@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}, 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 mL sterile normal saline. For the MT (microbiota transplantation) intervention groups, C57BL/6 mice received oral 0.2 mL faecal microorganisms from Uygur T2DM. All mice were treated daily for 8 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-β-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 {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 = {}, number = {}, pages = {}, doi = {10.1556/1886.2022.00017}, 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 {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 = {}, doi = {10.3390/nu14183726}, pmid = {36145102}, issn = {2072-6643}, support = {2021YFS0022//Science and Technology Department of Sichuan Province/ ; }, 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 {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 = {}, doi = {10.3390/microorganisms10091819}, pmid = {36144420}, issn = {2076-2607}, support = {F-10463/4800001918//Western Norway Regional Health Authority/ ; }, 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 = {}, doi = {10.3390/ijms231810729}, pmid = {36142642}, issn = {1422-0067}, support = {APVV-17-0505//Slovak Research and Development Agency/ ; APVV-21-0370//Slovak Research and Development Agency/ ; VEGA 1/0649/21//Ministry of Education, Science, Research and Sport of the Slovak Republic/ ; }, 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 = {}, doi = {10.3390/ijms231810643}, pmid = {36142552}, issn = {1422-0067}, support = {PID2020-115403RB C21//Spanish Ministry of Science and Innovation/ ; PID2020-115403RB C22//Spanish Ministry of Science and Innovation/ ; }, 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 = {}, doi = {10.3390/healthcare10091616}, 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 = {}, doi = {10.3390/biomedicines10092236}, pmid = {36140337}, issn = {2227-9059}, support = {VEGA 1/0393/20//Scientific Grant Agency of the Ministry of Education of Slovak Republic and Academy of Sciences/ ; }, 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 {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 = {}, doi = {10.3390/antibiotics11091234}, pmid = {36140013}, issn = {2079-6382}, support = {NA//Seres Therapeutics (United States)/ ; }, 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 = {}, doi = {10.3390/cells11182827}, pmid = {36139402}, issn = {2073-4409}, support = {FRG2021//University of Pavia/ ; }, 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 = {}, doi = {10.3390/vetsci9090502}, pmid = {36136718}, issn = {2306-7381}, support = {10232721//Regione del Veneto/ ; }, 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 = {}, doi = {10.3390/toxins14090596}, pmid = {36136534}, issn = {2072-6651}, support = {82000561//National Natural Science Foundation of China/ ; 81974062//National Natural Science Foundation of China/ ; 81720108006//National Natural Science Foundation of China/ ; 2020FCA014//Department of Science and Technology, Hubei Provincial People's Government/ ; 2021xhyn005//Science Foundation of Union Hospital/ ; }, 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 {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 AND AIMS: Fecal microbiota transplantation (FMT) emerged as rescue treatment for multiply recurrent Clostridioides difficile infection (rCDI) non-responsive to standard therapy. However, estimation of FMT efficacy varies among different protocols and formulations, while placebo-controlled clinical trials have excluded most rCDI patients due to medical co-morbidities. 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, multicentered, prospective real-world cohort.<br><br>METHODS: Clinical outcomes and adverse events after FMT performed for rCDI at six sites were captured in a prospective registry. FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota Microbiota Therapeutics Program, freeze-dried/encapsulated or frozen-thawed/liquid. FMT administration route was determined by the treating physician. rCDI cure rate was assessed at 1 and 2 months. Safety data was 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: Three hundred and one 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- 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. Additionally, post FMT antibiotic use was associated with FMT failure at 2-months. One SAE 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 to colo-FMT, without the procedural risks of colonoscopy. While highly effective overall, patient selection is a key factor to optimizing FMT success.}, }
@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 = {}, number = {}, pages = {}, doi = {10.1016/j.brainresbull.2022.09.014}, pmid = {36126873}, issn = {1873-2747}, 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}, support = {2022YFS0411//Science and Technology Plan Project of Sichuan Province (Key Research and Development Project)/ ; 2022YFS0411//Science and Technology Plan Project of Sichuan Province (Key Research and Development Project)/ ; 2022YFS0411//Science and Technology Plan Project of Sichuan Province (Key Research and Development Project)/ ; 2100601//2022 national famous and old Chinese medicine expert Zhang Shuwu inheritance studio construction project/ ; 2021MS023//Sichuan Provincial Administration of Traditional Chinese Medicine Scientific Research Project/ ; 2019-YF05- 00064-SN//Chengdu Science and Technology Bureau Technological Innovation R&amp;D Project/ ; }, 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 {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 = {}, number = {}, pages = {}, pmid = {36121613}, issn = {0975-0711}, 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 ≥6 and endoscopic Mayo Clinic subscore of ≥2) treated with FMT between September 2017 and December 2019 at Dayanand Medical College and Hospital, Ludhiana, 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±11.97 years, 61.8% [n=76] males) with moderate-severe UC (mean total Mayo Clinic and endoscopic Mayo Clinic scores 7.49±1.60 and 2.50±0.50, respectively) were treated with FMT. The mean aika was 2.29±0.75 h. The aika was smaller in patients who responded to FMT as compared to non-responders (2.13±0.75 h vs. 2.71±0.76 h, p=0.0002) as well as in patients achieving clinical remission (2.15±0.76 h vs. 2.42±0.76 h, p=0.05). There was no significant impact of aika on adverse effects except for the incidence of borborygmi after FMT, which was higher in patients with aika ≤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}, support = {SHDC2020CR1030B, SHDC2020CR4026//Clinical Research Plan of SHDC/ ; 21Y11908300//Shanghai Action Plan on Science, Technology and Innovation/ ; }, 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 ≥ 5.0×108 /mL and the living bacteria proportion is ≥ 83%; the living bacteria amount in powder is ≥ 2.0×106 /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 standard FMT capsule, from February to December 2021 (Clinical trial Registration Number: ChiCTR2100043929). Evaluation criteria: Trypan blue staining method was used to detect the living bacteria amount in fluid and powder. The Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the efficacy. Results: Compared with the parent donor, the standard donor was younger [(25.4±0.9) y vs. (30.7±3.2) y, t=-19.097, P=0.001] and had a lower body mass index [(19.7±0.5) kg/m2 vs. (20.8±1.3) kg/m2, t=-8.726, P=0.001], more in the living bacteria amount in powder [(7.47±1.52)×106/g vs. (5.03±1.38)×106/g, t=11.331, P=0.031], Chao index (205.4±6.8 vs. 194.2±7.2, t=10.415, P=0.001), and Shannon index (3.25±0.14 vs 2.72±0.27, t=19.465, P=0.001). The differences were statistically significant (all P<0.05). However, there were no significant differences in gender, drainage volume and total number of bacterial liquid colonies between the two groups (all P>0.05). Both the standard donor and the parent donor met the donor screening criteria, and the preparation fluid and powder met the treatment criteria. Eight patients received the treatment of HIFT combined with fecal microbiota transplantation (FMT). Preliminary statistical results showed that HIFT combined with FMT improved ABC and CARS at the 1st, 2nd, 3rd and 4th months. The differences were statistically significant (all P<0.05). No severe adverse reaction occurred. Conclusion: Based on the previous research on FMT preparation system and the clinical technology in our center, this study developed a high standard HIFT preparation system, and explored the clinical study of HIFT combined with FMT, in order to provide an innovative therapy for the treatment of diseases.}, }
@article {pmid36117371, year = {2022}, author = {Ye, C and Chen, QY and Ma, XQ and Lv, P and Yang, HL and Tian, D and Zhao, ZL and Lin, JQ and Cui, N and Li, HL and Qin, H}, title = {[Long-term outcomes of 328 patients with of autism spectrum disorder after fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {798-803}, doi = {10.3760/cma.j.cn441530-20220601-00238}, pmid = {36117371}, issn = {1671-0274}, support = {21Y11908300//Shanghai Action Plan on Science, Technology and Innovation/ ; SHDC2020CR1030B, SHDC2020CR4026//Clinical Research Plan of SHDC/ ; }, mesh = {*Autism Spectrum Disorder/etiology/therapy ; Child ; Child, Preschool ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Female ; *Gastrointestinal Diseases ; Humans ; Longitudinal Studies ; Male ; Retrospective Studies ; }, abstract = {Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of autism spectrum disorder (ASD). Methods: A longitudinal study was conducted. Clinical data from ASD patients with gastrointestinal symptoms and who underwent FMT in the Tenth People's Hospital affiliated to Tongji University or Jinling Hospital between May 2012 to May 2021 were retrospectively collected. Scores derived from the autism behavior checklist (ABC), the childhood autism rating scale (CARS), the Bristol stool form scale (BSFS), and the gastrointestinal symptom rating scale (GSRS) were analyzed at baseline and at the 1st, 3rd, 6th, 12th, 24th, 36th, 48th and 60th month after FMT. Records of any adverse reactions were collected. Generalized estimating equations were used for analysis of data on time points before and after FMT. Results: A total of 328 patients met the inclusion criteria for this study. Their mean age was 6.1±3.4 years old. The cohort included 271 boys and 57 girls. The percentage of patients remaining in the study for post-treatment follow-up at the 1st, 3rd, 12th, 24th, 36th, 48th and 60th month were as follows: 303 (92.4%), 284 (86.7%), 213 (64.9%), 190 (57.9%), 143 (43.6%), 79 (24.1%), 46 (14.0%), 31 (9.5%). After FMT, the average ABC score was significantly improved in the first 36 months and remained improved at the 48th month. However, the average score was not significantly different from baseline by the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.108). The average CARS score improved significantly during the first 48 months and remained improved at the 60th month (1st-48th month, P<0.001; 60th month, P=0.010). The average BSFS score was also significantly improved in the first 36 months (with an accompanying stool morphology that resembled type 4). This improvement was maintained at the 48th month. However, the average score was similar to baseline at the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.109). The average GSRS score was significantly improved during the first 24 months, but not afterwards (1st-24th month, P<0.001; 36th month, P=0.209; 48th month, P=0.996; 60th month, P=0.668). The adverse events recorded during treatment included abdominal distension in 21 cases (6.4%), nausea in 14 cases (4.3%), vomiting in 9 cases (2.7%), abdominal pain in 15 cases (4.6%), diarrhea in 18 cases (5.5%), fever in 13 cases (4.0%), and excitement in 24 cases (7.3%). All adverse reactions were mild to moderate and improved immediately after suspension of FMT or on treatment of symptoms. No serious adverse reactions occurred. Conclusion: FMT has satisfactory long-term efficacy and safety for the treatment of ASD with gastrointestinal symptoms.}, }
@article {pmid36117369, year = {2022}, author = {Lin, ZL and Lu, JB and Chen, QY and Cui, JQ and Ye, C and Tian, HL and Qin, HL and Li, N}, title = {[Clinical effectiveness of fecal microbiota transplantation combined with nutritional support and psychological intervention in patients with "Tetralogy of Tongji"].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {784-791}, doi = {10.3760/cma.j.cn441530-20220605-00245}, pmid = {36117369}, issn = {1671-0274}, support = {81972221//National Natural Science Foundation of China/ ; SHDC2020CR1030B//Clinical Research Plan of SHDC/ ; }, mesh = {Adolescent ; Adult ; Amenorrhea ; China ; Constipation ; Dopamine ; Fecal Microbiota Transplantation ; Female ; Fibrinogen ; *Gastrointestinal Diseases ; Humans ; Hydrocortisone ; Infant ; Longitudinal Studies ; Male ; *Malnutrition ; Middle Aged ; Norepinephrine ; Nutritional Support ; Prealbumin ; Psychosocial Intervention ; Quality of Life ; Treatment Outcome ; Young Adult ; }, abstract = {Objective: To summarize and analyze the clinical effect of fecal microbiota transplantation (FMT) combined with nutritional support and psychotherapy in patients with "Tetralogy of Tongji" (comprising chronic gastrointestinal dysfunction, mental and psychological disorders, malnutrition, and endocrine disorders). Methods: A longitudinal study was conducted. The inclusion criteria were as follows: (1) patients were under 70 years of age; (2) patients exhibited chronic gastrointestinal dysfunction (in accordance with the Rome IV diagnostic criteria for irritable bowel syndrome ie. chronic functional constipation, diarrhea, abdominal pain and abdominal distention) with onset occurring more than one year previously; (3) patients exhibited malnutrition (body mass index ≤ 18.5 kg/m2); (4) patients exhibited depression, anxiety, or state as diagnosed by a psychologist using the Hamilton anxiety rating scale (HAMA) and the Hamilton depression scale (HAMD); (5) patients were women of childbearing age with amenorrhea or menstrual disorder with a duration ≥6 months. Patients were excluded if they exhibited gastrointestinal bleeding, short bowel syndrome, radiation-induced intestinal injury, intestinal obstruction or inflammatory bowel disease, recurrent/metastatic tumors, systemic infectious diseases, life-threatening systemic comorbidities, intorlerate to nasojejunal, percutaneous gastrostomy / jejunostomy or FMT. The clinical data of 43 patients at Shanghai Tenth People's Hospital exhibiting the "Tetralogy of Tongji" and who received microflora transplantation combined with nutritional support and psychotherapy from June 2017 to June 2021 was prospectively collected. There were 12 males and 31 females with a mean age of 35.2±16.7 years. All 43 patients had chronic gastrointestinal dysfunction. Of these, 24 patients had depression and 19 had anxiety. There were 26 women of reproductive age, including 13 cases of menstrual disorder and 9 cases of amenorrhea. The treatment intervention was a combination of FMT (microflora solution or microflora capsule), nutritional support (enteral nutrition) and psychological intervention. The following were assessed before treatment and 1, 3, 6 months after treatment: (1) gastrointestinal function was assessed using the gastrointestinal symptoms rating scale (GSRS), where a higher score is indicative of more serious gastrointestinal symptoms, and the gastrointestinal quality of life index (GIQLI), where a higher score is indicative of higher quality of life; (2) psychological status was assessed using HAMA and HAMD scores, where a lower score is indicative of reduced severity of anxiety or depression symptoms, respectively; (3) nutritional status was assessed by measurements of total blood protein, albumin, fibrinogen and prealbumin, as well as measurements of body mass and body mass index (BMI); (4) neuroendocrine function was assessed by measurement of blood levels of cortisol, dopamine and noradrenaline, as well as menstruation in women of reproductive age. Results: The follow-up rates at 1, 3 and 6 months after treatment were 90.7% (39/43), 72.1% (31/43) and 55.8% (24/43), respectively. The total effective rate for chronic gastrointestinal dysfunction was 81.4% (35/43), of which the average GSRS score decreased from 29.35±3.56 before treatment to 18.25±2.56 in the sixth month (P<0.001). The average GIQLI score increased from 56.23±10.34 before treatment to 91.04±20.39 in the sixth month (P<0.001). All patients had malnutrition before treatment. After 6 months, their body weight had increased from 40.61±8.88 kg to 50.45±6.23 kg (P<0.001), and BMI had increased from 15.17±1.87 kg/m2 to 19.58±1.42 kg/m2 (P<0.001). The average total protein level was 60.99± 5.99 g/L before treatment. After 6 months, this had increased to 64.21±4.23 g/L (F=2.715, P=0.022). The average prealbumin level increased from 150.14±56.04 mg/L before treatment to 258.17±86.94 mg/L after 6 months (F=15.124, P<0.001). In this study, 24 patients with depression/depressed state were included. After treatment, the average HAMD score in these patients decreased from 22.79±6.63 before treatment to 9.92±7.24 after 6 months (P<0.001). There were 19 patients with anxiety disorder/anxiety state. After treatment, the average HAMA score in these patients decreased from 17.15±4.34 before treatment to 7.73±4.10 after 6 months (P<0.001). Observing the endocrine efficacy of 26 women of childbearing age, it was found that the effective rate of this treatment on endocrine regulation was 69.2% (18/26). Although there was no significant change in blood cortisol levels after 6 months, average blood dopamine levels decreased from 32.91±10.65 nmol/L before treatment to 13.02±5.58 nmol/L after 6 months (P<0.001). Average blood norepinephrine levels decreased from 49.75±15.23 ng/L before treatment to 19.21±9.58 ng/L after 6 months (P<0.001). Conclusion: The strategy of FMT combined with nutritional support and psychological intervention is effective in improving the symptoms of the "Tetralogy of Tongji".}, }
@article {pmid36117367, year = {2022}, author = {Chen, QY and Lu, JB and Qin, HL and Li, N}, title = {[Clinical significance and intervention strategy of gastrointestinal psychiatry].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {771-776}, doi = {10.3760/cma.j.cn441530-20220601-00236}, pmid = {36117367}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; SHDC2020CR4026//Clinical Research Plan of SHDC/ ; 21Y11908300//Shanghai Action Plan on Science, Technology and Innovation/ ; }, mesh = {*Gastrointestinal Diseases/drug therapy ; Humans ; *Mental Disorders/therapy ; Prebiotics ; *Probiotics ; *Psychiatry ; }, abstract = {With the development of global economy and society,the number of patients who suffer from functional gastrointestinal disorders (FGID) and mental illness is growing. In recent years, a substantial amount of high-quality research evidence shows that these two kinds of diseases often coexist, and they are mutually causal, and their common pathophysiology is the abnormal interaction of "bacteria-gut-brain axis". In clinical practice, there are some problems, such as insufficient recognition and attention of both doctors and patients to its clinical manifestations, lack of understanding of pathophysiological mechanism, and lack of overall and integrated views of intervention methods, which may be the main factors of poor curative effect at present. Therefore, according to the global research progress and the author's clinical experience, we put forward a new viewpoint of "gastrointestinal psychiatry", it concluded that clinical intervention strategies needed to include dietary and lifestyle changes as well as multidisciplinary interventions such as probiotics, prebiotic, fecal microbiota transplantation and cognitive psychology. On the basis of gastrointestinal psychiatry, this paper systematically elaborated the diagnosis and treatment of this kind of diseases.}, }
@article {pmid36117366, year = {2022}, author = {Qin, HL and Chen, QY and Li, N}, title = {[Further improve the standardization construction and development level of fecal microbiota transplantation (FMT) in China].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {766-770}, doi = {10.3760/cma.j.cn441530-20220601-00237}, pmid = {36117366}, issn = {1671-0274}, support = {81972221//National Natural Science Foundation of China/ ; SHDC2020CR1030B//Clinical Research Plan of SHDC/ ; }, mesh = {Capsules ; China ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Reference Standards ; }, abstract = {In the past ten years, the clinical application of fecal microbiota transplantation (FMT) in the treatment of intestinal and extraintestinal diseases has attracted much attention. In China, there are more than 300 hospitals that have developed FMT, but the development of FMT is still in its early stage. The clinical practice of FMT needs to form a standardized system, including management of donors and acceptors, preparation of capsules containing certain gut bacteria, evaluation of effectiveness, and study of fecal microbiota and disease. In order to promote the establishment of the standard system of FMT and the healthy development of FMT, this paper expounds the establishment of the standardization of domestic flora transplantation according to the relevant literature, as well as the experience of 10000 cases and 95300 times of FMT in our center.}, }
@article {pmid36117365, year = {2022}, author = {,  and , }, title = {[Chinese expert consensus on screening and management of fecal microbiota transplantation donors (2022 edition)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {757-765}, doi = {10.3760/cma.j.cn441530-20220606-00246}, pmid = {36117365}, issn = {1671-0274}, support = {81972221, 82100698//National Natural Science Foundation/ ; SHDC2020CR1030B//Major Clinical Research Projects of the Three-year Action Plan for Clinical Innovation of Shanghai Shenkang Hospital Development Center/ ; }, mesh = {China ; Consensus ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) has been recommended by clinical practical guidelines and consensus for the treatment of a variety of intestinal diseases, but in more and more medical institutions trying to develop this technology in clinical practice, how to screen and manage donors has become an urgent need for regulation. In view of this, based on evidence-based medical evidence, Society of Parenteral and Enteral Nutrition of Chinese Medical Association and Microecology Professional Committee of Shanghai Preventive Medicine Association jointly formulate an expert consensus on the screening and management of donors, including screening on the internet and in clinic, evaluation and selection during donation, establishment of the standard of donor management, the follow-up system and the professional support system, with a view to improving the quality of microbiota transplantation donors, reducing adverse events, and promoting the standardized clinical application of FMT.}, }
@article {pmid36117364, year = {2022}, author = {,  and ,  and , }, title = {[Expert consensus on clinical application management of fecal microbiota transplantation (2022 edition)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {747-756}, doi = {10.3760/cma.j.cn441530-20220725-00324}, pmid = {36117364}, issn = {1671-0274}, mesh = {Consensus ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Intestinal Diseases ; }, abstract = {Fecal microbiota transplantation (FMT) is to transplant the functional intestinal bacteria from human feces into the intestinal tract of patients, reconstruct the new intestinal flora and treat intestinal and extra-intestinal diseases. During the past 10 years, FMT has made a breakthrough in the treatment of intestinal and extra-intestinal diseases, and provided a brand-new strategy to the treatment of intestinal and extra-intestinal diseases. In view of the fact that FMT lacks a unified clinical management standard at home and abroad, relevant regulations and policies still need to be improved, and clinical application experience still needs to be accumulated, the National Institute of Hospital Administration, National Health Commission commissioned a clinical FMT expert working group to organize experts in related fields. Based on thorough analysis of relevant literature, policies and norms internationally, as well as the mature experience of FMT in many medical institutions in China, an expert consensus for clinical management of FMT in medical institutions is compiled to further strengthen its clinical application and standard management, so as to improve the safety and efficacy of FMT.}, }
@article {pmid36116455, year = {2022}, author = {Ianiro, G and Mullish, BH and Iqbal, TH and Terveer, EM and Baunwall, SMD and Link, A and Sokol, H and Kupcinskas, J and Masucci, L and Sanguinetti, M and Vehreschild, MJGT and Hvas, CL and Keller, JJ and Gasbarrini, A and Kujiper, EJ and Cammarota, G}, title = {Minimising the risk of monkeypox virus transmission during faecal microbiota transplantation: recommendations from a European expert panel.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2468-1253(22)00305-3}, pmid = {36116455}, issn = {2468-1253}, }
@article {pmid36114204, year = {2022}, author = {Pu, Y and Zhang, Q and Tang, Z and Lu, C and Wu, L and Zhong, Y and Chen, Y and Hashimoto, K and Luo, Y and Liu, Y}, title = {Correction: Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation.}, journal = {Translational psychiatry}, volume = {12}, number = {1}, pages = {387}, doi = {10.1038/s41398-022-02168-6}, pmid = {36114204}, issn = {2158-3188}, }
@article {pmid36110348, year = {2022}, author = {Abdelghafar, YA and AbdelQadir, YH and Motawea, KR and Nasr, SA and Omran, HAM and Belal, MM and Elhashash, MM and AbdelAzim, AA and Shah, J}, title = {Efficacy and safety of fecal microbiota transplant in irritable bowel syndrome: An update based on meta-analysis of randomized control trials.}, journal = {Health science reports}, volume = {5}, number = {5}, pages = {e814}, pmid = {36110348}, issn = {2398-8835}, abstract = {Background and Aims: Fecal microbiota transfer (FMT) is a potential treatment for irritable bowel syndrome (IBS). Several randomized trials have tested FMT effects using different routes of administration, doses, and sample sizes. We aim to assess the overall efficacy of FMT for IBS patients and the safety of the intervention.<br><br>Methods: We systematically searched four databases for randomized control trials that studied the efficacy and safety of FMT in IBS patients.<br><br>Results: We included 8 randomized trials (472 patients) that compared FMT with placebo in IBS patients. Pooled results showed no statistically significant difference between FMT and control groups in the overall change in IBS symptom severity (IBS-SSS) at 1 month (p = 0.94), 3/4 months (p = 0.82), and at the end of trials (p = 0.67). No significant difference in the total number of respondents between the FMT and control groups (risk ratios = 1.84, [95% confidence interval (CI) = 0.82-2.65], p = 0.19). Although the oral route of administration showed a significant difference in the number of respondents (p = 0.004), there was no statistically significant difference in the IBS-SSS when subgrouping the oral route of administration (mean difference = 47.57, [95% CI = -8.74-103.87], p = 0.10).<br><br>Conclusion: FMT is not an effective treatment to relieve all the symptoms of IBS. Even in the groups that showed relatively significant improvement after FMT, the effect was proven to wear off over time and the re-administration carries a low success rate. Future research should consider different bacterial-based interventions such as probiotics or specific antibiotics.}, }
@article {pmid36109637, year = {2022}, author = {Ianiro, G and Punčochář, M and Karcher, N and Porcari, S and Armanini, F and Asnicar, F and Beghini, F and Blanco-Míguez, A and Cumbo, F and Manghi, P and Pinto, F and Masucci, L and Quaranta, G and De Giorgi, S and Sciumè, GD and Bibbò, S and Del Chierico, F and Putignani, L and Sanguinetti, M and Gasbarrini, A and Valles-Colomer, M and Cammarota, G and Segata, N}, title = {Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {36109637}, issn = {1546-170X}, support = {716575//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 1U01CA230551//U.S. Department of Health &amp; Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics)/ ; 825410//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Excellent Science (H2020 Priority Excellent Science)/ ; 593-2020//European Molecular Biology Organization (EMBO)/ ; }, abstract = {Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficile infection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT (P = 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols.}, }
@article {pmid36109636, year = {2022}, author = {Schmidt, TSB and Li, SS and Maistrenko, OM and Akanni, W and Coelho, LP and Dolai, S and Fullam, A and Glazek, AM and Hercog, R and Herrema, H and Jung, F and Kandels, S and Orakov, A and Thielemann, R and von Stetten, M and Van Rossum, T and Benes, V and Borody, TJ and de Vos, WM and Ponsioen, CY and Nieuwdorp, M and Bork, P}, title = {Drivers and determinants of strain dynamics following fecal microbiota transplantation.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {36109636}, issn = {1546-170X}, support = {ERC-AdG-669830//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; ERC-AdG-669830//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 686070//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; ERC-AdG-669830//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; ERC-AdG-669830//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 686070//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; ERC-AdG-669830//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; ERC-AdG-669830//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; ALTF 137-2018//European Molecular Biology Organization (EMBO)/ ; APP1166180//Department of Health | National Health and Medical Research Council (NHMRC)/ ; LAMarCK: 031L0181A//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; 024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; 09150182010020//ZonMw (Netherlands Organisation for Health Research and Development)/ ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor-recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.}, }
