION: The study has demonstrated a mechanism by which the gut microbiome modulated oxidative stress in NAFLD mice induced by HFD. The traditional Chinese medicine TH improved NAFLD by regulating the gut microbiome, and its mechanism was related to the "Lactobacillus-5-MIAA-Nrf2" pathway. It provided a promising way for the intervention of NAFLD.}, }
@article {pmid36212876, year = {2022}, author = {Li, Y and Li, X and Wu, Y and Zhang, W}, title = {Effects of fecal microbiota transplantation from yaks on weaning diarrhea, fecal microbiota composition, microbial network structure and functional pathways in Chinese Holstein calves.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {898505}, pmid = {36212876}, issn = {1664-302X}, abstract = {This study was conducted to investigate the effect of fecal microbiota transplantation (FMT) from yaks on weaning diarrhea, fecal microbiota composition, microbial network structure and functional pathways in Chinese Holstein Calves. In this study, 50 calves were randomly divided into five groups of 10 each: NC group (no supplementation), Control group (normal saline), low concentration FMT group (LFMT, 1 × 10[8] CFU/ml), high concentration FMT group (HMFT, 1 × 10[9] CFU/ml), and sterilized FMT group (SMFT, sterilized bacterial solution). The test lasted for 30 days. We found that FMT reduced the incidence of diarrhea in weaned calves, and the anti-diarrhea effect of LFMT was stronger than those of HFMT and SFMT. Calf feces were collected by rectal palpation on days 5, 10, 15, and 20 post-weaning, and high-throughput sequencing of bacterial 16S rRNA and fungal internal transcribed spacer region of fecal microbiota was performed. We observed that the richness and diversity of bacterial microbiota in the LFMT, HFMT, and SFMT groups were higher than those in the NC and Control groups at day 20 after weaning. The treatment had a significant effect on bacterial richness (p < 0.05), but not on fungal diversity or richness. The analysis of gut microbiome showed that Firmicutes and Bacteroides were the main bacterial phyla in the feces of weaned calves, and norank_ f Muribaculaceae, UCG-005, Rikenellaceae_RC9_gut_group, Bacteroides, and Blautia were the main genera. Ascomycota and Basidiomycota were the main fungal phyla. Compared to abundance parameters in the Control and NC groups, relative abundances of Firmicutes in the FMT groups increased at different time points after weaning. The relative abundance of Blautia and Lactobacillus in the LFMT group increased significantly after weaning. In addition, abundances of Ruminococcus and Romboutsia, which produce short-chain fatty acids, were also increased in different FMT groups. FMT significantly increased the relative abundance of beneficial bacteria, enhanced the complexity of the fecal microbial network, and promoted important metabolic and cellular processes in weaned calves. In conclusion, our study provides a reference and theoretical basis for FMT to prevent calf weaning diarrhea and other intestinal diseases in ruminants.}, }
@article {pmid36212607, year = {2022}, author = {Nigam, M and Panwar, AS and Singh, RK}, title = {Orchestrating the fecal microbiota transplantation: Current technological advancements and potential biomedical application.}, journal = {Frontiers in medical technology}, volume = {4}, number = {}, pages = {961569}, pmid = {36212607}, issn = {2673-3129}, abstract = {Fecal microbiota transplantation (FMT) has been proved to be an effective treatment for gastrointestinal disorders caused due to microbial disbalance. Nowadays, this approach is being used to treat extragastrointestinal conditions like metabolic and neurological disorders, which are considered to have their provenance in microbial dysbiosis in the intestine. Even though case studies and clinical trials have demonstrated the potential of FMT in treating a variety of ailments, safety and ethical concerns must be answered before the technique is widely used to the community's overall benefit. From this perspective, it is not unexpected that techniques for altering gut microbiota may represent a form of medication whose potential has not yet been thoroughly addressed. This review intends to gather data on recent developments in FMT and its safety, constraints, and ethical considerations.}, }
@article {pmid36208299, year = {2022}, author = {Wang, YZ and Xiao, FF and Xiao, YM and Li, XL and Hu, H and Hong, K and Li, D and Le, J and Yu, GJ and Zhang, T}, title = {Fecal microbiota transplantation relieves abdominal bloating in children with functional gastrointestinal disorders via modulating the gut microbiome and metabolome.}, journal = {Journal of digestive diseases}, volume = {23}, number = {8-9}, pages = {482-492}, doi = {10.1111/1751-2980.13135}, pmid = {36208299}, issn = {1751-2980}, mesh = {Male ; Humans ; Child ; Female ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; *Gastrointestinal Diseases/therapy ; Metabolome ; Bacteria ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in functional gastrointestinal disorders (FGIDs) in children with abdominal bloating and changes in their gut microbiome and metabolome.<br><br>METHODS: Twelve pediatric FGID patients with predominant abdominal bloating who underwent FMT were enrolled in the study. Fourteen healthy controls and four stool donors were included for analysis. Clinical responses were assessed at 8&#x2009;weeks after FMT. Fecal bacterial composition was determined by 16S rRNA gene sequencing. The fecal metabolome was measured by targeted metabolomics analysis.<br><br>RESULTS: Median age of the 12 children with FGIDs was 6&#x2009;years, and nine were boys. Abdominal bloating was relieved in all patients by FMT at 8&#x2009;weeks. Meanwhile, FMT significantly improved abdominal pain and diarrhea. The a diversity was significantly lower in the FGID patients, while the fecal microbial community (&#x3b2; diversity) separated from that of healthy control (HCs). The relative abundances of multiple bacterial genera were significantly changed in the feces of the pediatric FGID patients. The levels of several short-chain fatty acids were lower, and lactic acid level was higher in FGID patients than in HCs. Altered bacterial composition was correlated with changes in the fecal metabolite profile and clinical symptoms in FGID patients. FMT modulated fecal microbiome and metabolome in FGID children toward a healthy state.<br><br>CONCLUSIONS: FMT relieves abdominal bloating and modulates fecal microbiome and metabolome toward a healthy state in children with FGIDs. FMT may provide an alternative therapy for children with FGIDs and abdominal bloating.}, }
@article {pmid36206121, year = {2022}, author = {Perez, R and Khanna, S and Tillotson, GS and Lett, JE and Prince, MA and Lattimer, C}, title = {Reducing Recurrence and Complications Related to Clostridioides difficile Infection: A Panel Discussion Summary.}, journal = {Professional case management}, volume = {27}, number = {6}, pages = {277-287}, pmid = {36206121}, issn = {1932-8095}, mesh = {Aftercare ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/prevention &amp; control ; Humans ; Patient Discharge ; Proton Pump Inhibitors/therapeutic use ; Quality of Life ; }, abstract = {BACKGROUND: The Centers for Disease Control and Prevention identifies Clostridioides difficile infection (CDI) as an urgent threat to people and health care systems. CDI leads to high health care utilizations and results in significantly reduced quality of life for patients. The high burden of disease is seen across all health care settings, outside of the hospital, in the community, and in younger people. Individuals with CDI transition from hospitals to long-term care facilities to the community, and management of these transitions can reduce the incidence of recurrence and rehospitalization.<br><br>PURPOSE: The most common cause of diarrhea occurring in a health care setting is Clostridioides difficile and is also the cause of antibiotic-associated colitis (L. C. McDonald, 2021). The infection results from a disruption in the microbial flora of the gastrointestinal tract, mostly after antibiotic use or other medications such as proton pump inhibitors (PPIs). As a result, infected individuals are colonized and shed the spores into the environment, exposing others-goals of treatment focus on reducing the exposure and individual susceptibility. Although the incidence of C. diff is stable, recurrence is increasing significantly, with severe complications also a concern. The increased incidence and potential for life-threatening conditions require reducing initial exposure, supporting prescribed treatment, and preventing recurrence.<br><br>PRIMARY PRACTICE SETTINGS: C. diff infection can be contracted in health care facilities and in the community. Case managers from nearly all practice settings may encounter patients with the infection.<br><br>FINDINGS/CONCLUSIONS: To avert the devastating complications of Clostridioides difficile infection, case managers play an essential role in the prevention of recurrence with education, advocacy of best practices, effective care coordination, and thorough transitions of care. Each recurrence of C. diff infection leaves the patient vulnerable to the potential for surgical intervention, sepsis, and death.<br><br>Mitigating the risk for readmission and recurrence will enhance C. diff infection care, safety, and outcomes to improve a patient's health care journey and quality of life. Case managers need to take a primary role in the transition and care coordination processes, including patient and support system education, coordination of any postdischarge services, connection to providers, adherence support activities, and follow-up for improvement or changes in condition. Supportive adherence activities and prevention education can result in the avoidance of recurrence. Case managers are well-equipped to locate resources to assist those patients challenged with the cost of medications, inability to attend appointments, or access basic needs. Although not directly related to C. diff, these challenges contribute to recurrence and readmission. Mitigating risk for readmission and recurrence results in an improved quality of life.}, }
@article {pmid36204709, year = {2022}, author = {Pan, H and Zhou, M and Ju, Z and Luo, J and Jin, J and Shen, L and Zhou, P and Huang, R}, title = {Potential role of gut microbiota-LCA-INSR axis in high fat-diet-induced non-alcoholic fatty liver dysfunction: From perspective of radiation variation.}, journal = {Current research in food science}, volume = {5}, number = {}, pages = {1685-1700}, pmid = {36204709}, issn = {2665-9271}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a progressive disease of the liver covering a range of conditions from hepatic steatosis to liver fibrosis. NAFLD could be induced by High-fat-diet(HFD). Ionizing radiation is widely used in medical diagnosis and therapy as well as is a common risk factor in occupational environment. Whether the exposure of various dose of radiation has effects on HFD-induced NAFLD remains unclear. Here, we reported that radiation exposure promoted HFD-induced NAFLD in a dose-response manner. Furthermore, the gut microbiota composition had significant difference among mice with or without radiation treatment. Specifically, the Bacteroidetes/Firmicutes ratio, the abundance of A. muciniphila, Butyricococcus, and Clostridiaceae decreased significantly in the mice with co-exposure of high dose of radiation and HFD treatment. A fecal transplantation trial (FMT) further verified the role of gut microbiota in the regulation of the liver response to co-exposure of high dose of radiation and HFD treatment. Notably, the gut microbiome analysis showed plasma lithocholic acid (LCA) level increased in the mice with co-exposure of high dose of radiation and HFD treatment. Following antibiotic and probiotic treatments there was a significantly decreased LCA bile acid concentration and subsequent promotion of INSR/PI3K/Akt insulin signaling in the liver tissues. Our results demonstrate that the co-exposure of radiation and HFD aggravates the HFD-induced NAFLD through gut microbiota-LCA-INSR axis. Probiotics supplementation is a potential way to protect against co-exposure of radiation and HFD-induced liver damage. Meanwhile, our study provide a new insight that population with potential HFD-induced damage should pay more attention on preventing from liver damage while exposing radiation.}, }
@article {pmid36203814, year = {2022}, author = {Biazzo, M and Allegra, M and Deidda, G}, title = {Clostridioides difficile and neurological disorders: New perspectives.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {946601}, pmid = {36203814}, issn = {1662-4548}, abstract = {Despite brain physiological functions or pathological dysfunctions relying on the activity of neuronal/non-neuronal populations, over the last decades a plethora of evidence unraveled the essential contribution of the microbial populations living and residing within the gut, called gut microbiota. The gut microbiota plays a role in brain (dys)functions, and it will become a promising valuable therapeutic target for several brain pathologies. In the present mini-review, after a brief overview of the role of gut microbiota in normal brain physiology and pathology, we focus on the role of the bacterium Clostridioides difficile, a pathogen responsible for recurrent and refractory infections, in people with neurological diseases, summarizing recent correlative and causative evidence in the scientific literature and highlighting the potential of microbiota-based strategies targeting this pathogen to ameliorate not only gastrointestinal but also the neurological symptoms.}, }
@article {pmid36201671, year = {2022}, author = {Gainey, AB and Daniels, R and Burch, AK and Hawn, J and Fackler, J and Biswas, B and Brownstein, MJ}, title = {Recurrent ESBL Escherichia coli Urosepsis in a Pediatric Renal Transplant Patient Treated With Antibiotics and Bacteriophage Therapy.}, journal = {The Pediatric infectious disease journal}, volume = {}, number = {}, pages = {}, doi = {10.1097/INF.0000000000003735}, pmid = {36201671}, issn = {1532-0987}, abstract = {INTRODUCTION: Treating recurrent multidrug resistant (MDR) urosepsis in pediatric transplant recipients can be challenging. Particularly when antibiotics fail to prevent future occurrence and the nidus is seemingly undiscoverable. While there is an increasing amount of data on phage therapy, to our knowledge, there are no published cases involving pediatric renal transplant recipients. Therefore, we present a challenging clinical case in which phage therapy was used in a pediatric renal transplant recipient who developed recurrent MDR urosepsis with an unclear source.<br><br>CASE PRESENTATION: Our patient was a 17-year-old female who initially developed urosepsis caused by extended-spectrum &#x3b2;-lactamase (ESBL) Escherichia coli, while being treated with an immunosuppressant regimen because of kidney rejection secondary to poor immunosuppression therapy compliance. She was admitted to our hospital intermittently for 4 months with 4 episodes of urosepsis caused by ESBL E. coli. She received multiple courses of antibiotics (mainly ertapenem) and underwent a fecal material transplant to eradicate her ESBL E. coli colonized gastrointestinal tract. Because of recurrent development of urosepsis after antibiotic treatment, she later underwent treatment with a phage cocktail consisting of 2 isolate-specific phages. After a prolonged antibiotic course and subsequent 3-week intravenous phage treatment, she had no ESBL E. coli in her urinary cultures for 4 years post-treatment.<br><br>DISCUSSION: This case highlights the challenges of treating recurrent ESBL E. coli infections in a pediatric renal transplant patient and provides evidence that phage therapy may prove useful in such cases.}, }
@article {pmid36199683, year = {2022}, author = {Zhang, T and Zhang, B and Tian, W and Wang, F and Zhang, J and Ma, X and Wei, Y and Tang, X}, title = {Research trends in ulcerative colitis: A bibliometric and visualized study from 2011 to 2021.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {951004}, pmid = {36199683}, issn = {1663-9812}, abstract = {Background: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease with repeated relapses and remissions. Despite decades of effort, numerous aspects, including the initiating event and pathogenesis of UC, still remain ambiguous, which requires ongoing investigation. Given the mass of publications on UC, there are multidimensional challenges to evaluating the scientific impact of relevant work and identifying the current foci of the multifaceted disease. Accordingly, herein, we aim to assess the global growth of UC research production, analyze patterns of research areas, and evaluate trends in this area. Methods: The Web of Science Core Collection of Clarivate Analytics was searched for articles related to UC published from 2011 to 2021. Microsoft Office Excel 2019 was used to visualize the number of publications over time. Knowledge maps were generated using CiteSpace and VOSviewer to analyze collaborations among countries, institutions, and authors and to present the journey of UC research as well as to reveal the current foci of UC research. Results: A total of 5,088 publications were evaluated in the present study. China had the most publications (1,099, 22.5%). Univ Calif San Diego was the most productive institution (126, 2.48%). William J Sandborn published the greatest number of articles (100, 1.97%). Toshifumi Hibi was the most influential author in the field with a betweenness centrality of 0.53. Inflammatory bowel diseases was identified as the most prolific journal (379, 7.45%). Gastroenterology was the most co-cited journal (3,730, 4.02%). "Vedolizumab," "tofacitinib," "Faecalibacterium prausnitzii," "fecal microbiota transplantation (FMT)," "toll-like receptor 4," and "nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome" were considered the hot topics. Conclusion: In UC research, manuscripts that had high impacts on the scientific community provided an evidence base. UC therapy has entered the era of personalized and precision therapy. As research on FMT, anti-integrin antibodies, Janus kinase inhibitors, and anti-tumor necrosis factor drugs continues to grow, their use in the clinical setting may also expand.}, }
@article {pmid36196151, year = {2022}, author = {Zhang, YW and Cao, MM and Li, YJ and Lu, PP and Dai, GC and Zhang, M and Wang, H and Rui, YF}, title = {Fecal microbiota transplantation ameliorates bone loss in mice with ovariectomy-induced osteoporosis via modulating gut microbiota and metabolic function.}, journal = {Journal of orthopaedic translation}, volume = {37}, number = {}, pages = {46-60}, pmid = {36196151}, issn = {2214-031X}, abstract = {BACKGROUND: Osteoporosis (OP) is a systemic metabolic bone disease characterized by decreased bone mass and destruction of bone microstructure, which tends to result in enhanced bone fragility and related fractures. The postmenopausal osteoporosis (PMOP) has a relatively high proportion, and numerous studies reveal that estrogen-deficiency is related to the imbalance of gut microbiota (GM), impaired intestinal mucosal barrier function and enhanced inflammatory reactivity. However, the underlying mechanisms remain unclear and the existing interventions are also scarce.<br><br>METHODS: In this study, we established a mouse model induced by ovariectomy (OVX) and conducted fecal microbiota transplantation (FMT) by gavage every day for 8 weeks. Subsequently, the bone mass and microarchitecture of mice were evaluated by the micro computed tomography (Micro-CT). The intestinal permeability, pro-osteoclastogenic cytokines expression, osteogenic and osteoclastic activities were detected by the immunohistological analysis, histological examination, enzyme-linked immunosorbent assay (ELISA) and western blot analysis accordingly. Additionally, the composition and abundance of GM were assessed by 16S rRNA sequencing and the fecal short chain fatty acids (SCFAs) level was measured by metabolomics.<br><br>RESULTS: Our results demonstrated that FMT inhibited the excessive osteoclastogenesis and prevented the OVX-induced bone loss. Specifically, compared with the OVX group, FMT enhanced the expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin) and suppressed the release of pro-osteoclastogenic cytokines (tumor necrosis factor-&#x3b1; (TNF-&#x3b1;) and interleukin-1&#x3b2; (IL-1&#x3b2;)). Furthermore, FMT also optimized the composition and abundance of GM, and increased the fecal SCFAs level (mainly acetic acid and propionic acid).<br><br>CONCLUSIONS: Collectively, based on GM-bone axis, FMT prevented the OVX-induced bone loss by correcting the imbalance of GM, improving the SCFAs level, optimizing the intestinal permeability and suppressing the release of pro-osteoclastogenic cytokines, which may be an alternative option to serve as a promising candidate for the prevention and treatment of PMOP in the future.<br><br>This study indicates the ingenious involvement of GM-bone axis in PMOP and the role of FMT in reshaping the status of GM and ameliorating the bone loss in OVX-induced mice. FMT might serve as a promising candidate for the prevention and treatment of PMOP in the future.}, }
@article {pmid36195899, year = {2022}, author = {Wang, J and Zhong, Y and Zhu, H and Mahgoub, OK and Jian, Z and Gu, L and Xiong, X}, title = {Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {245}, pmid = {36195899}, issn = {1742-2094}, mesh = {Animals ; Cytokines/metabolism ; Female ; *Gastrointestinal Microbiome ; Inflammation/etiology ; *Ischemic Stroke ; Male ; Mice ; RNA, Ribosomal, 16S/genetics ; *Stroke/therapy ; }, abstract = {BACKGROUND AND PURPOSE: Stroke is associated with high disability and mortality rates and increases the incidence of organ-related complications. Research has revealed that the outcomes and prognosis of stroke are regulated by the state of the intestinal microbiota. However, the possibility that the manipulation of the intestinal microbiota can alter sex-related stroke outcomes remain unknown.<br><br>METHODS: To verify the different effects of microbiota from different sexes on stroke outcomes, we performed mouse fecal microbiota transplantation (FMT) and established a model of ischemic stroke. Male and female mice received either male or female microbiota through FMT. Ischemic stroke was triggered by MCAO (middle cerebral artery occlusion), and sham surgery served as a control. Over the next few weeks, the mice underwent neurological evaluation and metabolite and inflammatory level detection, and we collected fecal samples for 16S ribosomal RNA analysis.<br><br>RESULTS: We found that when the female mice were not treated with FMT, the microbiota (especially the Firmicutes-to-Bacteroidetes ratio) and the levels of three main metabolites tended to resemble those of male mice after experimental stroke, indicating that stroke can induce an ecological imbalance in the biological community. Through intragastric administration, the gut microbiota of male and female mice was altered to resemble that of the other sex. In general, in female mice after MCAO, the survival rate was increased, the infarct area was reduced, behavioral test performance was improved, the release of beneficial metabolites was promoted and the level of inflammation was mitigated. In contrast, mice that received male microbiota were much more hampered in terms of protection against brain damage and the recovery of neurological function.<br><br>CONCLUSION: A female-like biological community reduces the level of systemic proinflammatory cytokines after ischemic stroke. Poor stroke outcomes can be positively modulated following supplementation with female gut microbiota.}, }