@article {pmid36107983, year = {2022}, author = {Koo, H and Morrow, CD}, title = {Time series strain tracking analysis post fecal transplantation identifies individual specific patterns of fecal dominant donor, recipient, and unrelated microbial strains.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0274633}, pmid = {36107983}, issn = {1932-6203}, mesh = {*Anti-Bacterial Agents ; *Fecal Microbiota Transplantation ; Feces ; Nucleotides ; Time Factors ; }, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) has been used with the therapeutic intent to change the functions of the gut microbial community in metabolism and host immunity. For most of these therapies, the recipients are not given antibiotics to eliminate the microbial community prior to transplant with donor fecal microbes resulting in the initial gut microbial community following FMT consisting of a consortium of donor and recipient microbes. The detailed analysis of the fecal samples from these FMT over time provides a unique opportunity to study the changes in the gut microbial strain community that occurs following the introduction of new microbial strains (donor) into an established community (recipient).<br><br>METHODS: In this study, we have metagenomic data set consisting of 5 FMT that contained donor, recipient and recipient post FMT taken multiple times for periods up to 535 days after the FMT. We used two established strain tracking methods, Window-based Single Nucleotide Variant (SNV) Similarity (WSS) and StrainPhlAn, to determine the presence of donor and recipient microbial strains following FMT. To assess recombination between donor and recipient strains of Bacteroides vulgatus post FMT, we used BLAST+ to analyze the data sets for Bacteroidales-specific antimicrobial proteins (BSAP-3) that have known functions to restrict species specific replication.<br><br>RESULTS: We found that Alistipes onderdonkii, Alistipes shahii, Alistipes putredinis, and Parabacteroides merdae, all had patterns post FMT consisting of either dominant donor or recipient microbial strains in the feces. In contrast, the analysis of Bacteroides spp. in five FMT pairs revealed inter-individual oscillation over time with the appearance of either donor or recipient fecal strain dominance. In some instances, B. vulgatus and B. uniformis were also identified after FMT that were not related to either the donor or recipient. Finally, in one of the FMT, we identified a distinct B. vulgatus strain post-FMT that matched the pre-FMT strain but was BSAP-3 positive, suggesting a possible recombination event between the donor and recipient strains.<br><br>CONCLUSION: The complex oscillating patterns of the appearance of fecal dominant donor, recipient or unrelated strains following extended times post FMT provide new insights into the dynamics of the microbial community interactions with the recipients following FMT. The result from our analysis has implications for the use of FMT to predictably change the biological functions of the gut community in metabolism and host immunity.}, }
@article {pmid36106327, year = {2022}, author = {Shi, D and Turroni, S and Gong, L and Wu, W and Yim, HCH}, title = {Editorial: Manipulation of gut microbiota as a key target to intervene on the onset and progression of digestive system diseases.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {999005}, pmid = {36106327}, issn = {2296-858X}, }
@article {pmid36105887, year = {2022}, author = {Deluce, J and Maleki Vareki, S and Fernandes, R}, title = {The role of gut microbiome in immune modulation in metastatic renal cell carcinoma.}, journal = {Therapeutic advances in medical oncology}, volume = {14}, number = {}, pages = {17588359221122714}, pmid = {36105887}, issn = {1758-8340}, abstract = {Treatment of metastatic renal cell carcinomas (mRCC) has drastically improved since the advent of immunotherapy with immune checkpoint inhibitors (ICIs), with a significant proportion of patients achieving durable responses. While this has revolutionized treatment and improved outcomes for mRCC patients, a large subset of patients still does not respond to treatment with ICIs. Moreover, ICIs can induce various immune-related adverse events, limiting their use in many patients. Therefore, there is a need to identify the predictive biomarkers of both efficacy and toxicity associated with ICIs, which would allow for a more personalized approach and help with clinical decision-making. This review aims to explore the role of the gut microbiome in RCC to overcome primary resistance and predict response to treatment with ICIs. First, current therapeutic strategies and mechanisms of action of ICI therapies for RCC treatment will be reviewed. With the technological development of shotgun whole-genome sequencing, the gut microbiome has emerged as an exciting field of research within oncology. Thus, the role of the microbiome and its bidirectional interaction with ICIs and other drugs will be explored, with a particular focus on the microbiome profile in RCC. Lastly, the rationale for future clinical interventions to overcome resistance to ICIs using fecal microbiota transplantation in patients with RCC will be presented.}, }
@article {pmid36103991, year = {2022}, author = {Wang, Y and Zhang, S and Borody, TJ and Zhang, F}, title = {Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {36103991}, issn = {2542-5641}, abstract = {ABSTRACT: Fecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT in global. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota-gut-liver axis, microbiota-gut-brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.}, }
@article {pmid36103760, year = {2022}, author = {Hu, C and Li, J and Liu, M and Lam, PKS and Chen, L}, title = {Young fecal transplantation modulates the visual toxicity of perfluorobutanesulfonate in aged zebrafish recipients.}, journal = {Aquatic toxicology (Amsterdam, Netherlands)}, volume = {251}, number = {}, pages = {106295}, doi = {10.1016/j.aquatox.2022.106295}, pmid = {36103760}, issn = {1879-1514}, abstract = {Perfluorobutanesulfonate (PFBS) is an emerging pollutant of potent toxicity to impair visual system. Previous studies highlighted the applicability of gut microbiota manipulation to mitigate the toxicities of PFBS. However, it remains unknown whether transplantation of whole fecal microbiota to PFBS-disturbed gut can restore the health of the recipient animals, especially for aged fish that are of high susceptibility. In the present study, aged zebrafish of 3 years old were first transplanted with feces from young counterparts and then exposed to environmentally relevant concentrations of PFBS. After exposure, toxic effects of PFBS on visual system of aged zebrafish were elucidated based on transcriptional, proteomic, biochemical, histological, and behavioral evidences. In addition, interaction between young fecal transplant and innate visual toxicity of PFBS was further explored in the aged. The results showed that PFBS singular exposure induced lipid peroxidation (by 1.9-fold) in aged male eyes, which were alleviated by young fecal transplantation. PFBS also disturbed the retinal structure of the aged, which was characterized by increases in plexiform layers, but decreases in ganglion neuron number (by 26.8% and 26.0% in males and females, respectively) and optic nerve width (by 14.1% and 12.7% in males and females, respectively). It was unexpected that young fecal transplant was very potent in re-organizing the histological assembly of aged eyes regardless of PFBS coexposure, underlining the intimate interplay between gut and retina. Proteomic profiling provided more clues about the visual toxicology mechanism of PFBS, which was found to typically interfere with synaptic neurotransmission occurring in plexiform layers. However, proteome perturbation of aged eyes by PFBS exposure was effectively shifted by the transplantation of young feces towards the control phenotype, suggesting the high ameliorative potential of young fecal transplantation along the gut-retina axis. Overall, the present study pinpoints the potent visual toxicity of PFBS in aged animals and highlights the efficacy of young fecal transplant to regulate the inherent toxicity of PFBS. Future studies are necessitated to sequence the gut microbiota and unveil the underlying interactive routes between gut microbes and visual system.}, }
@article {pmid36100953, year = {2022}, author = {Bai, X and Sun, Y and Li, Y and Li, M and Cao, Z and Huang, Z and Zhang, F and Yan, P and Wang, L and Luo, J and Wu, J and Fan, D and Chen, H and Zhi, M and Lan, P and Zeng, Z and Wu, X and Miao, Y and Zuo, T}, title = {Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {147}, pmid = {36100953}, issn = {2049-2618}, support = {82060107//National Natural Science Foundation of China/ ; U1802282//National Natural Science Foundation of China/ ; 82172323//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Archaea ; Bacteria/genetics ; Diet ; Ethnicity ; *Gastrointestinal Microbiome/genetics ; Geography ; Humans ; *Urbanization ; }, abstract = {BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis.<br><br>METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations.<br><br>RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the α-diversity (intrinsic microbial diversity) and the β-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization.<br><br>CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract.}, }
@article {pmid36100450, year = {2022}, author = {Pipek, B and Valentová, H and Fojtík, P and Urban, O}, title = {Faecal microbiota transplantation in the treatment of recurrent intestinal Clostridioides difficile infection - a ten-year single-center experience.}, journal = {Casopis lekaru ceskych}, volume = {161}, number = {3-4}, pages = {126-130}, pmid = {36100450}, issn = {0008-7335}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Clostridium Infections/etiology/microbiology ; Ecosystem ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Humans ; Male ; Prospective Studies ; Recurrence ; Young Adult ; }, abstract = {Clostridioides difficile (Clostridium difficile in older taxonomy) is a gram-positive anaerobic and bacteria enabled by endospores. Clostridioides difficile is currently the main cause of nosocomial infections in developed countries. Due to the high probability of developing bacterial resistance to treatment and the numerous recurrences in multiple chronic conditions in older adults of our society it causes a widespread medical problem. Faecal microbiota transplantation (FMT) is a highly effective method for treating recurrent intestinal Clostridioides difficile infections (CDI). With this method the potential mechanism of effect is the transmission of a complex intestinal ecosystem, including vital microorganisms, from the donor to the recipient. Presenting the results of monocentric prospective monitoring: Primary aim of the study was to evaluate long-term remission (the continued absence of clinical manifestations of CDI 3 months after FMT administration). The secondary aim of the study was to monitor the short-term remission in the 7 days after FMT administration. Demographic data, information about CDI and the details of therapy were obtained and completed by the treating physician of each patient or by targeted questioning of the patient or their family. We used clinical monitoring to determine the effect of the treatment. The examinations of stool donors and the preparation for a faecal microbiota transplantation were performed according to the currently valid guidelines of the Czech Society of Infectious Diseases for the treatment of the recurrent bacterial infection Clostridioides difficile with faecal microbiota transplantation. The follow-ups took place from February 2011 to July 2021 in the gastroenterology department at the AGEL Ostrava-Vítkovice Hospital and included 116 patients with their first and subsequent recurrence of CDI that were treated with faecal bacteriotherapy. The median age of our patients was 71 years old (the youngest was 19 years old, the oldest 103 years old). 69 women and 47 men took part in the study. 56 patients had their first recurrence of CDI, 41 had a second attack, and 20 patients had a third and subsequent recurrences. In 62 patients (53.4 %), the route of FMT administration was a local enema into the left colon. With 37 patients (31.9 %) we used a colonoscopy after standard anterograde bowel preparation. With 12 patients (10.3 %) gastroscopy administration (deep into the duodenum) was used. 4 patients (3.5 %) were given a nasoenteral tube and one patient (0.9 %) was administered FMT per percutaneous endoscopic gastrostomy (PEG). We applied a frozen universal donor FMT in 81 patients (69.8 %), and a freshly prepared FMT from a person living in the same household was used in 35 patients (30.1 %). The secondary endpoint (the absence of clinical manifestations of CDI within 7 days of FMT administration) was achieved with 102 patients (87.9 %) in our study. The fulfilment of the primary endpoint (the development of long-term remission) was observed with 93 patients (80.2 %). An early administration of FMT appears to be a significant predictor of treatment effect (p = 0.05; OR 5.11; 95% CI 1.65-15.8). Faecal microbiota transplantation is an effective and safe therapy for recurrent intestinal Clostridioides difficile infection, and it respects the up-to-date guidelines for treatment. Of the 116 patients included in our study with first and subsequent CDI, we achieved long-term remission in 80.2 % of them. An early administration of FMT appears to be a significant predictor of treatment effect.}, }
@article {pmid35655344, year = {2022}, author = {Zhang, ZJ and Lehmann, CJ and Cole, CG and Pamer, EG}, title = {Translating Microbiome Research From and To the Clinic.}, journal = {Annual review of microbiology}, volume = {76}, number = {}, pages = {435-460}, doi = {10.1146/annurev-micro-041020-022206}, pmid = {35655344}, issn = {1545-3251}, mesh = {*Disease ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Probiotics/therapeutic use ; *Therapeutics/trends ; }, abstract = {Extensive research has elucidated the influence of the gut microbiota on human health and disease susceptibility and resistance. We review recent clinical and laboratory-based experimental studies associating the gut microbiota with certain human diseases. We also highlight ongoing translational advances that manipulate the gut microbiota to treat human diseases and discuss opportunities and challenges in translating microbiome research from and to the bedside.}, }
@article {pmid36099923, year = {2022}, author = {Spindler, MP and Siu, SS and Mogno, I and Li, Z and Yang, C and Mehandru, S and Britton, GJ and Faith, JJ}, title = {Human gut microbiota stimulate defined innate immune responses that vary from phylum to strain.}, journal = {Cell host &amp; microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2022.08.009}, pmid = {36099923}, issn = {1934-6069}, abstract = {The potential of commensal bacteria to modulate host immunity remains largely uncharacterized, largely due to the vast number of strains that comprise the human gut microbiota. We have developed a screening platform to measure the innate immune responses of myeloid cells to 277 bacterial strains isolated from the gut microbiota of healthy individuals and those with inflammatory bowel diseases. The innate immune responses to gut-derived bacteria are as strong as those toward pathogenic bacteria, and they vary from phylum to strain. Myeloid cells differentially rely upon innate receptors TLR2 or TLR4 to sense taxa, with differential sensing of Bacteroidetes and Proteobacteria that predict in vivo functions. These innate immune responses can be modeled using combinations of up to 8 Toll-like receptor (TLR) agonists. Furthermore, the immunogenicity of strains is stable over time and following fecal microbiota transplantation into new human recipients. Collectively, this high-throughput approach provides an insight into how commensal microorganisms shape innate immune phenotypes.}, }
@article {pmid36094098, year = {2022}, author = {Vasiliu, O}, title = {Is fecal microbiota transplantation a useful therapeutic intervention for psychiatric disorders? A narrative review of clinical and preclinical evidence.}, journal = {Current medical research and opinion}, volume = {}, number = {}, pages = {1-32}, doi = {10.1080/03007995.2022.2124071}, pmid = {36094098}, issn = {1473-4877}, abstract = {The therapeutic management of psychiatric disorders is currently confronted with a critical need to find new therapeutic interventions due to the high rates of non-responsivity or low responsivity in the key pathologies, e.g., schizophrenia spectrum disorders, alcohol use disorders, or major depressive disorder. The modulation of intestinal microbiota has been explored in various organic and psychiatric dysfunctions, with different degrees of success. However, this type of intervention may represent a helpful add-on at a conceptual level since it does not associate negative pharmacokinetics interactions, significant adverse events, or risk for non-adherence in the long term. Oral administration of pre-, pro-, or synbiotics, and especially the treatment with fecal microbiota transplantation (FMT), are methods still in their early research phase for patients with psychiatric disorders, therefore an exploration of data regarding the potential benefits and adverse events of FMT was considered necessary. In order to accomplish this purpose, the available results of research dedicated to each category of psychiatric disorders, starting with depressive and anxiety disorders, continuing with schizophrenia, substance use disorders, and finishing with disorders diagnosed during childhood, were presented in this paper. Seven clinical trials, 16 preclinical studies, three meta-analyses/systematic reviews, and six case reports, all of these representing ten distinct categories of psychiatric disorders or manifestations, have been reviewed. Mood disorders, anxiety disorders, and alcohol dependence have been the most extensively investigated clinical entities from the FMT efficacy and tolerability perspective, and reviewed data are generally promising. Based on the current status of research, FMT may be considered a helpful intervention in specific psychiatric pathologies. Still, this review showed that most of the information is derived from entirely preclinical studies. Therefore, clinical trials with sound methodology and more participants are needed to clarify FMT's benefits and risks in psychiatric disorders.}, }
@article {pmid36093611, year = {2022}, author = {Korpela, K and de Vos, WM}, title = {Infant gut microbiota restoration: state of the art.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2118811}, doi = {10.1080/19490976.2022.2118811}, pmid = {36093611}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents ; Cesarean Section ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Pregnancy ; }, abstract = {The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. Recent years have witnessed an accumulation of understanding of the process of the colonization and development of the gut microbiota in infants. The natural gut microbiota colonization during birth is frequently disrupted due to C-section birth or intrapartum or postpartum antibiotic exposure, and consequently aberrant gut microbiota development is common. On a positive note, research has shown that restoration of normal gut microbiota development is feasible. We discuss here the current understanding of the infant microbiota, provide an overview of the sources of disturbances, and critically evaluate the evidence on early life gut microbiota restoration for improved health outcomes by analyzing published data from infant gut microbiota restoration studies.}, }
@article {pmid36093568, year = {2022}, author = {Li, Z and Zhang, Y and Hong, W and Wang, B and Chen, Y and Yang, P and Zhou, J and Fan, J and Zeng, Z and Du, S}, title = {Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2119055}, doi = {10.1080/19490976.2022.2119055}, pmid = {36093568}, issn = {1949-0984}, mesh = {Animals ; *Carcinoma, Hepatocellular/radiotherapy ; Dysbiosis/therapy ; *Gastrointestinal Microbiome ; Immunity ; *Liver Neoplasms/radiotherapy ; Mice ; Nucleotidyltransferases/metabolism ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Studies of the gut-liver axis have enhanced our understanding of the pathophysiology of various liver diseases and the mechanisms underlying the regulation of the effectiveness of therapies. Radiotherapy (RT) is an important therapeutic option for patients with unresectable hepatocellular carcinoma (HCC). However, the role of the microbiome in regulating the response to RT remains unclear. The present study characterizes the gut microbiome of patients responsive or non-responsive to RT and investigates the molecular mechanisms underlying the differences in patient response. We collected fecal samples for 16S rRNA sequencing from a prospective longitudinal trial of 24 HCC patients receiving RT. We used fecal microbiota transplantation (FMT), flow cytometry, and transcriptome sequencing to explore the effects of dysbiosis on RT. We also examined the role of stimulator of interferon genes (STING) in RT-associated antitumor immune responses mediated by gut microbiota in STING- (Tmem173-/-) and cGAS-knockout (Mb21d1-/-) mouse models. We propose that primary resistance to RT could be attributed to the disruption of the gut microbiome. Mechanistically, gut microbiome dysbiosis impairs antitumor immune responses by suppressing antigen presentation and inhibiting effector T cell functions through the cGAS-STING-IFN-I pathway. Cyclic-di-AMP - an emerging second messenger of bacteria - may act as a STING agonist and is thus a potential target for the prediction and modulation of responses to RT in HCC patients. Our study highlights the therapeutic potential of modulating the gut microbiome in HCC patients receiving RT and provides a new strategy for the radiosensitization of liver cancer.}, }
@article {pmid36091491, year = {2022}, author = {Zhang, F and Zuo, T and Wan, Y and Xu, Z and Cheung, C and Li, AY and Zhu, W and Tang, W and Chan, PKS and Chan, FKL and Ng, SC}, title = {Multi-omic analyses identify mucosa bacteria and fecal metabolites associated with weight loss after fecal microbiota transplantation.}, journal = {Innovation (Cambridge (Mass.))}, volume = {3}, number = {5}, pages = {100304}, pmid = {36091491}, issn = {2666-6758}, abstract = {Fecal microbiota transplantation (FMT) has shown promising results in animal models of obesity, while results in human studies are inconsistent. We aimed to determine factors associated with weight loss after FMT in nine obese subjects using serial multi-omics analysis of the fecal and mucosal microbiome. The mucosal microbiome, fecal microbiome, and fecal metabolome showed individual clustering in each subject after FMT. The colonic microbiome in patients showed more marked variance after FMT compared with the duodenal microbiome, characterized by an increased relative abundance of Bacteroides. Subjects who lost weight after FMT sustained enrichment of Bifidobacterium bifidum and Alistipes onderdonkii in the duodenal, colonic mucosal, and fecal microbiome and increased levels of phosphopantothenate biosynthesis and fecal metabolite eicosapentaenoic acid (EPA), compared with those without weight loss. Fecal levels of amino acid metabolism-associated were positively correlated with the fecal abundance of B. bifidum, and fatty acid metabolism-associated metabolites showed positive correlations with A. onderdonkii. We report for the first time the individualized response of fecal and mucosa microbiome to FMT in obese subjects and highlight that FMT is less capable of shaping the small intestine microbiota. These findings contribute to personalized microbe-based therapies for obesity.}, }
@article {pmid36088469, year = {2022}, author = {Ju, Z and Guo, P and Xiang, J and Lei, R and Ren, G and Zhou, M and Yang, X and Zhou, P and Huang, R}, title = {Low-dose radiation exaggerates HFD-induced metabolic dysfunction by gut microbiota through PA-PYCR1 axis.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {945}, pmid = {36088469}, issn = {2399-3642}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; *Insulin Resistance ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-akt ; }, abstract = {Co-exposure of High-fat-diet (HFD) behavior and environmental low-dose radiation (LDR) is common among majority occupational workers, but the synergism of this co-exposure in metabolic health is poorly understood. This study aimed to investigate the impact of gut microbiota and its metabolites on the regulation of HFD accompanied by LDR-associated with metabolic dysfunction and insulin resistance. Here, we reported that Parasutterella was markedly elevated in the gut microbiota of mice in co-exposure of HFD and LDR, accompanied by increased pyrrolidinecarboxylic acid (PA) level in both intestine and plasma. Transplantation of fecal microbiota from mice with co-exposure HFD and LDR with metabolic dysfunction resulted in increased disruption of metabolic dysfunction, insulin resistance and increased PYCR1 (Pyrroline-5-carboxylate reductase 1) expression. Mechanistically, intestinal barrier was damaged more serious in mice with co-exposure of HFD and LDR, leading high PA level in plasma, activating PYCR1 expression to inhibit insulin Akt/mTOR (AKT kinase-transforming protein/Serine threonine-protein kinase) signaling pathway to aggravate HFD-induced metabolic impairments. This study suggests a new avenue for interventions against western diet companied with low dose radiation exposure-driven metabolic impairments.}, }
@article {pmid35921199, year = {2022}, author = {Juárez-Fernández, M and Goikoetxea-Usandizaga, N and Porras, D and García-Mediavilla, MV and Bravo, M and Serrano-Maciá, M and Simón, J and Delgado, TC and Lachiondo-Ortega, S and Martínez-Flórez, S and Lorenzo, Ó and Rincón, M and Varela-Rey, M and Abecia, L and Rodríguez, H and Anguita, J and Nistal, E and Martínez-Chantar, ML and Sánchez-Campos, S}, title = {Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.32705}, pmid = {35921199}, issn = {1527-3350}, support = {//Asociación Española contra el Cáncer/ ; RY2013-13666//Ayudas Ramón y Cajal de la Agencia Estatal de Investigación/ ; //BIOEF (Basque Foundation for Innovation and Health Research)/ ; //Departamento de Industria del Gobierno Vasco/ ; //Fundación Científica de la Asociación Española Contra el Cancer (AECC Scientific Foundation) Rare Tumor Calls 2017/ ; DTS20/00138//Instituto de Salud Carlos III, Proyectos de Investigación en Salud/ ; GRS2126/A/2020//Junta de Castilla y León (FEDER)/ ; LE017P20//Junta de Castilla y León (FEDER)/ ; LE063U16//Junta de Castilla y León (FEDER)/ ; //Junta de Castilla y León cofunded by the European Social Fund/ ; //La Caixa Foundation Program/ ; RTC2019-007125-1//Ministerio de Ciencia e Innovación, Programa Retos-Colaboración/ ; FPU18/06257//Ministerio de Ciencia, Innovación y Universidades/ ; PID2020-117116RB-I00//Ministerio de Ciencia, Innovación y Universidades MICINN integrado en el Plan Estatal de Investigación Científica y Técnica y de Innovación, cofinanciado con Fondos FEDER/ ; BFU2017-87960-R//Ministerio de Economía y Competitividad/FEDER/ ; PID2020-120363RB-I0//Ministerio de Economía y Competitividad/FEDER/ ; //Proyecto Desarrollo Tecnologico CIBERehd/ ; }, abstract = {BACKGROUND AND AIMS: Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains unclear. Herein, we hypothesized that enhanced mitochondrial activity might reshape a specific microbiota signature that, when transferred to germ-free (GF) mice, could delay NASH progression.<br><br>APPROACH AND RESULTS: Wild-type and methylation-controlled J protein knockout (MCJ-KO) mice were fed for 6 weeks with either control or a choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD). One mouse of each group acted as a donor of cecal microbiota to GF mice, who also underwent the CDA-HFD model for 3 weeks. Hepatic injury, intestinal barrier, gut microbiome, and the associated fecal metabolome were then studied. Following 6 weeks of CDA-HFD, the absence of methylation-controlled J protein, an inhibitor of mitochondrial complex I activity, reduced hepatic injury and improved gut-liver axis in an aggressive NASH dietary model. This effect was transferred to GF mice through cecal microbiota transplantation. We suggest that the specific microbiota profile of MCJ-KO, characterized by an increase in the fecal relative abundance of Dorea and Oscillospira genera and a reduction in AF12, Allboaculum, and [Ruminococcus], exerted protective actions through enhancing short-chain fatty acids, nicotinamide adenine dinucleotide (NAD+) metabolism, and sirtuin activity, subsequently increasing fatty acid oxidation in GF mice. Importantly, we identified Dorea genus as one of the main modulators of this microbiota-dependent protective phenotype.<br><br>CONCLUSIONS: Overall, we provide evidence for the relevance of mitochondria-microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.}, }
@article {pmid35798626, year = {2022}, author = {Martín Legorburo, MJ and Pareja Sierra, T and Martínez Ramírez, M and Martin Alcalde, E and Torralba, M and Rodríguez Solís, J}, title = {[Fecal transplantation for the treatment of Clostridioides difficile recurrent infection].}, journal = {Revista espanola de geriatria y gerontologia}, volume = {57}, number = {4}, pages = {236-237}, doi = {10.1016/j.regg.2022.06.002}, pmid = {35798626}, issn = {1578-1747}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Reinfection ; Treatment Outcome ; }, }
@article {pmid35217892, year = {2022}, author = {Shaikh, FY and Gills, JJ and Mohammad, F and White, JR and Stevens, CM and Ding, H and Fu, J and Tam, A and Blosser, RL and Domingue, JC and Larman, TC and Chaft, JE and Spicer, JD and Reuss, JE and Naidoo, J and Forde, PM and Ganguly, S and Housseau, F and Pardoll, DM and Sears, CL}, title = {Murine fecal microbiota transfer models selectively colonize human microbes and reveal transcriptional programs associated with response to neoadjuvant checkpoint inhibitors.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {71}, number = {10}, pages = {2405-2420}, pmid = {35217892}, issn = {1432-0851}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; T32 CA009071/CA/NCI NIH HHS/United States ; T32CA009071/NH/NIH HHS/United States ; KL2TR001077/TR/NCATS NIH HHS/United States ; KL2 TR001077/TR/NCATS NIH HHS/United States ; P30 CA006973/NH/NIH HHS/United States ; K08 CA263316/CA/NCI NIH HHS/United States ; T32CA009071/NH/NIH HHS/United States ; P30 CA006973/NH/NIH HHS/United States ; KL2TR001077/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; *Carcinoma, Non-Small-Cell Lung ; Fecal Microbiota Transplantation ; Humans ; *Lung Neoplasms ; Mice ; Neoadjuvant Therapy ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; }, abstract = {Human gut microbial species found to associate with clinical responses to immune checkpoint inhibitors (ICIs) are often tested in mice using fecal microbiota transfer (FMT), wherein tumor responses in recipient mice may recapitulate human responses to ICI treatment. However, many FMT studies have reported only limited methodological description, details of murine cohorts, and statistical methods. To investigate the reproducibility and robustness of gut microbial species that impact ICI responses, we performed human to germ-free mouse FMT using fecal samples from patients with non-small cell lung cancer who had a pathological response or nonresponse after neoadjuvant ICI treatment. R-FMT mice yielded greater anti-tumor responses in combination with anti-PD-L1 treatment compared to NR-FMT, although the magnitude varied depending on mouse cell line, sex, and individual experiment. Detailed investigation of post-FMT mouse microbiota using 16S rRNA amplicon sequencing, with models to classify and correct for biological variables, revealed a shared presence of the most highly abundant taxa between the human inocula and mice, though low abundance human taxa colonized mice more variably after FMT. Multiple Clostridium species also correlated with tumor outcome in individual anti-PD-L1-treated R-FMT mice. RNAseq analysis revealed differential expression of T and NK cell-related pathways in responding tumors, irrespective of FMT source, with enrichment of these cell types confirmed by immunohistochemistry. This study identifies several human gut microbial species that may play a role in clinical responses to ICIs and suggests attention to biological variables is needed to improve reproducibility and limit variability across experimental murine cohorts.}, }
@article {pmid36085529, year = {2022}, author = {Xu, Q and Zhang, S and Quan, J and Wu, Z and Gu, S and Chen, Y and Zheng, B and Lv, L and Li, L}, title = {The evaluation of fecal microbiota transplantation vs vancomycin in a Clostridioides difficile infection model.}, journal = {Applied microbiology and biotechnology}, volume = {}, number = {}, pages = {}, pmid = {36085529}, issn = {1432-0614}, abstract = {Vancomycin is the preferred treatment for Clostridioides difficile infection (CDI) but has been associated with a high recurrence rate of CDI in treated patients. Fecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent CDI (rCDI). Herein, we present a mouse model of CDI to further define the changes in intestinal inflammation, flora, and metabolites following FMT versus vancomycin treatment and to find the potential therapy to restore colonization resistance. Both FMT and vancomycin treatment could ameliorate CDI-induced clinical features and intestinal tissue damage, with decrease in the levels of inflammatory mediators like IL-1β, IL-6, TNF-α, G-CSF, and MCP-1 in the colon and plasma. Observing the fecal gut microbiome profile revealed that unlike vancomycin, FMT could replenish intestinal microbiota by augmenting the relative abundance of the phylum Bacteroidetes and eliminating the abundance of the phylum Proteobacteria. FMT also reduced the levels of several carbohydrates, such as raffinose and fructose-6-phosphate, and amino acids, including tryptophan and glutamyl-valine, in the gut metabolome, thus suppressing C. difficile germination and growth. Our results suggest that the FMT-induced reconstruction of a specific gut community structure and restoration of metabolites promote the recovery of colonization resistance in mice better than vancomycin, thus offering new insights for the prevention of rCDI. KEY POINTS: • Both FMT and vancomycin ameliorate CDI-induced inflammatory response. • FMT restores a specific community structure and gut metabolites. • Mice treated with FMT may promote the recovery of colonization resistance and has a better outcome.}, }
@article {pmid36084869, year = {2022}, author = {Shi, C and Zhou, L and Li, H and Shi, X and Zhang, Y and Lu, Y and Zhu, H and Chen, D}, title = {Intestinal microbiota metabolizing Houttuynia cordata polysaccharides in H1N1 induced pneumonia mice contributed to Th17/Treg rebalance in gut-lung axis.}, journal = {International journal of biological macromolecules}, volume = {221}, number = {}, pages = {288-302}, doi = {10.1016/j.ijbiomac.2022.09.015}, pmid = {36084869}, issn = {1879-0003}, abstract = {Influenza A virus is intricately linked to dysregulation of gut microbiota and host immunity. Previous study revealed that Houttuynia cordata polysaccharides (HCP) exert the therapeutic effect on influenza A virus inducing lung and intestine damage via regulating pulmonary and intestinal mucosal immunity. However, whether this result was due to the regulation of gut microbiota in the gut-lung axis remains unclear. Here, we firstly found that the elimination of gut microbiota using antibiotic cocktails led to both loss of the protective effect of HCP on intestine and lung injury, and reduction of the efficacy on regulating Th17/Treg balance in gut-lung axis. Fecal microbiota transplantation study confirmed that the gut microbiota fermented with HCP under pathological conditions (H1N1 infection) was responsible for reducing pulmonary and intestinal injury. Moreover, the interaction of HCP and gut microbiota under pathological conditions exhibited not only much more abundant gut microbial diversity, but also higher content of the acetate. Our results demonstrated that the underlying mechanism to ameliorate viral pneumonia in mice involving Th17/Treg rebalance via the gut microbiota and HCP metabolite (acetate) metabolized in pneumonia mice. Our results provided a new insight for macromolecular polysaccharides through targeting intestinal microenvironment reducing distant pulmonary infection.}, }
@article {pmid36084774, year = {2022}, author = {Luo, Y and Wang, J and Wang, C and Wang, D and Li, C and Zhang, B and Zhong, X and Chen, L and Li, H and Su, H and Zheng, Q and Zhu, D and Tang, H and Guo, L}, title = {The fecal arsenic excretion, tissue arsenic accumulation, and metabolomics analysis in sub-chronic arsenic-exposed mice after in situ arsenic-induced fecal microbiota transplantation.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {158583}, doi = {10.1016/j.scitotenv.2022.158583}, pmid = {36084774}, issn = {1879-1026}, abstract = {Arsenic can be specifically enriched by rice, and the health hazards caused by high arsenic rice are gradually attracting attention. This study aimed to explore the potential of microbial detoxification via gut microbiome in the treatment of sub-chronic arsenic poisoning. We first exposed mice to high-dose arsenic feed (30 mg/kg, rice arsenic composition) for 60 days to promote arsenic-induced microbes in situ in the gastrointestinal tract, then transplanted their fecal microbiota (FMT) into another batch of healthy recipient mice, and dynamically monitored the microbial colonization by 16S rRNA sequencing and ITS sequencing. The results showed that in situ arsenic-induced fecal microbiome can stably colonized and interact with indigenous microbes in the recipient mice in two weeks, and established a more stable network of gut microbiome. Then, the recipient mice continued to receive high-dose arsenic exposure for 52 days. After above sub-chronic arsenic exposure, compared with the non-FMT group, fecal arsenic excretion, liver and plasma arsenic accumulation were significantly lower (P < 0.05), and that in kidney, hair, and thighbone present no significant differences. Metabolomics of feces- plasma-brain axis were also disturbed, some up-regulated metabolites in feces, plasma, and cerebral cortex may play positive roles for the host. Therefore, microbial detoxification has potential in the treatment of sub-chronic arsenic poisoning. However, gut flora is an extremely complex community with different microorganisms have different arsenic metabolizing abilities, and various microbial metabolites. Coupled with the matrix effects, these factors will have various effects on the efflux and accumulation of arsenic. The definite effects (detoxification or non-detoxification) could be not assured based on the current study, and more systematic and rigorous studies are needed in the future.}, }
@article {pmid36084771, year = {2022}, author = {Kong, B and Fu, H and Xiao, Z and Zhou, Y and Shuai, W and Huang, H}, title = {Gut microbiota dysbiosis induced by a high-fat diet increases susceptibility to atrial fibrillation.}, journal = {The Canadian journal of cardiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cjca.2022.08.231}, pmid = {36084771}, issn = {1916-7075}, abstract = {BACKGROUND: Obesity is a significant risk factor for atrial fibrillation (AF), and the gut microbiota is closely related to obesity-induced diseases. However, whether the gut microbiota is involved in regulating obesity-induced AF has not been studied. This study investigated whether gut microbiota dysbiosis affects obesity-related AF.<br><br>METHODS: Fecal microbes derived from normal diet (ND)-fed and high-fat diet (HD)-fed mice were transplanted into those fed normally. Morphological, biochemical, functional, histological, electrophysiological studies, molecular analysis, 16S rRNA gene amplicon sequencing, and RNA-sequencing were performed.<br><br>RESULTS: Transplantation of the HD gut microbes in ND-maintained (THD) mice led to a significant increase in the susceptibility to AF. Gut microbiota analysis showed a significant increase in Desulfovibrionaceae, which generated metabolic endotoxemia in THD mice. Transplantation with HD microbes also resulted in significantly increased levels of circulating lipopolysaccharide (LPS), significant disruption in the histological architecture of the intestinal tissue, and significantly increased pro-inflammatory cytokines in the left atrium, indicating that atrial inflammation likely contributed to AF susceptibility. RNA-sequencing showed that the THD group had enhanced activation of ferroptosis and TLR4/NF-κB/NLRP3 inflammasome signaling pathway. Inhibiting the ferroptosis or NLRP3 inflammasome signaling pathway significantly improved atrial fibrosis and reduced susceptibility to obesity-related gut dysbiosis-induced AF.<br><br>CONCLUSIONS: This study provides evidence showing an original causal role of gut microbiota dysbiosis in the pathogenesis of obesity-related AF, which showed elevated LPS and dysregulation of atrial pathological remodeling by activating ferroptosis and the TLR4/NF-κB/NLRP3 inflammasome signaling pathway.}, }
@article {pmid36079724, year = {2022}, author = {Zheng, Z and Wang, S and Wu, C and Cao, Y and Gu, Q and Zhu, Y and Zhang, W and Hu, W}, title = {Gut Microbiota Dysbiosis after Traumatic Brain Injury Contributes to Persistent Microglial Activation Associated with Upregulated Lyz2 and Shifted Tryptophan Metabolic Phenotype.}, journal = {Nutrients}, volume = {14}, number = {17}, pages = {}, doi = {10.3390/nu14173467}, pmid = {36079724}, issn = {2072-6643}, support = {OO20200485//Construction Fund of Medical Key Disciplines of Hangzhou/ ; }, mesh = {Animals ; *Brain Injuries, Traumatic/complications ; Dysbiosis/complications ; *Gastrointestinal Microbiome/physiology ; Humans ; Mice ; Mice, Inbred C57BL ; Microglia ; Phenotype ; RNA, Ribosomal, 16S/genetics/metabolism ; Tryptophan/metabolism ; }, abstract = {Traumatic brain injury (TBI) is a common cause of disability and mortality, affecting millions of people every year. The neuroinflammation and immune response post-TBI initially have neuroprotective and reparative effects, but prolonged neuroinflammation leads to secondary injury and increases the risk of chronic neurodegenerative diseases. Persistent microglial activation plays a critical role in chronic neuroinflammation post-TBI. Given the bidirectional communication along the brain-gut axis, it is plausible to suppose that gut microbiota dysbiosis post-TBI influences microglial activation. In the present study, hippocampal microglial activation was observed at 7 days and 28 days post-TBI. However, in TBI mice with a depletion of gut microbiota, microglia were activated at 7 days post-TBI, but not at 28 days post-TBI, indicating that gut microbiota contributes to the long-term activation of microglia post-TBI. In addition, in conventional mice colonized by the gut microbiota of TBI mice using fecal microbiota transplant (FMT), microglial activation was observed at 28 days post-TBI, but not at 7 days post-TBI, supporting the role of gut microbiota dysbiosis in persistent microglial activation post-TBI. The RNA sequencing of the hippocampus identified a microglial activation gene, Lyz2, which kept upregulation post-TBI. This persistent upregulation was inhibited by oral antibiotics and partly induced by FMT. 16s rRNA gene sequencing showed that the composition and function of gut microbiota shifted over time post-TBI with progressive dysbiosis, and untargeted metabolomics profiling revealed that the tryptophan metabolic phenotype was differently reshaped at 7 days and 28 days post-TBI, which may play a role in the persistent upregulation of Lyz2 and the activation of microglia. This study implicates that gut microbiota and Lyz2 are potential targets for the development of novel strategies to address persistent microglial activation and chronic neuroinflammation post-TBI, and further investigations are warranted to elucidate the specific mechanism.}, }
@article {pmid36078124, year = {2022}, author = {Lanthier, N and Delzenne, N}, title = {Targeting the Gut Microbiome to Treat Metabolic Dysfunction-Associated Fatty Liver Disease: Ready for Prime Time?.}, journal = {Cells}, volume = {11}, number = {17}, pages = {}, doi = {10.3390/cells11172718}, pmid = {36078124}, issn = {2073-4409}, abstract = {Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Animal studies have also shown a causal role of gut microbiota in liver metabolic disorders including steatosis whereas the human situation is less clear. Patients with metabolic dysfunction associated fatty liver disease (MAFLD) also have a modification in their gut microbiota composition but the changes are not fully characterized. The absence of consensus on a precise signature is probably due to disease heterogeneity, possible concomitant medications and different selection or evaluation criteria. The most consistent changes were increased relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia species and decreased abundance of Coprococcus and Eubacterium. Possible mechanisms linking the microbiota and MAFLD are increased intestinal permeability with translocation of microbial products into the portal circulation, but also changes in the bile acids and production of microbial metabolites such as ethanol, short chain fatty acids and amino acid derivatives able to modulate liver metabolism and inflammation. Several interventional studies exist that attempt to modulate liver disease by administering antibiotics, probiotics, prebiotics, synbiotics, postbiotics or fecal transplantation. In conclusion, there are both gaps and hopes concerning the interest of gut microbiome evaluation for diagnosis purposes of MAFLD and for new therapeutic developments that are often tested on small size cohorts.}, }
@article {pmid36077084, year = {2022}, author = {Hu, ML and Lian, WS and Wang, FS and Yang, CH and Huang, WT and Yang, JW and Chen, IY and Yang, MY}, title = {Presume Why Probiotics May Not Provide Protection in Inflammatory Bowel Disease through an Azoxymethane and Dextran Sodium Sulfate Murine Model.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, doi = {10.3390/ijms23179689}, pmid = {36077084}, issn = {1422-0067}, support = {CMRPG8K0861, CMRPG8K0862, CMRPG8K0863, CMRPD8H0011, CMRPD8J0011, CMRPD8J0012 and CMRPD8J0013//Chang Gung Memorial Hospital/ ; }, mesh = {Animals ; Azoxymethane/toxicity ; *Colitis/chemically induced/therapy ; *Colitis-Associated Neoplasms ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Dysbiosis/therapy ; *Inflammatory Bowel Diseases/therapy ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; *Probiotics/pharmacology ; Sulfates ; }, abstract = {Recent studies have shown dysbiosis is associated with inflammatory bowel disease (IBD). However, trying to restore microbial diversity via fecal microbiota transplantation (FMT) or probiotic intervention fails to achieve clinical benefit in IBD patients. We performed a probiotic intervention on a simulated IBD murine model to clarify their relationship. IBD was simulated by the protocol of azoxymethane and dextran sodium sulfate (AOM/DSS) to set up a colitis and colitis-associated neoplasm model on BALB/c mice. A single probiotic intervention using Clostridium butyricum Miyairi (CBM) on AOM/DSS mice to clarify the role of probiotic in colitis, colitis-associated neoplasm, gut microbiota, and immune cytokines was performed. We found dysbiosis occurred in AOM/DSS mice. The CBM intervention on AOM/DSS mice failed to improve colitis and colitis-associated neoplasms but changed microbial composition and unexpectedly increased expression of proinflammatory IL-17A in rectal tissue. We hypothesized that the probiotic intervention caused dysbiosis. To clarify the result, we performed inverse FMT using feces from AOM/DSS mice to normal recipients to validate the pathogenic effect of dysbiosis from AOM/DSS mice and found mice on inverse FMT did develop colitis and colon neoplasms. We presumed the probiotic intervention to some extent caused dysbiosis as inverse FMT. The role of probiotics in IBD requires further elucidation.}, }
@article {pmid36077063, year = {2022}, author = {D'Antonio, DL and Marchetti, S and Pignatelli, P and Piattelli, A and Curia, MC}, title = {The Oncobiome in Gastroenteric and Genitourinary Cancers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, doi = {10.3390/ijms23179664}, pmid = {36077063}, issn = {1422-0067}, mesh = {Bacteria ; Dysbiosis/microbiology ; Female ; *Genital Neoplasms, Female ; Humans ; Male ; *Microbiota/physiology ; Quality of Life ; Tumor Microenvironment ; *Urogenital Neoplasms ; Vagina/microbiology ; }, abstract = {Early evidence suggests a strong association of microorganisms with several human cancers, and great efforts have been made to understand the pathophysiology underlying microbial carcinogenesis. Bacterial dysbiosis causes epithelial barrier failure, immune dysregulation and/or genotoxicity and, consequently, creates a tumor-permissive microenvironment. The majority of the bacteria in our body reside in the gastrointestinal tract, known as gut microbiota, which represents a complex and delicate ecosystem. Gut microbes can reach the pancreas, stomach and colon via the bloodstream. Oral bacterial translocations can also occur. In the stomach, pancreas and colon, low microbial diversity is associated with cancer, in particular with a bad prognosis. The urogenital tract also harbors unique microbiota, distinct from the gut microbiota, which might have a role in the urinary and female/male reproductive cancers' pathogenesis. In healthy women, the majority of bacteria reside in the vagina and cervix and unlike other mucosal sites, the vaginal microbiota exhibits low microbial diversity. Genital dysbiosis might have an active role in the development and/or progression of gynecological malignancies through mechanisms including modulation of oestrogen metabolism. Urinary dysbiosis may influence the pathogenesis of bladder cancer and prostate cancer in males. Modulation of the microbiome via pre, pro and postbiotics, fecal or vaginal microbiota transplantation and engineering bacteria might prove useful in improving cancer treatment response and quality of life. Elucidating the complex host-microbiome interactions will result in prevention and therapeutic efficacy interventions.}, }
@article {pmid36075210, year = {2022}, author = {Cheng, J and Zhang, X and Zhang, D and Zhang, Y and Li, X and Zhao, Y and Xu, D and Zhao, L and Li, W and Wang, J and Zhou, B and Lin, C and Yang, X and Zhai, R and Cui, P and Zeng, X and Huang, Y and Ma, Z and Liu, J and Wang, W}, title = {Sheep fecal transplantation affects growth performance in mouse models by altering gut microbiota.}, journal = {Journal of animal science}, volume = {}, number = {}, pages = {}, doi = {10.1093/jas/skac303}, pmid = {36075210}, issn = {1525-3163}, abstract = {Animal growth traits are important and complex traits that determine the productivity of animal husbandry. There are many factors that affect growth traits, among which diet digestion is the key factor. In the process of animal digestion and absorption, the role of gastrointestinal microbes is essential. In this study, we transplanted two groups of sheep intestinal microorganisms with different body weight into the intestines of mice of the same age to observe the effect of fecal bacteria transplantation on the growth characteristics of the mouse model. The results showed that receiving FMT had a effect on the growth traits of recipient mice (p < 0.05). Interestingly, only mice receiving high-weight donor microorganisms showed differences. Use 16S rDNA sequencing technology to analyze the stool microorganisms of sheep and mice. The microbial analysis of mouse feces showed that receiving FMT could improve the diversity and richness of microorganisms (p < 0.05), and the microbial composition of mouse feces receiving low-weight donor microorganisms was similar to that of the control group, which was consistent with the change trend of growth traits. The feces of high-weight sheep may have higher colonization ability. The same five biomarkers were identified in the donor and recipient, all belonging to Firmicutes, and were positively correlated with the body weight of mice at each stage. These results suggest that FMT affects the growth traits of receptors by remodeling their gut microflora.}, }
@article {pmid36071979, year = {2022}, author = {Piazzesi, A and Putignani, L}, title = {Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {958346}, doi = {10.3389/fmicb.2022.958346}, pmid = {36071979}, issn = {1664-302X}, abstract = {Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.}, }
@article {pmid36071974, year = {2022}, author = {Liu, JY and Lin, TL and Chiu, CY and Hsieh, PF and Lin, YT and Lai, LY and Wang, JT}, title = {Decolonization of carbapenem-resistant Klebsiella pneumoniae from the intestinal microbiota of model mice by phages targeting two surface structures.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {877074}, doi = {10.3389/fmicb.2022.877074}, pmid = {36071974}, issn = {1664-302X}, abstract = {Background: Klebsiella pneumoniae is a normal component of the human gastrointestinal tract microbiota. However, in some cases, it can cause disease. Over the past 20 years, the prevalence of antibiotic-resistant bacteria, such as carbapenem-resistant K. pneumoniae (CRKP), has been increasing.<br><br>Materials and methods: We attempted to specifically eliminate CRKP from a mouse model with the human intestinal microbiota. To establish humanized microbiota-colonized mice, we administered K64 CRKP-containing human microbiota to germ-free mice by fecal microbiota transplantation. Then, we used two phages, one targeting the capsule (φK64-1) and one targeting O1 lipopolysaccharide (φKO1-1) of K64 K. pneumoniae, to eliminate CRKP.<br><br>Results: In untreated control and φKO1-1-treated K64-colonized mice, no change in CRKP was observed, while in mice treated with φK64-1, a transient reduction was observed. In half of the mice treated with both φKO1-1 and φK64-1, CRKP was undetectable in feces by PCR and culture for 60 days. However, in the other 50% of the mice, K. pneumoniae was transiently reduced but recovered 35 days after treatment.<br><br>Conclusion: Combination treatment with φK64-1 and φKO1-1 achieved long-term decolonization in 52.3% of mice carrying CRKP. Importantly, the composition of the intestinal microbiota was not altered after phage treatment. Therefore, this strategy may be useful not only for eradicating drug-resistant bacterial species from the intestinal microbiota but also for the treatment of other dysbiosis-associated diseases.}, }
@article {pmid35917175, year = {2022}, author = {Tchitchek, N and Nguekap Tchoumba, O and Pires, G and Dandou, S and Campagne, J and Churlaud, G and Fourcade, G and Hoffmann, TW and Strozzi, F and Gaal, C and Bonny, C and Le Chatelier, E and Erlich, SD and Sokol, H and Klatzmann, D}, title = {Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation.}, journal = {JCI insight}, volume = {7}, number = {17}, pages = {}, doi = {10.1172/jci.insight.159406}, pmid = {35917175}, issn = {2379-3708}, mesh = {Animals ; *Autoimmune Diseases ; Autoimmunity ; Dextran Sulfate/toxicity ; *Gastrointestinal Microbiome ; Humans ; Inflammation/therapy ; Interleukin-2/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; }, abstract = {Gut microbiota dysbiosis is associated with inflammatory bowel diseases and with cardiometabolic, neurological, and autoimmune diseases. Gut microbiota composition has a direct effect on the immune system, and vice versa, and it has a particular effect on Treg homeostasis. Low-dose IL-2 (IL-2LD) stimulates Tregs and is a promising treatment for autoimmune and inflammatory diseases. We aimed to evaluate the impact of IL-2LD on gut microbiota and correlatively on the immune system. We used 16S ribosomal RNA profiling and metagenomics to characterize gut microbiota of mice and humans treated or not with IL-2LD. We performed fecal microbiota transplantation (FMT) from IL-2LD-treated to naive recipient mice and evaluated its effects in models of gut inflammation and diabetes. IL-2LD markedly affected gut microbiota composition in mice and humans. Transfer of an IL-2-tuned microbiota by FMT protected C57BL/6J mice from dextran sulfate sodium-induced colitis and prevented diabetes in NOD mice. Metagenomic analyses highlighted a role for several species affected by IL-2LD and for microbial pathways involved in the biosynthesis of amino acids, short-chain fatty acids, and L-arginine. Our results demonstrate that IL-2LD induced changes in gut microbiota that are involved in the immunoregulatory effects of IL-2LD and suggest a crosstalk between Tregs and gut microbiota. These results provide potentially novel insight for understanding the mode of action of Treg-directed therapies.}, }
@article {pmid35576458, year = {2022}, author = {Lu, G and Wang, W and Li, P and Wen, Q and Cui, B and Zhang, F}, title = {Washed preparation of faecal microbiota changes the transplantation related safety, quantitative method and delivery.}, journal = {Microbial biotechnology}, volume = {15}, number = {9}, pages = {2439-2449}, doi = {10.1111/1751-7915.14074}, pmid = {35576458}, issn = {1751-7915}, support = {//the Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; 2015BAI13B07//China National Center for Clinical Research of Digestive Diseases/ ; //Intestine Initiative/ ; 81670495//National Natural Science Foundation of China/ ; 81873548//National Natural Science Foundation of China/ ; }, mesh = {*Colitis, Ulcerative/etiology/therapy ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Humans ; *Microbiota ; Retrospective Studies ; Treatment Outcome ; }, abstract = {The safety, quantitative method and delivery of faecal microbiota transplantation (FMT) vary a lot from different countries in practice. Recently, the improved methodology of FMT based on the automatic filtration, washing process and the related delivery was named as washed microbiota transplantation (WMT). First, this study aimed to describe the methodology development of FMT from manual to washing preparation from 2012 to 2021 in China Microbiota Transplantation System (CMTS), a centralized stool bank for providing a national non-profit service. The secondary aim is to describe donor screenings, the correlation between faecal weight and treatment doses, incidence of adverse events and delivery decision. The retrospective analysis on the prospectively recorded data was performed. Results showed that the success rate of donor screening was 3.1% (32/1036). The incidence rate of fever decreased significantly from 19.4% (6/31) in manual FMT to 2.7% (24/902) in WMT in patients with ulcerative colitis (UC), which made UC a considerable disease model to reflect the quality control of faecal microbiota preparation. We defined one treatment unit as 10 cm3 microbiota precipitation (1.0 × 1013 bacteria) based on enriched microbiota instead of rough faecal weight. For delivering microbiota, colonic transendoscopic enteral tube is a promising way especially for multiple WMTs or frequent colonic administration of drugs combined with WMT. This study should help improve the better practice of FMT for helping more patients in the future.}, }
@article {pmid35165993, year = {2022}, author = {Parker, G and Spoelma, MJ and Rhodes, N}, title = {Faecal microbiota transplantation for bipolar disorder: A detailed case study.}, journal = {Bipolar disorders}, volume = {24}, number = {5}, pages = {559-563}, doi = {10.1111/bdi.13187}, pmid = {35165993}, issn = {1399-5618}, mesh = {*Bipolar Disorder/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid36051343, year = {2022}, author = {Alberca, GGF and Cardoso, NSS and Solis-Castro, RL and Nakano, V and Alberca, RW}, title = {Intestinal inflammation and the microbiota: Beyond diversity.}, journal = {World journal of gastroenterology}, volume = {28}, number = {26}, pages = {3274-3278}, pmid = {36051343}, issn = {2219-2840}, mesh = {*Colitis, Ulcerative/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Intestinal Mucosa/microbiology ; *Microbiota ; }, abstract = {The recent manuscript entitled "Relationship between clinical features and intestinal microbiota in Chinese patients with ulcerative colitis" reported a difference in the intestinal microbiota of patients with ulcerative colitis according to the severity of the colitis. The influence of the intestinal microbiota on the development and progress of gastrointestinal disorders is well established. Besides the diversity in the microbiome, the presence of virulence factors and toxins by commensal bacteria may affect an extensive variety of cellular processes, contributing to the induction of a proinflammatory environment.}, }
@article {pmid36066910, year = {2022}, author = {Wang, JG and Liang, Q and Dou, HH and Ou, Y}, title = {The Global Incidence of Adverse Events Associated with Fecal Microbiota Transplantation in Children over the Past 20 Years: A Systematic Review and Meta-Analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15996}, pmid = {36066910}, issn = {1440-1746}, abstract = {OBJECTIVES: To understand the global incidence of the adverse events associated with fecal microbiota transplantation (FMT) in children over the past 20 years.<br><br>METHODS: We searched PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and Chongqing Weipu) for high-quality articles written over the past 20 years and made selections based on the quality standard score. The study characteristics and incidences of adverse events were extracted from each article, meta-analysis was performed using the R.3.6.3 software, and randomized- or fixed-effect meta-analyses were used to determine the incidence of adverse events. Subgroup analysis was performed to determine heterogeneity.<br><br>RESULTS: A total of 18 articles involving 681 children were included in the analysis. The total effective rate of FMT in children was 85.75% (95% CI: 76.23-93.15 %), of which the overall efficacy of FMT for the treatment of Clostridium difficile infection was 91.22% (95% CI: 83.49-96.68 %) and the overall adverse event rate was 28.86% (95% CI:19.56-39.15 %) .with a mild to moderate adverse event rate of 27.72% (95% CI: 17.86-38.83 %) and a severe adverse event rate of 0.90% (95% CI: 0.33-1.76 %). The most common mild to moderate adverse events were as follows: Bellyache, 14.02% (95% CI: 5.43-25.77 %); diarrhea, 7.75% (95% CI: 2.69-15.11 %); and bloating, 7.36% (95% CI: 1.79-16.28 %). Other adverse events included fever, 2.34%; vomiting, 3.12%; nausea, 1.50%; hematochezia, 2.30%; anorexia, 1.94%; and fatigue, 0.03%. The only death reported was in a study from China, in which the patient died of sepsis and liver failure four weeks after FMT. The other serious adverse event was an immunodeficiency patient with severe hematochezia. Another study in the United States described seven serious adverse events including one death which was not considered to be related to FMT; however, they did not describe the events in detail. There was no difference in the incidence of adverse events between the upper and lower gastrointestinal tracts (OR = 0.61, 95% CI: 0.02-15.42 , P = 0.76).<br><br>CONCLUSION: Adverse events related to FMT in children are mostly mild to moderate, of short duration, and self-limiting. Therefore, the use of FMT in children is safe and worthy of widespread promotion.}, }