@article {pmid36195536, year = {2022}, author = {An, J and Wang, L and Song, S and Tian, L and Liu, Q and Mei, M and Li, W and Liu, S}, title = {Electroacupuncture reduces blood glucose by regulating intestinal flora in type 2 diabetic mice.}, journal = {Journal of diabetes}, volume = {14}, number = {10}, pages = {695-710}, pmid = {36195536}, issn = {1753-0407}, mesh = {Animals ; Anti-Bacterial Agents ; Blood Glucose ; Cytokines ; *Diabetes Mellitus, Experimental ; *Diabetes Mellitus, Type 2/therapy ; *Electroacupuncture ; *Gastrointestinal Microbiome ; I-kappa B Kinase ; *Insulin Resistance ; Mice ; NF-kappa B ; Proto-Oncogene Proteins c-akt ; Tight Junction Proteins ; }, abstract = {BACKGROUND: The development of diabetes is closely related to the gut microbiota in recent studies, which can be influenced by intestinal motility. A few studies report that electroacupuncture (EA) can lower blood glucose. EA can promote colonic motility and influence gut microbes. In this study, we explored the effect of the EA on blood glucose level in mice with type 2 diabetes (T2D) and its mechanism.<br><br>METHODS: The T2D mice model, fecal microbiota transplantation mice model, and Kit[W/Wv] mice model &#xff08;Point mutation of mouse W locus encoding kit gene&#xff09;were used to investigate the effect of EA on blood glucose as well as the mechanism; The blood glucose and insulin resistance level and the intestinal flora were evaluated. The level of intestinal junction protein, inflammatory cytokines in the serum, interstitial cells of Cajal content, and colonic motility were detected. Lastly, the IKK&#x3b2;/NF-&#x3ba;B-JNK-IRS-1-AKT pathway was explored.<br><br>RESULTS: EA lowered the blood glucose level, altered the gut microbiota, and promoted colonic motility in T2D mice. EA-altered microbiota decreased the blood glucose level and insulin resistance in the antibiotics-treated diabetic mice. EA increased tight junction protein, lowered inflammatory factors, and regulated the IKK&#x3b2;/NF-&#x3ba;B-JNK-IRS-1-AKT pathway in the liver and muscles. EA could not reduce the blood glucose and regulated gut microbiota in the Kit[W/Wv] mice model.<br><br>CONCLUSIONS: EA promoted intestinal motility to regulate the intestinal flora, thereby reducing the level of systemic inflammation, and ultimately lowering the blood glucose by the IKK&#x3b2;/NF-&#x3ba;B-JNK-IRS-1-AKT signal pathway.}, }
@article {pmid36193874, year = {2022}, author = {Yang, Z and Chen, Z and Lin, X and Yao, S and Xian, M and Ning, X and Fu, W and Jiang, M and Li, N and Xiao, X and Feng, M and Lian, Z and Yang, W and Ren, X and Zheng, Z and Zhao, J and Wei, N and Lu, W and Roponen, M and Schaub, B and Wong, GWK and Su, Z and Wang, C and Li, J}, title = {Rural environment reduces allergic inflammation by modulating the gut microbiota.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2125733}, pmid = {36193874}, issn = {1949-0984}, mesh = {Animals ; Bacteria/genetics ; Dust ; Endotoxins ; *Gastrointestinal Microbiome ; *Hypersensitivity/microbiology/prevention &amp; control ; Immunoglobulin E ; Inflammation ; Mice ; Ovalbumin ; }, abstract = {Rural environments and microbiota are linked to a reduction in the prevalence of allergies. However, the mechanism underlying the reduced allergies modulated by rural residency is unclear. Here, we assessed gut bacterial composition and metagenomics in urban and rural children in the EuroPrevall-INCO cohort. Airborne dusts, including mattress and rural henhouse dusts, were profiled for bacterial and fungal composition by amplicon sequencing. Mice were repeatedly exposed to intranasal dust extracts and evaluated for their effects on ovalbumin (OVA)-induced allergic airway inflammation, and gut microbiota restoration was validated by fecal microbiota transplant (FMT) from dust-exposed donor mice. We found that rural children had fewer allergies and unique gut microbiota with fewer Bacteroides and more Prevotella. Indoor dusts in rural environments harbored higher endotoxin level and diversity of bacteria and fungi, whereas indoor urban dusts were enriched with Aspergillus and contained elevated pathogenic bacteria. Intranasal administration of rural dusts before OVA sensitization reduced respiratory eosinophils and blood IgE level in mice and also led to a recovery of gut bacterial diversity and Ruminiclostridium in the mouse model. FMT restored the protective effect by reducing OVA-induced lung eosinophils in recipient mice. Together, these results support a cause-effect relationship between exposure to dust microbiota and allergy susceptibility in children and mice. Specifically, rural environmental exposure modulated the gut microbiota, which was essential in reducing allergy in children from Southern China. Our findings support the notion that the modulation of gut microbiota by exposure to rural indoor dust may improve allergy prevention.}, }
@article {pmid36192796, year = {2022}, author = {Yin, L and Huang, G and Khan, I and Su, L and Xia, W and Law, BYK and Wong, VKW and Wu, Q and Wang, J and Leong, WK and Hsiao, WLW}, title = {Poria cocos polysaccharides exert prebiotic function to attenuate the adverse effects and improve the therapeutic outcome of 5-FU in Apc[Min/+] mice.}, journal = {Chinese medicine}, volume = {17}, number = {1}, pages = {116}, pmid = {36192796}, issn = {1749-8546}, abstract = {BACKGROUND: As a first-line chemotherapeutic agent, 5-fluorouracil (5-FU) exhibits many side effects, weakening its efficacy in cancer treatment. In this study, we hypothesize that Poria cocos polysaccharides (PCP), a traditional Chinese herbal medicine with various bioactivities and prebiotic effects, might improve the therapeutic effect of 5-FU by restoring the homeostasis of the gut microenvironment and the commensal gut microflora.<br><br>METHODS: Apc[Min/+] mice were employed to evaluate the anti-cancer effect of 5-FU in conjunction with PCP treatment. Body weight and food consumption were monitored weekly. Polyp count was used to assess the anti-cancer effect of PCP and 5-FU. Expressions of mucosal cytokines and gut epithelial junction molecules were measured using qRT-PCR. 16S rRNA gene sequencing of fecal DNAs was used to evaluate the compositional changes of gut microbiota (GM). Transplantation of Lactobacillus johnsonii and Bifidobacterium animalis were performed to verify the prebiotic effects of PCP in improving the efficacy of 5-FU.<br><br>RESULTS: The results showed that PCP treatment alleviated the weight loss caused by 5-FU treatment and reduced the polyp burden in Apc[Min/+] mice. Additionally, PCP treatment eased the cytotoxic effects of 5-FU by reducing the expressions of pro-inflammatory cytokines, increasing the anti-inflammatory cytokines; and significantly improving the gut barriers by enhancing the tight junction proteins and associated adhesion molecules. Furthermore, 16S rRNA gene sequencing data showed that PCP alone or with 5-FU could stimulate the growth of probiotic bacteria (Bacteroides acidifaciens, Bacteroides intestinihominis, Butyricicoccus pullicaecorum, and the genera Lactobacillus, Bifidobacterium, Eubacterium). At the same time, it inhibited the growth of potential pathogens (e.g., Alistipes finegoldii, Alistipes massiliensis, Alistipes putredinis., Citrobacter spp., Desulfovibrio spp., and Desulfovibrio desulfuricans). Moreover, the results showed that transplantation of L.johnsonii and B.animalis effectively reduced the polyp burden in Apc[Min/+] mice being treated with 5-FU.<br><br>CONCLUSION: Our study showed that PCP could effectively improve the anti-cancer effect of 5-FU by attenuating its side effects, modulating intestinal inflammation, improving the gut epithelial barrier, and modulating the gut microbiota of Apc[Min/+] mice.}, }
@article {pmid36191780, year = {2022}, author = {Lv, WJ and Ma, YM and Huang, JY and He, SQ and Li, SP and Lin, J and Chen, R and Lun, JC and Liu, J and Guo, SN}, title = {Polysaccharides derived from Shenling Baizhu San improve colitis via modulating tryptophan metabolism in mice.}, journal = {International journal of biological macromolecules}, volume = {222}, number = {Pt A}, pages = {1127-1136}, doi = {10.1016/j.ijbiomac.2022.09.246}, pmid = {36191780}, issn = {1879-0003}, mesh = {Mice ; Animals ; Tryptophan/metabolism ; *Colitis/chemically induced/drug therapy/microbiology ; *Drugs, Chinese Herbal/pharmacology ; Colon ; Polysaccharides/adverse effects ; Mice, Inbred C57BL ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; }, abstract = {Shenling Baizhu San has beneficial effects on the metabolism of the gut microbiota, however, the mechanisms underlying microbiota metabolites mediated anti-inflammation signaling are not well understood. Previously, we have demonstrated that supplementation with Shenling Baizhu San alleviated antibiotic-associated diarrhea (AAD). The current study intends to investigate the dynamic modulation of Shenling Baizhu San polysaccharides (SP) on colitis from the gut microbiota metabolites perspective. Administration of SP effectively relieved colitis induced by DSS in mice, including alleviating body weight loss, the downregulation of colon proinflammatory mediators, and the promotion of intestinal injury repair. Whereas, the efficacy was eliminated by antibiotics, which demonstrated that the efficacy of SP was dependent on the gut microbiota. Fecal microbiota transplantation (FMT) showed that the efficacy of SP can be transferred to gut microbiota. Serum metabolomics analysis showed that supplementation with SP significantly promoted tryptophan metabolism, which was consistent with the changed structure of the gut microbiota, including Bacteroides, Bifidobacterium and Ruminococcus regulated by SP. Especially, the tryptophan metabolites-kynurenine (KYN) activated the expression of amplifying aryl-hydrocarbon receptor (AhR) and Cyp1A1 to promote IL-10 expression in colon. These data suggested that SP positively affected colitis in mice by regulating tryptophan metabolic function of their gut microbiota.}, }
@article {pmid36189234, year = {2022}, author = {Cai, Y and Zhang, Y and Wang, W and Geng, J}, title = {Prospect of research hotspots in prevention and treatment of diseases based on intestinal microbiome.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {971457}, pmid = {36189234}, issn = {1664-3224}, mesh = {Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; }, abstract = {With the in-depth study of gut microbiota, the methods of preventing and treating diseases have gradually diversified. But there is still lack of precise therapies methods to better treat the diseases. Therefore, researcher must focus on how to accurately regulate gut microbiota to achieve it. In order to promote the rapid development of this field, we provide several insights in gut microbiome-based precision therapies while prospecting the future directions.}, }
@article {pmid36187601, year = {2022}, author = {Al-Beltagi, M and Saeed, NK}, title = {Epilepsy and the gut: Perpetrator or victim?.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {13}, number = {5}, pages = {143-156}, pmid = {36187601}, issn = {2150-5330}, abstract = {The brain and the gut are linked together with a complex, bi-path link known as the gut-brain axis through the central and enteric nervous systems. So, the brain directly affects and controls the gut through various neurocrine and endocrine processes, and the gut impacts the brain via different mechanisms. Epilepsy is a central nervous system (CNS) disorder with abnormal brain activity, causing repeated seizures due to a transient excessive or synchronous alteration in the brain's electrical activity. Due to the strong relationship between the enteric and the CNS, gastrointestinal dysfunction may increase the risk of epilepsy. Meanwhile, about 2.5% of patients with epilepsy were misdiagnosed as having gastrointestinal disorders, especially in children below the age of one year. Gut dysbiosis also has a significant role in epileptogenesis. Epilepsy, in turn, affects the gastrointestinal tract in different forms, such as abdominal aura, epilepsy with abdominal pain, and the adverse effects of medications on the gut and the gut microbiota. Epilepsy with abdominal pain, a type of temporal lobe epilepsy, is an uncommon cause of abdominal pain. Epilepsy also can present with postictal states with gastrointestinal manifestations such as postictal hypersalivation, hyperphagia, or compulsive water drinking. At the same time, antiseizure medications have many gastrointestinal side effects. On the other hand, some antiseizure medications may improve some gastrointestinal diseases. Many gut manipulations were used successfully to manage epilepsy. Prebiotics, probiotics, synbiotics, postbiotics, a ketogenic diet, fecal microbiota transplantation, and vagus nerve stimulation were used successfully to treat some patients with epilepsy. Other manipulations, such as omental transposition, still need more studies. This narrative review will discuss the different ways the gut and epilepsy affect each other.}, }
@article {pmid36187462, year = {2022}, author = {Yao, S and Yagi, S and Ogawa, E and Hirata, M and Miyachi, Y and Iwamura, S and Uozumi, R and Sugimoto, T and Asahara, T and Uemoto, S and Hatano, E}, title = {Dysbiosis and Depletion of Fecal Organic Acids Correlate With the Severity of Rejection After Rat Liver Transplantation.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {35}, number = {}, pages = {10728}, pmid = {36187462}, issn = {1432-2277}, mesh = {Alanine Transaminase ; Animals ; Anti-Bacterial Agents ; Bilirubin ; *Dysbiosis/microbiology ; Fatty Acids, Volatile/analysis ; Immunosuppressive Agents ; *Liver Transplantation/adverse effects ; Rats ; }, abstract = {The impact of T cell-mediated rejection (TCMR) after liver transplantation (LT) on the alterations in the gut microbiota (GM) and associated intestinal environment represented by fecal organic acids (OAs) require further elucidation. A rat allogeneic LT model was prepared without immunosuppressants or antibiotics, and a syngeneic model was used as a control. Qualitative and quantitative analyses of fecal samples at fixed time points were performed. Correlation analyses were also performed between liver function and GMs and OA levels. In the allogeneic TCMR group, the number of predominant obligate anaerobes decreased as liver function declined. Clostridioides difficile, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus were significantly increased. Regarding fecal OA concentration, short-chain fatty acid (SCFA) concentrations were depleted as liver function declined. In contrast, in the syngeneic group, GM and OAs exhibited only slight, transient, and reversible disturbances. In addition, alanine aminotransferase and total bilirubin were positively correlated with the number of Enterobacteriaceae and Enterococcus, and negatively correlated with the fecal concentration of SCFAs. The allogeneic TCMR model demonstrated distinct dysbiosis and depletion of fecal OAs as TCMR progressed after LT. The degree of graft injury was closely related to the number of specific bacterial strains and the concentrations of fecal SCFAs.}, }
@article {pmid36187337, year = {2022}, author = {Huang, HL and Zhu, JQ and Yang, LS and Wu, Q and Shou, DW and Chen, HT and Ma, J and Li, YQ and Xu, HM and Zhou, YJ}, title = {Fecal Microbiota Transplantation Combined with a Low FODMAP Diet for the Treatment of Irritable Bowel Syndrome with Predominant Diarrhea.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {5121496}, pmid = {36187337}, issn = {1942-0994}, mesh = {DNA, Ribosomal ; Diarrhea/therapy ; Diet ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Diseases ; Humans ; *Irritable Bowel Syndrome/therapy ; Prospective Studies ; Quality of Life ; Retrospective Studies ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been found to be effective in irritable bowel syndrome with predominant diarrhea (IBS-D). We conducted this study to determine the impact of a low FODMAP diet (LFD) on the gut microbiota and the efficacy of FMT in the treatment of IBS-D.<br><br>METHODS: A retrospective analysis of a single-arm open-label prospective study was conducted to investigate the impact of FMT alone (n = 40) and FMT+LFD (n = 40) in refractory IBS-D. The IBS-quality of life (QOL), IBS-severity scoring system (SSS), gastrointestinal symptom rating scale (GSRS), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD) were used to evaluate the efficacy, and partial 16S rDNA amplicon sequencing was used to profile the microbiota.<br><br>RESULTS: The response rates were higher in the FMT+LFD group than in the FMT group (1&#x2009;mo, 3&#x2009;mo, 6&#x2009;mo: 70.0% vs. 55.0%, 67.5% vs. 57.5%, 62.5% vs. 27.5%, respectively). The FMT+LFD group showed significantly better improvement in IBS-QOL at 1, 3, and 6 months; IBS-SSS at 6 months; and GSRS at 1 month compared to FMT alone. Changes in HAMA and HAMD were similar in the two groups. The LFD significantly upregulated the FMT-induced microbial diversity (OTUs: 666 vs. 574, Adonis: P = 0.02) and significantly strengthened the upregulation of Bacteroides, Alistipes, and Ruminococcaceae_UCG-002 and the downregulation of Bifidobacterium.<br><br>CONCLUSION: An LFD enhanced the efficacy of FMT, increased the gut microbial diversity after FMT, and strengthened the inhibitory effect of FMT on conditional pathogens.}, }
@article {pmid36185693, year = {2022}, author = {Kang, Y and Cai, Y and Zhao, Y and Yang, Y}, title = {The gut microbiome and Alopecia areata: Implications for early diagnostic biomarkers and novel therapies.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {979876}, pmid = {36185693}, issn = {2296-861X}, abstract = {Alopecia areata (AA) accounts for the autoimmune disorder mediated by T cells, whose prognostic outcome cannot be predicted and curative treatment is unavailable at present. The AA pathogenic mechanism remains largely unclear, even though follicular attack has been suggested to result from that attack of immune privilege-losing hair follicles driven by immunity. Recently, gut microbiota is suggested to have an important effect on immunoregulation under autoimmune situations like AA. Fecal microbial transplantation (FMT) may be used to treat AA. Nonetheless, related research remains at the initial stage. To promote the rapid progress of relevant research, the present work aimed to shed more lights on gut microbiota's effect on AA, early diagnostic biomarker and FMT therapeutics.}, }
@article {pmid36184305, year = {2022}, author = {Lockwood, MB and Chlipala, GE and Maeinschein-Cline, M and DeVon, HA and Lichvar, AB and Samra, MK and Park, CG and Campara, M and Doorenbos, AZ and Tussing-Humphreys, LM and Spaggiari, M and Bronas, UG and Steel, JL and Green, SS}, title = {Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation.}, journal = {Pain management nursing : official journal of the American Society of Pain Management Nurses}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pmn.2022.08.013}, pmid = {36184305}, issn = {1532-8635}, abstract = {BACKGROUND: Pain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation.<br><br>AIMS: Characterize associations between gut microbiome features and pain interference before and after kidney transplantation.<br><br>DESIGN: Longitudinal, repeated measures study of 19 living-donor kidney transplant recipients, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant.<br><br>SETTING: Participants were recruited at the Kidney Transplant Clinic at the University of Illinois Hospital &amp; Health Sciences System.<br><br>PARTICIPANTS/SUBJECTS: 19 living fonor kidney transplant recipients. (need to remove this from ``design''.<br><br>METHODS: We assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57.<br><br>RESULTS: We measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pretransplant versus no pain interference at 3-months posttransplant (R&#xa0;=&#xa0;.306, p&#xa0;=&#xa0;.022), and between pain interference groups posttransplant (R&#xa0;=&#xa0;.249, p&#xa0;=&#xa0;.041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction in Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene.<br><br>CONCLUSIONS: Gut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.}, }
@article {pmid36184150, year = {2022}, author = {Na, K and Wei, J and Zhang, L and Fang, Y and Li, X and Lu, S and Guo, X}, title = {Effects of chitosan oligosaccharides (COS) and FMT from COS-dosed mice on intestinal barrier function and cell apoptosis.}, journal = {Carbohydrate polymers}, volume = {297}, number = {}, pages = {120043}, doi = {10.1016/j.carbpol.2022.120043}, pmid = {36184150}, issn = {1879-1344}, mesh = {Animals ; Apoptosis ; *Chitosan/adverse effects ; *Colitis/chemically induced ; *Enterotoxigenic Escherichia coli ; Intestinal Mucosa ; Mice ; Oligosaccharides/pharmacology ; }, abstract = {Chitosan oligosaccharides (COS) show the potential to support the intestinal health, but the mechanism and role of COS-derived intestinal microbiota are unknown. We explored the protective effect of direct administration of COS on intestinal barrier function using an in vivo colitis mouse model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged IPEC-J2 cell model. COS directly enhanced the intestinal barrier function. COS intervention also promoted the abundance and diversity of intestinal flora. Importantly, FMT intervention with a COS-derived microbiome decreased the disease index level and alleviated histopathological changes, and improved gut barrier function in the colitis model. Both COS and COS-derived microbiota suppressed ETEC-induced cellular apoptosis in IPEC-J2 cells. This study firstly confirms transplantation of COS-modified fecal microbiota can enhance the intestinal barrier function. The mechanism underlying COS benefits is due to a direct intervention by COS supplementation and an indirect improvement of the gut microbiota induced by COS exposure.}, }