@article {pmid36060783, year = {2022}, author = {Wang, M and Xie, X and Zhao, S and Han, W and Zhang, Y}, title = {Global research trends and hotspots of fecal microbiota transplantation: A bibliometric and visualization study.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {990800}, pmid = {36060783}, issn = {1664-302X}, abstract = {Introduction: Fecal microbiota transplantation (FMT) has gained considerable attention in a variety of clinical research areas, and an increasing number of articles are being published. It is very critical to reveal the global status, future research trends, and hotspots in the FMT research and application.<br><br>Methods: We searched the Web of Science Core Collection up to May 10, 2022, and only articles and review articles about FMT were included finally. CiteSpace 5.8.R3, VOSviewer 1.6.18, Scimago Graphica and Microsoft Office Excel 2019 were used for data analysis and visualization. The results included publication characteristics, Co-authorships analysis, Co-cited analysis, Co-occurrence analysis, and burst analysis.<br><br>Results: Eleven thousand nine hundred seventy-two records were used for the analysis and visualization finally, these records were published between 1980 and 2022, and the publication about FMT is increasing year by year. Co-authorship analysis shown that the USA played a key role in this field. After data analysis and visualization, a total of 57 hotspots about FMT were produced. We summarized these hotspots and classified them into 7 grades according to the number of evidence sources. The evidence sources included top 25 of Web of Science categories, top 30 most Co-cited references, top 10 clusters of references, top 25 references with the strongest citation bursts, top 25 keywords with the most occurrence frequency, major 15 clusters of keywords, top 25 keywords with the strongest citation bursts, and top 35 disease keywords.<br><br>Conclusion: This bibliometric analysis is expected to provide overall perspective for FMT. FMT has gained increasing attention and interest, there are many hotspots in this field, which may help researchers to explore new directions for future research.}, }
@article {pmid36056902, year = {2022}, author = {Hole, MJ and Kaasen Jørgensen, K and Holm, K and Braadland, PR and Meyer-Myklestad, MH and Medhus, AW and Reikvam, DH and Götz, A and Grzyb, K and Boberg, KM and Karlsen, TH and Kummen, M and Hov, JR}, title = {A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.32773}, pmid = {36056902}, issn = {1527-3350}, abstract = {BACKGROUND AND AIMS: Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), while data on mucosal microbiota are less consistent. We aimed to utilize a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT.<br><br>APPROACH AND RESULTS: We included 84 PSC and 51 liver transplanted PSC patients (PSC-LT), and 40 healthy controls (HC) and performed sequencing of the 16S rRNA gene (V3-V4) from ileocolonic biopsies. The intra-individual microbial diversity was reduced in both PSC and PSC-LT vs. HC. An expansion of Proteobacteria was more pronounced in PSC-LT (up to 19% relative abundance) than in PSC (up to 11%) and HC (up to 8%), (QFDR < 0.05). When investigating PSC before (PSC vs. HC) and after LT (rPSC vs. no-rPSC), increased variability (dispersion) in the PSC group was found. Five genera associated with PSC before and after LT. A dysbiosis index calculated from the five genera, and the presence of the potential pathobiont Klebsiella associated with reduced LT-free survival. Concomitant IBD was associated with reduced Akkermansia.<br><br>CONCLUSION: Consistent mucosal microbiota features associated with PSC, PSC-IBD and disease severity, irrespective of LT status, highlights the utility of investigating PSC and rPSC in parallel, and suggests that the impact of gut microbiota on post-transplant liver health should be investigated further.}, }
@article {pmid36054423, year = {2022}, author = {Wang, Q and Guo, X and Yue, Q and Zhu, S and Guo, L and Li, G and Zhou, Q and Xiang, Y and Chen, G and Yin, W and Sun, J}, title = {Exploring the role and mechanism of gut microbiota in methamphetamine addiction using antibiotic treatment followed by fecal microbiota transplantation.}, journal = {Anatomical record (Hoboken, N.J. : 2007)}, volume = {}, number = {}, pages = {}, doi = {10.1002/ar.25055}, pmid = {36054423}, issn = {1932-8494}, support = {81671320//National Natural Science Foundation of China/ ; 81871044//National Natural Science Foundation of China/ ; }, abstract = {Recently, the role of the gut microbiota in the context of drug addiction has attracted the attention of researchers; however, the specific effects and underlying mechanisms require further exploration. To accomplish this, C57BL/6 mice were firstly treated with methamphetamine (MA). Conditioned place preference (CPP) behavior changes, gut permeability and function, microglial activation, and inflammatory cytokine expression were systematically analyzed in antibiotics-treated mice with microbiota depletion and in fecal microbiota transplantation mice with microbiota reconstitution. MA treatment altered microbiota composition and caused gut dysbiosis. Depletion of gut microbiota with antibiotics inhibited MA-induced CPP formation, and fecal microbiota transplantation reversed this inhibition. Mechanistic analyses indicated that antibiotic treatment decreased gut permeability and neuroinflammation, while fecal microbiota transplantation offset the impact of antibiotic treatment. Additionally, MA-induced microglial activation was suppressed by antibiotics but restored by microbiota transplantation, and this correlated well with the CPP score. Compared to antibiotic treatment, microbiota transplantation significantly increased 5-HT4 receptor expression in both the nucleus accumbens and the hippocampus. Furthermore, when fecal microbiota from healthy mice was transplanted into MA-treated mice, the CPP scores decreased. Our results provide a novel avenue for understanding MA addiction and suggest a potential future intervention strategy.}, }
@article {pmid36053300, year = {2022}, author = {Stallmach, A and Steube, A and Stallhofer, J and Grunert, PC and Merkel, U and Hartmann, M}, title = {[Fecal microbiota transplantation: indications, risks and opportunities].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {}, number = {}, pages = {}, pmid = {36053300}, issn = {2731-7099}, abstract = {Fecal microbiome transfer (FMT) involving the transfer of the microbiome of healthy stool donors to patients with various diseases has been performed in Germany in clinical studies and individual treatment attempts. There is no doubt that FMT is an effective therapeutic principle for recurrent Clostridium difficile infection and ulcerative colitis. From a medico-legal point of view, it should be stressed that, in Germany, the microbiome to be transferred is regarded as a drug, the manufacture of which is subject to the Medicines Act and the risk information from the Federal Institute for Drugs and Medical Devices. The background of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the potential risk of transmitting pathogens must also be considered. There is an obligation to notify the competent state authorities to perform FMTs in the context of individual treatment attempts. In the context of the limited availability and the fundamental problem of infection, future studies aim to identify the therapeutically active components in the microbiome. Recombinant production is the aim. Initial results represent preliminary steps, as these concepts are not yet established in clinical practice.}, }
@article {pmid36047142, year = {2022}, author = {Mukohda, M and Mizuno, R and Ozaki, H}, title = {[Gut microflora and metabolic syndrome: new insight into the pathogenesis of hypertension].}, journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica}, volume = {157}, number = {5}, pages = {311-315}, doi = {10.1254/fpj.22035}, pmid = {36047142}, issn = {0015-5691}, abstract = {Emerging evidences indicate that a microbial imbalance (dysbiosis) is linked to several diseases including metabolic cardiovascular diseases. A fecal microbiota transplantation from hypertensive human donor to germ-free mice caused blood pressure elevation. In addition, there is a report demonstrating that angiotensin II-induced hypertension and vascular dysfunction were attenuated in germ-free mice, suggesting that gut microbiome may mediate development of hypertension. Although detailed mechanism by which the dysbiosis induces an increased blood pressure remains unknown, changes in microbiome may modify host immune systems and induce inflammatory dysfunction in cardiovascular system, resulting in dysregulation of blood pressure. Some cohort studies demonstrated an association between a higher abundance of Streptococcaceae spp. and blood pressure. One recent report demonstrated that an increasing number of gram-positive Streptococcus was found in the feces of adult spontaneously hypertensive rats with an increased intestinal permeability. We hypothesized that increased bacterial toxin levels derived from gut Streptococcus may be a factor inducing blood pressure dysregulation. In this review, we discuss the possible role of microbiome in cardiovascular disease, especially hypertension.}, }
@article {pmid36045729, year = {2022}, author = {Chen, Y and Lian, B and Li, P and Yao, S and Hou, Z}, title = {Studies on irritable bowel syndrome associated with anxiety or depression in the last 20 years: A bibliometric analysis.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {947097}, doi = {10.3389/fpubh.2022.947097}, pmid = {36045729}, issn = {2296-2565}, abstract = {Irritable bowel syndrome (IBS) associated with anxiety or depression is ubiquitous in clinical practice, and multiple related articles have been published. However, studies that utilize bibliometric analyses to address this topic are rare. In our study, we aimed to reveal research trends in IBS with anxiety or depression. Publications on IBS in relation to anxiety or depression in the last 20 years were obtained from the Web of Science Core Collection (WoSCC). CiteSpace software (5.8.R3) and GraphPad Prism 8 were used to perform bibliometric analysis of authors, countries, institutions, journals, keywords, and references involved in this topic. A total of 2,562 publications from 716 academic journals were included in this study. The majority of publications (n = 833, 32.51%) were from the USA, and the University of California, Los Angeles, contributed the most publications (n = 97, 3.79%). Active cooperations among countries and institutions were observed. Neurogastroenterology and Motility [impact factor (IF) 2020 = 3.598] published the most papers (170 publications, 6.64%), followed by Alimentary Pharmacology Therapeutics (IF 2020 = 8.171; 88 publications; 3.44%). The literatures related to IBS and anxiety or depression were primarily published in journals related to medicine/medical/clinical, neurology/sports/ophthalmology, and molecular/biology/immunology. Cryan JF and Drossman DA, with the largest number of articles (84 publications) and citations (917 citations), respectively, were considered as the most influential authors in this field. A total of 336 co-cited references were divided into 17 clusters, and #1 fecal microbiota transplantation contained most of the documents published in recent years. Moreover, the keyword "psychosocial factor" had the largest burst strength of 13.52, followed by the keyword "gut microbiota" with a burst strength of 11.71. This study shows the research performance of IBS related to anxiety or depression from 2002 to 2021 and helps researchers master the trend in this field, which should receive more attention.}, }
@article {pmid36044059, year = {2022}, author = {Kempski, J and Huber, S}, title = {[Role of the gut microbiome in the pathogenesis and treatment of inflammatory bowel diseases].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {}, number = {}, pages = {}, pmid = {36044059}, issn = {2731-7099}, abstract = {Inflammatory bowel diseases (IBD) are systemic diseases that mainly manifest in the gastrointestinal tract. Due to chronically impaired intestinal homeostasis, they often require permanent and in some cases systemic therapy. The exact causes of IBD are largely unknown. It is postulated that these complex diseases arise in genetically susceptible individuals through a misdirected immune response, promoted by barrier defects, environmental toxins, and the gut microbiome. In this regard, the importance of the microbiome and its pathogenic changes (dysbiosis) in the pathogenesis of IBD is increasingly coming into focus. This review article presents the current state of research on the role of the microbiome in the development of IBD. Therapeutic approaches aimed at correcting intestinal dysbiosis are also discussed.}, }
@article {pmid36043345, year = {2022}, author = {Tan, B and Liu, YX and Tang, H and Chen, D and Xu, Y and Chen, MJ and Li, Y and Wang, MZ and Qian, JM}, title = {Gut microbiota shed new light on the management of immune-related adverse events.}, journal = {Thoracic cancer}, volume = {}, number = {}, pages = {}, doi = {10.1111/1759-7714.14626}, pmid = {36043345}, issn = {1759-7714}, support = {82000526//National Natural Science Foundation of China/ ; 7192172//Natural Science Foundation of Beijing Municipality/ ; }, abstract = {Immunotherapy has dramatically revolutionized the therapeutic landscape for patients with cancer. Although immune checkpoint inhibitors are now accepted as effective anticancer therapies, they introduce a novel class of toxicity, termed immune-related adverse events, which can lead to the temporary or permanent discontinuation of immunotherapy and life-threatening tumor progression. Therefore, the effective prevention and treatment of immune-related adverse events is a clinical imperative to maximize the utility of immunotherapies. Immune-related adverse events are related to the intestinal microbiota, baseline gut microbiota composition is an important determinant of immune checkpoint inhibitor-related colitis, and antibiotics exacerbate these undesirable side-effects. Supplementation with specific probiotics reduces immune checkpoint inhibitor-related colitis in mice, and fecal microbiota transplantation has now been shown to effectively treat refractory immune checkpoint inhibitor-related colitis in the clinic. Hence, modifying the microbiota holds great promise for preventing and treating immune-related adverse events. Microbiomes and their metabolites play important roles in the potential underlying mechanisms through interactions with both innate and adaptive immune cells. Here we review the gut microbiota and immune regulation; the changes occurring in the microbiota during immune checkpoint inhibitor therapy; the relationship between the microbiota and immune-related adverse events, antibiotics, probiotics/prebiotics, and fecal microbiota transplantation in immune checkpoint inhibitor-related colitis; and the protective mechanisms mediated by the microbiome and metabolites in immune-related adverse events.}, }
@article {pmid36042459, year = {2022}, author = {Jiang, H and Peng, Y and Zhang, W and Chen, Y and Jiang, Q and Zhou, Y}, title = {Gut microbiome-targeted therapies in liver cirrhosis: a protocol for systematic review and meta-analysis.}, journal = {Systematic reviews}, volume = {11}, number = {1}, pages = {181}, pmid = {36042459}, issn = {2046-4053}, abstract = {BACKGROUND: Microbiome-targeted therapies (MTTs), including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), have been proposed as a potential treatment for cirrhosis via modulation of gut microbiome, while the impact of gut microflora alteration on liver function in cirrhosis trajectory is unclear, and no related systematic review has been published. We aim to comprehensively assess the effects of MTTs in patients with liver cirrhosis.<br><br>METHODS: We will search databases of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) with no time restriction. Only randomized controlled trials published in English will be included. Two independent reviewers will be responsible for study identification and selection, data extraction, and risk of bias assessment, with discrepancies resolved by consensus or referral to a third author. Heterogeneity of studies will be examined using Cochrane Q-test and I2 statistics. The data will be pooled using either a fixed- or random-effects model based on I2 statistics. The results will be presented as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). We will perform subgroup analysis on the type of MTTs and assess the reporting biases. Sensitivity analysis will be conducted to test the stability of each outcome result.<br><br>DISCUSSION: There is no current study about the role of MTTs in developing the liver function, and the therapeutic effects of MTTs are inconsistent. By investigating the liver-specific indicators when treating with multiple MTTs on course of cirrhosis, our findings will give more conclusive and stronger evidence about the efficacy of MTTs and provide new insight into the action mechanisms of these MTTs.<br><br>PROSPERO CRD42021253198.}, }
@article {pmid36042181, year = {2022}, author = {Liu, Y and Jiang, Z and Yang, H and Yuan, J and Zeng, J and Wu, J and Xu, Z}, title = {Gui Shao Tea Extracts Inhibit Gastric Cancer Growth in Vitro and in Vivo and Prolong Survival in Nude Mice.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {27}, number = {8}, pages = {250}, doi = {10.31083/j.fbl2708250}, pmid = {36042181}, issn = {2768-6698}, support = {S202112121124//Undergraduate Innovation and Entrepreneurship Training Program of Guangdong/ ; 202112121348//Undergraduate Innovation and Entrepreneurship Training Program of Guangdong/ ; 2015A010107005//Science and Technology Planning Project of Guangdong Province/ ; 2017A030310022//Natural Science Foundation of Guangdong Province/ ; }, abstract = {BACKGROUND: Gui Shao Tea (GST), a long-aged tea with a Chinese herbal aroma, can treat many stubborn and malignant diseases, according to traditional Chinese medicine. This research aimed to discover and define GST, study the anti-gastric cancer effects of GST extracts and preliminarily elucidate the mechanism of action in the PI3K/Akt signaling pathway and the gut microbiota.<br><br>METHODS: GST was analyzed by GC/MS and HPLC. Cell proliferation, the cell cycle and apoptosis were evaluated by a CCK8 assay and flow cytometry. The effects of GST extracts on tumor inhibition and survival time were explored by a gastric cancer xenograft model in nude mice. The PI3K/Akt signaling pathway was assessed by western blotting and immunohistochemistry. Gut microbiota detection and fecal microbiota transplantation were performed to examine whether the tumor inhibition observed in mice was related to gut microbiota changes.<br><br>RESULTS: The ingredients in GST, mostly terpenes and their derivatives, were novel and more concentrated than those in tea made from the branches and leaves of the same plant species, Camellia sinensis, picked and produced the same year, while the levels of polyphenols and alkaloids were significantly reduced. In BGC-823, MGC-803, and SGC-7901 gastric cancer cells, GST extracts significantly inhibited proliferation (p = 0.037), induced G0/G1 arrest (p < 0.001) and promoted early apoptosis (p = 0.041). In mice, gastric tumor growth was significantly inhibited in both the high-dose (HTF) and middle-dose (MTF) GST-fed groups. The inhibition rate in the HTF group was 33.77% on Day 14 (p = 0.042), and that in the MTF group was 55.21% on Day 14 (p = 0.002) and 61.6% on Day 28 (p = 0.008). The survival time of MTF group mice was significantly prolonged by 22.2% (p = 0.013). GST extracts inhibited the PI3K/AKT signaling pathway in gastric cancer cells (p = 0.016) and tissues (p = 0.029), downregulated the protein p-Rb and further downregulated E2F1, thereby affecting the cell cycle and proliferation. GST extracts altered the gut microbiota in mice, but these alterations alone were insufficient to inhibit gastric cancer growth.<br><br>CONCLUSIONS: We confirmed the anti-gastric cancer effects of GST extracts, which might provide new approaches and methods for research and development of gastric cancer drugs.}, }
@article {pmid35914438, year = {2022}, author = {Medel-Matus, JS and Simpson, CA and Ahdoot, AI and Shin, D and Sankar, R and Jacobs, JP and Mazarati, AM}, title = {Modification of post-traumatic epilepsy by fecal microbiota transfer.}, journal = {Epilepsy &amp; behavior : E&amp;B}, volume = {134}, number = {}, pages = {108860}, doi = {10.1016/j.yebeh.2022.108860}, pmid = {35914438}, issn = {1525-5069}, mesh = {Animals ; *Brain Injuries, Traumatic ; *Epilepsy ; *Epilepsy, Post-Traumatic ; Fecal Microbiota Transplantation ; Humans ; Male ; Prospective Studies ; Rats ; Rats, Sprague-Dawley ; Seizures ; }, abstract = {It has been well established that traumatic brain injury (TBI) modifies the composition of gut microbiome. Epilepsy, which represents one of the common sequelae of TBI, has been associated with dysbiosis. Earlier study showed that the risk of post-traumatic epilepsy (PTE) after lateral fluid percussion injury (LFPI) in rats can be stratified based on pre-existing (i.e., pre-TBI) gut microbiome profile. In the present study, we examined whether fecal microbiota transfer (FMT) from naïve rats with different prospective histories of PTE would affect the trajectory of PTE in recipients. Fecal samples were collected from naïve adult male Sprague-Dawley rats, followed by LFPI. Seven months later, upon four weeks of vide-EEG monitoring (vEEG), the rats were categorized as those with and without PTE. Recipients were subjected to LFPI, followed by FMT from donors with and without impending PTE. Control groups included auto-FMT and no-FMT subjects. Seven month after LFPI, recipients underwent four-week vEEG to detect spontaneous seizures. After completing vEEG, rats of all groups underwent kindling of basolateral amygdala. Fecal microbiota transfer from donors with impending PTE exerted mild-to-moderate pro-epileptic effects in recipients, evident as marginal increase in multiple spontaneous seizure incidence, and facilitation of kindling. Analysis of fecal samples in selected recipients and their respective donors confirmed that FMT modified microbiota in recipients along the donors' lines, albeit without full microbiome conversion. The findings provide further evidence that gut microbiome may actively modulate the susceptibility to epilepsy.}, }
@article {pmid36037843, year = {2022}, author = {Rathour, D and Shah, S and Khan, S and Singh, PK and Srivastava, S and Singh, SB and Khatri, DK}, title = {ROLE OF GUT MICROBIOTA IN DEPRESSION: UNDERSTANDING MOLECULAR PATHWAYS, RECENT RESEARCH, AND FUTURE DIRECTION.}, journal = {Behavioural brain research}, volume = {}, number = {}, pages = {114081}, doi = {10.1016/j.bbr.2022.114081}, pmid = {36037843}, issn = {1872-7549}, abstract = {Gut microbiota, also known as the "second brain" in humans because of the regulatory role it has on the central nervous system via neuronal, chemical and immune pathways. It has been proven that there exists a bidirectional communication between the gut and the brain. Increasing evidence supports that this crosstalk is linked to the etiology and treatment of depression. Reports suggest that the gut microbiota control the host epigenetic machinery in depression and gut dysbiosis causes negative epigenetic modifications via mechanisms like histone acetylation, DNA methylation and non-coding RNA mediated gene inhibition. The gut microbiome can be a promising approach for the management of depression. The diet and dietary metabolites like kynurenine, tryptophan, and propionic acid also greatly influence the microbiome composition and thereby, the physiological activities. This review gives a bird-eye view on the pathological updates and currently used treatment approaches targeting the gut microbiota in depression.}, }
@article {pmid36037770, year = {2022}, author = {Han, Q and Deng, LR and Zou, M and Tang, HZ and Huang, CY and Chen, FJ and Tomlinson, B and Li, YH}, title = {Anemoside B4 protects against chronic relapsing colitis in mice by modulating inflammatory response, colonic transcriptome and the gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {106}, number = {}, pages = {154416}, doi = {10.1016/j.phymed.2022.154416}, pmid = {36037770}, issn = {1618-095X}, abstract = {BACKGROUND: Anemoside B4 (AB4) is reported to prevent acute colitis when given via intraperitoneal injection by two recent studies. However, whether oral AB4 protects against chronic colitis which resembles the clinical phenotype of ulcerative colitis (UC) and its mechanism of action are largely unknown.<br><br>PURPOSE: To systemically investigate the effects of oral AB4 against chronic colitis and illustrate the underlying mechanism of action.<br><br>METHODS: The preventive, therapeutic, and dose-dependent effects of AB4 against UC were examined in mice with acute or chronic relapsing colitis induced by dextran sulfate sodium (DSS). The inflammatory responses, colonic transcriptome, and 16S rDNA sequencing of the intestinal content of mice were analyzed.<br><br>RESULTS: Oral administration of AB4 alleviated disease severity and colon shortening in mice with chronic relapsing colitis in a dose-dependent manner. The effects of AB4 were comparable to those of two positive-control compounds: tofacitinib and berberine. Unlike tofacitinib, AB4 did not have a deleterious effect on DSS-induced splenic swelling and anemia. Furthermore, AB4 inhibited the inflammatory responses of colitis, as evidenced by in-vivo, ex-vivo, and in-vitro studies. Transcriptomics revealed that AB4 treatment reversed the DSS-mediated decrease in the expression of colonic Pelo, B3gat2 and Mir8010. In addition, AB4 reversed DSS-induced alterations in the intestinal microbiome in mice. Through fecal microbiota transplantation, we proved that AB4 partially exerted its anti-colitis effects by modulating the gut microbiota.<br><br>CONCLUSIONS: We demonstrated for the first time that AB4 has dose-dependent therapeutic effects against chronic relapsing colitis by modulating the inflammatory response, colonic gene expression, and intestinal microbiota.}, }
@article {pmid36034975, year = {2022}, author = {Qiu, J and Wu, C and Gao, Q and Li, S and Li, Y}, title = {Effect of fecal microbiota transplantation on the TGF-β1/Smad signaling pathway in rats with TNBS-induced colitis.}, journal = {Annals of translational medicine}, volume = {10}, number = {15}, pages = {825}, doi = {10.21037/atm-22-3227}, pmid = {36034975}, issn = {2305-5839}, abstract = {Background: Traditional treatments for inflammatory bowel disease (IBD) have adverse side effects, and patients who receive such treatments have high recurrence rates. Fecal microbiota transplantation (FMT) has become an increasingly popular therapeutic option for patients with IBD. However, the mechanism by which FMT alleviates this disease remains unclear.<br><br>Methods: In this study, a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis was established and used to explore whether the transforming growth factor-beta 1 (TGF-β1)/small mothers against decapentaplegic (Smad) signaling pathway plays a critical role in the FMT alleviation of IBD.<br><br>Results: After the FMT intervention, the disease activity index and histologic scores were significantly decreased. In addition, the TGF-β1 expression level in the FMT group was significantly decreased by approximately 0.72-fold relative to the level in the TNBS colitis group, whereas the Smad3, Smad4, and Smad7 expression levels had increased by approximately 1.21, 1.40, and 1.18 folds, respectively. Similarly, SB431542 inhibited the expression of TGF-β1 and promoted the expression of Smad3, Smad4, and Smad7. Further, the serum levels of the inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were significantly decreased, whereas that of the interferon-gamma (IFN-γ) was not significantly changed after the FMT intervention.<br><br>Conclusions: These results suggest that FMT inhibits the TGF-β1/Smad signaling pathway to attenuate inflammation.}, }
@article {pmid36034838, year = {2022}, author = {Shi, X and Wu, H and Liu, Y and Huang, H and Liu, L and Yang, Y and Jiang, T and Zhou, M and Dai, M}, title = {Inhibiting vascular smooth muscle cell proliferation mediated by osteopontin via regulating gut microbial lipopolysaccharide: A novel mechanism for paeonol in atherosclerosis treatment.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {936677}, doi = {10.3389/fphar.2022.936677}, pmid = {36034838}, issn = {1663-9812}, abstract = {Background: Although the gut microbiota is involved in metabolic disease such as atherosclerosis, the underlying mechanism remains elusive. Paeonol (Pae) is a natural phenolic compound isolated from Cortex Moutan, which exhibits anti-atherosclerotic effects. Our previous research demonstrated gut microbiota as a site of Pae action. However, the mechanism by which Pae exerts its anti-atherosclerotic effect by the regulation of gut microbiota remains unclear. Objective: To investigate a potential mechanistic link between the gut microbial lipopolysaccharide (LPS) and vascular smooth muscle cell (VSMC) proliferation in atherosclerosis progression and explore the possible role of Pae. Methods: Experimental atherosclerosis was established in ApoE-/- mice, and the atherosclerosis mice were treated with Pae for 4 weeks before being sacrificed for analyses while conducting fecal microbiota transplantation (FMT). The plaque area, levels of serum LPS, expressions of inflammatory factors in serum or aorta, and intestinal barrier permeability were determined. VSMCs were co-cultured with THP-1 cells. CCK-8 assay and EdU staining were performed to assess the proliferative capacity of VSMCs. Immunofluorescence staining was performed to observe the nuclear transfer of p65. Western blotting was used to detect the candidate protein expression level, and quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression level in tissues or cells of each group. Results: During atherosclerosis progression, gut dysbiosis leads to the peripheral accumulation of gut microbial LPS, which acts as a trigger to stimulate osteopontin (OPN) production from circulating monocytes, inducing cell-to-cell crosstalk to promote VSMC proliferation in the aorta. Importantly, the elevation of LPS and OPN concentrations in the blood was also observed in patients with atherosclerosis. Pae could significantly improve atherosclerosis, suppress gut microbial LPS accumulation, and inhibit monocyte/macrophage activation and VSMC proliferation. Conclusions: The present study provides a mechanistic scenario for how long-term stimulation of gut microbial LPS in circulating blood generates a pathological secondary response that leads to abnormal proliferation of VSMCs using high OPN expression in circulating monocytes and suggests a novel strategy for atherosclerosis therapy by remodeling the gut microbiota.}, }