@article {pmid36183340, year = {2022}, author = {Mironova, M and Ehrlich, AC and Grinspan, A and Protano, MA}, title = {Fecal microbiota transplantation may reduce the mortality of patients with severe and fulminant Clostridioides difficile infection compared to standard-of-care antibiotics in a community hospital.}, journal = {Journal of digestive diseases}, volume = {23}, number = {8-9}, pages = {500-505}, doi = {10.1111/1751-2980.13134}, pmid = {36183340}, issn = {1751-2980}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; Hospitals, Community ; Treatment Outcome ; Recurrence ; *Clostridium Infections/drug therapy ; }, abstract = {OBJECTIVES: Clostridioides difficile infection (CDI) is known for significant morbidity and mortality. Fecal microbiota transplantation (FMT) is an effective therapy for recurrent and resistant CDI. However, its impact on the mortality rate of patients with severe and fulminant CDI has not been rigorously studied yet. We aimed to evaluate the effectiveness of FMT on the mortality rate of patients with severe or fulminant CDI in a community hospital system.<br><br>METHODS: Our study included 106 inpatients with severe or fulminant CDI. Both standard-of-care (SOC) and FMT were provided to 14 (13.2%) patients (the FMT group). SOC antibiotics alone were provided to 92 (86.8%) patients, out of whom 28 patients were included via propensity score matching in a 2:1 ratio (the SOC group). The primary outcome was defined as the composite end-point of mortality during admission, within 30 and 90&#x2009;days after discharge, and discharge with comfort measures only. Each component was a secondary end-point.<br><br>RESULTS: The primary outcome rate in the FMT group was 7.1% (1/14) compared to 25.0% (7/28) in the SOC group. Univariate analysis demonstrated that FMT decreases mortality (odds ratio&#xa0;[OR] 0.08, 95% confidence interval [CI] 0.01-0.58, P&#xa0;=&#xa0;0.01). However, multivariate regression did not show statistical significance (OR 0.15, 95% CI 0.01-2.53, P&#xa0;=&#xa0;0.19), possibly due to the small sample size.<br><br>CONCLUSIONS: FMT may decrease the mortality of patients with severe and fulminant CDI. Large studies are needed to validate these findings.}, }
@article {pmid36183156, year = {2022}, author = {Kim, YM and Choi, JO and Cho, YJ and Hong, BK and Shon, HJ and Kim, BJ and Park, JH and Kim, WU and Kim, D}, title = {Mycobacterium potentiates protection from colorectal cancer by gut microbial alterations.}, journal = {Immunology}, volume = {}, number = {}, pages = {}, doi = {10.1111/imm.13586}, pmid = {36183156}, issn = {1365-2567}, abstract = {Not only are many Mycobacteria pathogens, but they can act as strong non-specific immunopotentiators, generating beneficial effects on the pathogenesis of some diseases. However, there has been no direct evidence of the effect of mycobacterial species on colorectal cancer (CRC). Herein, we showed that there may be a meaningful inverse correlation between the incidence of tuberculosis and CRC based on global statistics and that heat-killed Mycobacterial tuberculosis and live Mycobacterium bovis (Bacillus Calmette-Guérin strain) could ameliorate CRC development. In particular, using a faecal microbiota transplantation and a comparison between separate housing and cohousing, we demonstrated that the gut microbiota is involved in the protective effects. The microbial alterations can be elucidated by the modulation of antimicrobial activities including those of the Reg3 family genes. Furthermore, interleukin-22 production by T helper cells contributed to the anti-inflammatory activity of Mycobacteria. Our results revealed a novel role of Mycobacteria involving gut microbial alterations in dampening inflammation-associated CRC and an immunological mechanism underlying the interaction between microbes and host immunity.}, }
@article {pmid36182105, year = {2022}, author = {Landau, HJ and Orlando, E and Rodriguez, ES and Applebaum, A and Mitchell, HR and Peled, JU and Khan, N and Funnell, T and Chung, D and Scordo, M and Shah, GL and LeStrange, NJ and Hambright, KA and McElrath, CM and Cazeau, N and Devlin, SM and Perales, MA and Giralt, SA}, title = {Pilot Trial of Homebound Hematopoietic Cell Transplantation.}, journal = {Transplantation and cellular therapy}, volume = {28}, number = {12}, pages = {832.e1-832.e7}, doi = {10.1016/j.jtct.2022.09.014}, pmid = {36182105}, issn = {2666-6367}, support = {K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Quality of Life ; Pilot Projects ; *Hematopoietic Stem Cell Transplantation/methods ; Transplantation, Autologous/methods ; Melphalan/therapeutic use ; *Multiple Myeloma/therapy ; *Immunoglobulin Light-chain Amyloidosis/drug therapy ; }, abstract = {For eligible patients with multiple myeloma (MM) and amyloid light chain (AL) amyloidosis, high-dose chemotherapy and autologous hematopoietic cell transplantation (HCT) is a standard and widely used consolidation therapy. Autologous HCT requires specialized care at a transplantation center and investment from patients and caregivers. We studied the safety and feasibility of delivering transplantation care in a homebound setting to decrease the burden of therapy and increase access to autologous HCT. Patients with MM and AL amyloidosis undergoing autologous HCT were eligible if they resided in designated ZIP codes and had a full-time caregiver, Wi-Fi connection, HCT Comorbidity Index ≤3, and Karnofsky Performance Status score ≥80. High-dose melphalan (on day -2) and hematopoietic cell reinfusion (day 0) were administered in the outpatient clinic. Protocol-specific home care was provided from day +1 through engraftment. Patients were assessed and blood was drawn daily by advanced practice providers. Interventions were delivered by registered nurses. Attending physicians communicated daily through telemedicine. Quality of life, patient and caregiver satisfaction, and fecal microbiota profiling data were collected. Fifteen patients were enrolled and received transplantation care at home starting on day +1 following hematopoietic cell infusion. Patients remained in the program for an average of 12 days and required an average of 2 outpatient visits while receiving home care. Seven of 15 patients were admitted for a median of 4 days (range, 3 to 10 days); admission occurred on day +7 in 5 patients, on day +8 in 1 patient, and on day +12 in 1 patient for neutropenic fever in 2 patients, fever attributed to engraftment syndrome in 2 patients, diarrhea in 2 patients, and dehydration in 1 patient. Only 1 patient had a documented infection (Clostridioides difficile). One patient admitted with neutropenic fever required intensive care unit admission for a gastrointestinal bleed. Forty-seven percent of the patients experienced a grade ≥3 nonhematologic toxicity. There were no deaths on the study. Patients and caregivers reported high satisfaction with care. Microbiota diversity patterns were similar to those of autologous HCT recipients who did not receive post-HCT care at home, although a subset of the cohort maintained microbiota diversity throughout. Homebound HCT in an urban setting is safe and feasible, with less than one-half of patients requiring inpatient admission. Despite increased patient and caregiver responsibility in the homebound setting compared with an inpatient setting, patient and caregiver satisfaction was high. These results support expansion of homebound transplantation care programs.}, }
@article {pmid36182084, year = {2022}, author = {Zhang, T and Cheng, JK and Hu, YM}, title = {Gut microbiota as a promising therapeutic target for age-related sarcopenia.}, journal = {Ageing research reviews}, volume = {81}, number = {}, pages = {101739}, doi = {10.1016/j.arr.2022.101739}, pmid = {36182084}, issn = {1872-9649}, mesh = {Aging/physiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Muscle, Skeletal/physiology ; *Sarcopenia ; }, abstract = {Sarcopenia is characterized by a progressive loss of skeletal muscle mass and function with aging. Recently, sarcopenia has been shown to be closely related with gut microbiota. Strategies such as probiotics and fecal microbiota transplantation have shown potential to ameliorate the muscle loss. This review will focus on the age-related sarcopenia, in particular on the relationship between gut microbiota and age-related sarcopenia, how gut microbiota is engaged in sarcopenia, and the potential role of gut microbiota in the treatment of age-related sarcopenia.}, }
@article {pmid36181412, year = {2022}, author = {Yao, J and Fekadu, G and Ng, SC and You, JHS}, title = {Fecal microbiota transplantation for patients with active ulcerative colitis: A cost-effectiveness analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16015}, pmid = {36181412}, issn = {1440-1746}, abstract = {BACKGROUND AND AIM: Growing studies have demonstrated clinical benefits of fecal microbiota transplantation (FMT) therapy (administered by colonoscopy, enema, or both) for active ulcerative colitis (UC). This study aimed to evaluate the cost-effectiveness of standard treatment with and without FMT therapy for mild-to-moderate active UC from the perspective of US healthcare provider.<br><br>METHODS: A 10-year Markov model was developed to evaluate the costs and quality-adjusted life-years (QALYs) of standard treatment plus FMT therapy versus standard treatment alone. Model inputs were retrieved from publish data in literature. Base-case and sensitivity analyses were performed.<br><br>RESULTS: In the base-case analysis, standard treatment plus FMT therapy was more effective than standard treatment alone (by 0.068 QALYs). Comparing to standard treatment alone, standard treatment plus FMT therapy varied from cost-saving to incremental cost, subject to the number of FMT administrations. One-way sensitivity analysis identified the relative risk of achieving remission with FMT therapy to be the most influential factor on the incremental cost-effectiveness ratio of standard treatment plus FMT therapy. Monte-Carlo simulations showed that standard treatment plus FMT therapy with 3 and 6 administrations per FMT course was cost-effective (at willingness-to-pay threshold&#xa0;=&#xa0;50&#xa0;000 USD/QALY) in 90.77% and 67.03% of time, respectively.<br><br>CONCLUSIONS: Standard treatment plus FMT therapy appears to be more effective in gaining higher QALYs than standard therapy alone for patients with mild-to-moderate active UC. Cost-effectiveness of standard treatment plus FMT therapy is highly subject to the relative improvement in achieving remission with standard therapy plus FMT therapy and number of FMT administrations per FMT course.}, }
@article {pmid36181407, year = {2022}, author = {Shen, J and Guo, H and Liu, S and Jin, W and Zhang, ZW and Zhang, Y and Liu, K and Mao, S and Zhou, Z and Xie, L and Wang, G and Hao, H and Liang, Y}, title = {Aberrant branched-chain amino acid accumulation along the microbiota-gut-brain axis: Crucial targets affecting the occurrence and treatment of ischaemic stroke.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.15965}, pmid = {36181407}, issn = {1476-5381}, abstract = {BACKGROUND AND PURPOSE: Although increasing evidence illustrated that the bidirectional communication between the brain and the gut is closely related to the occurrence of various complex diseases. Limited effort has been made to explore the influence of intestinal flora on the risk of ischaemic stroke. The present study aims to identify microbiota and specialized microbiota metabolites related to the occurrence and treatment of ischaemic stroke.<br><br>EXPERIMENTAL APPROACH: The role of microbiota in the occurrence and the treatment of ischaemic stroke was evaluated on ischaemia/reperfusion (I/R), pseudo-germ-free and faecal transplantation animals. The target microbiota and specialized metabolites were identified by comparing their distribution in flora and metabolomic profiles in ischaemic stroke patients and animals with compared with healthy controls. The effects and mechanisms involved of the targeted metabolites in ischaemic stroke were explored in ischaemia/reperfusion rats, hypoxia/reoxygenation PC12 cells and LPS-induced inflammatory BV2 cells.<br><br>KEY RESULTS: Both ischaemic stroke patients and I/R rats had significant accumulation of branched-chain amino acids, which were closely associated with gut microflora dysbiosis and the development of ischaemic stroke. Lactobacillus helveticus (L.hel) and Lactobacillus brevis (L.bre) are identified as the microbiota most affected by ischaemia/reperfusion modelling and treatment. L.hel and L.bre colonization exhibited significant neuroprotective activity and could greatly alleviate the accumulation of branched-chain amino acids. In addition, branched-chain amino acid (BCAA) accumulation was shown to exacerbate microglia-induced neuroinflammation by activating AKT/STAT3/NF-&#x3ba;B signalling.<br><br>CONCLUSION AND IMPLICATIONS: Our findings demonstrated the crucial role of intestinal flora and microbiota metabolites in the occurrence and treatment of ischaemic stroke.}, }
@article {pmid36180583, year = {2022}, author = {Hitch, TCA and Hall, LJ and Walsh, SK and Leventhal, GE and Slack, E and de Wouters, T and Walter, J and Clavel, T}, title = {Microbiome-based interventions to modulate gut ecology and the immune system.}, journal = {Mucosal immunology}, volume = {15}, number = {6}, pages = {1095-1113}, pmid = {36180583}, issn = {1935-3456}, mesh = {Prebiotics ; *Microbiota ; *Gastrointestinal Microbiome ; *Probiotics ; Immune System ; }, abstract = {The gut microbiome lies at the intersection between the environment and the host, with the ability to modify host responses to disease-relevant exposures and stimuli. This is evident in how enteric microbes interact with the immune system, e.g., supporting immune maturation in early life, affecting drug efficacy via modulation of immune responses, or influencing development of immune cell populations and their mediators. Many factors modulate gut ecosystem dynamics during daily life and we are just beginning to realise the therapeutic and prophylactic potential of microbiome-based interventions. These approaches vary in application, goal, and mechanisms of action. Some modify the entire community, such as nutritional approaches or faecal microbiota transplantation, while others, such as phage therapy, probiotics, and prebiotics, target specific taxa or strains. In this review, we assessed the experimental evidence for microbiome-based interventions, with a particular focus on their clinical relevance, ecological effects, and modulation of the immune system.}, }
@article {pmid36179877, year = {2023}, author = {Liang, J and Zhang, M and Wang, H and Ren, Y and Wu, Q and Huang, R and Xie, J and Yin, J and Zhu, J}, title = {Cholestyramine resin administration alleviated cerebral ischemic injury in obese mice by improving gut dysbiosis and modulating the bile acid profile.}, journal = {Experimental neurology}, volume = {359}, number = {}, pages = {114234}, doi = {10.1016/j.expneurol.2022.114234}, pmid = {36179877}, issn = {1090-2430}, mesh = {Mice ; Animals ; Dysbiosis/complications/metabolism ; Mice, Obese ; Bile Acids and Salts ; Cholestyramine Resin/therapeutic use ; *Neuroprotective Agents ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Obesity/complications ; *Stroke/complications ; *Brain Injuries/complications ; }, abstract = {Obesity is a risk factor for cerebrovascular diseases. Accumulating evidence has revealed that gut dysbiosis plays an important role in the pathophysiology of cerebrovascular diseases. However, little is known about the role of gut dysbiosis in stroke in obesity. In this study, we established a rodent middle cerebral artery occlusion (MCAO) model to investigate whether obesity-induced gut dysbiosis exacerbates cerebral ischemic injury and the role of the bile salt sequestrant cholestyramine resin (CR) in gut microbiota and stroke outcome in obese mice. Long-term 45% high-fat diet (HFD) diet (8 weeks) induced an obesity phenotype and caused gut dysbiosis, resulting in a larger infarct volume and higher serum levels of inflammatory cytokines after stroke, compared to those in the lean counterparts. LC-MS/MS and GC analysis revealed that obese mice with stroke developed an obviously perturbed bile acid (BA) profile characterized by higher levels of deoxycholic acid and its conjugated forms, and lower levels of butyrate in the cecal content. CR administration improved the obesity-induced dysbiotic microbiome, attenuated ischemic brain injury and modulated the stroke-perturbed BA profile. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that the impact of obesity on stroke and the neuroprotective effects of CR were mediated by gut microbiota. In conclusion, Obesity induces gut dysbiosis, worsens stroke outcomes, and perturbs the BA profile. The dysbiotic microbiome is an important linkage between obesity and stroke. CR confers metabolic benefits and neuroprotective effects in obesity, perhaps by modulating gut microbial composition and BA metabolism.}, }
@article {pmid36178211, year = {2022}, author = {Yao, S and Yagi, S and Hirata, M and Miyachi, Y and Ogawa, E and Uozumi, R and Sugimoto, T and Asahara, T and Uemoto, S and Hatano, E}, title = {Chronological changes in the gut microbiota and intestinal environment in recipients and donors of living donor liver transplantation.}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {}, number = {}, pages = {}, doi = {10.1002/jhbp.1241}, pmid = {36178211}, issn = {1868-6982}, abstract = {BACKGROUND/PURPOSE: This prospective study aimed to investigate the dynamic changes in the gut microbiota (GM) and associated intestinal environment, which were assessed by measuring fecal organic acid (OA) concentrations, during the early period after liver transplantation (LT). To understand the fundamental characteristics of the human GM, data obtained from living donors were also analyzed.<br><br>METHODS: Fixed-point observation was performed in 23 recipients and 21 donors for up to 2&#x2009;weeks after LT. The GM and OA concentrations were investigated using ribosomal RNA-targeted reverse-transcription quantitative polymerase chain reaction and high-performance liquid chromatography, respectively.<br><br>RESULTS: Before LT, the recipients exhibited remarkable dysbiosis and OA depletion, which were proportional to the model for end-stage liver disease score. Correlations between the abundances of some specific strains and OA concentrations were observed. After LT, while donor lobectomy caused only slight, transient and reversible changes in the GM and OA concentrations, recipients exhibited delayed recovery in these factors. However, no clear evidence of causality was observed between the GM or OA concentrations and LT outcomes.<br><br>CONCLUSIONS: The GM and intestinal environment in LT recipients exhibited characteristics that were clearly different from those in donors. LT did not normalize but rather disrupted the GM during the early post-LT period, but its negative clinical impact could be minimized with perioperative management.}, }
@article {pmid36178158, year = {2022}, author = {Rudiansyah, M and Abdalkareem Jasim, S and S Azizov, B and Samusenkov, V and Kamal Abdelbasset, W and Yasin, G and Mohammad, HJ and Jawad, MA and Mahmudiono, T and Hosseini-Fard, SR and Mirzaei, R and Karampoor, S}, title = {The emerging microbiome-based approaches to IBD therapy: From SCFAs to urolithin A.}, journal = {Journal of digestive diseases}, volume = {23}, number = {8-9}, pages = {412-434}, doi = {10.1111/1751-2980.13131}, pmid = {36178158}, issn = {1751-2980}, mesh = {Adult ; Child ; Humans ; *Inflammatory Bowel Diseases/pathology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/complications ; }, abstract = {Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal inflammatory conditions which can be life-threatening, affecting both children and adults. Crohn's disease and ulcerative colitis are the two main forms of IBD. The pathogenesis of IBD is complex and involves genetic background, environmental factors, alteration in gut microbiota, aberrant immune responses (innate and adaptive), and their interactions, all of which provide clues to the identification of innovative diagnostic or prognostic biomarkers and the development of novel treatments. Gut microbiota provide significant benefits to its host, most notably via maintaining immunological homeostasis. Furthermore, changes in gut microbial populations may promote immunological dysregulation, resulting in autoimmune diseases, including IBD. Investigating the interaction between gut microbiota and immune system of the host may lead to a better understanding of the pathophysiology of IBD as well as the development of innovative immune- or microbe-based therapeutics. In this review we summarized the most recent findings on innovative therapeutics for IBD, including microbiome-based therapies such as fecal microbiota transplantation, probiotics, live biotherapeutic products, short-chain fatty acids, bile acids, and urolithin A.}, }
@article {pmid36177467, year = {2022}, author = {Hu, L and Li, G and Shu, Y and Hou, X and Yang, L and Jin, Y}, title = {Circadian dysregulation induces alterations of visceral sensitivity and the gut microbiota in Light/Dark phase shift mice.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {935919}, pmid = {36177467}, issn = {1664-302X}, abstract = {BACKGROUND: It is well-established that several features of modern lifestyles, such as shift work, jet lag, and using electronics at night, disturb normal circadian rhythm and increase the risk of suffering from functional gastrointestinal disease. Although substantial evidence demonstrates that shift work is closely correlated with the symptoms of visceral hypersensitivity, few basic studies have revealed the mechanism of visceral hypersensitivity induced by circadian rhythm disturbance, especially light/dark phase shifts. Our study explored the mechanism underlying visceral hypersensitivity caused by light/dark phase shift in mice.<br><br>METHODS: A 6-h delay light/dark phase shift mice model was constructed. Visceral hypersensitivity was assessed by abdominal withdrawal reflex (AWR) score induced by colorectal distention (CRD) in vivo and contraction of colonic muscle strips induced by acetylcholine ex vivo. Intestinal permeability was evaluated by transepithelial resistance (TEER) and FD4 permeability. The expression of tight junction proteins was detected by western blotting and immunofluorescence staining. The gut microbiota was examined by 16S rDNA sequencing. Fecal microbiota transplantation (FMT) was performed to confirm the relationship between the light/dark phase shift, gut microbiota, and visceral hypersensitivity.<br><br>RESULTS: We found that light/dark phase shift increased visceral sensitivity and disrupted intestinal barrier function, caused low-grade intestinal inflammation. Moreover, we found decreased microbial species richness and diversity and a shift in microbial community with a decreased proportion of Firmicutes and an elevated abundance of Proteobacteria at the phylum level. Besides, after the light/dark phase shift, the microflora was significantly enriched in biosynthesizing tryptophan, steroid hormone, secondary metabolites, lipids, and lipopolysaccharides. Mice that underwent FMT from the light/dark phase shift mice model exhibited higher visceral hypersensitivity and worse barrier function. Dysbiosis induced by light/dark phase shift can be transmitted to the mice pretreated with antibiotics by FMT not only at the aspect of microbiota composition but also at the level of bacterial function.<br><br>CONCLUSION: Circadian rhythm disturbance induced by the light/dark phase shift produces visceral hypersensitivity similar to the pathophysiology of IBS through modulating the gut microbiota, which may disrupt intestinal barrier function or induce a low-degree gut inflammation.}, }
@article {pmid36177048, year = {2022}, author = {Hazime, R and Eddehbi, FE and El Mojadili, S and Lakhouaja, N and Souli, I and Salami, A and M'Raouni, B and Brahim, I and Oujidi, M and Guennouni, M and Bousfiha, AA and Admou, B}, title = {Inborn errors of immunity and related microbiome.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {982772}, pmid = {36177048}, issn = {1664-3224}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Immune System Diseases/genetics/microbiology ; Immunoglobulin A ; Receptors, Interleukin-10 ; }, abstract = {Inborn errors of immunity (IEI) are characterized by diverse clinical manifestations that are dominated by atypical, recurrent, chronic, or severe infectious or non-infectious features, including autoimmunity, lymphoproliferative disease, granulomas, and/or malignancy, which contribute substantially to morbidity and mortality. Some data suggest a correlation between clinical manifestations of IEI and altered gut microbiota. Many IEI display microbial dysbiosis resulting from the proliferation of pro-inflammatory bacteria or a decrease in anti-inflammatory bacteria with variations in the composition and function of numerous microbiota. Dysbiosis is considered more established, mainly within common variable immunodeficiency, selective immunoglobulin A deficiency, severe combined immunodeficiency diseases, Wiskott-Aldrich syndrome, Hyper-IgE syndrome, autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED), immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, IL-10 receptor deficiency, chronic granulomatous disease, and Kostmann disease. For certain IEIs, the specific predominance of gastrointestinal, respiratory, and cutaneous involvement, which is frequently associated with dysbiosis, justifies the interest for microbiome identification. With the better understanding of the relationship between gut microbiota, host immunity, and infectious diseases, the integration of microbiota modulation as a therapeutic approach or a preventive measure of infection becomes increasingly relevant. Thus, a promising strategy is to develop optimized prebiotics, probiotics, postbiotics, and fecal microbial transplantation to rebalance the intestinal microbiota and thereby attenuate the disease activity of many IEIs.}, }
@article {pmid36177041, year = {2022}, author = {Xu, H and Cao, C and Ren, Y and Weng, S and Liu, L and Guo, C and Wang, L and Han, X and Ren, J and Liu, Z}, title = {Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {949490}, pmid = {36177041}, issn = {1664-3224}, mesh = {Dysbiosis/therapy ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Humans ; Immune Checkpoint Inhibitors ; *Microbiota/physiology ; *Neoplasms/therapy ; }, abstract = {Fecal microbiome transplantation (FMT) from healthy donors is one of the techniques for restoration of the dysbiotic gut, which is increasingly being used to treat various diseases. Notably, mounting evidence in recent years revealed that FMT has made a breakthrough in the oncology treatment area, especially by improving immunotherapy efficacy to achieve antitumor effects. However, the mechanism of FMT in enhancing antitumor effects of immune checkpoint blockers (ICBs) has not yet been fully elucidated. This review systematically summarizes the role of microbes and their metabolites in the regulation of tumor immunity. We highlight the mechanism of action of FMT in the treatment of refractory tumors as well as in improving the efficacy of immunotherapy. Furthermore, we summarize ongoing clinical trials combining FMT with immunotherapy and further focus on refined protocols for the practice of FMT in cancer treatment, which could guide future directions and priorities of FMT scientific development.}, }
@article {pmid36176029, year = {2022}, author = {Shen, Q and Huang, Z and Ma, L and Yao, J and Luo, T and Zhao, Y and Xiao, Y and Jin, Y}, title = {Extracellular vesicle miRNAs promote the intestinal microenvironment by interacting with microbes in colitis.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2128604}, pmid = {36176029}, issn = {1949-0984}, mesh = {Animals ; Bacteria/genetics ; *Colitis/chemically induced/microbiology ; Dextran Sulfate ; Disease Models, Animal ; *Extracellular Vesicles ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; Intestines ; *MicroRNAs/genetics ; *Microbiota ; }, abstract = {Inflammatory bowel disease (IBD) is a global disease with no cure. Disruption of the microbial ecosystem is considered to be an important cause of IBD. Extracellular vesicles (EVs) are vital participants in cell-cell and cell-organism communication. Both host-derived EVs and bacteria-derived membrane vesicles (OMVs) contribute to homeostasis in the intestine. However, the roles of EVs-miRNAs and MVs in host-microbe interactions in colitis remain unclear. In the present study, the animal model of colitis was established by dextran sulfate sodium (DSS) to investigate the changes of miRNAs in colonic EVs from colitis. Several miRNAs were significantly altered in colitis EVs. miR-181b-5p transplantation inhibited M1 macrophage polarization and promoted M2 polarization to reduce the levels of inflammation both in acute and remission of chronic colitis. miR-200b-3p could interact with bacteria and regulate the composition of the microbiota, which contributed to intestinal barrier integrity and homeostasis. Notably, MVs from normal feces could effectively reverse the composition of the intestinal microbiota, restore the intestinal barrier and rescue colitis, and BMVs from colitis would also have similar effects after miR-200b-3p treatment. Our results preliminarily identify a vesicle-based host-microbe interaction cycle in colitis and provide new ideas for colitis treatment.}, }
@article {pmid36175995, year = {2022}, author = {Carpén, N and Brodin, P and de Vos, WM and Salonen, A and Kolho, KL and Andersson, S and Helve, O}, title = {Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial.}, journal = {BMC pediatrics}, volume = {22}, number = {1}, pages = {565}, pmid = {36175995}, issn = {1471-2431}, mesh = {Cesarean Section/adverse effects ; Child, Preschool ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Intestines ; Milk, Human ; Pregnancy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: A complication of elective cesarean section (CS) delivery is its interference with the normal intestinal colonization of the infant, affecting the immune and metabolic signaling in early life- a process that has been associated with long-term morbidity, such as allergy and diabetes. We evaluate, in CS-delivered infants, whether the normal intestinal microbiome and its early life development can be restored by immediate postnatal transfer of maternal fecal microbiota (FMT) to the newborn, and how this procedure influences the maturation of the immune system.<br><br>METHODS: Sixty healthy mothers with planned elective CS are recruited and screened thoroughly for infections. A maternal fecal sample is taken prior to delivery and processed according to a transplantation protocol. After double blinded randomization, half of the newborns will receive a diluted aliquot of their own mother's stool orally administered in breast milk during the first feeding while the other half will be similarly treated with a placebo. The infants are clinically followed, and fecal samples are gathered weekly until the age of 4&#xa0;weeks, then at the ages of 8&#xa0;weeks, 3, 6, 12 and 24&#xa0;months. The parents fill in questionnaires until the age of 24&#xa0;months. Blood samples are taken at the age of 2-3&#xa0;days and 3, 6, 12 and 24&#xa0;months to assess development of major immune cell populations and plasma proteins throughout the first years of life.<br><br>DISCUSSION: This is the first study to assess long-time effects on the intestinal microbiome and the development of immune system of a maternal fecal transplant given to term infants born by CS.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04173208 , registration date 21.11.2019.}, }
@article {pmid36175620, year = {2022}, author = {Eaton, SE and Kaczmarek, J and Mahmood, D and McDiarmid, AM and Norarfan, AN and Scott, EG and Then, CK and Tsui, HY and Kiltie, AE}, title = {Exploiting dietary fibre and the gut microbiota in pelvic radiotherapy patients.}, journal = {British journal of cancer}, volume = {127}, number = {12}, pages = {2087-2098}, pmid = {36175620}, issn = {1532-1827}, abstract = {With an ageing population, there is an urgent need to find alternatives to current standard-of-care chemoradiation schedules in the treatment of pelvic malignancies. The gut microbiota may be exploitable, having shown a valuable role in improving patient outcomes in anticancer immunotherapy. These bacteria feed on dietary fibres, which reach the large intestine intact, resulting in the production of beneficial metabolites, including short-chain fatty acids. The gut microbiota can impact radiotherapy (RT) treatment responses and itself be altered by the radiation. Evidence is emerging that manipulation of the gut microbiota by dietary fibre supplementation can improve tumour responses and reduce normal tissue side effects following RT, although data on tumour response are limited to date. Both may be mediated by immune and non-immune effects of gut microbiota and their metabolites. Alternative approaches include use of probiotics and faecal microbiota transplantation (FMT). Current evidence will be reviewed regarding the use of dietary fibre interventions and gut microbiota modification in improving outcomes for pelvic RT patients. However, data regarding baseline (pre-RT) gut microbiota of RT patients and timing of dietary fibre manipulation (before or during RT) is limited, heterogenous and inconclusive, thus more robust clinical studies are required before these strategies can be applied clinically.}, }
@article {pmid36175117, year = {2022}, author = {Liu, Q and Cammarota, G and Ianiro, G}, title = {Evaluating microbial determinants of donor efficacy to translate faecal microbiota transplantation from research to clinical practice.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2022-328573}, pmid = {36175117}, issn = {1468-3288}, }
@article {pmid36174640, year = {2022}, author = {Malard, F and Gaugler, B and Mohty, M}, title = {Faecal microbiota transplantation in patients with haematological malignancies undergoing cellular therapies: from translational research to routine clinical practice.}, journal = {The Lancet. Haematology}, volume = {9}, number = {10}, pages = {e776-e785}, doi = {10.1016/S2352-3026(22)00223-X}, pmid = {36174640}, issn = {2352-3026}, mesh = {Cell- and Tissue-Based Therapy ; Fecal Microbiota Transplantation/adverse effects ; *Graft vs Host Disease/etiology ; *Hematologic Neoplasms/therapy ; Humans ; Translational Research, Biomedical ; }, abstract = {The effect of the gut microbiota on patients' outcomes after allogeneic haematopoietic cell transplantation (HCT) is now well established. In particular, gut microbiota dysbiosis has been associated with acute graft-versus-host disease (GVHD). Furthermore, increasing data also suggest an effect of the gut microbiota on outcome after autologous HCT and CAR T cells. In fact, the bacterial gut microbiota interplays with the immune system and contributes to immunological complication and antitumour response to treatment. Therefore, faecal microbiota transplantation has been evaluated in patients with haematological malignancies for various indications, including Clostridioides difficile infection, eradication of multidrug-resistant bacteria, and steroid refractory acute GVHD. In addition, use of prophylactic faecal microbiota transplantation to restore the gut microbiota and improve patients' outcomes is being developed in the setting of allogeneic HCT, but also probably very soon in patients receiving autologous HCT or CAR T cells.}, }
@article {pmid36172516, year = {2022}, author = {Lin, X and Zhou, R and Liang, D and Xia, L and Zeng, L and Chen, X}, title = {The role of microbiota in autism spectrum disorder: A bibliometric analysis based on original articles.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {976827}, pmid = {36172516}, issn = {1664-0640}, abstract = {BACKGROUND: Gastrointestinal (GI) symptoms can be observed in autism spectrum disorder (ASD) children. It is suggested that the gut microbiota and its metabolites are associated, not only with GI symptoms, but also with behaviors of ASD. The aim of this study was to explore the development context, research hotspots and frontiers of gut microbiota and ASD from January 1, 1980 to April 1, 2022 by bibliometric analysis.<br><br>MATERIALS AND METHODS: Publications of ASD and gut microbiota research from 1 January 1980 to 1 April 2022 were retrieved from the Web of Science Core Collection (WoSCC). Publications and citations trends were analyzed by Excel 2010. CiteSpace was used to analyze countries/regions, authors, institutes, references, and keywords and to visualize the knowledge map.<br><br>RESULTS: A total of 1027 studies were retrieved, and 266 original articles were included after screening. The most published countries and institutes were the United States and King Saud University. Afaf El-Aansary published the most articles, while Finegold SM had the highest co-citations. Hotspots and emerging trends in this area may be indicated by co-cited references and keywords and their clusters, including "gut-brain axis," "behavior," "chain fatty acid," "brain," "feces," "propionic acid," "clostridium perfringens," and "species clostridium innocuum."<br><br>CONCLUSION: The United States dominants the research in this field, which focuses on the alterations of gut microbiota composition and its metabolites, among which the roles of the genus Clostridium and metabolites of short-chain fatty acids, especially propionic acid, are priorities. Fecal microbiota transplantation (FMT) is a promising complementary therapy. In general, research in this area is sparse, but it still has great research prospects.}, }
@article {pmid36171751, year = {2022}, author = {Meng, Y and Feng, Y and Hang, L and Zhou, Y and Wang, E and Yuan, J}, title = {No synergistic effect of fecal microbiota transplantation and shugan decoction in water avoidance stress-induced IBS-D rat model.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {995567}, pmid = {36171751}, issn = {1664-302X}, abstract = {BACKGROUND: It has been reported that 5-hydroxytryptamine (5-HT, serotonin) metabolism is involved in the pathogenesis of irritable bowel syndrome (IBS) and that either Shugan decoction (SGD) or fecal microbiota transplantation (FMT) can alleviate the symptoms of IBS in patients and animal models. But the synergistic effect of FMT and SGD on 5-HT metabolism and IBS symptoms has not been investigated.<br><br>AIM: The main purpose of this study is to observe the synergistic effect of FMT with SGD on symptoms and 5-HT metabolism in IBS-D rats induced by water avoidance stress (WAS). Moreover, the possible material basis of the FMT was investigated.<br><br>METHODS: In experiment I, rats were randomly divided into seven groups. Control group: routine feeding; WAS&#x2192; Control group: routine feeding with fecal microbiota liquid (FML) 1 (derived from rats in WAS group) gavage since the fourth day; WAS group: 10 days WAS with routine feeding; SGD group: 10 days WAS with SGD gavage since the fourth day on the base of routine feeding; Control&#x2192; WAS group: 10 days WAS with FML2 (derived from rats in Control group) gavage since the fourth day with routine feeding; SGD&#x2192; WAS group: 10 days WAS with FML3 (derived from rats in SGD group) gavage since the fourth day with routine feeding; SGD + (Control&#x2192; WAS) group: 10 days WAS with SGD and FML2 (derived from rats in Control group) gavage since the fourth day with routine feeding. In experiment II, rats were randomly divided into three groups. Control group: routine feeding; Control&#x2192; WAS group: 10 days WAS with FML2 gavage since the fourth day with routine feeding; FControl&#x2192; WAS group: 10 days WAS with FML2 filtrate gavage since the fourth day. The number of fecal pellets output (FPT) and the pain pressure threshold (PPT) were recorded. The histological changes in colon mucosa were observed by hematoxylin-eosin (HE) stain. The number of enterochromaffin cells (ECs), the content of 5-HT, and the expression of serotonin reuptake transporter (SERT) protein in the colon were measured by immunofluorescence or western blotting.<br><br>RESULTS: Compared with that in the control group, the PPT and the expression of SERT in the WAS group and that in the WAS&#x2192; Control group were decreased with the increased number of ECs and the level of 5-HT in colon. But the FPT was not increased in the WAS&#x2192; Control group although that was increased in the WAS group. Compared with that in the WAS group, the FPT, the PPT, the number of ECs, the level of 5-HT, and the expression of SERT protein in colon in the SGD group, control&#x2192; WAS group, SGD&#x2192; WAS group, and SGD+(Control&#x2192; WAS) group were all recovered. The recovery of these indicators in the Control&#x2192; WAS group and that in the FControl&#x2192; WAS group was not significantly different.<br><br>CONCLUSION: No synergistic effect of SGD with FMT on IBS symptoms induced by WAS was found. The metabolites of intestinal microbiota may be the main active substances of the FML derived from normal rats to alleviate WAS-induced IBS symptoms.}, }
@article {pmid36168377, year = {2022}, author = {Ramesh, AS and Munoz Tello, C and Jamil, D and Tran, HH and Mansoor, M and Butt, SR and Satnarine, T and Ratna, P and Sarker, A and Khan, S}, title = {Role of Fecal Microbiota Transplantation in Reducing Clostridioides difficile Infection-Associated Morbidity and Mortality: A Systematic Review.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e28402}, pmid = {36168377}, issn = {2168-8184}, abstract = {Clostridioides difficile (C. difficile) is a gram-positive, anaerobic, spore-forming bacterium that produces toxins A and B, disrupting the intestinal brush border and resulting in severe diarrhea. The most common causes of infection include prolonged antibiotic use, proton pump inhibitors (PPIs), and long-term hospitalization resulting in complications such as pseudomembranous colitis and toxic megacolon. This systematic review aims to consider fecal microbiota transplantation (FMT) as an early treatment modality in C. difficile infection to prevent complications and reduce related morbidity and mortality. We systematically screened three databases using regular keywords such as "fecal microbiota transplantation," "C. difficile," "pseudomembranous colitis," and "toxic megacolon" and Medical Subject Headings (MeSH) terms. We applied the inclusion and exclusion criteria and performed a thorough quality appraisal using standardized checklists. We were finally left with 10 articles, including seven case reports, one case series, and two observational studies. Questions remain as to the route of administration of FMT, timing, safety, availability, and the number of sittings required. More randomized controlled trials are needed to address all these questions and to assess the safety of FMT. We believe the role of FMT is very important as it can prevent C. difficile related complications and would be an ideal treatment option in a population group that is often unfit for surgical management.}, }
@article {pmid36167905, year = {2022}, author = {Qiao, X and Biliński, J and Wang, L and Yang, T and Luo, R and Fu, Y and Yang, G}, title = {Safety and efficacy of fecal microbiota transplantation in the treatment of graft-versus-host disease.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {36167905}, issn = {1476-5365}, abstract = {This article evaluates the efficacy and safety of FMT in the treatment of GVHD after HSCT using a systematic literature search to conduct a meta-analysis constructed of studies involving GVHD patients treated with FMT. 23 studies were included, among which 2 prospective cohort studies, 10 prospective single arm studies, 2 retrospective single arm studies, 2 case series and 7 case reports, comprise a total of 242 patients with steroid-resistant or steroid-dependent GVHD secondary to HSCT who were treated with FMT. 100 cases achieved complete responses, while 61 cases showed partial responses, and 81 cases presented no effect after FMT treatment. The estimate of clinical remission odds ratio was 5.51 (95% CI 1.49-20.35) in cohort studies, and the pooled clinical remission rate is 64% (51-77%) in prospective single arm studies and 81% (62-95%) in retrospective studies, case series and case reports. Five (2.1%) patients had FMT-related infection events, but all recovered after treatment. Other adverse effects were mild and acceptable. Microbiota diversity and composition, donor type, and other related issues were also analyzed. The data proves that FMT is a promising treatment modality of GVHD, but further validation of its safety and efficacy is still needed with prospective control studies.Clinical trial registration: Registered in https://www.crd.york.ac.uk/PROSPERO/ CRD42022296288.}, }