@article {pmid36034698, year = {2022}, author = {Cui, C and Han, Y and Li, H and Yu, H and Zhang, B and Li, G}, title = {Curcumin-driven reprogramming of the gut microbiota and metabolome ameliorates motor deficits and neuroinflammation in a mouse model of Parkinson's disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {887407}, doi = {10.3389/fcimb.2022.887407}, pmid = {36034698}, issn = {2235-2988}, abstract = {Background: Parkinson's disease (PD) is a common neurodegenerative disorder, accompanied by motor deficits as well as gastrointestinal dysfunctions. Recent studies have proved that the disturbance of gut microbiota and metabolism contributes to the pathogenesis of PD; however, the mechanisms underlying these effects have yet to be elucidated. Curcumin (CUR) has been reported to provide neuroprotective effects on neurological disorders and modulate the gut flora in intestinal-related diseases. Therefore, it is of significant interest to investigate whether CUR could exert a protective effect on PD and whether the effect of CUR is dependent on the intestinal flora and subsequent changes in metabolites.<br><br>Methods: In this study, we investigated the neuroprotective effects of CUR on a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16S rRNA sequencing was performed to explore the profile of the gut microbiota among controls, MPTP-treated mice and CUR-treated mice. Then, antibiotic treatment (ABX) and fecal microbiota transplantation (FMT) experiments were conducted to examine the role of intestinal microbes on the protective effects of CUR in PD mice. Furthermore, ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics analysis was used to identify the landscape of the CUR-driven serum metabolome. Finally, Pearson's analysis was conducted to investigate correlations between the gut flora-metabolite axis and CUR-driven neuroprotection in PD.<br><br>Results: Our results showed that CUR intervention effectively improved motor deficits, glial cell activation, and the aggregation of α-synuclein (α-syn) in MPTP-treated mice. 16S rRNA sequencing showed elevated abundances of Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Eggerthellaceae but depleted abundances of Aerococcaceae and Staphylococcaceae in CUR-treated mice when compared with MPTP mice. ABX and FMT experiments further confirmed that the gut microbiota was required for CUR-induced protection in PD mice. Serum metabolomics analysis showed that CUR notably upregulated the levels of tyrosine, methionine, sarcosine and creatine. Importantly, strong correlations were identified among crucial taxa (Aerococcaceae, Staphylococcaceae, Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Eggerthellaceae), pivotal metabolites (tyrosine, methionine, sarcosine and creatine) and the motor function and pathological results of mice. CUR treatment led to a rapid increase in the brain levels of tyrosine and levodopa (dopa) these changes were related to the abundances of Lactobacillaceae and Aerococcaceae.<br><br>Conclusions: CUR exerts a protective effect on the progression of PD by modulating the gut microbiota-metabolite axis. Lactobacillaceae and Aerococcaceae, along with key metabolites such as tyrosine and dopa play a dominant role in CUR-associated neuroprotection in PD mice. Our findings offer unique insights into the pathogenesis and potential treatment of PD.}, }
@article {pmid36034697, year = {2022}, author = {Wang, Z and Li, Y and Liao, W and Huang, J and Liu, Y and Li, Z and Tang, J}, title = {Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {935723}, doi = {10.3389/fcimb.2022.935723}, pmid = {36034697}, issn = {2235-2988}, abstract = {The incidence of hyperuricemia (HUA) and gout continuously increases and has become a major public health problem. The gut microbiota, which colonizes the human intestine, has a mutually beneficial and symbiotic relationship with the host and plays a vital role in the host's metabolism and immune regulation. Structural changes or imbalance in the gut microbiota could cause metabolic disorders and participate in the synthesis of purine-metabolizing enzymes and the release of inflammatory cytokines, which is closely related to the occurrence and development of the metabolic immune disease HUA and gout. The gut microbiota as an entry point to explore the pathogenesis of HUA and gout has become a new research hotspot. This review summarizes the characteristics of the gut microbiota in patients with HUA and gout. Meanwhile, the influence of different dietary structures on the gut microbiota, the effect of the gut microbiota on purine and uric acid metabolism, and the internal relationship between the gut microbiota and metabolic endotoxemia/inflammatory factors are explored. Moreover, the intervention effects of probiotics, prebiotics, and fecal microbial transplantation on HUA and gout are also systematically reviewed to provide a gut flora solution for the prevention and treatment of related diseases.}, }
@article {pmid36034447, year = {2022}, author = {Liu, L and Zhang, J and Cheng, Y and Zhu, M and Xiao, Z and Ruan, G and Wei, Y}, title = {Gut microbiota: A new target for T2DM prevention and treatment.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {958218}, doi = {10.3389/fendo.2022.958218}, pmid = {36034447}, issn = {1664-2392}, abstract = {Type 2 diabetes mellitus (T2DM), one of the fastest growing metabolic diseases, has been characterized by metabolic disorders including hyperglycemia, hyperlipidemia and insulin resistance (IR). In recent years, T2DM has become the fastest growing metabolic disease in the world. Studies have indicated that patients with T2DM are often associated with intestinal flora disorders and dysfunction involving multiple organs. Metabolites of the intestinal flora, such as bile acids (BAs), short-chain fatty acids (SCFAs) and amino acids (AAs)may influence to some extent the decreased insulin sensitivity associated with T2DM dysfunction and regulate metabolic as well as immune homeostasis. In this paper, we review the changes in the gut flora in T2DM and the mechanisms by which the gut microbiota modulates metabolites affecting T2DM, which may provide a basis for the early identification of T2DM-susceptible individuals and guide targeted interventions. Finally, we also highlight gut microecological therapeutic strategies focused on shaping the gut flora to inform the improvement of T2DM progression.}, }
@article {pmid36033885, year = {2022}, author = {Gang, J and Wang, H and Xue, X and Zhang, S}, title = {Microbiota and COVID-19: Long-term and complex influencing factors.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {963488}, doi = {10.3389/fmicb.2022.963488}, pmid = {36033885}, issn = {1664-302X}, abstract = {The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization statistics, more than 500 million individuals have been infected and more than 6 million deaths have resulted worldwide. Although COVID-19 mainly affects the respiratory system, considerable evidence shows that the digestive, cardiovascular, nervous, and reproductive systems can all be involved. Angiotensin-converting enzyme 2 (AEC2), the target of SARS-CoV-2 invasion of the host is mainly distributed in the respiratory and gastrointestinal tract. Studies found that microbiota contributes to the onset and progression of many diseases, including COVID-19. Here, we firstly conclude the characterization of respiratory, gut, and oral microbial dysbiosis, including bacteria, fungi, and viruses. Then we explore the potential mechanisms of microbial involvement in COVID-19. Microbial dysbiosis could influence COVID-19 by complex interactions with SARS-CoV-2 and host immunity. Moreover, microbiota may have an impact on COVID-19 through their metabolites or modulation of ACE2 expression. Subsequently, we generalize the potential of microbiota as diagnostic markers for COVID-19 patients and its possible association with post-acute COVID-19 syndrome (PACS) and relapse after recovery. Finally, we proposed directed microbiota-targeted treatments from the perspective of gut microecology such as probiotics and prebiotics, fecal transplantation and antibiotics, and other interventions such as traditional Chinese medicine, COVID-19 vaccines, and ACE2-based treatments.}, }
@article {pmid36032720, year = {2022}, author = {Dong, Y and Xu, T and Xiao, G and Hu, Z and Chen, J}, title = {Opportunities and challenges for synthetic biology in the therapy of inflammatory bowel disease.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {10}, number = {}, pages = {909591}, doi = {10.3389/fbioe.2022.909591}, pmid = {36032720}, issn = {2296-4185}, abstract = {Inflammatory bowel disease (IBD) is a complex, chronic intestinal inflammatory disorder that primarily includes Crohn's disease (CD) and ulcerative colitis (UC). Although traditional antibiotics and immunosuppressants are known as the most effective and commonly used treatments, some limitations may be expected, such as limited efficacy in a small number of patients and gut flora disruption. A great many research studies have been done with respect to the etiology of IBD, while the composition of the gut microbiota is suggested as one of the most influential factors. Along with the development of synthetic biology and the continuing clarification of IBD etiology, broader prospects for novel approaches to IBD therapy could be obtained. This study presents an overview of the currently existing treatment options and possible therapeutic targets at the preclinical stage with respect to microbial synthesis technology in biological therapy. This study is highly correlated to the following topics: microbiota-derived metabolites, microRNAs, cell therapy, calreticulin, live biotherapeutic products (LBP), fecal microbiota transplantation (FMT), bacteriophages, engineered bacteria, and their functional secreted synthetic products for IBD medical implementation. Considering microorganisms as the main therapeutic component, as a result, the related clinical trial stability, effectiveness, and safety analysis may be the major challenges for upcoming research. This article strives to provide pharmaceutical researchers and developers with the most up-to-date information for adjuvant medicinal therapies based on synthetic biology.}, }
@article {pmid36032113, year = {2022}, author = {Kleber, KT and Iranpur, KR and Perry, LM and Cruz, SM and Razmara, AM and Culp, WTN and Kent, MS and Eisen, JA and Rebhun, RB and Canter, RJ}, title = {Using the canine microbiome to bridge translation of cancer immunotherapy from pre-clinical murine models to human clinical trials.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {983344}, doi = {10.3389/fimmu.2022.983344}, pmid = {36032113}, issn = {1664-3224}, abstract = {The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade (1-6). Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation (7, 8). Consequently, studies evaluating microbiota-host immune and metabolic interactions remain an area of high impact research. While observations in murine models have highlighted the importance of the microbiome in response to therapy, we lack sufficient understanding of the exact mechanisms underlying these interactions. Furthermore, mouse and human gut microbiome composition may be too dissimilar for discovery of all relevant gut microbial biomarkers. Multiple cancers in dogs, including lymphoma, high grade gliomas, melanomas and osteosarcoma (OSA) closely resemble their human analogues, particularly in regard to metastasis, disease recurrence and response to treatment. Importantly, dogs with these spontaneous cancers also have intact immune systems, suggesting that microbiome analyses in these subjects may provide high yield information, especially in the setting of novel immunotherapy regimens which are currently expanding rapidly in canine comparative oncology (9, 10). Additionally, as onco-microbiotic therapies are developed to modify gut microbiomes for maximal responsiveness, large animal models with intact immune systems will be useful for trialing interventions and monitoring adverse events. Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.}, }
@article {pmid36032108, year = {2022}, author = {He, L and Chen, R and Zhang, B and Zhang, S and Khan, BA and Zhu, D and Wu, Z and Xiao, C and Chen, B and Chen, F and Hou, K}, title = {Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes mellitus.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {930872}, doi = {10.3389/fimmu.2022.930872}, pmid = {36032108}, issn = {1664-3224}, abstract = {Type 1 diabetes mellitus (T1DM) is an autoimmune-mediated disease characterized by a reduced or absolute lack of insulin secretion and often associated with a range of vascular and neurological complications for which there is a lack of effective treatment other than lifestyle interventions and pharmacological treatments such as insulin injections. Studies have shown that the gut microbiota is involved in mediating the onset and development of many fecal and extrafecal diseases, including autoimmune T1DM. In recent years, many cases of gut microbiota transplantation for diseases of the bowel and beyond have been reported worldwide, and this approach has been shown to be safe and effective. Here, we conducted an experimental treatment study in two adolescent patients diagnosed with autoimmune T1DM for one year. Patients received one to three rounds of normal fecal microbiota transplants (FMT) and were followed for up to 30 weeks. Clinical outcomes were measured, including biochemical indices, medication regimen, and dosage adjustment. Fecal microbiota metagenomic sequencing after transplantation provides a reference for more reasonable and effective microbiota transplantation protocols to treat autoimmune T1DM. Our results suggest that FMT is an effective treatment for autoimmune T1DM.<br><br>Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2100045789.}, }
@article {pmid36030278, year = {2022}, author = {Zhang, Y and Gu, Y and Jiang, J and Cui, X and Cheng, S and Liu, L and Huang, Z and Liao, R and Zhao, P and Yu, J and Wang, J and Jia, Y and Jin, W and Zhou, F}, title = {Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {38}, pmid = {36030278}, issn = {2396-8370}, support = {81774213//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82174299//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81973802//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82074424//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81673949//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Stigmasterol (ST) has been shown to improve both lipid and bile acid (BA) metabolism. However, the mechanism(s) by which ST prevents dyslipidemia via BA metabolism, and the potential involvement of other regulatory mechanisms, remains unclear. Here, we found that ST treatment effectively alleviates lipid metabolism disorder induced by a high-fat diet (HFD). Moreover, we also show that fecal microbiota transplantation from ST-treated rats displays similar protective effects in rats fed on an HFD. Our data confirm that the gut microbiota plays a key role in attenuating HFD-induced fat deposition and metabolic disorders. In particular, ST reverses HFD-induced gut microbiota dysbiosis in rats by reducing the relative abundance of Erysipelotrichaceae and Allobaculum bacteria in the gut. In addition, ST treatment also modifies the serum and fecal BA metabolome profiles in rats, especially in CYP7A1 mediated BA metabolic pathways. Furthermore, chenodeoxycholic acid combined with ST improves the therapeutic effects in HFD-induced dyslipidemia and hepatic steatosis. In addition, this treatment strategy also alters BA metabolism profiles via the CYP7A1 pathway and gut microbiota. Taken together, ST exerts beneficial effects against HFD-induced hyperlipidemia and obesity with the underlying mechanism being partially related to both the reprogramming of the intestinal microbiota and metabolism of BAs in enterohepatic circulation. This study provides a theoretical basis for further study of the anti-obesity effects of ST and consideration of the gut microbiota as a potential target for the treatment of HFD-induced dyslipidemia.}, }
@article {pmid36028255, year = {2022}, author = {Badran, M and Khalyfa, A and Ericsson, A and Puech, C and McAdams, Z and Bender, SB and Gozal, D}, title = {Gut microbiota mediate vascular dysfunction in a murine model of sleep apnea: effect of probiotics.}, journal = {The European respiratory journal}, volume = {}, number = {}, pages = {}, doi = {10.1183/13993003.00002-2022}, pmid = {36028255}, issn = {1399-3003}, abstract = {RATIONALE: Obstructive sleep apnea (OSA) is a chronic prevalent condition characterised by intermittent hypoxia (IH) and is associated with endothelial dysfunction and coronary artery disease (CAD). OSA can induce major changes in gut microbiome (GM) diversity and composition, which in turn may induce the emergence of OSA-associated morbidities. However, the causal effects of IH-induced GM changes on the vasculature remain unexplored.<br><br>OBJECTIVES: To assess if vascular dysfunction induced by IH is mediated through GM changes.<br><br>METHODS: Fecal microbiota transplantation (FMT) was conducted on C57BL/6J naïve mice for 6 weeks to receive either IH or room air (RA) fecal slurry with or without probiotics (VSL3). In addition to 16S rRNA amplicon sequencing of their GM, FMT recipients underwent arterial blood pressure (aBP) and coronary artery and aorta function testing, and their trimethylamine N-oxide (TMAO) and plasma acetate levels were determined. Finally, C57BL/6J mice were exposed to IH, IH treated with VSL3, or RA for 6 weeks, and assessed aBP and coronary artery function.<br><br>RESULTS: GM taxonomic profiles correctly segregated IH from RA in FMT mice, and the normalising effect of probiotics emerged. Furthermore, IH-FMT mice exhibited increased aBP and TMAO levels, and impairments in aortic and coronary artery function (p<0.05) that were abrogated by probiotic administration. Lastly, Treatment with VSL3 under IH conditions did not attenuate elevations in aBP or CAD.<br><br>CONCLUSIONS: Thus, GM alterations induced by chronic IH underlie, at least partially, the typical cardiovascular disturbances of sleep apnea, and can be mitigated by concurrent administration of probiotics.}, }
@article {pmid36028087, year = {2022}, author = {Roth, RS and Liden, M and Huttner, A}, title = {The urobiome in men and women: a clinical review.}, 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.2022.08.010}, pmid = {36028087}, issn = {1469-0691}, abstract = {BACKGROUND: Antibiotic therapy alone is unable to control recurrent urinary tract infection (UTI); uropathogens have become multiresistant and alternative strategies are needed. Far from sterile, the urinary tract contains various low-biomass microbiota, some of whose members appear to protect against clinical UTI.<br><br>OBJECTIVES: This narrative review summarises (1) current knowledge of the male and female urobiomes in healthy and diseased states, as well as their interplay among sexual partners, and (2) clinical trials to date assessing probiotic and other non-antibiotic measures to reduce UTI.<br><br>SOURCES: We used the Pubmed interface to search Ovid Medline for articles describing urogenital flora, UTI, UTI dysbiosis, the effects of sexual intercourse on urogenital flora, and clinical trials of probiotics as UTI prophylaxis.<br><br>CONTENT: The healthy urobiome of women contains several Lactobacillus species, some of which may impede E. coli growth in the urinary tract. While Lactobacilli have been found in male urethral microbiota, their presence in male bladder microbiota is less certain. Distal male urethral and vaginal microbiomes of male and sexual female partners influence one another, but more research is needed on the direct interplay of their full urobiomes. Clinical trials assessing the therapeutic potential of Lactobacilli have been largely underpowered and highly varied in tested formulations and routes and frequencies of administration; as such they have failed to show a clear benefit. Fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection was shown, in a retrospective study of seven patients, to reduce recurrent UTI as a side effect.<br><br>IMPLICATIONS: The urobiome in men and women is complex, variable, and still understudied. While there is hope that Lactobacilli and FMT could be future non-antibiotic options for recurrent UTI, both require more pharmacologic and clinical research to identify optimal preparations and routes of administration.}, }
@article {pmid36014889, year = {2022}, author = {Zhai, Z and Dong, W and Sun, Y and Gu, Y and Ma, J and Wang, B and Cao, H}, title = {Vitamin-Microbiota Crosstalk in Intestinal Inflammation and Carcinogenesis.}, journal = {Nutrients}, volume = {14}, number = {16}, pages = {}, doi = {10.3390/nu14163383}, pmid = {36014889}, issn = {2072-6643}, abstract = {Inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) are common diseases of the digestive system. Vitamin deficiencies and gut microbiota dysbiosis have a close relationship with the risk, development, and progression of IBD and CAC. There is a strong link between vitamins and the gut microbiome. Vitamins are extremely crucial for maintaining a healthy gut microbiota, promoting growth and development, metabolism, and innate immunity. Gut microbiota can not only influence the transport process of vitamins, but also produce vitamins to compensate for insufficient food intake. Emerging evidence suggests that oral vitamin supplementation can reduce inflammation levels and improve disease prognosis. In addition, improving the diet structure and consuming foods rich in vitamins not only help to improve the vitamin deficiency, but also help to reduce the risk of IBD. Fecal microbiota transplantation (FMT) and the application of vitamin-producing probiotics can better assist in the treatment of intestinal diseases. In this review, we discuss the interaction and therapeutic roles of vitamins and gut microbiota in IBD and CAC. We also summarize the methods of treating IBD and CAC by modulating vitamins. This may highlight strategies to target gut-microbiota-dependent alterations in vitamin metabolism in the context of IBD and CAC therapy.}, }
@article {pmid36013342, year = {2022}, author = {Al, KF and Chmiel, JA and Stuivenberg, GA and Reid, G and Burton, JP}, title = {Long-Duration Space Travel Support Must Consider Wider Influences to Conserve Microbiota Composition and Function.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, doi = {10.3390/life12081163}, pmid = {36013342}, issn = {2075-1729}, abstract = {The microbiota is important for immune modulation, nutrient acquisition, vitamin production, and other aspects for long-term human health. Isolated model organisms can lose microbial diversity over time and humans are likely the same. Decreasing microbial diversity and the subsequent loss of function may accelerate disease progression on Earth, and to an even greater degree in space. For this reason, maintaining a healthy microbiome during spaceflight has recently garnered consideration. Diet, lifestyle, and consumption of beneficial microbes can shape the microbiota, but the replenishment we attain from environmental exposure to microbes is important too. Probiotics, prebiotics, fermented foods, fecal microbiota transplantation (FMT), and other methods of microbiota modulation currently available may be of benefit for shorter trips, but may not be viable options to overcome the unique challenges faced in long-term space travel. Novel fermented food products with particular impact on gut health, immune modulation, and other space-targeted health outcomes are worthy of exploration. Further consideration of potential microbial replenishment to humans, including from environmental sources to maintain a healthy microbiome, may also be required.}, }
@article {pmid36012266, year = {2022}, author = {Won, SM and Oh, KK and Gupta, H and Ganesan, R and Sharma, SP and Jeong, JJ and Yoon, SJ and Jeong, MK and Min, BH and Hyun, JY and Park, HJ and Eom, JA and Lee, SB and Cha, MG and Kwon, GH and Choi, MR and Kim, DJ and Suk, KT}, title = {The Link between Gut Microbiota and Hepatic Encephalopathy.}, journal = {International journal of molecular sciences}, volume = {23}, number = {16}, pages = {}, doi = {10.3390/ijms23168999}, pmid = {36012266}, issn = {1422-0067}, support = {Hallym University Research Fund//Hallym University Research Fund/ ; NRF-2020R1I1A3073530 and NRF-2020R1A6A1A03043026//Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology/ ; }, abstract = {Hepatic encephalopathy (HE) is a serious complication of cirrhosis that causes neuropsychiatric problems, such as cognitive dysfunction and movement disorders. The link between the microbiota and the host plays a key role in the pathogenesis of HE. The link between the gut microbiome and disease can be positively utilized not only in the diagnosis area of HE but also in the treatment area. Probiotics and prebiotics aim to resolve gut dysbiosis and increase beneficial microbial taxa, while fecal microbiota transplantation aims to address gut dysbiosis through transplantation (FMT) of the gut microbiome from healthy donors. Antibiotics, such as rifaximin, aim to improve cognitive function and hyperammonemia by targeting harmful taxa. Current treatment regimens for HE have achieved some success in treatment by targeting the gut microbiota, however, are still accompanied by limitations and problems. A focused approach should be placed on the establishment of personalized trial designs and therapies for the improvement of future care. This narrative review identifies factors negatively influencing the gut-hepatic-brain axis leading to HE in cirrhosis and explores their relationship with the gut microbiome. We also focused on the evaluation of reported clinical studies on the management and improvement of HE patients with a particular focus on microbiome-targeted therapy.}, }
@article {pmid36009962, year = {2022}, author = {Beyi, AF and Wannemuehler, M and Plummer, PJ}, title = {Impacts of Gut Microbiota on the Immune System and Fecal Microbiota Transplantation as a Re-Emerging Therapy for Autoimmune Diseases.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, doi = {10.3390/antibiotics11081093}, pmid = {36009962}, issn = {2079-6382}, abstract = {The enormous and diverse population of microorganisms residing in the digestive tracts of humans and animals influence the development, regulation, and function of the immune system. Recently, the understanding of the association between autoimmune diseases and gut microbiota has been improved due to the innovation of high-throughput sequencing technologies with high resolutions. Several studies have reported perturbation of gut microbiota as one of the factors playing a role in the pathogenesis of many diseases, such as inflammatory bowel disease, recurrent diarrhea due to Clostridioides difficile infections. Restoration of healthy gut microbiota by transferring fecal material from a healthy donor to a sick recipient, called fecal microbiota transplantation (FMT), has resolved or improved symptoms of autoimmune diseases. This (re)emerging therapy was approved for the treatment of drug-resistant recurrent C. difficile infections in 2013 by the U.S. Food and Drug Administration. Numerous human and animal studies have demonstrated FMT has the potential as the next generation therapy to control autoimmune and other health problems. Alas, this new therapeutic method has limitations, including the risk of transferring antibiotic-resistant pathogens or transmission of genes from donors to recipients and/or exacerbating the conditions in some patients. Therefore, continued research is needed to elucidate the mechanisms by which gut microbiota is involved in the pathogenesis of autoimmune diseases and to improve the efficacy and optimize the preparation of FMT for different disease conditions, and to tailor FMT to meet the needs in both humans and animals. The prospect of FMT therapy includes shifting from the current practice of using the whole fecal materials to the more aesthetic transfer of selective microbial consortia assembled in vitro or using their metabolic products.}, }
@article {pmid36009566, year = {2022}, author = {Drapkina, OM and Yafarova, AA and Kaburova, AN and Kiselev, AR}, title = {Targeting Gut Microbiota as a Novel Strategy for Prevention and Treatment of Hypertension, Atrial Fibrillation and Heart Failure: Current Knowledge and Future Perspectives.}, journal = {Biomedicines}, volume = {10}, number = {8}, pages = {}, doi = {10.3390/biomedicines10082019}, pmid = {36009566}, issn = {2227-9059}, abstract = {Cardiovascular diseases (CVDs) remain the major public health concern worldwide. Over the last two decades, a considerable amount of literature has been published on gut microbiota (GMB) composition and its metabolites, involved in the pathophysiology of CVDs, including arterial hypertension, atrial fibrillation, and congestive heart failure. Although many types of medicines are available to treat CVD, new therapeutic tools are needed to improve clinical outcomes. A challenge that often arises in the researchers' community is how to manipulate the GMB to manage cardiovascular risk factors. Therapeutic strategies designed to manipulate GMB composition and/or its metabolites include dietary approaches, prebiotics/probiotics supplementation, and fecal microbiota transplantation (FMT). In this review, we have focused on three main cardiovascular pathologies (arterial hypertension, atrial fibrillation and heart failure) due to their shared common pathophysiological pathways and structural changes in myocardium, such as inflammation, hypertrophy, fibrosis, and myocardial remodeling. The main aims of the review are: (1) to summarize current knowledge on the key pathophysiologic links between GMB and CVDs, and (2) discuss the results of the studies on GMB modulation for the prevention and treatment of selected CVDs.}, }
@article {pmid36008350, year = {2022}, author = {Ren, Y and Wang, Z and Xue, J}, title = {[Gut-derived uremic toxin trimethylamine-N-oxide in cardiovascular disease under end-stage renal disease: an injury mechanism and therapeutic target].}, journal = {Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi}, volume = {39}, number = {4}, pages = {848-852}, doi = {10.7507/1001-5515.202110017}, pmid = {36008350}, issn = {1001-5515}, abstract = {The main cause of death in patients with end-stage renal disease (ESRD) is cardiovascular disease, and trimethylamine-N-oxide (TMAO) has been found to be one of the specific risk factors in the pathogenic process in recent years. TMAO is derived from intestinal bacterial metabolism of dietary choline, carnitine and other substances and subsequently catalyzed by flavin monooxygenase enzymes in the liver. The changes of intestinal bacteria in ESRD patients have contributed to the accumulation of gut-derived uremic toxins such as TMAO, indoxyl sulfate and indole-3-acetic acid. While elevated TMAO concentration accelerates atherosclerosis through mechanisms such as inflammation, increased scavenger receptor expression, and inhibition of reverse cholesterol transport. In this review, this research introduces the biological function, metabolic processes of TMAO and mechanisms by which TMAO promotes the progression of cardiovascular disease in ESRD patients and summarizes current interventions that may be used to reverse gut microbiota disturbances, such as activated carbon, fecal microbial transplantation, dietary improvement, probiotic and probiotic introduction. It also focuses on exploring intervention targets to reduce the gut-derived uremic toxin TMAO in order to explore the possibility of more cardiovascular disease treatments for ESRD patients.}, }
@article {pmid36006314, year = {2022}, author = {Tuniyazi, M and Hu, X and Fu, Y and Zhang, N}, title = {Canine Fecal Microbiota Transplantation: Current Application and Possible Mechanisms.}, journal = {Veterinary sciences}, volume = {9}, number = {8}, pages = {}, doi = {10.3390/vetsci9080396}, pmid = {36006314}, issn = {2306-7381}, abstract = {Fecal microbiota transplantation (FMT) is an emerging therapeutic option for a variety of diseases, and is characterized as the transfer of fecal microorganisms from a healthy donor into the intestinal tract of a diseased recipient. In human clinics, FMT has been used for treating diseases for decades, with promising results. In recent years, veterinary specialists adapted FMT in canine patients; however, compared to humans, canine FMT is more inclined towards research purposes than practical applications in most cases, due to safety concerns. Therefore, in order to facilitate the application of fecal transplant therapy in dogs, in this paper, we review recent applications of FMT in canine clinical treatments, as well as possible mechanisms that are involved in the process of the therapeutic effect of FMT. More research is needed to explore more effective and safer approaches for conducting FMT in dogs.}, }
@article {pmid36005641, year = {2022}, author = {Cai, L and Li, M and Zhou, S and Zhu, X and Zhang, X and Xu, Q}, title = {Trans-Species Fecal Transplant Revealed the Role of the Gut Microbiome as a Contributor to Energy Metabolism and Development of Skeletal Muscle.}, journal = {Metabolites}, volume = {12}, number = {8}, pages = {}, doi = {10.3390/metabo12080769}, pmid = {36005641}, issn = {2218-1989}, abstract = {The aim of this study was to investigate the influence of the exogenous gut microbiome at early life stages on the development of mice skeletal muscle in adulthood. First, the characteristics of skeletal muscle and the gut microbiota composition of the gut microbiota donors-Erhualian (EH) pigs (a native Chinese breed)-were studied. EH pigs had significantly higher fiber densities and thinner fiber diameters than Duroc × Landrace × Yorkshire crossed (DLY) pigs (p < 0.05). The expression levels of genes related to oxidized muscle fibers, mitochondrial function, and glucose metabolism in the skeletal muscle of EH pigs were significantly higher than those in DLY pigs (p < 0.05). Moreover, the abundances of 8 gut microbial phyla and 35 genera correlated with the skeletal muscle fiber diameters and densities exhibited significant differences (p < 0.05) between EH and DLY pigs. Subsequently, newborn mice were treated with saline (CG) and fecal microbiota suspensions collected from EH pigs (AG), respectively, for 15 days, starting from the day of birth. In adulthood (60 days), the relative abundances of Parabacteroides, Sutterella, and Dehalobacterium were significantly higher in the feces of the AG mice than those of the CG mice. The microbes contribute to improved functions related to lipid and carbohydrate metabolism. The weight, density, and gene expression related to the oxidized muscle fibers, mitochondrial function, and glucose metabolism of the AG group were significantly higher than those of the CG group (p < 0.05), whereas the fiber diameters in the skeletal muscle of the AG mice were significantly lower (p < 0.05) than those of the CG mice. These results suggested that intervention with exogenous microbiota at early stages of life can affect the fiber size and energy metabolism of their skeletal muscle.}, }
@article {pmid36004633, year = {2022}, author = {Lee, MR and Kim, ES}, title = {[Clostridioides Infection in Patients with Inflammatory Bowel Disease].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {80}, number = {2}, pages = {66-71}, doi = {10.4166/kjg.2022.097}, pmid = {36004633}, issn = {2233-6869}, abstract = {Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal tract, which is often accompanied by altered gut microbial composition. Gut dysbiosis in IBD is considered to be the reason for the high risk of Clostridioides difficile infection (CDI) in patients with IBD. Therefore, CDI should be evaluated in IBD patients with a symptom flare. Medical treatment of non-severe CDI in IBD is similar to that in non-IBD patients and includes oral vancomycin or fidaxomicin. The risk of recurrent CDI in IBD is higher than in non-IBD patients and this could be mitigated by fecal microbiota transplantation. As CDI may worsen the clinical outcomes of IBD, patients should be carefully monitored and an escalation of IBD therapy needs to be considered when there is no improvement seen with the antimicrobial treatment of CDI. This review discusses the risk, pathophysiology, diagnosis, and management of CDI in IBD.}, }
@article {pmid36003287, year = {2022}, author = {Xie, YC and Jing, XB and Chen, X and Chen, LZ and Zhang, SH and Cai, XB}, title = {Fecal microbiota transplantation treatment for type 1 diabetes mellitus with malnutrition: a case report.}, journal = {Therapeutic advances in chronic disease}, volume = {13}, number = {}, pages = {20406223221117449}, doi = {10.1177/20406223221117449}, pmid = {36003287}, issn = {2040-6223}, abstract = {Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease. Not only genetics, but the intestinal environment affected by gut microbiota is also the key to pathogenesis. Besides the occurrence of diabetes, gut microbiota dysbiosis may also contribute to the development of diabetes-related complications. Fecal microbiota transplantation (FMT) is an emerging technique that had shown its potential as a treatment for metabolic disease. Here, we report the first case of T1DM with malnutrition and gastrointestinal symptoms treated with FMT. A 24-year-old T1DM patient suffered from poor blood glucose control, recurrent nausea and vomiting, severe malnutrition, and intractable constipation after insulin treatment. The clinical response of the patients after FMT was well, especially nausea and vomiting were significantly relieved. In addition, constipation, nutritional status, and blood glucose control (fasting blood glucose, HbA1c) gradually improved. A degree of similarity was found in gut microbiota composition between the patient and healthy donor after FMT while it was totally different before the treatment. Furthermore, pathway function analysis of MetaCYC database implies that the potential mechanism of the response of FMT may be driven by specific bacteria involved in several metabolic pathways that need further exploration. To sum up, we believe that the reconstruction of intestinal flora by FMT may be a new choice for the treatment of T1DM patients with malnutrition.}, }
@article {pmid35992705, year = {2022}, author = {Qin, S and Wang, Y and Wang, S and Ning, B and Huai, J and Yang, H}, title = {Gut microbiota in women with gestational diabetes mellitus has potential impact on metabolism in pregnant mice and their offspring.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {870422}, doi = {10.3389/fmicb.2022.870422}, pmid = {35992705}, issn = {1664-302X}, abstract = {Studies have shown that gestational diabetes mellitus (GDM) is closely related to abnormalities in the gut microbiota, and the offspring of these women have an increased risk of diabetes. There is no direct evidence of whether bacteria in women with GDM colonize the intestinal tract of offspring and cause hyperglycemia. In this fecal microbiota transplantation (FMT), pregnant mouse model study, two groups of germ-free (GF) mice after FMT showed different colonization patterns of gut microbiota and phenotype. Compared with the control group (healthy-FMT), we found in the GDM-FMT group as a lower relative abundance of Akkermansia and Faecalibacterium; a lower content of short-chain fatty acids and naringenin in feces; an elevated blood glucose; an inflammatory factor expression (TNF-α, CXCL-15, and IL-6), and a hepatic fat deposition. In addition, the influence of the gut microbiota continued in offspring. The gut microbiota of the offspring of GDM-FMT mice was still different from that of the control group as a lower relative abundance of Akkermansia and Parvibacter; and a higher relative abundance of bacteria such as Oscillibacter, Romboutsia, and Harryflintia. In addition, the offspring of GDM-FMT mice had higher body weight and blood glucose levels than the control offspring.}, }
@article {pmid35985814, year = {2022}, author = {Holle, J and Bartolomaeus, H and Löber, U and Behrens, F and Bartolomaeus, T and Anandakumar, H and Wimmer, M and Vu, DL and Kuhring, M and Brüning, U and Maifeld, A and Geisberger, S and Kempa, S and Schumacher, F and Kleuser, B and Bufler, P and Querfeld, U and Kitschke, S and Engler, D and Kuhrt, L and Drechsel, O and Eckardt, KU and Forslund, S and Thürmer, A and McParland, V and Kirwan, J and Wilck, N and Mueller, D}, title = {Inflammation in Children with Chronic Kidney Disease Linked to Gut Dysbiosis and Metabolite Imbalance.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {}, number = {}, pages = {}, doi = {10.1681/ASN.2022030378}, pmid = {35985814}, issn = {1533-3450}, abstract = {Background: Chronic kidney disease (CKD) is characterized by a sustained proinflammatory response of the immune system, promoting hypertension and cardiovascular disease. The underlying mechanisms are incompletely understood, but may be linked to gut dysbiosis. Dysbiosis has been described in adults with CKD; however, comorbidities limit CKD-specific conclusions. Methods: We analyzed the fecal microbiome, metabolites, and immune phenotypes in 48 children (normal kidney function, CKD stage G3-G4, G5 treated by hemodialysis (HD) or kidney transplantation) with a mean age of 10.6 ± 3.8 years. Results: Serum TNF-α and sCD14 were stage-dependently elevated, indicating inflammation, gut barrier dysfunction, and endotoxemia. We observed compositional and functional alterations of the microbiome, including diminished production of short-chain fatty acids. Plasma metabolite analysis revealed a stage-dependent increase of tryptophan metabolites of bacterial origin. Serum from HD patients activated the aryl hydrocarbon receptor and stimulated TNF-α production in monocytes, corresponding to a proinflammatory shift from classical to non classical and intermediate monocytes. Unsupervised analysis of T cells revealed a loss of mucosa-associated invariant T (MAIT) cells and regulatory T cell subtypes in HD patients. Conclusions: Gut barrier dysfunction and microbial metabolite imbalance apparently mediate the pro-inflammatory immune phenotype, thereby driving the susceptibility to cardiovascular disease. The data highlight the importance of the microbiota-immune axis in CKD, irrespective of confounding comorbidities.}, }
@article {pmid35987480, year = {2022}, author = {Ren, Z and Chen, S and Lv, H and Peng, L and Yang, W and Chen, J and Wu, Z and Wan, C}, title = {Effect of Bifidobacterium animalis subsp. lactis SF on enhancing the tumor suppression of irinotecan by regulating the intestinal flora.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106406}, doi = {10.1016/j.phrs.2022.106406}, pmid = {35987480}, issn = {1096-1186}, abstract = {The gut microbiota plays a role in tumor therapy by participating in immune regulation. Here, we demonstrated through 8-day probiotic supplementation experiments and fecal microbiota transplantation experiments that Bifidobacterium animalis subsp. lactis SF enhanced the antitumor effect of irinotecan and prevented the occurrence of intestinal damage by modulating the gut microbiota and reducing the relative abundance of pro-inflammatory microbiota. Therefore, the intestinal inflammation was inhibited, the TGF-β leakage was reduced, and the PI3K/AKT pathway activation was inhibited. Thus, the tumor apoptotic autophagy was finally promoted. Simultaneously, the reduction of TGF-β relieved the immunosuppression caused by CPT-11, promoted the differentiation of CD4+ and CD8+ T cells in tumor tissue, and consequently inhibited tumor growth and invasion. This study disclosed the mechanism of B. lactis SF assisting CPT-11 in antitumor activity and suggested that B. lactis SF plays a new role in anticancer effects as a nutritional intervention.}, }
@article {pmid35980280, year = {2022}, author = {Park, SH and Lee, JH and Kim, JS and Kim, TJ and Shin, J and Im, JH and Cha, B and Lee, S and Kwon, KS and Shin, YW and Ko, SB and Choi, SH}, title = {Fecal microbiota transplantation can improve cognition in patients with cognitive decline and Clostridioides difficile infection.}, journal = {Aging}, volume = {14}, number = {undefined}, pages = {}, doi = {10.18632/aging.204230}, pmid = {35980280}, issn = {1945-4589}, abstract = {After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although the gut microbiome has been associated with cognitive function, it remains to be elucidated whether fecal microbiota transplantation can improve cognition in patients with cognitive decline. The study included 10 patients (age range, 63-90 years; female, 80%) with dementia and severe CDI who were receiving FMT. Also, 10 patients (age range, 62-91; female, 80%) with dementia and severe CDI who were not receiving FMT. They were evaluated using cognitive function tests (Mini-Mental State Examination [MMSE] and Clinical Dementia Rating scale Sum of Boxes [CDR-SB]) at 1 month before and after FMT or antibiotics treatment (control group). The patients' fecal samples were analyzed to compare the composition of their gut microbiota before and 3 weeks after FMT or antibiotics treatment. Ten patients receiving FMT showed significantly improvements in clinical symptoms and cognitive functions compared to control group. The MMSE and CDR-SB of FMT group were improved compare to antibiotics treatment (MMSE: 16.00, median, 13.00-18.00 [IQR] vs. 10.0, median, 9.8-15.3 [IQR]); CDR-SB: 5.50, median, 4.00-8.00 [IQR]) vs. 8.0, median, 7.9-12.5, [IQR]). FMT led to changes in the recipient's gut microbiota composition, with enrichment of Proteobacteria and Bacteroidetes. Alanine, aspartate, and glutamate metabolism pathways were also significantly different after FMT. This study revealed important interactions between the gut microbiome and cognitive function. Moreover, it suggested that FMT may effectively delay cognitive decline in patients with dementia.}, }
@article {pmid35978650, year = {2022}, author = {Quaranta, G and Ianiro, G and De Maio, F and Guarnaccia, A and Fancello, G and Agrillo, C and Iannarelli, F and Bibbo, S and Amedei, A and Sanguinetti, M and Cammarota, G and Masucci, L}, title = {"Bacterial Consortium": A Potential Evolution of Fecal Microbiota Transplantation for the Treatment of Clostridioides difficile Infection.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {5787373}, doi = {10.1155/2022/5787373}, pmid = {35978650}, issn = {2314-6141}, abstract = {Fecal microbiota transplantation (FMT) consists of infusion of feces from a donor to a recipient patient in order to restore the resident microbial population. FMT has shown to be a valid clinical option for Clostridioides difficile infections (CDI). However, this approach shows several criticalities, such as the recruiting and screening of voluntary donors. Our aim was to evaluate the therapeutic efficacy of a synthetic bacterial suspension defined "Bacterial Consortium" (BC) infused in the colon of CDI patients. The suspension was composed by 13 microbial species isolated by culturomics protocols from healthy donors' feces. The efficacy of the treatment was assessed both clinically and by metagenomics typing. Fecal samples of the recipient patients were collected before and after infusion. DNA samples obtained from feces at different time points (preinfusion, 7, 15, 30, and 90 days after infusion) were analyzed by next-generation sequencing. Before infusion, patient 1 showed an intestinal microbiota dominated by the phylum Bacteroidetes. Seven days after the infusion, Bacteroidetes decreased, followed by an implementation of Firmicutes and Verrucomicrobia. Patient 2, before infusion, showed a strong abundance of Proteobacteria and a significant deficiency of Bacteroidetes and Verrucomicrobia. Seven days after infusion, Proteobacteria strongly decreased, while Bacteroidetes and Verrucomicrobia increased. Metagenomics data revealed an "awakening" by microbial species absent or low concentrated at time T0 and present after the infusion. In conclusion, the infusion of selected bacteria would act as a trigger factor for "bacterial repopulation" representing an innovative treatment in patients with Clostridioides difficile infections.}, }
@article {pmid35977403, year = {2022}, author = {Kong, CY and Li, ZM and Chen, HL and Mao, YQ and Han, B and Guo, JJ and Wang, LS}, title = {An Energy-Restricted Diet Including Yogurt, Fruit, and Vegetables Alleviates High-Fat Diet-Induced Metabolic Syndrome in Mice By Modulating the Gut Microbiota.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1093/jn/nxac181}, pmid = {35977403}, issn = {1541-6100}, abstract = {BACKGROUND: The importance of the composition of an energy-restricted diet in the treatment of metabolic syndrome (MetS) is unknown.<br><br>OBJECTIVES: This study aimed to investigate the benefits of a novel dietary treatment (50% calorie restriction diet composed of yogurt, fruit, and vegetables (CR-YD)) on MetS mice.<br><br>METHODS: Forty 7-week-old male C57BL/6 J mice were randomly assigned to 4 groups (n = 10/group) that consumed for 14week ad libitum a normal diet (ND, 10:70:20% energy from fat: carbohydrate: protein) or a high-fat diet (HFD, 60:20:20) or the HFD for 12week followed by 2week of consuming at 50% calorie-restriction the HFD (CR-HFD) or YD (CR-YD, 21.2: 65.4: 13.4% energy). Body weight, fat deposition, hepatic steatosis, serum concentrations of inflammatory biomarkers, and glucose homeostasis were assessed. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in MetS.<br><br>RESULTS: The HFD group had 50% greater body weight and 475% greater fat deposition than the ND group (P < 0.05). Compared with the HFD group, the CR-HFD and CR-YD groups had 22% and 31% lower body weight and 49% and 75% less fat deposition, respectively (P < 0.05). Compared with the CR-HFD group, the CR-YD group had 11% lower body weight, 96% less fat deposition, 500% less hepatic steatosis, 75% lower glucose, 450% greater hepatic Akkermansia (P < 0.05). The CR-YD group also had 50% lower histopathology scores, and 1.35-fold higher levels of Claudin4 than the CR-HFD group (P < 0.05). HFD + CR-YD fecal group had 10.6% lower body weight, 119% lower steatosis, and 17.9% lower glucose (P < 0.05) than HFD + CR-HFD fecal group.<br><br>CONCLUSIONS: Compared with CR alone, the CR-YD diet has a better therapeutic effect in mice with HFD-induced MetS.}, }
@article {pmid35975640, year = {2022}, author = {Kang, GU and Park, S and Jung, Y and Jee, JJ and Kim, MS and Lee, S and Lee, DW and Shin, JH and Koh, H}, title = {Exploration of Potential Gut Microbiota-Derived Biomarkers to Predict the Success of Fecal Microbiota Transplantation in Ulcerative Colitis: A Prospective Cohort in Korea.}, journal = {Gut and liver}, volume = {}, number = {}, pages = {}, doi = {10.5009/gnl210369}, pmid = {35975640}, issn = {2005-1212}, abstract = {Background/Aims: Although fecal microbiota transplantation (FMT) has been proven as one of the promising treatments for patients with ulcerative colitis (UC), potential prognostic markers regarding the clinical outcomes of FMT remain elusive.<br><br>Methods: We collected fecal samples of 10 participants undergoing FMT to treat UC and those from the corresponding donors. We categorized them into two groups: responders and nonresponders. Sequencing of the bacterial 16S rRNA gene was conducted on the samples to explore bacterial composition.<br><br>Results: Analyzing the gut microbiota of patients who showed different outcomes in FMT presented a distinct microbial niche. Source tracking analysis showed the nonresponder group had a higher rate of preservation of donor microbiota, underscoring that engraftment degrees are not one of the major drivers for the success of FMT. At the phylum level, Bacteroidetes bacteria were significantly depleted (p<0.003), and three genera, including Enterococcus, Rothia, and Pediococcus, were enriched in the responder group before FMT (p=0.003, p=0.025, and p=0.048, respectively). Furthermore, we applied a machine learning algorithm to build a prediction model that might allow the prediction of FMT outcomes, which yielded an area under the receiver operating characteristic (ROC) curve of 0.844. Notably, the microbiota-based model was much better at predicting outcomes than the clinical features model (area under the ROC curve=0.531).<br><br>Conclusions: This study is the first to suggest the significance of indigenous microbiota of recipients as a critical factor. The result highlights that bacterial composition should be evaluated before FMT to select suitable patients and achieve better efficiency.}, }
@article {pmid35975460, year = {2022}, author = {Shang, J and Zhang, Y and Guo, R and Liu, W and Zhang, J and Yan, G and Wu, F and Cui, W and Wang, P and Zheng, X and Wang, T and Dong, Y and Zhao, J and Wang, L and Xiao, J and Shang, H and Zhao, Z}, title = {Gut Microbiome Analysis Can Be Used as a Noninvasive Diagnostic Tool and Plays an Essential Role in the Onset of Membranous Nephropathy.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2201581}, doi = {10.1002/advs.202201581}, pmid = {35975460}, issn = {2198-3844}, support = {81873611//National Natural Science Foundation of China/ ; 82170738//National Natural Science Foundation of China/ ; //2020 key project of Medical Science and Technology/ ; //Biobank of The First Affiliated Hospital of Zhengzhou University/ ; 2005DKA21300//National Human Genetic Resources Sharing Service Platform/ ; }, abstract = {Membranous nephropathy (MN) is a common cause of nephrotic syndrome. The aim is to establish a non-invasive diagnostic model of MN using differential gut microbiome analysis, and to explore the relationship between the gut microbiome and MN pathogenesis in vivo. 825 fecal samples from MN patients and healthy participants are collected from multiple medical centers across China. Key operational taxonomic units (OTUs) obtained through 16S rRNA sequencing are used to establish a diagnostic model. A rat model of MN is developed to explore the relationship between the gut microbiome and the pathogenesis of MN. The diversity and richness of the gut microbiome are significantly lower in patients with MN than in healthy individuals. The diagnostic model based on seven OTUs achieves an excellent efficiency of 98.36% in the training group and also achieves high efficiency in cross-regional cohorts. In MN rat model, gut microbiome elimination prevents model establishment, but fecal microbiome transplantation restores the phenotype of protein urine. Gut microbiome analysis can be used as a non-invasive tool for MN diagnosis. The onset of MN depends on the presence of naturally colonized microbiome. Early intervention in the gut microbiome may help reduce urinary protein level in MN.}, }
@article {pmid35969165, year = {2022}, author = {Letsinger, AC and Yang, F and Menon, R and Little-Letsinger, SE and Granados, JZ and Breidenbach, B and Iyer, AR and Padovani, TC and Nagel, EC and Jayaraman, A and Lightfoot, JT}, title = {Reduced Wheel Running via a High-Fat Diet Is Reversed by a Chow Diet with No Added Benefit from Fecal Microbial Transplants.}, journal = {Medicine and science in sports and exercise}, volume = {54}, number = {9}, pages = {1437-1447}, doi = {10.1249/MSS.0000000000002941}, pmid = {35969165}, issn = {1530-0315}, mesh = {Animals ; *Diet, High-Fat ; *Fatty Liver ; Fecal Microbiota Transplantation ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity ; }, abstract = {PURPOSE: Chronic overfeeding via a high-fat/high-sugar (HFHS) diet decreases wheel running and substantially alters the gut metabolome of C57BL/6J mice. In this study, we tested the hypothesis that fecal microbial transplants can modulate the effect of diet on wheel running.<br><br>METHODS: Singly housed, 6-wk-old male C57BL/6J mice were fed either a grain-based diet (CHOW) or HFHS diet and provided a running wheel for 13 wk. Low-active, HFHS-exposed mice were then either switched to a CHOW diet and given an oral fecal microbial transplant from mice fed the CHOW diet, switched to a CHOW diet and given a sham transplant, or remained on the HFHS diet and given a fecal microbial transplant from mice fed the CHOW diet. Total wheel running, nutrient intake, body composition, fecal microbial composition, fecal metabolite composition, and liver steatosis were measured at various times throughout the study.<br><br>RESULTS: We found that an HFHS diet decreases wheel running activity, increases body fat, and decreases microbial alpha diversity compared with a CHOW diet. Improvements in wheel running, body composition, and microbial alpha diversity were accomplished within 2 wk for mice switched from an HFHS diet to a CHOW diet with no clear evidence of an added benefit from fecal transplants. A fecal transplant from mice fed a CHOW diet without altering diet did not improve wheel running or body composition. Wheel running, body composition, fecal microbial composition, fecal metabolite composition, and liver steatosis percentage were primarily determined by diet.<br><br>CONCLUSIONS: Our results suggest that diet is a primary mediator of wheel running with no clear effect from fecal microbial transplants.}, }
@article {pmid35973639, year = {2022}, author = {Ciccia, F and Gandolfo, S}, title = {Will fecal microbiota transplantation eventually be an effective therapeutic strategy for systemic lupus erythematosus?.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {}, number = {}, pages = {109096}, doi = {10.1016/j.clim.2022.109096}, pmid = {35973639}, issn = {1521-7035}, abstract = {Gut microbiota dysbiosis serves as a potential trigger that may contribute to metabolic and immune dysregulation that underlies the development of autoimmune diseases. Fecal microbiota transplantation (FMT) is restoration of disturbed microbiota by transplanting foreign gut microbiota from healthy individuals into the gastrointestinal tract of diseased individuals. In this issue of the Journal of Autoimmunity, Huang et al. conducted a 12-week, single-arm pilot clinical trial of oral FMT capsules in patients with active SLE. No serious adverse events (AEs) or deaths were observed and the rate of the primary endpoint (SLE Responder Index-4) was 42.12%. Alternations in bacteria, metabolites and immune parameters were linked to FMT treatment and clinical response in SLE patients. This is the first FMT trial in SLE patients and provides supportive evidence that FMT appears to be a safe, feasible and potentially effective treatment modality in SLE. We await future investigations conducting larger, randomized FMT clinical trials with a longer follow-up to confirm the long-term safety, effectiveness, and potential benefits of FMT-based intervention in SLE and to further demonstrate the underlying microbiological mechanisms.}, }
@article {pmid35868075, year = {2022}, author = {Hu, C and Liu, M and Sun, B and Tang, L and Zhou, X and Chen, L}, title = {Young fecal transplantation mitigates the toxicity of perfluorobutanesulfonate and potently refreshes the reproductive endocrine system in aged recipients.}, journal = {Environment international}, volume = {167}, number = {}, pages = {107418}, doi = {10.1016/j.envint.2022.107418}, pmid = {35868075}, issn = {1873-6750}, mesh = {Animals ; Endocrine System ; Fecal Microbiota Transplantation ; Fluorocarbons ; Gonadal Steroid Hormones/metabolism ; Reproduction ; Sulfonic Acids ; *Water Pollutants, Chemical/toxicity ; *Zebrafish/metabolism ; }, abstract = {The aging process leads to the gradual impairment of physiological functions in the elderly, making them more susceptible to the toxicity of environmental pollutants. In this study, aged zebrafish were first transplanted with the feces from young donors and subsequently exposed to perfluorobutanesulfonate (PFBS), an emerging persistent toxic pollutant. The interaction between young fecal transplant and PFBS inherent toxicity was investigated, focusing on reproductive performance and the underlying endocrine mechanism. The results showed that PFBS single exposure increased the percentage of primary oocytes in aged ovaries, implying a blockage of oogenesis. However, transplantation of young feces completely abolished the effects of PFBS and promoted oocyte growth, as inferred by the obviously lower percentage of primary oocytes, accompanied by a higher percentage of cortical-alveolar oocytes. Measurement of sex hormones found that PFBS significantly increased the blood concentration of estradiol and disrupted the balance of sex hormones in the elderly, which were, however, efficiently ameliorated by young fecal transplantation. Based on gene transcription along the hypothalamic-pituitary-gonadal axis, hierarchical clustering analysis showed similar profiles of the reproductive endocrine system between young zebrafish and their aged counterparts transplanted with young feces, implying that young fecal transplantation might refresh the endocrine system of aged recipients, regardless of PFBS exposure. The increased transcription levels of mRNAs encoding vitellogenin, activinBA, and membrane bound progestin receptors would cooperatively enhance the growth and maturation of oocytes in the ovaries of aged zebrafish receiving young fecal transplantation. Overall, the findings highlighted the potent efficacy of young fecal transplantation to improve the reproductive function of the elderly and to mitigate the endocrine disruption of an environmental pollutant. These findings are expected to broaden our understanding of the efficacy, mechanisms, and application of fecal transplantation.}, }
@article {pmid35967846, year = {2022}, author = {Cai, T and Zheng, SP and Shi, X and Yuan, LZ and Hu, H and Zhou, B and Xiao, SL and Wang, F}, title = {Therapeutic effect of fecal microbiota transplantation on chronic unpredictable mild stress-induced depression.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {900652}, doi = {10.3389/fcimb.2022.900652}, pmid = {35967846}, issn = {2235-2988}, abstract = {Background and objective: Depression is a complex neuropsychiatric disease with extensive morbidity. Its pathogenesis remains unclear, and it is associated with extremely low rates of cure and complete remission. It is vital to study the pathogenesis of depression to develop effective treatments. This study aimed to explore the therapeutic effects and mechanisms of fecal microbiota transplantation (FMT) for the treatment of depression in rats.<br><br>Methods: Thirty Sprague-Dawley (SD) rats were randomly divided into three groups: control, chronic unpredictable mild stress (CUMS) to model depression, and CUMS+FMT. For the CUMS and CUMS+FMT groups, after CUMS intervention (four weeks), the rats were given normal saline or FMT (once/week for three weeks), respectively. Behavior, colonic motility, 16S rDNA amplicon sequencing, and untargeted metabolomics on fecal samples were compared between the three rat groups. The following markers were analyzed: 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), glutamate (Glu), and brain-derived neurotrophic factor (BDNF) levels in the hippocampus; glucagon-like peptide 1 (GLP-1), lipopolysaccharide (LPS), and interleukin (IL)-6 levels in the serum; and GLP-1, GLP-1 receptor (GLP-1R), and serotonin 4 receptor (5-HT4R) levels in colonic tissues.<br><br>Results: FMT improved symptoms of depression and colonic motility in rats exposed to CUMS. The expression levels of 5-HT, GABA, BDNF, and other biochemical indices, significantly differed among the three groups. Meanwhile, the intestinal microbiota in the CUMS+FMT group was more similar to that of the control group with a total of 13 different fecal metabolites.<br><br>Conclusion: FMT exerted antidepressant effects on CUMS-induced depression in rats, and the mechanism involved various neurotransmitters, inflammatory factors, neurotrophic factors, and glucagon-like peptides.}, }