@article {pmid36165762, year = {2022}, author = {Zhou, H and Yu, B and Sun, J and Chen, H and Liu, Z and Ge, L and Chen, D}, title = {Comparison of maternal and neonatal gut microbial community and function in a porcine model.}, journal = {Animal biotechnology}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/10495398.2022.2126367}, pmid = {36165762}, issn = {1532-2378}, abstract = {Our knowledge of the difference in maternal and neonatal gut microbiota composition is not fully understood. Using the Bama miniature pig model, the bacterial community in the feces from sows and piglets was analyzed on an IonS5TMXL platform targeting the single-end reads strategy. Results revealed that the maternal and neonatal bacteria profile in the pig model was distinct. Compared with the piglets, sows had higher proportions of bacteria in Spirochetes, Clostridiales, and Spirochaetales (p < 0.10) and had a lower abundance of bacteria in Tyzzerella (p < 0.05) and Alistipes (p < 0.10). Meanwhile, the proportions of bacteria in Oscillibacter and the index of Chao1, Shannon, and observed_species increased in the sows compared with those in the piglets (p < 0.05). Moreover, the abundance of bacteria associated with the human disease was higher (p < 0.05) and the population of bacteria associated with cellular processes was lower (p < 0.05) in the piglets compared with those in the sows. Collectively, the diversity and beneficial bacteria populations in the sow fecal microbiota exhibit more than those in the piglets. This study indicates that maternal fecal microbiota may be a beneficial source of transplanted bacteria to promote healthy function in neonates.}, }
@article {pmid36164761, year = {2022}, author = {Hooi, SL and Dwiyanto, J and Rasiti, H and Toh, KY and Wong, RKM and Lee, JWJ}, title = {A case report of improvement on ADHD symptoms after fecal microbiota transplantation with gut microbiome profiling pre- and post-procedure.}, journal = {Current medical research and opinion}, volume = {38}, number = {11}, pages = {1977-1982}, doi = {10.1080/03007995.2022.2129232}, pmid = {36164761}, issn = {1473-4877}, mesh = {Female ; Humans ; Young Adult ; Adult ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Clostridioides difficile ; *Attention Deficit Disorder with Hyperactivity/therapy ; *Clostridium Infections ; Feces ; }, abstract = {BACKGROUND: Recent studies demonstrate the association of the gut microbiome in regulating interactions between the central nervous system and intestinal function. Individuals with attention-deficit hyperactivity disorder (ADHD) have been shown to have unique gut microbial signature, with depletion of beneficial commensal microbes. Fecal microbiota transplant (FMT) restores the imbalanced gut microbiome and may replete missing microbes to increase production of hormones and neurotransmitters regulating human behavior and cognition.<br><br>RESEARCH DESIGN &amp; METHODS: Here, we present an interesting case of a 22-year-old woman treated with FMT primarily to treat recurrent Clostridioides difficile infection, which coincidentally alleviated her ADHD symptoms. We also present the pre- and post-FMT gut microbiota profiles conducted using shotgun metagenomic sequencing on the patient's fecal samples to thereby highlight potential microbial-associated mechanisms associated with the relief of ADHD symptoms.<br><br>RESULTS &amp; CONCLUSIONS: Our case report provides preliminary evidence regarding the use of FMT in a patient with C. difficile and ADHD. We speculate that gut microbiome modulation, in particular the gain or loss of specific microbial species and pathways involving the metabolism of SCFAs, tryptophan and GABA, may merit further exploration as a potential therapeutic strategy for ADHD.}, }
@article {pmid36162378, year = {2022}, author = {Pasokh, A and Farzipour, M and Mahmoudi, J and Sadigh-Eteghad, S}, title = {The effect of fecal microbiota transplantation on stroke outcomes: A systematic review.}, journal = {Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association}, volume = {31}, number = {11}, pages = {106727}, doi = {10.1016/j.jstrokecerebrovasdis.2022.106727}, pmid = {36162378}, issn = {1532-8511}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; Feces ; *Gastrointestinal Microbiome ; }, abstract = {BACKGROUND AND PURPOSE: Fecal microbiota transplantation (FMT) is a novel microbiota-based therapeutic method that transfers stool from donor into a recipient and its application is under investigating for neurological disorders such as stroke. In this systematic review, we assessed the effect of FMT in progression and treatment of stroke and recovery of post-stroke complications.<br><br>METHODS: Preliminary studies were searched in MEDLINE via PubMed, Scopus, COCHRANE library and Google Scholar, databases up to February 2022. The search strategy was restricted to articles about FMT in stroke. The initial search yielded 4570 articles, of which 19 publications were included in our systematic review.<br><br>RESULTS: Based on outcomes transferring microbiome from healthy or ischemic donor to other ischemic recipient can affect brain infarct volume and survival rate, neurological and behavioral outcomes, and inflammatory pathways.<br><br>CONCLUSIONS: Our systematic review on preclinical studies showed that manipulating gut microbiota via FMT can be a possible therapeutic approach for treatment of stroke and recovery of post-stroke complications.}, }
@article {pmid36161997, year = {2022}, author = {Gill, VJS and Soni, S and Shringarpure, M and Anusheel,  and Bhardwaj, S and Yadav, NK and Patel, A and Patel, A}, title = {Gut Microbiota Interventions for the Management of Obesity: A Literature Review.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e29317}, pmid = {36161997}, issn = {2168-8184}, abstract = {The gut microbiota (GM) has been recognized as an important factor in the development of metabolic diseases such as obesity; it has been reported that the composition of the GM differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. Dysbiosis occurs due to an imbalance in the composition of gut bacteria, changes in the metabolic process, or changes in the distribution of microbiota within the gut. Dysbiosis can change the functioning of the intestinal barrier and the gut-associated lymphoid tissues (GALT). Microbial manipulation may help with preventing or treating weight gain and associated comorbidities. Approaches to this may range from dietary manipulation, which is suitable to treat the individual's microflora, to probiotics, prebiotics, synbiotics, and fecal microbiota transplant (FMT).}, }
@article {pmid36161939, year = {2022}, author = {Gomez-Nguyen, A and Gupta, N and Sanaka, H and Gruszka, D and Pizarro, A and DiMartino, L and Basson, A and Menghini, P and Osme, A and DeSalvo, C and Pizarro, T and Cominelli, F}, title = {Chronic stress induces colonic tertiary lymphoid organ formation and protection against secondary injury through IL-23/IL-22 signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {40}, pages = {e2208160119}, pmid = {36161939}, issn = {1091-6490}, mesh = {Animals ; *Colitis ; *Crohn Disease ; Cytokines ; Dextran Sulfate/toxicity ; Dextrans ; Disease Models, Animal ; Inflammation ; Interleukin-23 ; Mice ; Mice, Knockout ; Phenylmercury Compounds ; }, abstract = {Psychological stress has been previously reported to worsen symptoms of inflammatory bowel disease (IBD). Similarly, intestinal tertiary lymphoid organs (TLOs) are associated with more severe inflammation. While there is active debate about the role of TLOs and stress in IBD pathogenesis, there are no studies investigating TLO formation in the context of psychological stress. Our mouse model of Crohn's disease-like ileitis, the SAMP1/YitFc (SAMP) mouse, was subjected to 56 consecutive days of restraint stress (RS). Stressed mice had significantly increased colonic TLO formation. However, stress did not significantly increase small or large intestinal inflammation in the SAMP mice. Additionally, 16S analysis of the stressed SAMP microbiome revealed no genus-level changes. Fecal microbiome transplantation into germ-free SAMP mice using stool from unstressed and stressed mice replicated the behavioral phenotype seen in donor mice. However, there was no difference in TLO formation between recipient mice. Stress increased the TLO formation cytokines interleukin-23 (IL-23) and IL-22 followed by up-regulation of antimicrobial peptides. SAMP × IL-23r[-/-] (knockout [KO]) mice subjected to chronic RS did not have increased TLO formation. Furthermore, IL-23, but not IL-22, production was increased in KO mice, and administration of recombinant IL-22 rescued TLO formation. Following secondary colonic insult with dextran sodium sulfate, stressed mice had reduced colitis on both histology and colonoscopy. Our findings demonstrate that psychological stress induces colonic TLOs through intrinsic alterations in IL-23 signaling, not through extrinsic influence from the microbiome. Furthermore, chronic stress is protective against secondary insult from colitis, suggesting that TLOs may function to improve the mucosal barrier.}, }
@article {pmid36161855, year = {2022}, author = {Watane, A and Raolji, S and Cavuoto, K and Galor, A}, title = {Microbiome and immune-mediated dry eye: a review.}, journal = {BMJ open ophthalmology}, volume = {7}, number = {1}, pages = {}, pmid = {36161855}, issn = {2397-3269}, support = {I01 CX002015/CX/CSRD VA/United States ; I01 BX004893/BX/BLRD VA/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; R61 EY032468/EY/NEI NIH HHS/United States ; R01 EY026174/EY/NEI NIH HHS/United States ; }, mesh = {Anti-Inflammatory Agents ; *Autoimmune Diseases ; *Dry Eye Syndromes/therapy ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {In this review, we aim to summarise key articles that explore relationships between the gut and ocular surface microbiomes (OSMs) and immune-mediated dry eye. The gut microbiome has been linked to the immune system by way of stimulating or mitigating a proinflammatory or anti-inflammatory lymphocyte response, which may play a role in the severity of autoimmune diseases. Although the 'normal' gut microbiome varies among individuals and demographics, certain autoimmune diseases have been associated with characteristic gut microbiome changes. Less information is available on relationships between the OSM and dry eye. However, microbiome manipulation in multiple compartments has emerged as a therapeutic strategy, via diet, prebiotics and probiotics and faecal microbial transplant, in individuals with various autoimmune diseases, including immune-mediated dry eye.}, }
@article {pmid36161048, year = {2022}, author = {Li, YG and Yu, ZJ and Li, A and Ren, ZG}, title = {Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions.}, journal = {World journal of gastroenterology}, volume = {28}, number = {28}, pages = {3555-3572}, pmid = {36161048}, issn = {2219-2840}, mesh = {Animals ; Antiviral Agents ; *Gastrointestinal Microbiome ; Hepatitis B virus ; *Hepatitis B, Chronic/complications/therapy ; Humans ; Inventions ; Liver Cirrhosis/complications ; *Liver Neoplasms/complications ; Rifaximin ; }, abstract = {Hepatitis B virus (HBV) has posed a threat to public health, mainly resulting in liver damage. With long-term accumulation of extracellular matrix, patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma. The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality. With deeper understanding of the bidirectional interaction between the liver and the gut (gut-liver axis), there is a growing consensus that the human health closely relates to the gut microbiota. Supported by animal and human studies, the gut microbiota alters as the HBV-related liver fibrosis initials and progresses, characterized as the decrease of the ratio between "good" and "potentially pathogenic" microbes. When the primary disease is controlled via antiviral treatment, the gut microbiota dysfunction tends to be improved. Conversely, the recovery of gut microbiota can promote the regression of liver fibrosis. Therapeutic strategies targeted on gut microbiota (rifaximin, probiotics, engineered probiotics and fecal microbiota transplantation) have been applied to animal models and patients, obtaining satisfactory results.}, }
@article {pmid36159503, year = {2022}, author = {Ma, J and Chen, S and Li, Y and Wu, X and Song, Z}, title = {Arbutin improves gut development and serum lipids via Lactobacillus intestinalis.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {948573}, pmid = {36159503}, issn = {2296-861X}, abstract = {Arbutin has been widely studied in whitening, anti-inflammatory, and antioxidant. However, the interaction between arbutin and intestinal microbes has been rarely studied. Thus, mice were treated with arbutin concentrations of 0, 0.1, 0.2, 0.4, and 1 mg/ml. We found that arbutin promoted gut development such as villus length, villus areas, and villus length/crypt depth (L/D). Total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were significantly reduced by low concentrations of arbutin. Importantly, we analyzed the microbial composition in the control and 0.4 mg/ml arbutin group and found that the abundance of Lactobacillus intestinalis (L. intestinalis) was highest and enhanced in arbutin. Further, mice were fed with oral antibiotics and antibiotics + 0.4 mg/ml arbutin and then we transplanted fecal microbes from oral 0.4 mg/ml arbutin mice to mice pretreated with antibiotics. Our results showed that arbutin improves gut development, such as villus width, villus length, L/D, and villus areas. In addition, L. intestinalis monocolonization was carried out after a week of oral antibiotics and increased villus length, crypt depth, and villus areas. Finally, in vitro arbutin and L. intestinalis co-culture showed that arbutin promoted the growth and proliferation of L. intestinalis. Taken together, our results suggest that arbutin improves gut development and health of L. intestinalis. Future studies are needed to explore the function and mechanism of L. intestinalis affecting gut development.}, }
@article {pmid36159020, year = {2022}, author = {Ikeda, Y and Taniguchi, K and Sawamura, H and Tsuji, A and Matsuda, S}, title = {Promising role of D-amino acids in irritable bowel syndrome.}, journal = {World journal of gastroenterology}, volume = {28}, number = {31}, pages = {4471-4474}, pmid = {36159020}, issn = {2219-2840}, mesh = {Amines ; Amino Acids/metabolism/therapeutic use ; Feces ; Fermentation ; *Gastrointestinal Microbiome/physiology ; Humans ; *Irritable Bowel Syndrome ; *Microbiota ; }, abstract = {Irritable bowel syndrome (IBS) is an important health care concern. Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS. Some dietary intake could contribute to produce various metabolites including D-amino acids by the fermentation by the gut microbiota. D-amino acids are the enantiomeric counterparts of L-amino acids, in general, which could play key roles in cellular physiological processes against various oxidative stresses. Therefore, the presence of D-amino acids has been shown to be linked to the protection of several organs in the body. In particular, the gut microbiota could play significant roles in the stability of emotion via the action of D-amino acids. Here, we would like to shed light on the roles of D-amino acids, which could be used for the treatment of IBS.}, }
@article {pmid36158925, year = {2022}, author = {Spanu, D and Pretta, A and Lai, E and Persano, M and Donisi, C and Mariani, S and Dubois, M and Migliari, M and Saba, G and Ziranu, P and Pusceddu, V and Puzzoni, M and Astara, G and Scartozzi, M}, title = {Hepatocellular carcinoma and microbiota: Implications for clinical management and treatment.}, journal = {World journal of hepatology}, volume = {14}, number = {7}, pages = {1319-1332}, pmid = {36158925}, issn = {1948-5182}, abstract = {Gut microbiota plays an essential role in host homeostasis. It is involved in several physiological processes such as nutrients digestion and absorption, maintenance of intestinal epithelial barrier integrity and immune system self-tolerance. Especially the gut microbiota is assumed to play a crucial role in many gastrointestinal, pancreatic and liver disorders. Its role in hepatic carcinogenesis is also gaining increasing interest, especially regarding the development of therapeutic strategies. Different studies are highlighting a link between some bacterial strains and liver disease, including hepatocellular carcinoma (HCC). Indeed, HCC represents an interesting field of research in this perspective, due to the gut-liver axis, to the implication of microbiota in the immune system and to the increasing number of immunotherapy agents investigated in this tumour. Thus, the assessment of the role of microbiota in influencing clinical outcome for patients treated with these drugs is becoming of increasing importance. Our review aims to give an overview on the relationship between microbiota and HCC development/progression and treatment. We focus on potential implications on the available treatment strategies and those under study in the various stages of disease. We highlight the pathogenic mechanisms and investigate the underlying molecular pathways involved. Moreover, we investigate the potential prognostic and/or predictive role of microbiota for target therapies, immune checkpoint inhibitors and loco-regional treatment. Finally, given the limitation of current treatments, we analyze the gut microbiota-mediated therapies and its potential options for HCC treatment focusing on fecal microbiota transplantation.}, }
@article {pmid36158494, year = {2022}, author = {Nishida, A and Nishino, K and Ohno, M and Sakai, K and Owaki, Y and Noda, Y and Imaeda, H}, title = {Update on gut microbiota in gastrointestinal diseases.}, journal = {World journal of clinical cases}, volume = {10}, number = {22}, pages = {7653-7664}, pmid = {36158494}, issn = {2307-8960}, abstract = {The human gut is a complex microbial ecosystem comprising approximately 100 trillion microbes collectively known as the "gut microbiota". At a rough estimate, the human gut microbiome contains almost 3.3 million genes, which are about 150 times more than the total human genes present in the human genome. The vast amount of genetic information produces various enzymes and physiologically active substances. Thus, the gut microbiota contributes to the maintenance of host health; however, when healthy microbial composition is perturbed, a condition termed "dysbiosis", the altered gut microbiota can trigger the development of various gastrointestinal diseases. The gut microbiota has consequently become an extremely important research area in gastroenterology. It is also expected that the results of research into the gut microbiota will be applied to the prevention and treatment of human gastrointestinal diseases. A randomized controlled trial conducted by a Dutch research group in 2013 showed the positive effect of fecal microbiota transplantation (FMT) on recurrent Clostridioides difficile infection (CDI). These findings have led to the development of treatments targeting the gut microbiota, such as probiotics and FMT for inflammatory bowel diseases (IBD) and other diseases. This review focuses on the association of the gut microbiota with human gastrointestinal diseases, including CDI, IBD, and irritable bowel syndrome. We also summarize the therapeutic options for targeting the altered gut microbiota, such as probiotics and FMT.}, }
@article {pmid36157139, year = {2022}, author = {Philips, CA and Schnabl, B and Bajaj, JS}, title = {Gut Microbiome and Alcohol-associated Liver Disease.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {5}, pages = {1349-1359}, pmid = {36157139}, issn = {0973-6883}, abstract = {Changes in gut microbiota (GM) may be associated with the causation and progression of multiple liver diseases such as metabolic-associated liver disease, alcohol-associated liver disease (ALD), alcohol-associated hepatitis (AH), primary biliary cholangitis, primary sclerosing cholangitis, autoimmune liver disease, and most importantly, complications of cirrhosis and portal hypertension such as hepatic encephalopathy (HE), infection, and hepatocellular carcinoma. ALD includes simple steatosis, steatohepatitis, AH, cirrhosis, and acute-on-chronic liver failure. Alcohol consumption is associated with GM changes even before ALD development, and continued alcohol intake results in progressive dysbiosis and development of clinical events such as AH, infection, and HE. The composition and function of GM, specific changes in bacterial communities, and the functional metabolism of GM are affected in the spectrum of ALD, as revealed using high-throughput sequencing. It was reported in preliminary studies that modulation of disrupted GM improves adverse clinical events and ameliorates disease progression in ALD. In this review, we exhaustively discuss the preclinical and clinical studies on GM in ALD and critically discuss GM modulation and its effects based on various human and animal models of ALD.}, }
@article {pmid36156924, year = {2022}, author = {Soveral, LF and Korczaguin, GG and Schmidt, PS and Nunes, IS and Fernandes, C and Zárate-Bladés, CR}, title = {Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection.}, journal = {World journal of gastroenterology}, volume = {28}, number = {33}, pages = {4762-4772}, pmid = {36156924}, issn = {2219-2840}, mesh = {Bile Acids and Salts ; *Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; Fatty Acids, Volatile ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; Humans ; Inflammation Mediators ; Neoplasm Recurrence, Local ; Recurrence ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.}, }
@article {pmid36156162, year = {2022}, author = {Sabanov, A and Mehdorn, M and Gockel, I and Stelzner, S}, title = {[64/m-Fresh blood on the stool : Preparation for the medical specialist examination: part 20].}, journal = {Chirurgie (Heidelberg, Germany)}, volume = {93}, number = {Suppl 1}, pages = {88-94}, pmid = {36156162}, issn = {2731-698X}, mesh = {Feces ; *Medicine ; }, }
@article {pmid36155806, year = {2022}, author = {Benech, N and Koppe, L}, title = {Is there a place for faecal microbiota transplantation in chronic kidney disease?.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {37}, number = {12}, pages = {2303-2306}, doi = {10.1093/ndt/gfac277}, pmid = {36155806}, issn = {1460-2385}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Renal Insufficiency, Chronic/therapy ; }, }
@article {pmid36155217, year = {2022}, author = {Zhai, Y and Zhou, W and Yan, X and Qiao, Y and Guan, L and Zhang, Z and Liu, H and Jiang, J and Liu, J and Peng, L}, title = {Astragaloside IV ameliorates diet-induced hepatic steatosis in obese mice by inhibiting intestinal FXR via intestinal flora remodeling.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {107}, number = {}, pages = {154444}, doi = {10.1016/j.phymed.2022.154444}, pmid = {36155217}, issn = {1618-095X}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Ceramides/metabolism/pharmacology ; Diet, High-Fat/adverse effects ; Fibroblast Growth Factors/metabolism ; *Gastrointestinal Microbiome ; Glucagon-Like Peptide 1/metabolism ; Intestines ; Liver ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; RNA, Ribosomal, 16S ; Receptors, Cytoplasmic and Nuclear/metabolism ; *Saponins/metabolism/pharmacology ; Sterols/metabolism ; Triterpenes ; }, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major clinical and public health burden worldwide with no established pharmacological therapy. Changes in the intestinal flora and associated metabolite bile acids (BAs) have been described in NAFLD. Astragaloside IV (AS-IV) is a low drug permeability saponin with protective effects against multiple diseases. However, the specific mechanism underlying the involvement of AS-IV in the regulation of NAFLD is yet to be clarified.<br><br>PURPOSE: This study aimed to investigate the effect of AS-IV on NAFLD and explore whether intestinal flora was involved.<br><br>METHODS: The effect of AS-IV was evaluated on high-fat diet-fed mice. Real-time PCR, immunohistochemistry, immunofluorescence, and biochemical analyses were performed. 16S rRNA gene sequencing and UPLC-TQMS were used to determine the alterations in the intestinal flora and concentration of BAs. Fecal microbiota transplantation (FMT) and intestine-specific farnesoid X receptor (FXR) knockout were also performed.<br><br>RESULTS: AS-IV treatment alleviated diet-induced metabolic impairments, particularly hepatic steatosis. These changes occurred in the setting of decreased intestinal bile salt hydrolase (BSH)-expressing flora. Further analysis showed that the reduced BSH activity increased intestinal tauro-&#x3b2;-muricholic acid levels, an inhibitor of intestinal FXR. Inhibition of intestinal FXR signaling by AS-IV was accompanied by decreased expression of intestinal fibroblast growth factor 15 and subsequent hepatic FXR activation as well as increased glucagon-like peptide-1 and decreased ceramide production, all of which contribute to the inhibition of sterol regulatory element-binding protein-1c-mediated hepatic steatosis. Furthermore, intestine-specific Fxr knockout and FMT further demonstrated an FXR- and intestinal flora-dependent preventive effect of AS-IV on hepatic steatosis.<br><br>CONCLUSION: These results show that the changes in intestinal flora and BAs serve an essential role in the remission of hepatic steatosis by AS-IV, thereby suggesting that AS-IV may be used as a prebiotic agent to provide viable treatment for NAFLD.}, }
@article {pmid36154539, year = {2022}, author = {Zoghi, S and Abbasi, A and Heravi, FS and Somi, MH and Nikniaz, Z and Moaddab, SY and Ebrahimzadeh Leylabadlo, H}, title = {The gut microbiota and celiac disease: Pathophysiology, current perspective and new therapeutic approaches.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-21}, doi = {10.1080/10408398.2022.2121262}, pmid = {36154539}, issn = {1549-7852}, abstract = {Celiac disease (CD) as a chronic gluten-sensitive intestinal condition, mainly affects genetically susceptible hosts. The primary determinants of CD have been identified as environmental and genetic variables. The development of CD is significantly influenced by environmental factors, including the gut microbiome. Therefore, gut microbiome re-programming-based therapies using probiotics, prebiotics, postbiotics, gluten-free diet, and fecal microbiota transplantation have shown promising results in the modification of the gut microbiome. Due to the importance and paucity of information regarding the CD pathophysiology, in this review, we have covered the association between CD development and gut microbiota, the effects of infectious agents, particularly the recent Covid-19 infection in CD patients, and the efficacy of potential therapeutic approaches in the CD have been discussed. Hence, scientific literature indicates that the diverse biological functions of the gut microbiota against immunomodulatory responses have made microbiome-based therapy an alternative therapeutic paradigm to ameliorate the symptoms of CD and quality of life. However, the exact potential of microbiota-based techniques that aims to quantitatively and qualitatively alter the gut microbiota to be used in the treatment and ameliorate the symptoms of CD will be determined with further research in the future.}, }
@article {pmid36153786, year = {2022}, author = {Najmi, M and Tran, T and Witt, RG and Nelson, KC}, title = {Modulation of the Gut Microbiome to Enhance Immunotherapy Response in Metastatic Melanoma Patients: A Clinical Review.}, journal = {Dermatology and therapy}, volume = {12}, number = {11}, pages = {2489-2497}, pmid = {36153786}, issn = {2193-8210}, abstract = {For patients with metastatic melanoma, immunotherapy agents represent a promising treatment option, and researchers are actively seeking to identify factors that may predict a favorable response in patients. Recent studies have elucidated possible associations between the gut microbiome and the effects of immunotherapy, where variations in the gut microbiome may influence treatment response and frequency of adverse effects. In this clinical review, we describe the current literature related to the gut microbiome in the setting of immunotherapy, and we provide an overview of interventions under investigation that may modulate the gut microbiome. These interventions include fecal microbiota transplantation, probiotics, and dietary modifications.}, }
@article {pmid36152636, year = {2022}, author = {Baunwall, SMD and Andreasen, SE and Hansen, MM and Kelsen, J and Høyer, KL and Rågård, N and Eriksen, LL and Støy, S and Rubak, T and Damsgaard, EMS and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {12}, pages = {1083-1091}, doi = {10.1016/S2468-1253(22)00276-X}, pmid = {36152636}, issn = {2468-1253}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; Vancomycin/therapeutic use ; *Clostridium Infections/therapy ; Diarrhea/therapy/drug therapy ; Double-Blind Method ; }, abstract = {BACKGROUND: Clostridioides difficile infection is an urgent antibiotic-associated health threat with few treatment options. Microbiota restoration with faecal microbiota transplantation is an effective treatment option for patients with multiple recurring episodes of C difficile. We compared the efficacy and safety of faecal microbiota transplantation compared with placebo after vancomycin for first or second C difficile infection.<br><br>METHODS: We did a randomised, double-blind, placebo-controlled trial (EarlyFMT) at a university hospital in Aarhus, Denmark. Eligible patients were aged 18 years or older with first or second C difficile infection (defined as &#x2265;3 watery stools [Bristol stool chart score 6-7] per day and a positive C difficile PCR test). Patients were randomly assigned (1:1) to faecal microbiota transplantation or placebo administered on day 1 and between day 3 and 7, after they had received 125 mg oral vancomycin four times daily for 10 days. Randomisation was done by investigators using a computer-generated randomisation list provided by independent staff. Patients and investigators were masked to the treatment group. The primary endpoint was resolution of C difficile-associated diarrhoea (CDAD) 8 weeks after treatment. We followed up patients for 8 weeks or until recurrence. We planned to enrol 84 patients with a prespecified interim analysis after 42 patients. The primary outcome and safety outcomes were analysed in the intention-to-treat population, which included all randomly assigned patients. The trial is registered with ClinicalTrials.gov, NCT04885946.<br><br>FINDINGS: Between June 21, 2021, and April 1, 2022, we consecutively screened 86 patients, of whom 42 were randomly assigned to faecal microbiota transplantation (n=21) or placebo (n=21). The trial was stopped after the interim analysis done on April 7, 2022 for ethical reasons because a significantly lower rate of resolution was identified in the placebo group compared with the faecal microbiota transplantation group (Haybittle-Peto boundary limit p<0&#xb7;001). 19 (90%; 95% CI 70-99) of 21 patients in the faecal microbiota transplantation group and seven (33%, 95% CI 15-57) of 21 patients in the placebo group had resolution of CDAD at week 8 (p=0&#xb7;0003). The absolute risk reduction was 57% (95% CI 33-81). Overall, 204 adverse events occurred, with one or more adverse events being reported in 20 of 21 patients in the faecal microbiota transplantation group and all 21 patients in the placebo group. Diarrhoea (n=23 in the faecal microbiota transplantation group; n=14 in the placebo group) and abdominal pain (n=14 in the faecal microbiota transplantation group; n=11 in the placebo group) were the most common adverse events. Three serious adverse events possibly related to study treatment occurred (n=1 in the faecal microbiota transplantation group; n=2 in the placebo group), but no deaths or colectomies during the 8-week follow-up.<br><br>INTERPRETATION: In patients with first or second C difficile infection, first-line faecal microbiota transplantation is highly effective and superior to the standard of care vancomycin alone in achieving sustained resolution from C difficile.<br><br>FUNDING: Innovation Fund Denmark.}, }
@article {pmid36152634, year = {2022}, author = {Allegretti, JR}, title = {Should faecal microbiota transplantation be used earlier in the treatment framework?.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {12}, pages = {1062-1063}, doi = {10.1016/S2468-1253(22)00301-6}, pmid = {36152634}, issn = {2468-1253}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; *Colitis, Ulcerative/therapy ; }, }
@article {pmid36151544, year = {2022}, author = {Wang, C and Wang, Y and Yang, H and Tian, Z and Zhu, M and Sha, X and Ran, J and Li, L}, title = {Uygur type 2 diabetes patient fecal microbiota transplantation disrupts blood glucose and bile acid levels by changing the ability of the intestinal flora to metabolize bile acids in C57BL/6 mice.}, journal = {BMC endocrine disorders}, volume = {22}, number = {1}, pages = {236}, pmid = {36151544}, issn = {1472-6823}, mesh = {Animals ; Bile Acids and Salts ; Blood Glucose/metabolism ; Chromatography, Liquid ; DNA, Ribosomal ; Deoxycholic Acid ; *Diabetes Mellitus, Type 2 ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Glucagon-Like Peptide 1 ; Humans ; Insulin ; Mice ; Mice, Inbred C57BL ; Receptors, Calcitriol ; Saline Solution ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Our epidemiological study showed that the intestinal flora of Uygur T2DM patients differed from that of normal glucose-tolerant people. However, whether the Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and the mechanism behind has not been reported. This study was designed to explore whether Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and its mechanism.<br><br>METHODS: The normal diet and high fat diet group consisted of C57BL/6 mice orally administered 0.2&#x2009;mL sterile normal saline. For the MT (microbiota transplantation) intervention groups, C57BL/6 mice received oral 0.2&#x2009;mL faecal microorganisms from Uygur T2DM. All mice were treated daily for 8&#x2009;weeks and Blood glucose levels of mice were detected. Mice faecal DNA samples were sequenced and quantified using 16S rDNA gene sequencing. Then we detected the ability of the intestinal flora to metabolize bile acids (BAs) through co-culture of fecal bacteria and BAs. BA levels in plasma were determined by UPLC-MS. Further BA receptors and glucagon-like peptide-1 (GLP-1) expression levels were determined with RT-q PCR and western blotting.<br><br>RESULTS: MT impaired insulin and oral glucose tolerance. Deoxycholic acid increased and tauro-&#x3b2;-muricholic acid and the non-12-OH BA:12-OH BA ratio decreased in plasma. MT improved the ability of intestinal flora to produce deoxycholic acid. Besides, the vitamin D receptor in the liver and ileum and GLP-1 in the ileum decreased significantly.<br><br>CONCLUSIONS: Uygur T2DM fecal microbiota transplantation disrupts glucose metabolism by changing the ability of intestinal flora to metabolize BAs and the BAs/GLP-1 pathway.}, }
@article {pmid36150095, year = {2022}, author = {Zhang, Y and Zhang, L and Mao, L and Fan, J and Jiang, X and Li, N and Fan, Y and Jiang, Z and Qin, X and Qiu, F and Jiang, Y and Liu, G and Zhang, J and Chen, C and Zou, Z}, title = {Intestinal Microbiota-derived Propionic Acid Protects against Zinc Oxide Nanoparticle-induced Lung Injury.}, journal = {American journal of respiratory cell and molecular biology}, volume = {67}, number = {6}, pages = {680-694}, doi = {10.1165/rcmb.2021-0515OC}, pmid = {36150095}, issn = {1535-4989}, support = {CQYC2020058650//Chongqing Talents: Exceptional Young Talents Project/United States ; 81903358//National Natural Science Foundation of China/United States ; cstc2021ycjh-bgzxm0105//Natural Science Foundation of Chongqing/United States ; cstc2020jcyj-msxmX0155//Natural Science Foundation of Chongqing/United States ; cstc2021jcyj-msxmX0141//Natural Science Foundation of Chongqing/United States ; KJCXZD2020020//Science and Technology Research Program of Chongqing Municipal Education Commission/United States ; KYYJ202005//Science and Technology Research Program of Chongqing Municipal Education Commission/United States ; }, mesh = {Mice ; Humans ; Animals ; *Zinc Oxide/pharmacology ; *Gastrointestinal Microbiome ; Propionates/pharmacology ; *Nanoparticles ; *Acute Lung Injury/chemically induced/prevention &amp; control ; Acetates ; }, abstract = {With the rapid development of nanotechnology, the risks of accidental and/or occupational exposure to zinc oxide nanoparticles (ZnONPs) are increasing. Inhalation of ZnONPs induces metal fume fever in humans and acute lung injury (ALI) in animal models. Although the intestinal microbiota is considered an important modulator of various diseases, the role and mechanism of intestinal microbiota in the pathology of ZnONP-induced ALI are unclear. Herein, we established an intratracheal instillation of a ZnONP-induced ALI mouse model and found that the inhalation of ZnONPs caused ALI along with a perturbation of intestinal flora. Antibiotic cocktail treatment-mediated depletion of intestinal microbiota aggravated ZnONP-induced ALI, and in contrast, fecal microbiota transplantation-mediated restoration of intestinal microbiota exerted the opposite effects. A decrease in short-chain fatty acids, the intestinal microbiota-derived metabolites in the plasma-in particular, acetic acid and propionic acid-occurred after exposure to ZnONPs. It is important to note that supplementation with propionic acid, but not acetic acid, ameliorated ZnONP-induced ALI. We also showed that the source of inflammatory cytokines might partially be the infiltration of macrophages. Supplementation with propionic acid was found to act on macrophages through the receptor GPR43, because knockdown of GPR43 sharply reversed the protective effects of propionic acid during the ZnONP-induced inflammatory response and oxidative stress in both primary alveolar macrophages and RAW 264.7 macrophage cell lines. Altogether, a novel gut-lung axis mechanism is revealed in which intestinal microbiota and their derived metabolite propionic acid play protective roles against ZnONP-induced ALI and suggest that fecal microbiota transplantation and supplementation with propionic acid are potential remedy strategies.}, }
@article {pmid36149765, year = {2022}, author = {Ziegler, S and Bereswill, S and Heimesaat, MM}, title = {Modulation of the intestinal microbiota impacts the efficacy of immunotherapy in cancer patients - A recent literature survey.}, journal = {European journal of microbiology &amp; immunology}, volume = {12}, number = {3}, pages = {63-72}, pmid = {36149765}, issn = {2062-509X}, abstract = {In line with the current development of individualized cancer treatments, targeted and specialized therapeutic regimens such as immunotherapy gain importance and factors improving its efficacy come into the focus of actual research. Given the orchestrated interaction of the intestinal microbiota with host immunity the modulation of the human gut microbiota represents a therapy-enhancing factor. We therefore performed an actual literature survey on the role of the gut microbiota composition and the effects of its modification during immunotherapy of cancer patients. The included 23 studies published in the past 10 years revealed that both, distinct bacterial species and genera including Faecalibacterium prausnitzii and Bifidobacterium, respectively, enhanced distinct immunotherapy responses following PD-1/PD-L1 and CTLA-4 blockage, for instance, resulting in a better clinical outcome of cancer patients. Conversely, a high intestinal abundance of Bacteroidetes and Fusobacterium species correlated with a less efficient immunotherapy resulting in shorter progress-free survival outcomes. In conclusion, modifications of the gut microbiota by fecal microbiota transplantation or application of probiotic compounds represent potential adjunct options for immunotherapy in cancer patients which needs to be further addressed in future trials to provide individually tailored and safe adjuvant therapeutic measures in the combat of cancer.}, }
@article {pmid36148693, year = {2022}, author = {López Cardona, J and Senosiaín Lalastra, C and Mesonero Gismero, F and García de la Filia Molina, I and Escribano Cruz, S and Trigo Gallego, G and Albillos, A}, title = {Exocrine pancreatic insufficiency and graft-versus-host disease.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {}, number = {}, pages = {}, doi = {10.17235/reed.2022.9143/2022}, pmid = {36148693}, issn = {1130-0108}, abstract = {We present the case of a 59-year-old man with acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two years later, he consulted for diarrhea and steatorrhea of 2-3 months of evolution with significant weight loss. Stool cultures and study of parasites were negative. Thyroid and celiac profile, cytomegalovirus viremia and colonoscopy, were normal. Fecal calprotectin and fecal clearance of alpha-1-Antitrypsin were normal but with almost undetectable fecal elastase (<15 ug/g). Pancreatic magnetic resonance reveals a generalized atrophy of the pancreas without other parenchymal or ductal alterations. The patient had no risk factors for chronic pancreatitis and was diagnosed with exocrine pancreatic insufficiency (EPI) associated with chronic graft-versus-host disease (GVHD). GVHD is caused by an immune-mediated reaction by donor T cells recognizing foreign antigens from the recipient. GVHD occurs in 80% of patients after allo-HSCT. Diarrhea is one of the most frequent manifestations, most often due to intestinal damage, opportunistic infections or chemoradiation effects.}, }
@article {pmid36145102, year = {2022}, author = {Chang, C and Yuan, X and Zhang, X and Chen, X and Li, K}, title = {Gastrointestinal Microbiome and Multiple Health Outcomes: Umbrella Review.}, journal = {Nutrients}, volume = {14}, number = {18}, pages = {}, pmid = {36145102}, issn = {2072-6643}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; *Synbiotics ; }, abstract = {In recent years, there has been growing concern about the impact of the gastrointestinal microbiome on human health outcomes. To clarify the evidence for a link between the gastrointestinal microbiome and a variety of health outcomes in humans, we conducted an all-encompassing review of meta-analyses and systematic reviews that included 195 meta-analyses containing 950 unique health outcomes. The gastrointestinal microbiome is related to mortality, gastrointestinal disease, immune and metabolic outcomes, neurological and psychiatric outcomes, maternal and infant outcomes, and other outcomes. Existing interventions for intestinal microbiota (such as probiotics, fecal microbiota transplant, etc.) are generally safe and beneficial to a variety of human health outcomes, but the quality of evidence is not high, and more detailed and well-designed randomized controlled trials are necessary.}, }
@article {pmid36144471, year = {2022}, author = {Siddiqui, R and Mungroo, MR and Alharbi, AM and Alfahemi, H and Khan, NA}, title = {The Use of Gut Microbial Modulation Strategies as Interventional Strategies for Ageing.}, journal = {Microorganisms}, volume = {10}, number = {9}, pages = {}, pmid = {36144471}, issn = {2076-2607}, abstract = {Gut microbial composition codevelops with the host from birth and is influenced by several factors, including drug use, radiation, psychological stress, dietary changes and physical stress. Importantly, gut microbial dysbiosis has been clearly associated with several diseases, including cancer, rheumatoid arthritis and Clostridium difficile-associated diarrhoea, and is known to affect human health and performance. Herein, we discuss that a shift in the gut microbiota with age and reversal of age-related modulation of the gut microbiota could be a major contributor to the incidence of numerous age-related diseases or overall human performance. In addition, it is suggested that the gut microbiome of long-lived animals such as reptiles should be investigated for their unique properties and contribution to the potent defense system of these species could be extrapolated for the benefit of human health. A range of techniques can be used to modulate the gut microbiota to have higher abundance of "beneficial" microbes that have been linked with health and longevity.}, }