@article {pmid35967586, year = {2022}, author = {Wu, H and Guo, K and Zhuo, Z and Zeng, R and Luo, Y and Yang, Q and Li, J and Jiang, R and Huang, Z and Sha, W and Chen, H}, title = {Current therapy option for necrotizing enterocolitis: Practicalities and challenge.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {954735}, doi = {10.3389/fped.2022.954735}, pmid = {35967586}, issn = {2296-2360}, abstract = {Necrotizing enterocolitis (NEC) is one of the most prevalent neonatal gastrointestinal disorders. Despite ongoing breakthroughs in its treatment and prevention, the incidence and mortality associated with NEC remain high. New therapeutic approaches, such as breast milk composition administration, stem cell therapy, immunotherapy, and fecal microbiota transplantation (FMT) have recently evolved the prevention and the treatment of NEC. This study investigated the most recent advances in NEC therapeutic approaches and discussed their applicability to bring new insight to NEC treatment.}, }
@article {pmid35966768, year = {2022}, author = {Wang, F and Gu, Y and Xu, C and Du, K and Zhao, C and Zhao, Y and Liu, X}, title = {Transplantation of fecal microbiota from APP/PS1 mice and Alzheimer's disease patients enhanced endoplasmic reticulum stress in the cerebral cortex of wild-type mice.}, journal = {Frontiers in aging neuroscience}, volume = {14}, number = {}, pages = {858130}, doi = {10.3389/fnagi.2022.858130}, pmid = {35966768}, issn = {1663-4365}, abstract = {Background and purpose: The gut-brain axis is bidirectional and the imbalance of the gut microbiota usually coexists with brain diseases, including Alzheimer's disease (AD). Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a core lesion in AD and persistent ER stress promotes AD pathology and impairs cognition. However, whether the imbalance of the gut microbiota is involved in triggering the ER stress in the brain remains unknown.<br><br>Materials and methods: In the present study, fecal microbiota transplantation (FMT) was performed with gut microbiota from AD patients and APP/PS1 mice, respectively, resulting in two mouse models with dysregulated gut microbiota. The ER stress marker protein levels in the cerebral cortex were assessed using western blotting. The composition of the gut microbiota was assessed using 16S rRNA sequencing.<br><br>Results: Excessive ER stress was induced in the cerebral cortex of mice after FMT. Elevated ER stress marker proteins (p-perk/perk, p-eIF2α/eIF2α) were observed, which were rescued by 3,3-dimethyl-1-butanol (DMB). Notably, DMB is a compound that significantly attenuates serum trimethylamine-N-oxide (TMAO), a metabolite of the gut microbiota widely reported to affect cognition.<br><br>Conclusion: The findings indicate that imbalance of the gut microbiota induces ER stress in the cerebral cortex, which may be mediated by TMAO.}, }
@article {pmid35966709, year = {2022}, author = {Chen, G and Shi, F and Yin, W and Guo, Y and Liu, A and Shuai, J and Sun, J}, title = {Gut microbiota dysbiosis: The potential mechanisms by which alcohol disrupts gut and brain functions.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {916765}, doi = {10.3389/fmicb.2022.916765}, pmid = {35966709}, issn = {1664-302X}, abstract = {Alcohol use disorder (AUD) is a high-risk psychiatric disorder and a key cause of death and disability in individuals. In the development of AUD, there is a connection known as the microbiota-gut-brain axis, where alcohol use disrupts the gut barrier, resulting in changes in intestinal permeability as well as the gut microbiota composition, which in turn impairs brain function and worsens the patient's mental status and gut activity. Potential mechanisms are explored by which alcohol alters gut and brain function through the effects of the gut microbiota and their metabolites on immune and inflammatory pathways. Alcohol and microbiota dysregulation regulating neurotransmitter release, including DA, 5-HT, and GABA, are also discussed. Thus, based on the above discussion, it is possible to speculate on the gut microbiota as an underlying target for the treatment of diseases associated with alcohol addiction. This review will focus more on how alcohol and gut microbiota affect the structure and function of the gut and brain, specific changes in the composition of the gut microbiota, and some measures to mitigate the changes caused by alcohol exposure. This leads to a potential intervention for alcohol addiction through fecal microbiota transplantation, which could normalize the disruption of gut microbiota after AUD.}, }
@article {pmid35966681, year = {2022}, author = {Jing, H and Chang, Q and Xu, Y and Wang, J and Wu, X and Huang, J and Wang, L and Zhang, Z}, title = {Effect of aging on acute pancreatitis through gut microbiota.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {897992}, doi = {10.3389/fmicb.2022.897992}, pmid = {35966681}, issn = {1664-302X}, abstract = {Background: Compared to younger people, older people have a higher risk and poorer prognosis of acute pancreatitis, but the effect of gut microbiota on acute pancreatitis is still unknown. We aim to investigate the effect of aging gut microbiota on acute pancreatitis and explore the potential mechanism of this phenomenon.<br><br>Methods: Eighteen fecal samples from healthy adult participants, including nine older and nine younger adults were collected. C57BL/6 mice were treated with antibiotics for fecal microbiota transplantation from older and younger participants. Acute pancreatitis was induced by cerulein and lipopolysaccharide in these mice. The effect of the aged gut microbiota was further tested via antibiotic treatment before or after acute pancreatitis induction.<br><br>Results: The gut microbiota of older and younger adults differed greatly. Aged gut microbiota exacerbated acute pancreatitis during both the early and recovery stages. At the same time, the mRNA expression of multiple antimicrobial peptides in the pancreas and ileum declined in the older group. Antibiotic treatment before acute pancreatitis could remove the effect of aging gut microbiota, but antibiotic treatment after acute pancreatitis could not.<br><br>Conclusion: Aging can affect acute pancreatitis through gut microbiota which characterizes the deletion of multiple types of non-dominant species. This change in gut microbiota may potentially regulate antimicrobial peptides in the early and recovery stages. The level of antimicrobial peptides has negative correlations with a more severe phenotype.}, }
@article {pmid35965832, year = {2022}, author = {Wei, ZJ and Dong, HB and Ren, YT and Jiang, B}, title = {Efficacy and safety of fecal microbiota transplantation for the induction of remission in active ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Annals of translational medicine}, volume = {10}, number = {14}, pages = {802}, doi = {10.21037/atm-22-3236}, pmid = {35965832}, issn = {2305-5839}, abstract = {Background: Fecal microbiota transplantation (FMT) is a novel management strategy for ulcerative colitis (UC). However, its effectiveness remains controversial. This study sought to assess the effectiveness of FMT in the treatment of active UC by performing a meta-analysis of randomized controlled trials (RCTs).<br><br>Methods: We searched the Cochrane, Embase, PubMed, and Web of Science databases from their inception to December 2021. RCTs that recruited patients with active UC and treated them with FMT, a placebo or a suitable comparator were included in the meta-analysis. PICOS: Patients, active UC; Intervention, FMT; Control, placebo or a suitable comparator; Outcomes, remission rate; Studies, RCTs. The risk of bias assessment was performed with Revised Cochrane risk-of-bias tool (version 2). Meta-analyses of risk ratios (RRs) were performed to estimate the differences in remission rates and the risk of serious adverse events (SAEs) between the FMT-treated and control patients.<br><br>Results: A total of 9 RCTs comprising 425 UC patients (213 FMT and 212 control) were included in the meta-analysis. The risk of bias was low in these RCTs. Clinical remission was observed in 86 of the 213 patients in the FMT groups and 47 of the 212 patients in the control groups [RR: 1.84; 95% confidence interval (CI): 1.37, 2.47; P<0.0001]. Clinical remission was better when the FMT delivery route was via the lower gut, the FMT dose was >300 grams, and the fecal specimen from multiple donors. Endoscopic remission (observed in 7 RCTs) was achieved in 33 of the 195 FMT-treated patients compared to 17 of the 194 control patients (RR: 1.94; 95% CI: 1.14, 3.31; P=0.01). SAEs were reported in 22 of the 213 FMT-treated patients but only 11 of the 212 control patients (RR: 2.05; 95% CI: 1.03, 4.09; P=0.04).<br><br>Discussion: FMT is an effective treatment for patients with active UC. Significantly higher clinical and endoscopic remission rates are observed with FMT than with control treatments. However, FMT may cause a significantly higher incidence of SAEs than control treatments. Future studies should delineate the effects of donor selection, dosage, delivery route, and antibiotic pretreatment and should evaluate the safety profile of FMT.}, }
@article {pmid35964945, year = {2022}, author = {Kapoor, B and Gulati, M and Rani, P and Gupta, R}, title = {Psoriasis: Interplay between dysbiosis and host immune system.}, journal = {Autoimmunity reviews}, volume = {}, number = {}, pages = {103169}, doi = {10.1016/j.autrev.2022.103169}, pmid = {35964945}, issn = {1873-0183}, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of both gut and skin microbiota in the pathogenesis of psoriasis. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts, have been identified as possible triggers for recurrent episodes of psoriasis. Mechanistically, gut dysbiosis leads to "leaky gut syndrome" via disruption of epithelial bilayer, thereby, resulting in translocation of bacteria and other endotoxins to systemic circulation, which in turn, results in inflammatory response. Similarly, skin dysbiosis disrupts the cutaneous homeostasis, leading to invasion of bacteria and other pathogens to deeper layers of skin or even systemic circulation further enhanced by injury caused by pruritus-induced scratching, and elicit innate and adaptive inflammation. The present review explores the correlation of both skin and gut microbiota dysbiosis with psoriasis. Also, the studies highlighting the potential of bacteriotherapeutic approaches including probiotics, prebiotics, metabiotics, and fecal microbiota transplantation for the management of psoriasis have been discussed.}, }
@article {pmid35962694, year = {2022}, author = {Dobrek, Ł}, title = {POTENTIAL THERAPEUTIC OPTIONS TARGETING THE GUT DYSBIOSIS IN CHRONIC KIDNEY DISEASE.}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {75}, number = {6}, pages = {1757-1764}, doi = {10.36740/WLek202207127}, pmid = {35962694}, issn = {0043-5147}, abstract = {The gut microbiota plays an important physiological role in controlling not only the function of the gastrointestinal tract, but also in maintaining systemic homeostasis. Quantitative and /or qualitative disturbances of the gut microbiota (dysbiosis) are an important element in the complex pathogenesis of many diseases, including chronic kidney disease (CKD). In the disease, the mutual interactions between disturbed gut microbiota and the progression of CKD (pathophysiological "kidney-gut axis") have been demonstrated. The kidney failure causes water and nitrogen waste retention which leads to disturbances of motility, secretion and absorption in the gastrointestinal tract. These abnormalities contribute to the development of gut dysbiosis, accompanied by overproduction of toxic bacterial metabolites, with their translocation to the peripheral blood and development of endotoxemia. As a consequence, chronic kidney "low-grade" inflammation and oxidative stress develop, with further deterioration of kidney function in the mechanism of the "vicious cycle" of the kidney-gut axis. Considering the key role of gut dysbiosis and the kidney-gut axis, the attempts to restore the gut eubiosis seem to have an important role in the treatment of CKD and may be even regarded as a form of causal therapeutic intervention. The paper briefly discusses the basics of the pathophysiological kidney-gut axis in CKD and potential methods of modulating the abnormal gut microbiota in this disease, including the use of probiotic or prebiotic preparations, agents that absorb bacterial-derived toxins in the intestinal lumen, fecal microbiota transplantation and drugs used so far for other indications (acarbose, meclofenamate, lubiprostone).}, }
@article {pmid35962454, year = {2022}, author = {Huang, C and Huang, Z and Ding, L and Fu, Y and Fan, J and Mei, Q and Lou, L and Wang, J and Yin, N and Lu, Y and Guo, S and Zeng, Y}, title = {Fecal microbiota transplantation versus glucocorticoids for the induction of remission in mild to moderate ulcerative colitis.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {354}, pmid = {35962454}, issn = {1479-5876}, support = {SHDC12017X09//Shanghai Hospital Development Center/ ; SHDC2020CR2014A//Shanghai Hospital Development Center/ ; 20181813//School of Medicine, Shanghai Jiao Tong University/ ; 81970555//National Natural Science Foundation of China/ ; }, abstract = {OBJECTIVE: To compare efficacy and safety of fecal microbiota transplantation (FMT) with glucocorticoid as induction therapy in ulcerative colitis (UC).<br><br>METHODS: The patients with active mild to moderate UC were recruited into the single-center, prospective cohort study. The patients were treated with either FMT (FMT group) or glucocorticoids (GCs group). Patients received FMT administration for 3 days. The primary outcome was clinical and endoscopic remission at week 12. Inflammatory parameters were assessed by routine blood tests. Safety was assessed by adverse events recorded. The serum levels of TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10 IL-8, IL-12p70, IL-13, IL-17A and IL-23 following FMT were measured by Luminex multiplex assay.<br><br>RESULTS: Of the 122 patients, 62 patients were treated with FMT and 60 with glucocorticoids. 34 patients in FMT group (54.8%) and 29 in GCs group (48.3%) reached the primary outcome (p = 0.30). The incidence of adverse events in GCs group (35/60, 58.3%) was significantly higher than that in FMT group (14/62, 22.6%) and two serious adverse events were observed following GCs. Patients in FMT group were stratified into responders (RE) and non-responders (NR) groups. The level of TNF-α and IL-6 decreased significantly in RE group, while IL-10 decreased significantly in NR group.<br><br>CONCLUSION: FMT therapy was as effective as glucocorticoids to induce remission in active mild to moderate UC, accompanied by fewer adverse events. The modification of serum TNF-α, IL-6 and IL-10 might be related to the efficacy of FMT in UC. Trial registration This study was registered with ClinicalTrials.gov (NCT02435160). Registered on 6 April, 2015. https://clinicaltrials.gov/ct2/results?cond=&amp;term=NCT02435160&amp;cntry=&amp;state=&amp;city=&amp;dist=.}, }
@article {pmid35809615, year = {2022}, author = {Camilleri, M and Dilmaghani, S}, title = {Treatment of Irritable Bowel Syndrome Using Fecal Microbiota Transplantation: A Step Forward?.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2022.06.087}, pmid = {35809615}, issn = {1528-0012}, }
@article {pmid35947590, year = {2022}, author = {Koopman, N and van Leeuwen, P and Brul, S and Seppen, J}, title = {History of fecal transplantation; camel feces contains limited amounts of Bacillus subtilis spores and likely has no traditional role in the treatment of dysentery.}, journal = {PloS one}, volume = {17}, number = {8}, pages = {e0272607}, doi = {10.1371/journal.pone.0272607}, pmid = {35947590}, issn = {1932-6203}, mesh = {Animals ; *Bacillus subtilis ; Camelus ; *Dysentery ; Fecal Microbiota Transplantation ; Feces ; Humans ; Spores, Bacterial ; }, abstract = {INTRODUCTION: A widely cited story on the origins of fecal transplantation suggests that German soldiers in North Africa used camel feces containing Bacillus subtilis to treat dysentery in World War 2. We investigated if this story is accurate and if there is sufficient Bacillus subtilis in camel feces to be potentially therapeutic.<br><br>METHODS AND RESULTS: A literature analysis shows that all references to the story are based on a single review paper that mentions the use of camel feces in passing and only provides indirect evidence for this claim. An extensive literature search failed to find independent evidence that camel feces has traditionally been used in the treatment of dysentery in North Africa. With 16S sequence analysis we did not detect Bacillus subtilis in feces from two different Egyptian camels. Using a more sensitive culture-based assay we could detect low amounts of Bacillus subtilis spores in these fecal samples, with comparable concentrations to those present in human feces and soil.<br><br>CONCLUSIONS: Because we could not find evidence for the use of camel feces in the treatment of diarrhea and because we show that only low amounts of Bacillus subtilis spores are present in camel feces, we conclude that the use of camel feces should no longer be mentioned in the context of origins of fecal transplantation.}, }
@article {pmid35950704, year = {2022}, author = {Jin, J and Gao, L and Zou, X and Zhang, Y and Zheng, Z and Zhang, X and Li, J and Tian, Z and Wang, X and Gu, J and Zhang, C and Wu, T and Wang, Z and Zhan, Q}, title = {Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages and Trophoblasts.}, journal = {Circulation research}, volume = {}, number = {}, pages = {101161CIRCRESAHA122320771}, doi = {10.1161/CIRCRESAHA.122.320771}, pmid = {35950704}, issn = {1524-4571}, abstract = {BACKGROUND: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated.<br><br>METHODS: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development.<br><br>RESULTS: We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. Akkermansia muciniphila, propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of Akkermansia, Oscillibacter, and short-chain fatty acids that could accurately diagnose preeclampsia.<br><br>CONCLUSIONS: Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut-placenta axis theory and contribute to the development of microecological products for preeclampsia.}, }
@article {pmid35949981, year = {2022}, author = {Xie, C and Teng, J and Wang, X and Xu, B and Niu, Y and Ma, L and Yan, X}, title = {Multi-omics analysis reveals gut microbiota-induced intramuscular fat deposition via regulating expression of lipogenesis-associated genes.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {9}, number = {}, pages = {84-99}, doi = {10.1016/j.aninu.2021.10.010}, pmid = {35949981}, issn = {2405-6383}, abstract = {The gut microbiome has great effects on the digestion, absorption, and metabolism of lipids. However, the microbiota composition that can alter the fat deposition and the meat quality of pigs remains unclear. Here, we used Laiwu (LW) pigs (a native Chinese breed with higher intramuscular fat) compared with commercial crossbreed Duroc × (Landrace × Yorkshire) (DLY) pigs to investigate the effects of microbiota on meat quality, especially in intramuscular fat content. A total of 32 DLY piglets were randomly allotted to 4 groups and transplanted with fecal microbiota from healthy LW pigs. The results indicated that the high dose of fecal microbiota transplantation (HFMT) selectively enhanced fat deposition in longissimus dorsi (P < 0.05) but decreased backfat thickness (P < 0.05) compared with control group. HFMT significantly altered meat color and increased feed conversation ratio (P < 0.05). Furthermore, the multi-omics analysis revealed that Bacteroides uniformis, Sphaerochaeta globosa, Hydrogenoanaerobacterium saccharovorans, and Pyramidobacter piscolens are the core species which can regulate lipid deposition. A total of 140 male SPF C57BL/6j mice were randomly allotted into 7 groups and administrated with these 4 microbes alone or consortium to validate the relationships between microbiota and lipid deposition. Inoculating the bacterial consortium into mice increased intramuscular fat content (P < 0.05) compared with control mice. Increased expressions of lipogenesis-associated genes including cluster of differentiation 36 (Cd36), diacylglycerol O-acyltransferase 2 (Dgat2), and fatty acid synthase (FASN) were observed in skeletal muscle in the mice with mixed bacteria compared with control mice. Together, our results suggest that the gut microbiota may play an important role in regulating the lipid deposition in the muscle of pigs and mice.}, }
@article {pmid35949351, year = {2022}, author = {Zheng, L and Ji, YY and Wen, XL and Duan, SL}, title = {Fecal microbiota transplantation in the metabolic diseases: Current status and perspectives.}, journal = {World journal of gastroenterology}, volume = {28}, number = {23}, pages = {2546-2560}, doi = {10.3748/wjg.v28.i23.2546}, pmid = {35949351}, issn = {2219-2840}, abstract = {With the development of microbiology and metabolomics, the relationship between the intestinal microbiome and intestinal diseases has been revealed. Fecal microbiota transplantation (FMT), as a new treatment method, can affect the course of many chronic diseases such as metabolic syndrome, malignant tumor, autoimmune disease and nervous system disease. Although the mechanism of action of FMT is now well understood, there is some controversy in metabolic diseases, so its clinical application may be limited. Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection, and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases. However, the initial results are varied, suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT. The success of FMT depends on the microbial diversity and composition of donor feces. Therefore, clinical trials may fail due to the selection of ineffective donors, and not to faulty indication selection for FMT. A new understanding is that FMT not only improves insulin sensitivity, but may also alter the natural course of type 1 diabetes by modulating autoimmunity. In this review, we focus on the main mechanisms and deficiencies of FMT, and explore the optimal design of FMT research, especially in the field of cardiometabolic diseases.}, }
@article {pmid35943661, year = {2022}, author = {Ma, W and Drew, DA and Staller, K}, title = {The Gut Microbiome and Colonic Motility Disorders: A Practical Framework for the Gastroenterologist.}, journal = {Current gastroenterology reports}, volume = {}, number = {}, pages = {}, pmid = {35943661}, issn = {1534-312X}, support = {K23DK120945/DK/NIDDK NIH HHS/United States ; K01DK120742/DK/NIDDK NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Colonic motility disorders may be influenced by the gut microbiota, which plays a role in modulating sensory and motor function. However, existing data are inconsistent, possibly due to complex disease pathophysiology, fluctuation in symptoms, and difficulty characterizing high-resolution taxonomic composition and function of the gut microbiome.<br><br>RECENT FINDINGS: Increasingly, human studies have reported associations between gut microbiome features and colonic motility disorders, such as irritable bowel syndrome and constipation. Several microbial metabolites have been identified as regulators of colonic motility in animal models. Modulation of the gut microbiota via dietary intervention, probiotics, and fecal microbiota transplant is a promising avenue for treatment for these diseases. An integration of longitudinal multi-omics data will facilitate further understanding of the causal effects of dysbiosis on disease. Further understanding of the microbiome-driven mechanisms underlying colonic motility disorders may be leveraged to develop personalized, microbiota-based approaches for disease prevention and treatment.}, }
@article {pmid35660380, year = {2022}, author = {Liu, M and Sun, B and Zhou, X and Chen, L}, title = {Disturbed glucose metabolism by perfluorobutanesulfonate pollutant and benefit of young fecal transplantation in aged zebrafish.}, journal = {Ecotoxicology and environmental safety}, volume = {241}, number = {}, pages = {113721}, doi = {10.1016/j.ecoenv.2022.113721}, pmid = {35660380}, issn = {1090-2414}, mesh = {Animals ; *Environmental Pollutants/metabolism ; Fecal Microbiota Transplantation ; Fluorocarbons ; Glucose/metabolism ; Liver ; Proteomics ; Sulfonic Acids ; *Water Pollutants, Chemical/toxicity ; Zebrafish/metabolism ; alpha-Amylases ; }, abstract = {Perfluorobutanesulfonate (PFBS) is an environmental pollutant of emerging concern, which significantly impacts the metabolism and health of animals. Because of the loss of functional capacity, the aged animals are regarded more susceptible to the toxicity of environmental pollutants. In the present study, aged zebrafish were employed as the toxicological animal and transplanted with the feces collected from young donors for 14 days, after which the acclimated elderly were exposed to PFBS at environmentally relevant concentrations (0 and 100 μg/L) for another 14 days. When the exposure was concluded, glucose metabolic disturbances of PFBS in the aged and efficacy of young fecal transplant to mitigate the toxicity of PFBS were explored along the gut-liver axis. The results showed that PFBS exposure significantly inhibited the enzymatic activity of α-amylase in the gut, but increased the alanine aminotransferase (ALT) activity in the blood of the aged zebrafish, suggesting the impairment of intestinal digestive functions of carbohydrates and the induction of liver damage by PFBS. However, young fecal transplantation successfully ameliorated the toxicity of PFBS on α-amylase and ALT, underlining the benefits conveyed to the health of the elderly. In addition, transplantation of young feces was efficient to alleviate the hyperglycemia symptom in the elderly via stimulating the secretion of insulin. PFBS exposure increased blood glucagon level, disrupted insulin receptor transcription, and depleted hepatic glycogen store, which were all mitigated by young fecal transplant. Hepatic proteomic analysis also found dynamic interactions between young fecal transplantation and PFBS pollutant on the metabolic pathways of glucose and glycogen, involving glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis. Overall, the present findings highlighted the beneficial effects of young fecal transplantation to protect the aged from the glucose metabolism toxicity of PFBS, thus providing a plausible measure to improve the health aging status.}, }
@article {pmid35935787, year = {2022}, author = {Jung, JH and Kim, SE and Suk, KT and Kim, DJ}, title = {Gut microbiota-modulating agents in alcoholic liver disease: Links between host metabolism and gut microbiota.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {913842}, doi = {10.3389/fmed.2022.913842}, pmid = {35935787}, issn = {2296-858X}, abstract = {Alcoholic liver disease (ALD) involves a wide spectrum of diseases, including asymptomatic hepatic steatosis, alcoholic hepatitis, hepatic fibrosis, and cirrhosis, which leads to morbidity and mortality and is responsible for 0.9% of global deaths. Alcohol consumption induces bacterial translocation and alteration of the gut microbiota composition. These changes in gut microbiota aggravate hepatic inflammation and fibrosis. Alteration of the gut microbiota leads to a weakened gut barrier and changes host immunity and metabolic function, especially related to bile acid metabolism. Modulation and treatment for the gut microbiota in ALD has been studied using probiotics, prebiotics, synbiotics, and fecal microbial transplantation with meaningful results. In this review, we focused on the interaction between alcohol and gut dysbiosis in ALD. Additionally, treatment approaches for gut dysbiosis, such as abstinence, diet, pro-, pre-, and synbiotics, antibiotics, and fecal microbial transplantation, are covered here under ALD. However, further research through human clinical trials is warranted to evaluate the appropriate gut microbiota-modulating agents for each condition related to ALD.}, }
@article {pmid35934034, year = {2022}, author = {Liu, Y and Kang, W and Liu, S and Li, J and Liu, J and Chen, X and Gan, F and Huang, K}, title = {Gut microbiota-bile acid-intestinal Farnesoid X receptor signaling axis orchestrates cadmium-induced liver injury.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {157861}, doi = {10.1016/j.scitotenv.2022.157861}, pmid = {35934034}, issn = {1879-1026}, abstract = {Cadmium (Cd) is a widely prevalent environmental pollutant that accumulates in the liver and induces liver injury. The mechanism of Cd-induced liver injury remains elusive. Our study aimed to clarify the mechanism by which changes in the gut microbiota contribute to Cd-induced liver injury. Here, a murine model of liver injury induced by chronic Cd exposure was used. Liver injury was assessed by biochemistry and histopathology. Expression profiles of genes involved in bile acid (BA) homeostasis, inflammation and injury were assessed via Realtime-PCR and Western-blot. 16S rRNA gene sequencing and mass spectrometry-based metabolomics were used to investigate changes in the gut microbiota and its metabolites in the regulation of Cd-induced liver injury. Here, we showed that Cd exposure induced hepatic ductular proliferation, hepatocellular damage and inflammatory infiltration in mice. Cd exposure induced gut microbiota dysbiosis and reduced the fecal bile salt hydrolase activity leading to an increase of tauro-β-muricholic acid levels in the intestine. Cd exposure decreased intestine FXR/FGF-15 signaling and promoted hepatic BA synthesis. Furthermore, the mice receiving fecal microbiota transplantation from Cd-treated mice showed reduced intestinal FXR/FGF-15 signaling, increased hepatic BA synthesis, and liver injury. However, the depletion of the commensal microbiota by antibiotics failed to change these indices in Cd-treated mice. Finally, the administration of the intestine-restricted FXR agonist fexaramine attenuated the liver injury, improved the intestinal barrier, and decreased hepatic BA synthesis in the Cd-treated mice. Our study identified a new mechanism of Cd-induced liver injury. Cd-induced gut microbiota dysbiosis, decreased feces BSH activity, and increased intestinal T-βMCA levels led to an inhibition of intestinal FXR/FGF-15 signaling and an increase in hepatic BA synthesis, ultimately facilitating the development of hepatic ductular proliferation, inflammation, and injury in mice. This study expands our understanding of the health hazards caused by environmental Cd pollution.}, }