@article {pmid36144420, year = {2022}, author = {Mazzawi, T and Hausken, T and Refsnes, PF and Hatlebakk, JG and Lied, GA}, title = {The Effect of Anaerobically Cultivated Human Intestinal Microbiota Compared to Fecal Microbiota Transplantation on Gut Microbiota Profile and Symptoms of Irritable Bowel Syndrome, a Double-Blind Placebo-Controlled Study.}, journal = {Microorganisms}, volume = {10}, number = {9}, pages = {}, pmid = {36144420}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) from healthy donors has been shown to improve the symptoms of irritable bowel syndrome (IBS) and changes the profile of the gut microbiota for the recipients. Alternatively, anaerobically cultivated human intestinal microbiota (ACHIM) can be used to manipulate the gut microbiota. The aim of the current study was to compare the efficacy and safety of ACHIM suspension with donor-FMT and placebo (patient's own feces) to treat IBS. Out of the 62 originally included eligible patients with diarrhea-predominant IBS and their respective donors, only 43 patients completed the study by answering the questionnaires and delivering fecal samples before transplantation and after 1, 4, 12 and 24 weeks. The patients were randomized into three subgroups for receiving ACHIM suspension (n = 17), donor-FMT (n = 11), or placebo (n = 15), and were followed up for 24 weeks. Fecal samples were analyzed by sequencing 16S rRNA gene using the GA-map Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). IBS symptom questionnaires improved in all three subgroups. Bacterial strain signals in IBS patients were more significant for Actinobacteria spp. and Bifidobacteria spp. after receiving donor-FMT compared to placebo and for Alistipes onderdonkii before and after treatment in the subgroups of ACHIM and donor-FMT vs. placebo. These signals change after treatment with ACHIM suspension and donor FMT towards those measured for healthy controls, but not after placebo. IBS symptom questionnaires improved in all three forms of transplantation. Some bacterial strain signals were significantly different between ACHIM and donor-FMT vs. placebo. However, the placebo subgroup failed to change the gut microbiota towards signals measured for healthy controls. The safety and efficacy of ACHIM and donor-FMT seems similar in the current study, but further larger studies are needed.}, }
@article {pmid36142642, year = {2022}, author = {Belvoncikova, P and Maronek, M and Gardlik, R}, title = {Gut Dysbiosis and Fecal Microbiota Transplantation in Autoimmune Diseases.}, journal = {International journal of molecular sciences}, volume = {23}, number = {18}, pages = {}, pmid = {36142642}, issn = {1422-0067}, mesh = {Animals ; *Autoimmune Diseases/therapy ; Autoimmunity ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Gut microbiota dysbiosis has recently been reported in a number of clinical states, including neurological, psychiatric, cardiovascular, metabolic and autoimmune disorders. Yet, it is not completely understood how colonizing microorganisms are implicated in their pathophysiology and molecular pathways. There are a number of suggested mechanisms of how gut microbiota dysbiosis triggers or sustains extraintestinal diseases; however, none of these have been widely accepted as part of the disease pathogenesis. Recent studies have proposed that gut microbiota and its metabolites could play a pivotal role in the modulation of immune system responses and the development of autoimmunity in diseases such as rheumatoid arthritis, multiple sclerosis or type 1 diabetes. Fecal microbiota transplantation (FMT) is a valuable tool for uncovering the role of gut microbiota in the pathological processes. This review aims to summarize the current knowledge about gut microbiota dysbiosis and the potential of FMT in studying the pathogeneses and therapies of autoimmune diseases. Herein, we discuss the extraintestinal autoimmune pathologies with at least one published or ongoing FMT study in human or animal models.}, }
@article {pmid36142552, year = {2022}, author = {Santiso-Bellón, C and Gozalbo-Rovira, R and Buesa, J and Rubio-Del-Campo, A and Peña-Gil, N and Navarro-Lleó, N and Cárcamo-Calvo, R and Yebra, MJ and Monedero, V and Rodríguez-Díaz, J}, title = {Replication of Human Norovirus in Mice after Antibiotic-Mediated Intestinal Bacteria Depletion.}, journal = {International journal of molecular sciences}, volume = {23}, number = {18}, pages = {}, pmid = {36142552}, issn = {1422-0067}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; *Caliciviridae Infections ; DNA, Ribosomal ; Feces/microbiology ; Humans ; Infant ; Interleukin-13 ; Interleukin-4 ; Mice ; *Norovirus/genetics ; Toll-Like Receptor 2 ; Tumor Necrosis Factor-alpha ; }, abstract = {Human noroviruses (HuNoVs) are the main cause of acute gastroenteritis causing more than 50,000 deaths per year. Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement with that of human individuals susceptible to HuNoVs infection could favor viral replication in mice. Four groups of mice (n = 5) were used, including a control group and three groups that were treated with antibiotics to eliminate the autochthonous intestinal microbiota. Two of the antibiotic-treated groups received fecal microbiota transplantation from a pool of feces from infants (age 1-3 months) or an auto-transplantation with mouse feces that obtained prior antibiotic treatment. The inoculation of the different mouse groups with a HuNoVs strain (GII.4 Sydney [P16] genotype) showed that the virus replicated more efficiently in animals only treated with antibiotics but not subject to microbiota transplantation. Viral replication in animals receiving fecal microbiota from newborn infants was intermediate, whereas virus excretion in feces from auto-transplanted mice was as low as in the control mice. The analysis of the fecal microbiota by 16S rDNA NGS showed deep variations in the composition in the different mice groups. Furthermore, differences were observed in the gene expression of relevant immunological mediators, such as IL4, CXCL15, IL13, TNFα and TLR2, at the small intestine. Our results suggest that microbiota depletion eliminates bacteria that restrict HuNoVs infectivity and that the mechanism(s) could involve immune mediators.}, }
@article {pmid36141228, year = {2022}, author = {Yang, M and Liu, S and Zhang, C}, title = {The Related Metabolic Diseases and Treatments of Obesity.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {9}, pages = {}, pmid = {36141228}, issn = {2227-9032}, abstract = {Obesity is a chronic disease characterized by the abnormal or excessive accumulation of body fat, affecting more than 1 billion people worldwide. Obesity is commonly associated with other metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular diseases, chronic kidney disease, and cancers. Factors such as a sedentary lifestyle, overnutrition, socioeconomic status, and other environmental and genetic conditions can cause obesity. Many molecules and signaling pathways are involved in the pathogenesis of obesity, such as nuclear factor (NF)-κB, Toll-like receptors (TLRs), adhesion molecules, G protein-coupled receptors (GPCRs), programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), and sirtuin 1 (SIRT1). Commonly used strategies of obesity management and treatment include exercise and dietary change or restriction for the early stage of obesity, bariatric surgery for server obesity, and Food and Drug Administration (FDA)-approved medicines such as semaglutide and liraglutide that can be used as monotherapy or as a synergistic treatment. In addition, psychological management, especially for patients with obesity and distress, is a good option. Gut microbiota plays an important role in obesity and its comorbidities, and gut microbial reprogramming by fecal microbiota transplantation (FMT), probiotics, prebiotics, or synbiotics shows promising potential in obesity and metabolic syndrome. Many clinical trials are ongoing to evaluate the therapeutic effects of different treatments. Currently, prevention and early treatment of obesity are the best options to prevent its progression to many comorbidities.}, }
@article {pmid36140337, year = {2022}, author = {Štofilová, J and Kvaková, M and Kamlárová, A and Hijová, E and Bertková, I and Guľašová, Z}, title = {Probiotic-Based Intervention in the Treatment of Ulcerative Colitis: Conventional and New Approaches.}, journal = {Biomedicines}, volume = {10}, number = {9}, pages = {}, pmid = {36140337}, issn = {2227-9059}, abstract = {Although there are number of available therapies for ulcerative colitis (UC), many patients are unresponsive to these treatments or experience secondary failure during treatment. Thus, the development of new therapies or alternative strategies with minimal side effects is inevitable. Strategies targeting dysbiosis of gut microbiota have been tested in the management of UC due to the unquestionable role of gut microbiota in the etiology of UC. Advanced molecular analyses of gut microbiomes revealed evident dysbiosis in UC patients, characterized by a reduced biodiversity of commensal microbiota. Administration of conventional probiotic strains is a commonly applied approach in the management of the disease to modify the gut microbiome, improve intestinal barrier integrity and function, and maintain a balanced immune response. However, conventional probiotics do not always provide the expected health benefits to a patient. Their benefits vary significantly, depending on the type and stage of the disease and the strain and dose of the probiotics administered. Their mechanism of action is also strain-dependent. Recently, new candidates for potential next-generation probiotics have been discovered. This could bring to light new approaches in the restoration of microbiome homeostasis and in UC treatment in a targeted manner. The aim of this paper is to provide an updated review on the current options of probiotic-based therapies, highlight the effective conventional probiotic strains, and outline the future possibilities of next-generation probiotic and postbiotic supplementation and fecal microbiota transplantation in the management of UC.}, }
@article {pmid36140180, year = {2022}, author = {Girlanda, R and Liggett, JR and Jayatilake, M and Kroemer, A and Guerra, JF and Hawksworth, JS and Radkani, P and Matsumoto, CS and Zasloff, M and Fishbein, TM}, title = {The Microbiome and Metabolomic Profile of the Transplanted Intestine with Long-Term Function.}, journal = {Biomedicines}, volume = {10}, number = {9}, pages = {}, pmid = {36140180}, issn = {2227-9059}, abstract = {We analyzed the fecal microbiome by deep sequencing of the 16S ribosomal genes and the metabolomic profiles of 43 intestinal transplant recipients to identify biomarkers of graft function. Stool samples were collected from 23 patients with stable graft function five years or longer after transplant, 15 stable recipients one-year post-transplant and four recipients with refractory rejection and graft loss within one-year post-transplant. Lactobacillus and Streptococcus species were predominant in patients with stable graft function both in the short and long term, with a microbiome profile consistent with the general population. Conversely, Enterococcus species were predominant in patients with refractory rejection as compared to the general population, indicating profound dysbiosis in the context of graft dysfunction. Metabolomic analysis demonstrated significant differences between the three groups, with several metabolites in rejecting recipients clustering as a distinct set. Our study suggests that the bacterial microbiome profile of stable intestinal transplants is similar to the general population, supporting further application of this non-invasive approach to identify biomarkers of intestinal graft function.}, }
@article {pmid36140013, year = {2022}, author = {Khanna, S and Sims, M and Louie, TJ and Fischer, M and LaPlante, K and Allegretti, J and Hasson, BR and Fonte, AT and McChalicher, C and Ege, DS and Bryant, JA and Straub, TJ and Ford, CB and Henn, MR and Wang, EEL and von Moltke, L and Wilcox, MH}, title = {SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI).}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {9}, pages = {}, pmid = {36140013}, issn = {2079-6382}, abstract = {Clostridioides&amp;nbsp;difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20-25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p < 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response.}, }
@article {pmid36139402, year = {2022}, author = {Campagnoli, LIM and Marchesi, N and Vairetti, M and Pascale, A and Ferrigno, A and Barbieri, A}, title = {Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention.}, journal = {Cells}, volume = {11}, number = {18}, pages = {}, pmid = {36139402}, issn = {2073-4409}, mesh = {Aged ; Ecosystem ; Humans ; Lipids ; *Non-alcoholic Fatty Liver Disease/metabolism ; *Probiotics/therapeutic use ; Reactive Oxygen Species ; }, abstract = {Human aging, a natural process characterized by structural and physiological changes, leads to alterations of homeostatic mechanisms, decline of biological functions, and subsequently, the organism becomes vulnerable to external stress or damage. In fact, the elderly population is prone to develop diseases due to deterioration of physiological and biological systems. With aging, the production of reactive oxygen species (ROS) increases, and this causes lipid, protein, and DNA damage, leading to cellular dysfunction and altered cellular processes. Indeed, oxidative stress plays a key role in the pathogenesis of several chronic disorders, including hepatic diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common liver disorder in the Western world, is characterized by intrahepatic lipid accumulation; is highly prevalent in the aging population; and is closely associated with obesity, insulin resistance, hypertension, and dyslipidemia. Among the risk factors involved in the pathogenesis of NAFLD, the dysbiotic gut microbiota plays an essential role, leading to low-grade chronic inflammation, oxidative stress, and production of various toxic metabolites. The intestinal microbiota is a dynamic ecosystem of microbes involved in the maintenance of physiological homeostasis; the alteration of its composition and function, during aging, is implicated in different liver diseases. Therefore, gut microbiota restoration might be a complementary approach for treating NAFLD. The administration of probiotics, which can relieve oxidative stress and elicit several anti-aging properties, could be a strategy to modify the composition and restore a healthy gut microbiota. Indeed, probiotics could represent a valid supplement to prevent and/or help treating some diseases, such as NAFLD, thus improving the already available pharmacological intervention. Moreover, in aging, intervention of prebiotics and fecal microbiota transplantation, as well as probiotics, will provide novel therapeutic approaches. However, the relevant research is limited, and several scientific research works need to be done in the near future to confirm their efficacy.}, }
@article {pmid36136718, year = {2022}, author = {Innocente, G and Patuzzi, I and Furlanello, T and Di Camillo, B and Bargelloni, L and Giron, MC and Facchin, S and Savarino, E and Azzolin, M and Simionati, B}, title = {Machine Learning and Canine Chronic Enteropathies: A New Approach to Investigate FMT Effects.}, journal = {Veterinary sciences}, volume = {9}, number = {9}, pages = {}, pmid = {36136718}, issn = {2306-7381}, abstract = {Fecal microbiota transplantation (FMT) represents a very promising approach to decreasing disease activity in canine chronic enteropathies (CE). However, the relationship between remission mechanisms and microbiome changes has not been elucidated yet. The main objective of this study was to report the clinical effects of oral freeze-dried FMT in CE dogs, comparing the fecal microbiomes of three groups: pre-FMT CE-affected dogs, post-FMT dogs, and healthy dogs. Diversity analysis, differential abundance analysis, and machine learning algorithms were applied to investigate the differences in microbiome composition between healthy and pre-FMT samples, while Canine Chronic Enteropathy Clinical Activity Index (CCECAI) changes and microbial diversity metrics were used to evaluate FMT effects. In the healthy/pre-FMT comparison, significant differences were noted in alpha and beta diversity and a list of differentially abundant taxa was identified, while machine learning algorithms predicted sample categories with 0.97 (random forest) and 0.87 (sPLS-DA) accuracy. Clinical signs of improvement were observed in 74% (20/27) of CE-affected dogs, together with a statistically significant decrease in CCECAI (median value from 5 to 2 median). Alpha and beta diversity variations between pre- and post-FMT were observed for each receiver, with a high heterogeneity in the response. This highlighted the necessity for further research on a larger dataset that could identify different healing patterns of microbiome changes.}, }
@article {pmid36136534, year = {2022}, author = {Liu, A and Gao, W and Zhu, Y and Hou, X and Chu, H}, title = {Gut Non-Bacterial Microbiota: Emerging Link to Irritable Bowel Syndrome.}, journal = {Toxins}, volume = {14}, number = {9}, pages = {}, pmid = {36136534}, issn = {2072-6651}, mesh = {Dysbiosis ; *Fungicides, Industrial ; *Gastrointestinal Microbiome/physiology ; Humans ; *Irritable Bowel Syndrome/diagnosis/drug therapy ; *Microbiota ; }, abstract = {As a common functional gastrointestinal disorder, irritable bowel syndrome (IBS) significantly affects personal health and imposes a substantial economic burden on society, but the current understanding of its occurrence and treatment is still inadequate. Emerging evidence suggests that IBS is associated with gut microbial dysbiosis, but most studies focus on the bacteria and neglect other communities of the microbiota, including fungi, viruses, archaea, and other parasitic microorganisms. This review summarizes the latest findings that link the nonbacterial microbiota with IBS. IBS patients show less fungal and viral diversity but some alterations in mycobiome, virome, and archaeome, such as an increased abundance of Candida albicans. Moreover, fungi and methanogens can aid in diagnosis. Fungi are related to distinct IBS symptoms and induce immune responses, intestinal barrier disruption, and visceral hypersensitivity via specific receptors, cells, and metabolites. Novel therapeutic methods for IBS include fungicides, inhibitors targeting fungal pathogenic pathways, probiotic fungi, prebiotics, and fecal microbiota transplantation. Additionally, viruses, methanogens, and parasitic microorganisms are also involved in the pathophysiology and treatment. Therefore, the gut nonbacterial microbiota is involved in the pathogenesis of IBS, which provides a novel perspective on the noninvasive diagnosis and precise treatment of this disease.}, }
@article {pmid36135360, year = {2022}, author = {Gomez-Simmonds, A and Annavajhala, MK and Nunez, MP and Macesic, N and Park, H and Uhlemann, AC}, title = {Intestinal Dysbiosis and Risk of Posttransplant Clostridioides difficile Infection in a Longitudinal Cohort of Liver Transplant Recipients.}, journal = {mSphere}, volume = {7}, number = {5}, pages = {e0036122}, pmid = {36135360}, issn = {2379-5042}, support = {R01 AI116939/AI/NIAID NIH HHS/United States ; K23 AI137316/AI/NIAID NIH HHS/United States ; TL1 TR001875/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Clostridioides difficile/genetics ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/complications ; *Liver Transplantation/adverse effects ; *Clostridium Infections/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) has a higher incidence in solid organ transplant recipients than other hospitalized patients and can lead to poor outcomes. Perturbations to the intestinal microbiome are common in patients undergoing liver transplant (LT); however, the impacts of microbial diversity and composition on risk of CDI in this patient population is incompletely understood. Here, we assessed patients in an established, longitudinal LT cohort for development of CDI within 1 year of transplant. Clinical data were compared for patients with and without CDI using univariable models. 16S rRNA sequencing of fecal samples was performed at multiple pre- and posttransplant time points to compare microbiome α- and β-diversity and enrichment of specific taxa in patients with and without CDI. Of 197 patients who underwent LT, 18 (9.1%) developed CDI within 1 year. Pre-LT Child-Pugh class C liver disease, postoperative biliary leak, and use of broad-spectrum antibiotics were significantly associated with CDI. Patients who developed CDI had significantly lower α-diversity than patients without CDI overall and in samples collected at months 1, 3, and 6. Microbial composition (β-diversity) differed between patients with and without CDI and across sampling time points, particularly later in their posttransplant course. We also identified 15 (8%) patients with toxigenic C. difficile colonization who did not develop CDI and may have had additional protective factors. In summary, clinical and microbiome factors are likely to converge to impart CDI risk. Along with enhanced preventive measures, there may be a role for microbiome modulation to restore microbial diversity in high-risk LT patients. IMPORTANCE Liver transplant (LT) recipients have high rates of Clostridioides difficile infection (CDI), which has been associated with poor outcomes, including graft-related complications and mortality, in prior studies. Susceptibility to CDI is known to increase following perturbations in intestinal commensal bacteria that enable germination of C. difficile spores and bacterial overgrowth. In LT patients, changes in the intestinal microbiome resulting from advanced liver disease, surgery, and other clinical factors is common and most pronounced during the early posttransplant period. However, the relationship between microbiome changes and CDI risk after LT remains unclear. In this study, we investigated clinical and microbiome factors associated with development of CDI within the first year after LT. The importance of this work is to identify patients with high-risk features that should receive enhanced preventive measures and may benefit from the study of novel strategies to reconstitute the intestinal microbiome after LT.}, }
@article {pmid36131643, year = {2023}, author = {Mörkl, S and Butler, MI and Lackner, S}, title = {Advances in the gut microbiome and mood disorders.}, journal = {Current opinion in psychiatry}, volume = {36}, number = {1}, pages = {1-7}, doi = {10.1097/YCO.0000000000000829}, pmid = {36131643}, issn = {1473-6578}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Mood Disorders/therapy ; *Depressive Disorder, Major/therapy ; *Probiotics/therapeutic use ; *Bipolar Disorder/therapy ; }, abstract = {PURPOSE OF REVIEW: The gut microbiome is in constant bidirectional communication with the brain through the microbiota-gut-brain-axis. Mood disorders are among the most common psychiatric disorders and include major depressive disorder and bipolar disorder. The gut microbiome is altered in individuals with mood disorders and has a role in its inflammatory pathophysiology. In this article, we performed a narrative review of clinical studies, randomized controlled trials and meta-analyses addressing advances in gut microbiome research in mood disorders and included articles that were published between 2021 and 2022.<br><br>RECENT FINDINGS: Studies highlight transdiagnostic alterations of microbiota in mood disorders, with reductions of butyrate-producing bacteria. Participants with major depressive disorder showed altered beta-diversity, while participants with bipolar disorder showed reduced alpha-diversity. Both disorders exhibit alterations in the metabolome. Early pilot studies addressed the possibility of using the gut microbiome for the prediction of treatment response and the blood microbiome for the diagnosis of psychiatric disorders. Findings from clinical trials support the use of probiotics as an add-on therapy for major depressive disorder. The second published case report in the literature reported a favourable outcome of a patient with bipolar disorder after faecal microbiota transplantation.<br><br>SUMMARY: Gut microbiome modulations allow new treatment strategies including the use of psychobiotics for the treatment and prevention of mood disorders. Well designed clinical trials aiming for personalized medicine are needed to investigate the efficacy and safety of psychobiotic interventions.}, }
@article {pmid36128620, year = {2022}, author = {Li, Y and Sun, H and Huang, Y and Yin, A and Zhang, L and Han, J and Lyu, Y and Xu, X and Zhai, Y and Sun, H and Wang, P and Zhao, J and Sun, S and Dong, H and Zhu, F and Wang, Q and Augusto Rohde, L and Xie, X and Sun, X and Xiong, L}, title = {Gut metagenomic characteristics of ADHD reveal low Bacteroides ovatus-associated host cognitive impairment.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2125747}, pmid = {36128620}, issn = {1949-0984}, mesh = {Animals ; *Attention Deficit Disorder with Hyperactivity/microbiology ; Bacteroides ; Cognition ; *Cognitive Dysfunction ; *Gastrointestinal Microbiome/physiology ; Humans ; Rats ; }, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can have three phenotypical presentations: inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD). Environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota compositions and whether patients could benefit from the correction of aberrant bacterial colonization are still largely unclear. We carried out metagenomic shotgun analysis with 207 human fecal samples to characterize the gut microbial profiles of patients with ADHD grouped according to their phenotypical presentation. Then, we transplanted the candidate low-abundance bacteria identified in patient subgroups into ADHD rats and evaluated ADHD-associated behaviors and neuronal activation in these rats. Patients with C-ADHD had a different gut microbial composition from that of healthy controls (HCs) (p = .02), but not from that of I-ADHD patients. Eight species became progressively attenuated or enriched when comparing the compositions of HCs to those of I-ADHD and C-ADHD; in particular, the abundance of Bacteroides ovatus was depleted in patients with C-ADHD. In turn, Bacteroides ovatus supplementation ameliorated spatial working memory deficits and reversed θ electroencephalogram rhythm alterations in ADHD rats. In addition, Bacteroides ovatus induced enhanced neuronal activation in the hippocampal CA1 subregion. These findings indicate that gut microbial characteristics that are unique to patients with C-ADHD may be masked when considering a more heterogeneous group of patients. We link the gut microbiota to brain function in an ADHD animal model, suggesting the relevance of testing a potential bacteria-based intervention for some aspects of ADHD.}, }
@article {pmid36126907, year = {2022}, author = {Vaughn, BP and Fischer, M and Kelly, CR and Allegretti, JR and Graiziger, C and Thomas, J and McClure, E and Kabage, AJ and Khoruts, A}, title = {Effectiveness and Safety of Colonic and Capsule Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2022.09.008}, pmid = {36126907}, issn = {1542-7714}, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) emerged as rescue treatment for multiply recurrent Clostridioides difficile infections (rCDIs) nonresponsive to standard therapy. However, estimation of FMT efficacy varies among different protocols and formulations, while placebo-controlled clinical trials have excluded most rCDI patients because of medical comorbidities. This study aimed to determine the safety and effectiveness of capsule FMT (cap-FMT) and colonoscopy FMT (colo-FMT) for rCDI using standardized products in a large, multicenter, prospective, real-world cohort.<br><br>METHODS: Clinical outcomes and adverse events after FMT performed for rCDI at 6 sites were captured in a prospective registry. FMT was performed using 1 of 2 standardized formulations of microbiota manufactured by the University of Minnesota Microbiota Therapeutics Program, freeze-dried/encapsulated or frozen-thawed/liquid. The FMT administration route was determined by the treating physician. The rCDI cure rate was assessed at 1 and 2 months. Safety data were collected within the first 72 hours and at 1 and 2 months. Logistic regression was used to investigate factors associated with FMT failure.<br><br>RESULTS: A total of 301 FMTs were performed in 269 unique patients. Two-thirds were cap-FMT. CDI cure rates were 86% (95% CI, 82%-90%) at 1 month and 81% (95% CI, 75%-86%) at 2 months. There was no difference in the 1-month or 2-month cure rate between cap-FMT and colo-FMT. Cap-FMT recipients were older and less likely to be immunosuppressed or have inflammatory bowel disease. Patient factors of older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression. In addition, post-FMT antibiotic use was associated with FMT failure at 2 months. One serious adverse event was related to colonoscopy (aspiration pneumonia), otherwise no new safety signals were identified.<br><br>CONCLUSIONS: Cap-FMT using freeze-dried capsules has a similar safety and effectiveness profile compared with colo-FMT, without the procedural risks of colonoscopy. Although highly effective overall, patient selection is a key factor to optimizing FMT success.}, }
@article {pmid36126902, year = {2022}, author = {Cooper, TE and Scholes-Robertson, N and Craig, JC and Hawley, CM and Howell, M and Johnson, DW and Teixeira-Pinto, A and Jaure, A and Wong, G}, title = {Synbiotics, prebiotics and probiotics for solid organ transplant recipients.}, journal = {The Cochrane database of systematic reviews}, volume = {9}, number = {9}, pages = {CD014804}, pmid = {36126902}, issn = {1469-493X}, mesh = {Adult ; Albumins ; Anti-Bacterial Agents/therapeutic use ; *Cardiovascular Diseases ; Dysbiosis ; Endotoxins ; Humans ; Lipids ; *Organ Transplantation ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {BACKGROUND: Solid organ transplantation has seen improvements in both surgical techniques and immunosuppression, achieving prolonged survival. Essential to graft acceptance and post-transplant recovery, immunosuppressive medications are often accompanied by a high prevalence of gastrointestinal (GI) symptoms and side effects. Apart from GI side effects, long-term exposure to immunosuppressive medications has seen an increase in drug-related morbidities such as diabetes mellitus, hyperlipidaemia, hypertension, and malignancy. Non-adherence to immunosuppression can lead to an increased risk of graft failure. Recent research has indicated that any microbial imbalances (otherwise known as gut dysbiosis or leaky gut) may be associated with cardiometabolic diseases in the long term. Current evidence suggests a link between the gut microbiome and the production of putative uraemic toxins, increased gut permeability, and transmural movement of bacteria and endotoxins and inflammation. Early observational and intervention studies have been investigating food-intake patterns, various synbiotic interventions (antibiotics, prebiotics, or probiotics), and faecal transplants to measure their effects on microbiota in treating cardiometabolic diseases. It is believed high doses of synbiotics, prebiotics and probiotics are able to modify and improve dysbiosis of gut micro-organisms by altering the population of the micro-organisms. With the right balance in the gut flora, a primary benefit is believed to be the suppression of pathogens through immunostimulation and gut barrier enhancement (less permeability of the gut).<br><br>OBJECTIVES: To assess the benefits and harms of synbiotics, prebiotics, and probiotics for recipients of solid organ transplantation.<br><br>SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 9 March 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.<br><br>SELECTION CRITERIA: We included randomised controlled trials measuring and reporting the effects of synbiotics, prebiotics, or probiotics, in any combination and any formulation given to solid organ transplant recipients (any age and setting). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.<br><br>DATA COLLECTION AND ANALYSIS: Data extraction was independently carried out by two authors using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.<br><br>MAIN RESULTS: Five studies (250 participants) were included in this review. Study participants were adults with a kidney (one study) or liver (four studies) transplant. One study compared a synbiotic to placebo, two studies compared a probiotic to placebo, and two studies compared a synbiotic to a prebiotic. Overall, the quality of the evidence is poor. Most studies were judged to have unclear (or high) risk of bias across most domains. Of the available evidence, meta-analyses undertaken were of limited data from small studies. Across all comparisons, GRADE evaluations for all outcomes were judged to be very low certainty evidence. Very low certainty evidence implies that we are very uncertain about results (not estimable due to lack of data or poor quality). Synbiotics had uncertain effects on the change in microbiota composition (total plasma p-cresol), faecal characteristics, adverse events, kidney function or albumin concentration (1 study, 34 participants) compared to placebo. Probiotics had uncertain effects on GI side effects, infection rates immediately post-transplant, liver function, blood pressure, change in fatty liver, and lipids (1 study, 30 participants) compared to placebo. Synbiotics had uncertain effects on graft health (acute liver rejection) (2 studies, 129 participants: RR 0.73, 95% CI 0.43 to 1.25; 2 studies, 129 participants; I&#xb2; = 0%), the use of immunosuppression, infection (2 studies, 129 participants: RR 0.18, 95% CI 0.03 to 1.17; I&#xb2; = 66%), GI function (time to first bowel movement), adverse events (2 studies, 129 participants: RR 0.79, 95% CI 0.40 to 1.59; I&#xb2; = 20%), serious adverse events (2 studies, 129 participants: RR 1.49, 95% CI 0.42 to 5.36; I&#xb2; = 81%), death (2 studies, 129 participants), and organ function measures (2 studies; 129 participants) compared to prebiotics.<br><br>AUTHORS' CONCLUSIONS: This review highlights the severe lack of high-quality RCTs testing the efficacy of synbiotics, prebiotics or probiotics in solid organ transplant recipients. We have identified significant gaps in the evidence. Despite GI symptoms and postoperative infection being the most common reasons for high antibiotic use in this patient population, along with increased morbidity and the growing antimicrobial resistance, we found very few studies that adequately tested these as alternative treatments. There is currently no evidence to support or refute the use of synbiotics, prebiotics, or probiotics in solid organ transplant recipients, and findings should be viewed with caution. We have identified an area of significant uncertainty about the efficacy of synbiotics, prebiotics, or probiotics in solid organ transplant recipients. Future research in this field requires adequately powered RCTs comparing synbiotics, prebiotics, and probiotics separately and with placebo measuring a standard set of core transplant outcomes. Six studies are currently ongoing (822 proposed participants); therefore, it is possible that findings may change with their inclusion in future updates.}, }
@article {pmid36126873, year = {2022}, author = {Zhang, Q and Li, T and Niu, J and Xiao, J and Zhang, M and Zhang, R and Chen, D and Shi, Y and Zhang, X and Hu, X and Yu, B and Feng, J and Fang, Q}, title = {Inhibitory effects of antibiotic-induced gut microbiota depletion on acute itch behavior in mice.}, journal = {Brain research bulletin}, volume = {190}, number = {}, pages = {50-61}, doi = {10.1016/j.brainresbull.2022.09.014}, pmid = {36126873}, issn = {1873-2747}, mesh = {Animals ; Mice ; Male ; *Gastrointestinal Microbiome/physiology ; Mice, Inbred C57BL ; Anti-Bacterial Agents/pharmacology ; Pruritus/chemically induced/drug therapy ; Serotonin/pharmacology ; }, abstract = {BACKGROUND: The gut microbiota is known to be associated with the regulation of many neurological diseases and behaviors, including chronic pain. However, it is unclear whether the gut microbiota is critical to the itch sensation. In this study, we investigated the effects of gut microbiota depletion on acute itch.<br><br>METHODS: First, an antibiotic cocktail was orally administered to deplete the gut microbiota in male C57BL/6 mice. Then, pruritogens were intradermally injected to induce acute itch behavior. In addition, antibiotic-treated mice received transplantation of fecal microbiota from untreated mice, followed by tests for acute itch. The changes in c-Fos expression in trigeminal ganglia (TG) neurons were also investigated by immunofluorescence staining.<br><br>RESULTS: Our results indicated that chronic antibiotic treatment significantly reduced the diversity and richness of the gut microbiota of mice. Compared to vehicle-treated mice, antibiotic-treated mice showed reductions in acute itch behavior induced by compound 48/80, chloroquine (CQ), and serotonin (5-HT), respectively. Moreover, repositioning of microbiota reversed the reductions in acute itch behavior in antibiotic-treated mice. In addition, immunofluorescence staining revealed that antibiotic-treated mice displayed decreased c-Fos expression in ipsilateral TG compared to controls.<br><br>CONCLUSIONS: Our study, for the first time, discovered that antibiotic-induced gut microbiota depletion could reduce acute itch behavior, which may be connected with decreased TG neuronal activity.}, }
@article {pmid36125532, year = {2022}, author = {Xia, Y and Tian, Y and Zhou, D and Zhang, L and Cai, Y and Fu, S and Zhang, X and Gao, Y and Chen, Q and Gao, P}, title = {Gut microbiota involved in spermatogenic function of Sancai Lianmei granules in obese mice.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {36125532}, issn = {1432-1912}, abstract = {Obesity is a well-established cause of reduced fertility and semen quality in men. Current evidence suggests that Sancai Lianmei granules (SCLM) effectively improve sexual function and semen quality in diabetic patients, while the gut microbiota can influence disease metabolism through various mechanisms. However, the effect of SCLM on the obesity-induced decrease in semen quality and on the gut microbiota is unclear. This study aimed to investigate the effects of SCLM on spermatogenic function and gut microbiota in obese mice. Obese mice were induced by a high-fat diet, and lipid metabolism, spermatogenic function, inflammatory factors, oxidative stress, and autophagy were analyzed to determine the effects of SCLM and SCLM-fecal microbiota transplantation (FMT). In addition, changes in the gut microbiota of mice were analyzed. SCLM and SCLM + FMT could effectively reduce the levels of total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); decrease the expression of oxidative stress products malondialdehyde (MDA) and 8-hydroxyde-oxyguanosine (8-OHdG); and increase sperm density and sperm viability in obese mice while inhibiting the inflammatory responses and excessive cellular autophagy, indicating that SCLM and SCLM + FMT exerted a protective effect on spermatogenic functions. Furthermore, SCLM affected the gut microbiota composition in mice. This study determined that obesity can lead to reduced sperm motility and affect the composition of the gut microbiota, while SCLM can regulate blood lipids in mice directly or indirectly by regulating gut microbiota changes, and may improve sperm motility in obese mice by reducing oxidative stress and autophagy. In addition, FMT enhanced this effect, which may be related to the diversity of gut microbiota.}, }
@article {pmid36123355, year = {2022}, author = {Noguès, EB and Kropp, C and Bétemps, L and de Sousa, C and Chain, F and Auger, S and Azevedo, V and Langella, P and Chatel, JM}, title = {Lactococcus lactis engineered to deliver hCAP18 cDNA alleviates DNBS-induced colitis in C57BL/6 mice by promoting IL17A and IL10 cytokine expression.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {15641}, pmid = {36123355}, issn = {2045-2322}, mesh = {Animals ; Cathelicidins/*metabolism ; *Colitis/chemically induced/genetics/therapy ; Cytokines/metabolism ; DNA, Complementary/metabolism ; Dinitrofluorobenzene/analogs &amp; derivatives ; Interleukin-10/genetics/metabolism ; Interleukin-17/metabolism ; *Lactococcus lactis/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; }, abstract = {With its antimicrobial and immunomodulating properties, the cathelicidin (LL37) plays an important role in innate immune system. Here, we attempted to alleviate chemically induced colitis using a lactococci strain that either directly expressed the precursor to LL37, hCAP18 (LL-pSEC:hCAP18), or delivered hCAP18 cDNA to host cells under the control of the cytomegalovirus promoter (LL-Probi-H1:hCAP18). We also investigated whether the alleviation of symptoms could be explained through modification of the gut microbiota by hCAP18. Mice were administered daily doses of LL-pSEC:hCAP18 or LL-Probi-H1:hCAP18. On day 7, colitis was induced by DNBS. During autopsy, we assessed macroscopic tissue damage in the colon and collected tissue samples for the characterization of inflammation markers and histological analysis. Feces were collected at day 7 for 16S DNA sequencing. We also performed a fecal transplant experiment in which mice underwent colon washing and received feces from Lactococcus lactis-treated mice before DNBS-colitis induction. Treatment with LL-Probi-H1:hCAP18 reduced the severity of colitis symptoms. The protective effects were accompanied by increased levels of IL17A and IL10 in mesenteric lymph node cells. L. lactis administration altered the abundance of Lachnospiraceae and Muribaculaceae. However, fecal transplant from L. lactis-treated mice did not improve DNBS-induced symptoms in recipient mice.}, }
@article {pmid36121613, year = {2022}, author = {Singh, A and Mahajan, R and Kahlon, BK and Dhaliwal, AS and Midha, V and Mehta, V and Bansal, N and Singh, D and Sood, A}, title = {Early fecal microbiome transfer after donor defecation determines response in patients with moderate to severe ulcerative colitis.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {41}, number = {4}, pages = {389-396}, pmid = {36121613}, issn = {0975-0711}, mesh = {Adult ; *Colitis, Ulcerative/etiology/therapy ; Defecation ; Fecal Microbiota Transplantation/methods ; Feces ; Humans ; Male ; *Microbiota ; Middle Aged ; Remission Induction ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiome transfer (FMT) targeting gut microbiome dysbiosis is an emerging therapy for ulcerative colitis (UC). There is however no consensus on protocols for performing FMT in UC, especially in relation to time after donor feces defecation.<br><br>METHODS: This is a single-center retrospective analysis of patients with moderate-severe UC (total Mayo Clinic score &#x2265;6 and endoscopic Mayo Clinic subscore of &#x2265;2) treated with FMT between September 2017 and December 2019 at Dayanand Medical College and Hospital, Ludhiana,&#xa0;India. Fresh fecal samples from unrelated healthy voluntary donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. Time interval between donor feces defecation and FMT procedure was recorded for each FMT session and the mean time of seven sessions was designated aika. Impact of aika on clinical response and safety of FMT was evaluated.<br><br>RESULTS: During the study period, 123 adult patients (mean age 33.75&#xb1;11.97 years, 61.8% [n=76] males) with moderate-severe UC (mean total Mayo Clinic and endoscopic Mayo Clinic scores 7.49&#xb1;1.60 and 2.50&#xb1;0.50, respectively) were treated with FMT. The mean aika was 2.29&#xb1;0.75 h. The aika was smaller in patients who responded to FMT as compared to non-responders (2.13&#xb1;0.75&#xa0;h vs. 2.71&#xb1;0.76 h, p=0.0002) as well as in patients achieving clinical remission (2.15&#xb1;0.76 h vs. 2.42&#xb1;0.76 h, p=0.05). There was no significant impact of aika on adverse effects except for&#xa0;the incidence of borborygmi after FMT, which was higher in patients with aika &#x2264;2 h.<br><br>CONCLUSION: Early FMT after donor feces defecation favorably impacts the clinical response rates in patients with active UC.}, }
@article {pmid36117374, year = {2022}, author = {Ye, C and Chen, QY and Yan, YM and Lv, XQ and Ma, CL and Li, N and Qin, HL}, title = {[Establishment and preliminary clinical application of human intestinal fluid transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {819-825}, doi = {10.3760/cma.j.cn441530-20220601-00239}, pmid = {36117374}, issn = {1671-0274}, mesh = {Bacteria ; Child ; Fecal Microbiota Transplantation/methods ; *Glycerol ; Humans ; Powders ; *Trypan Blue ; }, abstract = {Objective: To explore and establish the preparation system of human intestinal fluid transplantation (HIFT) and HIFT capsule, and to preliminarily apply it to clinic. Methods: Strict standards for donor screening and management were established. The nasojejunal tube was catheterized into the distal jejunum, and then it was connected with an improved disposable sterile negative pressure collection device for the collection of human intestinal fluid. After that, it was prepared into capsules by filtering, adding 10% glycerin protectant and freeze-drying method. The amount of living bacteria was used as the standard of therapeutic dose. The living bacteria amount in fluid is ≥ 5.0×10[8] /mL and the living bacteria proportion is ≥ 83%; the living bacteria amount in powder is ≥ 2.0×10[6] /g and the living bacteria proportion is ≥ 81%; The observational indicators included: (1) the basic information of the donor, the amount of living bacteria in the HIF and powder. (2) Preliminary analysis of the treatment for ASD, which combined HIFT capsule with stand