@article {pmid35933808, year = {2022}, author = {Huang, J and Liu, W and Kang, W and He, Y and Yang, R and Mou, X and Zhao, W}, title = {Effects of microbiota on anticancer drugs: Current knowledge and potential applications.}, journal = {EBioMedicine}, volume = {83}, number = {}, pages = {104197}, doi = {10.1016/j.ebiom.2022.104197}, pmid = {35933808}, issn = {2352-3964}, abstract = {Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation. As such, human microbiota presents as an exciting prospect for developing biomarkers for predicting treatment outcomes and interventional approaches for improving therapeutic effects. In this review, we analyze the current knowledge of the interplays among gut microorganisms, host responses and anticancer therapies (including cytotoxic chemotherapy and targeted therapy), with an emphasis on the immunomodulation function of microbiota which facilitates the efficacy of immune checkpoint inhibitors. Moreover, we propose several microbiota-modulating strategies including fecal microbiota transplantation and probiotics, which can be pursued to optimize the use and development of anticancer treatments. We anticipate that future clinical and preclinical studies will highlight the significance of human microbiome as a promising target towards precision medicine in cancer therapies. FUNDING: National Key Research and Development Program of China (2020YFA0907800), Shenzhen Science and Technology Innovation Program (KQTD20200820145822023) and National Natural Science Foundation of China (31900056 and 32000096).}, }
@article {pmid35932662, year = {2022}, author = {Chen, Y and Lin, J and Xiao, L and Zhang, X and Zhao, L and Wang, M and Li, L}, title = {Gut microbiota in systemic lupus erythematosus: A fuse and a solution.}, journal = {Journal of autoimmunity}, volume = {132}, number = {}, pages = {102867}, doi = {10.1016/j.jaut.2022.102867}, pmid = {35932662}, issn = {1095-9157}, abstract = {Gut commensals help shape and mold host immune system and deeply influence human health. The disease spectrum of mankind that gut microbiome may associate with is ever-growing, but the mechanisms are still enigmas. Characterized by loss of self-tolerance and sustained self-attack, systemic lupus erythematosus (SLE) is labeled with chronic inflammation, production of autoantibodies and multisystem injury, which so far are mostly incurable. Gut microbiota and their metabolites, now known as important environmental triggers of local/systemic immune responses, have been proposed to be involved in SLE development and progression probably through the following mechanisms: translocation beyond their niches; molecular mimicry to cross-activate immune response targeting self-antigens; epitope spreading to expand autoantibodies spectrum; and bystander activation to promote systemic inflammation. Gut microbiota which varies between individuals may also influence the metabolism and bio-transformation of disease-modifying anti-rheumatic drugs, thus associated with the efficacy and toxicity of these drugs, adding another explanation for heterogenic therapeutic responses. Modulation of gut microbiota via diet, probiotics/prebiotics, antibiotics/phages, fecal microbiota transplantation, or helminth to restore immune tolerance and homeostasis is expected to be a promising neoadjuvant therapy for SLE. We reviewed the advances in this territory and discussed the application prospect of modulating gut microbiota in controlling SLE.}, }
@article {pmid35931074, year = {2022}, author = {Podlesny, D and Durdevic, M and Paramsothy, S and Kaakoush, NO and Högenauer, C and Gorkiewicz, G and Walter, J and Fricke, WF}, title = {Identification of clinical and ecological determinants of strain engraftment after fecal microbiota transplantation using metagenomics.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {100711}, doi = {10.1016/j.xcrm.2022.100711}, pmid = {35931074}, issn = {2666-3791}, abstract = {Fecal microbiota transplantation (FMT) is a promising therapeutic approach for microbiota-associated pathologies, but our understanding of the post-FMT microbiome assembly process and its ecological and clinical determinants is incomplete. Here we perform a comprehensive fecal metagenome analysis of 14 FMT trials, involving five pathologies and >250 individuals, and determine the origins of strains in patients after FMT. Independently of the underlying clinical condition, conspecific coexistence of donor and recipient strains after FMT is uncommon and donor strain engraftment is strongly positively correlated with pre-FMT recipient microbiota dysbiosis. Donor strain engraftment was enhanced through antibiotic pretreatment and bowel lavage and dependent on donor and recipient ɑ-diversity; strains from relatively abundant species were more likely and from predicted oral, oxygen-tolerant, and gram-positive species less likely to engraft. We introduce a general mechanistic framework for post-FMT microbiome assembly in alignment with ecological theory, which can guide development of optimized, more targeted, and personalized FMT therapies.}, }
@article {pmid35928832, year = {2022}, author = {Zhu, W and Hong, Y and Li, Y and Li, Y and Zhong, J and He, X and Zheng, N and Sheng, L and Li, H}, title = {Microbial and Transcriptomic Profiling Reveals Diet-Related Alterations of Metabolism in Metabolic Disordered Mice.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {923377}, doi = {10.3389/fnut.2022.923377}, pmid = {35928832}, issn = {2296-861X}, abstract = {Metabolic disorders are the prelude of metabolic diseases, which are mainly due to the high-energy intake and genetic contribution. High-fat diet (HFD) or high-sucrose diet is widely used for inducing metabolic disorders characterized by increased body weight, insulin resistance, hepatic steatosis, and alteration of gut microbiome. However, the triangle relationship among diets, gut microbiome, and host metabolism is poorly understood. In our study, we investigated the dynamic changes in gut microbiota, and host metabolism in mice that were fed with either chow diet, HFD, or chow diet with 30% sucrose in drinking water (HSD) for continued 12 weeks. The gut microbiota was analyzed with 16S rDNA sequencing on feces. Hepatic gene expression profile was tested with transcriptomics analysis on liver tissue. The host metabolism was evaluated by measuring body weight, insulin sensitivity, serum lipids, and expression of proteins involved in lipid metabolism of liver. The results showed that HFD feeding affected body weight, insulin resistance, and hepatic steatosis more significantly than HSD feeding. 16S rRNA gene sequencing showed that HFD rapidly and steadily suppressed species richness, altered microbiota structure and function, and increased the abundance of bacteria responsible for fatty acid metabolism and inflammatory signaling. In contrast, HSD had minor impact on the overall bacteria structure or function but activated microbial bile acid biosynthesis. Fecal microbiota transplantation suggested that some metabolic changes induced by HFD or HSD feeding were transferrable, especially in the weight of white adipose tissue and hepatic triglyceride level that were consistent with the phenotypes in donor mice. Moreover, transcriptomic results showed that HFD feeding significantly inhibited fatty acid degradation and increase inflammation, while HSD increased hepatic de novo lipogenesis and inhibited primary bile acid synthesis alternative pathway. In general, our study revealed the dynamic and diversified impacts of HFD and HSD on gut microbiota and host metabolism.}, }
@article {pmid35928828, year = {2022}, author = {Yang, Z and Liu, X and Wu, Y and Peng, J and Wei, H}, title = {Effect of the Microbiome on Intestinal Innate Immune Development in Early Life and the Potential Strategy of Early Intervention.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {936300}, doi = {10.3389/fimmu.2022.936300}, pmid = {35928828}, issn = {1664-3224}, abstract = {Early life is a vital period for mammals to be colonized with the microbiome, which profoundly influences the development of the intestinal immune function. For neonates to resist pathogen infection and avoid gastrointestinal illness, the intestinal innate immune system is critical. Thus, this review summarizes the development of the intestinal microbiome and the intestinal innate immune barrier, including the intestinal epithelium and immune cells from the fetal to the weaning period. Moreover, the impact of the intestinal microbiome on innate immune development and the two main way of early-life intervention including probiotics and fecal microbiota transplantation (FMT) also are discussed in this review. We hope to highlight the crosstalk between early microbial colonization and intestinal innate immunity development and offer some information for early intervention.}, }
@article {pmid35926806, year = {2022}, author = {He, N and Shen, G and Jin, X and Li, H and Wang, J and Xu, L and Chen, J and Cao, X and Fu, C and Shi, D and Song, X and Liu, S and Li, Y and Zhao, T and Li, J and Zhong, J and Shen, Y and Zheng, M and Chen, YY and Wang, LL}, title = {Resveratrol suppressed microglia activation and promoted functional recovery of traumatic spinal cord via improving intestinal microbiota.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106377}, doi = {10.1016/j.phrs.2022.106377}, pmid = {35926806}, issn = {1096-1186}, abstract = {Spinal cord injury (SCI) can change the intestinal microbiota pattern and modify corresponding metabolites, which in turn affect the prognosis of SCI. Among many metabolites, short-chain fatty acids (SCFAs) are critical for neurological recovery after SCI. Recent research showed that resveratrol exerts anti-inflammatory properties. But it is unknown if the anti-inflammatory properties of resveratrol are associated with intestinal microbiota and metabolites. Here, we thus investigated the alteration in gut microbiota and determined the consequent change of SCFAs following resveratrol treatment. The SCI mouse models with retention of gut microbiota (donor) and depletion of gut microbiota (recipient) were established. Fecal microbiota transplantation from donors to recipients was performed with intragastrical administration. Spinal cord tissues of mice were examined by H&amp;E, Nissl, and immunofluorescence staining. The expressions of the inflammatory profile were examined by qPCR and cytometric bead array. Fecal samples of mice were collected and sent to 16S rRNA sequencing. The results showed that resveratrol inhibited the microglial activation and promoted the functional recovery of SCI. The analysis of intestinal microbiota and metabolite indicated that SCI caused dysbiosis and the decrease in butyrate, while resveratrol restored microbiota pattern, reversed intestinal dysbiosis, and increased the concentration of butyrate. Both fecal supernatants from resveratrol-treated donors and separate butyrate suppressed the expression of proinflammation genes in BV2 microglia. Our result demonstrated that fecal microbiota transplantation from resveratrol-treated donors had beneficial effects on the functional recovery of SCI. One mechanism of resveratrol effects was to restore the disrupted gut microbiota and butyrate to normal patterns.}, }
@article {pmid35926310, year = {2022}, author = {Tian, B and Zhang, Y and Deng, C and Guo, C}, title = {Efficacy of Probiotic Consortium Transplantation on Experimental Necrotizing Enterocolitis.}, journal = {The Journal of surgical research}, volume = {279}, number = {}, pages = {598-610}, doi = {10.1016/j.jss.2022.05.030}, pmid = {35926310}, issn = {1095-8673}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is a promising therapy, but it has not been used to treat neonatal necrotizing enterocolitis (NEC) due to reports of adverse side effects. Probiotics are considered relatively safe with practicable administrative procedures; however, no systematic research has compared the results of FMT and probiotic consortium transplantation (PCT) on oxidative stress in the intestines of patients with NEC. We conducted this study to provide a basis for optimizing NEC therapy.<br><br>METHODS: Eight-day-old newborn C57BL/6 mice were randomly divided into the following four groups: the dam-fed group (control group); the NEC induction group (NEC group); the NEC induction and transplantation of Lactobacillus reuteri and Bifidobacterium infantis consortium group (NEC + PCT group); and the NEC induction and the FMT group (NEC + FMT). Intestinal injury, oxidative stress indexes, intestinal barrier function, and inflammatory cytokines were assessed in the terminal ileum.<br><br>RESULTS: FMT more effectively modulates oxidative stress in the intestine than does PCT; however, the difference between the effects of PCT and FMT was not significant. The protective effect was associated with enhanced antioxidant capacity, regulation of the main components of the mucus layer, reduced inflammatory reactions, and improved intestinal integrity.<br><br>CONCLUSIONS: Intestinal dysbiosis affects oxidative stress, inflammatory response, and mucosal integrity. Although FMT is more effective than PCT in regulating oxidative stress, PCT may be preferred in pediatrics because the proportion and dose of transplanted bacteria can be standardized and individualized according to individual conditions.}, }
@article {pmid35924173, year = {2022}, author = {Qin, H and Yuan, B and Huang, W and Wang, Y}, title = {Utilizing Gut Microbiota to Improve Hepatobiliary Tumor Treatments: Recent Advances.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {924696}, doi = {10.3389/fonc.2022.924696}, pmid = {35924173}, issn = {2234-943X}, abstract = {Hepatobiliary tumors, which include cholangiocarcinoma, hepatocellular carcinoma (HCC), and gallbladder cancer, are common cancers that have high morbidity and mortality rates and poor survival outcomes. In humans, the microbiota is comprised of symbiotic microbial cells (10-100 trillion) that belong to the bacterial ecosystem mainly residing in the gut. The gut microbiota is a complicated group that can largely be found in the intestine and has a dual role in cancer occurrence and progression. Previous research has focused on the crucial functions of the intestinal microflora as the main pathophysiological mechanism in HCC development. Intestinal bacteria produce a broad range of metabolites that exhibit a variety of pro- and anticarcinogenic effects on HCC. Therefore, probiotic alteration of the gut microflora could promote gut flora balance and help prevent the occurrence of HCC. Recent evidence from clinical and translational studies suggests that fecal microbiota transplant is one of the most successful therapies to correct intestinal bacterial imbalance. We review the literature describing the effects and mechanisms of the microbiome in the gut in the context of HCC, including gut bacterial metabolites, probiotics, antibiotics, and the transplantation of fecal microbiota, and discuss the potential influence of the microbiome environment on cholangiocarcinoma and gallbladder cancer. Our findings are expected to reveal therapeutic targets for the prevention of hepatobiliary tumors, and the development of clinical treatment strategies, by emphasizing the function of the gut microbiota.}, }
@article {pmid35923396, year = {2022}, author = {Huang, S and Zheng, G and Men, H and Wang, W and Li, S}, title = {The Response of Fecal Microbiota and Host Metabolome in Dairy Cows Following Rumen Fluid Transplantation.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {940158}, doi = {10.3389/fmicb.2022.940158}, pmid = {35923396}, issn = {1664-302X}, abstract = {Rumen fluid transplantation (RFT) has been used to rebuild rumen bacterial homeostasis, reshape rumen function, and restore rumen fermentation, whereas the effect of RFT on fecal microbiota and host metabolism in cows remains poorly understood. In our study, a combination of 16S rRNA sequencing and serum non-targeted metabolomics was performed to investigate the response of fecal microbiota and serum metabolome in dairy cows following RFT. Twenty-four prepartum dairy cows were randomly assigned to 3 groups (n = 8) for infusion of either saline (Con), fresh rumen fluid (FR), or sterilized rumen fluid (SR) after calving. Fourteen days after calving, fecal microbiota and serum metabolome were analyzed. The sequencing data of fecal samples revealed no changes in alpha diversity and relative abundance of dominant genera such as Ruminococcaceae UCG-005, Rikenellaceae RC9 gut and Eubacterium coprostanoligenes. However, the other genus level taxa, such as Eubacterium oxidoreducens, Anaerorhabdus furcosa, Bacillus and Selenomonas, showed distinct changes following RFT. Serum metabolome analysis showed that FR or SR infusion affected amino acids metabolism, bile acids metabolism and fatty acids metabolism (including linoleic acid, oleic acid and palmitic acid). Furthermore, correlation analysis showed that taxa from genera Clostridiales were positively correlated with metabolites involved in tryptophan and bile acid metabolisms, such as OTU1039 from genera unclassified o_Clostridiales was positively correlated to indoleacetic acid and taurolithocholic acid. These results suggest that RFT altered the composition of the fecal microbiota and modulated microbial metabolic pathways, which is vital for the development and safety assessment of rumen microbial intervention strategies.}, }
@article {pmid35857570, year = {2022}, author = {Leonardi, I}, title = {Beyond the gut.}, journal = {Science (New York, N.Y.)}, volume = {377}, number = {6602}, pages = {165}, doi = {10.1126/science.abq6056}, pmid = {35857570}, issn = {1095-9203}, mesh = {Animals ; *Candida/physiology ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Host-Pathogen Interactions ; Humans ; *Immunity ; Mice ; Microbial Interactions ; *Mycobiome/physiology ; }, abstract = {Mycobiota modulate immunity and behavior.}, }
@article {pmid35921529, year = {2022}, author = {Khan, MH and Onyeaghala, GC and Rashidi, A and Holtan, SG and Khoruts, A and Israni, A and Jacobson, PA and Staley, C}, title = {Fecal β-glucuronidase activity differs between hematopoietic cell and kidney transplantation and a possible mechanism for disparate dose requirements.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2108279}, doi = {10.1080/19490976.2022.2108279}, pmid = {35921529}, issn = {1949-0984}, abstract = {The intestinal microbiota produces β-glucuronidase that plays an essential role in the metabolism of the immunosuppressant mycophenolate mofetil (MMF). This drug is commonly used in organ and hematopoietic cell transplantation (HCT), with variations in dosing across transplant types. We hypothesized that β-glucuronidase activity differs between transplant types, which may account for differences in dosing requirements. We evaluated fecal β-glucuronidase activity in patients receiving MMF post-allogeneic HCT and post-kidney transplant. Kidney transplant patients had significantly greater β-glucuronidase activity (8.48 ± 6.21 nmol/hr/g) than HCT patients (3.50 ± 3.29 nmol/hr/g; P = .001). Microbially mediated β-glucuronidase activity may be a critical determinant in the amount of mycophenolate entering the systemic circulation and an important factor to consider for precision dosing of MMF.}, }
@article {pmid35919409, year = {2022}, author = {Philip, S and Tageldin, O and Mansoor, MS and Richter, S}, title = {Successful Fecal Microbiota Transplant Delivered by Foley Catheter Through a Loop Ileostomy in a Patient With Severe Complicated Clostridioides difficile Infection.}, journal = {ACG case reports journal}, volume = {9}, number = {7}, pages = {e00801}, doi = {10.14309/crj.0000000000000801}, pmid = {35919409}, issn = {2326-3253}, abstract = {Clostridioides difficile infection (CDI) is a potentially life-threatening cause of diarrhea that can result in multiple complications. Fulminant CDI that is nonresponsive to antibiotics may require surgical ileostomy or fecal microbiota transplant (FMT). We present a case of a patient with fulminant CDI requiring surgical loop ileostomy who underwent a successful FMT delivered by Foley catheter through the ileostomy with symptom resolution. Delivery of FMT using a foley catheter in a patient with an ileostomy may be safe and effective for patients who are at a higher risk of complications associated with the instillation of FMT through colonoscopy with anesthesia.}, }
@article {pmid35918343, year = {2022}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Halaweish, H and Kaiser, T and Holtan, SG and Khoruts, A and Weisdorf, DJ and Staley, C}, title = {Compilation of longitudinal gut microbiome, serum metabolome, and clinical data in acute myeloid leukemia.}, journal = {Scientific data}, volume = {9}, number = {1}, pages = {468}, pmid = {35918343}, issn = {2052-4463}, support = {KL2TR002492//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; UL1TR002494//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; }, abstract = {Induction chemotherapy for patients with acute myeloid leukemia (AML) is a unique clinical scenario. These patients spend several weeks in the hospital, receiving multiple antibiotics, experiencing gastrointestinal mucosal damage, and suffering severe impairments in their immune system and nutrition. These factors cause major disruptions to the gut microbiota to a level rarely seen in other clinical conditions. Thus, the study of the gut microbiota in these patients can reveal novel aspects of microbiota-host relationships. When combined with the circulating metabolome, such studies could shed light on gut microbiota contribution to circulating metabolites. Collectively, gut microbiota and circulating metabolome are known to regulate host physiology. We have previously deposited amplicon sequences from 566 fecal samples from 68 AML patients. Here, we provide sample-level details and a link, using de-identified patient IDs, to additional data including serum metabolomics (260 samples from 36 patients) and clinical metadata. The detailed information provided enables comprehensive multi-omics analysis. We validate the technical quality of these data through 3 examples and demonstrate a method for integrated analysis.}, }
@article {pmid35917710, year = {2022}, author = {Liu, J and Zhang, X and Ta, X and Luo, M and Chang, X and Wang, H}, title = {Fecal microbiome transplantation attenuates manganese-induced neurotoxicity through regulation of the apelin signaling pathway by inhibition of autophagy in mouse brain.}, journal = {Ecotoxicology and environmental safety}, volume = {242}, number = {}, pages = {113925}, doi = {10.1016/j.ecoenv.2022.113925}, pmid = {35917710}, issn = {1090-2414}, abstract = {Manganese (Mn) is a common environmental pollutant. Mn exposure can lead to neurodegenerative diseases resembling Parkinson's disease, and has become a major public health concern. However, the mechanism of Mn-induced neurotoxicity in the brain is not clear. Fecal microbiome transplantation (FMT) may alleviate the neurotoxicity of Mn exposure by remodeling the gut microbiota. In this study, MnCl2 (manganese chloride) was administered to mice as in drinking water (Mn: 200 mg/L), and fecal matter from donor mice was administered by oral gavage every other day to the recipient mice. The Mn exposure model (Mn group) and FMT model (Mn+FMT group) were established and analyzed 5 weeks post-exposure. The Wipi1 gene exhibited the most significant increase associated with Mn exposure and Mn+FMT treatment groups based on transcriptome analysis. Combined analysis of transcriptomics and proteomics demonstrated that the apelin signaling pathway is the main pathway affected by FMT during Mn exposure. Immunofluorescence and Western blot showed that the expression of key proteins (Beclin-1, LC-3B, and PINK1) associated with autophagy in the hippocampus was robustly activated in the Mn exposure group, but attenuation was observed in Mn+FMT mice, suggesting a critical role of autophagy in neurotoxicity induced by Mn exposure. Our research provides evidence for the neurotoxic effects of Mn exposure through autophagy activation and provides an underlying mechanism of FMT protection against Mn-induced neurotoxicity through regulation of the apelin signaling pathway.}, }
@article {pmid35914739, year = {2022}, author = {Geng, J and Liu, C and Xu, J and Wang, X and Li, X}, title = {Potential relationship between Tourette syndrome and gut microbiome.}, journal = {Jornal de pediatria}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jped.2022.06.002}, pmid = {35914739}, issn = {1678-4782}, abstract = {OBJECTIVE: In this article, the author aims to discuss and review the relationship between gut microbiota and Tourette syndrome, and whether the change in gut microbiota can affect the severity of Tourette syndrome.<br><br>SOURCES: Literature from PubMed, Google Scholar, and China National Knowledge Infrastructure was mainly reviewed. Both original studies and review articles were discussed. The articles were required to be published as of May 2022.<br><br>SUMMARY OF THE FINDINGS: Current studies on the gut microbiome have found that the gut microbiome and brain seem to interact. It is named the brain-gut-axis. The relationship between the brain-gut axis and neurological and psychiatric disorders has been a topic of intense interest. Tourette syndrome is a chronic neurological disease that seriously affects the quality of life of children, and there appears to be an increase in Ruminococcaceae and Bacteroides in the gut of patients with Tourette syndrome. After clinical observation and animal experiments, there appear to be particular gut microbiota changes in Tourette syndrome. It provides a new possible idea for the treatment of Tourette syndrome. Probiotics and fecal microbial transplantation have been tried to treat Tourette syndrome, especially Tourette syndrome which is not sensitive to drugs, and some results have been achieved.<br><br>CONCLUSIONS: The relationship between gut microbiota and Tourette syndrome and how to alleviate Tourette syndrome by improving gut microbiota are new topics, more in-depth and larger sample size research is still needed.}, }
@article {pmid35913161, year = {2022}, author = {Lesniak, NA and Tomkovich, S and Henry, A and Taylor, A and Colovas, J and Bishop, L and McBride, K and Schloss, PD}, title = {Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities.}, journal = {mBio}, volume = {}, number = {}, pages = {e0136422}, doi = {10.1128/mbio.01364-22}, pmid = {35913161}, issn = {2150-7511}, abstract = {Fecal communities transplanted into individuals can eliminate recurrent Clostridioides difficile infection (CDI) with high efficacy. However, this treatment is only used once CDI becomes resistant to antibiotics or has recurred multiple times. We sought to investigate whether a fecal community transplant (FCT) pretreatment could be used to prevent CDI altogether. We treated male C57BL/6 mice with either clindamycin, cefoperazone, or streptomycin and then inoculated them with the microbial community from untreated mice before challenge with C. difficile. We measured colonization and sequenced the V4 region of the 16S rRNA gene to understand the dynamics of the murine fecal community in response to the FCT and C. difficile challenge. Clindamycin-treated mice became colonized with C. difficile but cleared it naturally and did not benefit from the FCT. Cefoperazone-treated mice became colonized by C. difficile, but the FCT enabled clearance of C. difficile. In streptomycin-treated mice, the FCT was able to prevent C. difficile from colonizing. We then diluted the FCT and repeated the experiments. Cefoperazone-treated mice no longer cleared C. difficile. However, streptomycin-treated mice colonized with 1:102 dilutions resisted C. difficile colonization. Streptomycin-treated mice that received an FCT diluted 1:103 became colonized with C. difficile but later cleared the infection. In streptomycin-treated mice, inhibition of C. difficile was associated with increased relative abundance of a group of bacteria related to Porphyromonadaceae and Lachnospiraceae. These data demonstrate that C. difficile colonization resistance can be restored to a susceptible community with an FCT as long as it complements the missing populations. IMPORTANCE Antibiotic use, ubiquitous with the health care environment, is a major risk factor for Clostridioides difficile infection (CDI), the most common nosocomial infection. When C. difficile becomes resistant to antibiotics, a fecal microbiota transplant from a healthy individual can effectively restore the gut bacterial community and eliminate the infection. While this relationship between the gut bacteria and CDI is well established, there are no therapies to treat a perturbed gut community to prevent CDI. This study explored the potential of restoring colonization resistance to antibiotic-induced susceptible gut communities. We described the effect that gut bacterial community variation has on the effectiveness of a fecal community transplant for inhibiting CDI. These data demonstrated that communities susceptible to CDI can be supplemented with fecal communities but that the effectiveness depended on the structure of the community following the perturbation. Thus, a reduced bacterial community may be able to recover colonization resistance in patients treated with antibiotics.}, }
@article {pmid35911731, year = {2022}, author = {Huang, J and Zheng, X and Kang, W and Hao, H and Mao, Y and Zhang, H and Chen, Y and Tan, Y and He, Y and Zhao, W and Yin, Y}, title = {Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {874922}, doi = {10.3389/fimmu.2022.874922}, pmid = {35911731}, issn = {1664-3224}, abstract = {Anti-PD-1 immunotherapy has saved numerous lives of cancer patients; however, it only exerts efficacy in 10-15% of patients with colorectal cancer. Fecal microbiota transplantation (FMT) is a potential approach to improving the efficacy of anti-PD-1 therapy, whereas the detailed mechanisms and the applicability of this combination therapy remain unclear. In this study, we evaluated the synergistic effect of FMT with anti-PD-1 in curing colorectal tumor-bearing mice using a multi-omics approach. Mice treated with the combination therapy showed superior survival rate and tumor control, compared to the mice received anti-PD-1 therapy or FMT alone. Metagenomic analysis showed that composition of gut microbiota in tumor-bearing mice treated with anti-PD-1 therapy was remarkably altered through receiving FMT. Particularly, Bacteroides genus, including FMT-increased B. thetaiotaomicron, B. fragilis, and FMT-decreased B. ovatus might contribute to the enhanced efficacy of anti-PD-1 therapy. Furthermore, metabolomic analysis upon mouse plasma revealed several potential metabolites that upregulated after FMT, including punicic acid and aspirin, might promote the response to anti-PD-1 therapy via their immunomodulatory functions. This work broadens our understanding of the mechanism by which FMT improves the efficacy of anti-PD-1 therapy, which may contribute to the development of novel microbiota-based anti-cancer therapies.}, }
@article {pmid35911670, year = {2022}, author = {Wang, J and Jia, R and Celi, P and Zhuo, Y and Ding, X and Zeng, Q and Bai, S and Xu, S and Yin, H and Lv, L and Zhang, K}, title = {Resveratrol Alleviating the Ovarian Function Under Oxidative Stress by Alternating Microbiota Related Tryptophan-Kynurenine Pathway.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {911381}, doi = {10.3389/fimmu.2022.911381}, pmid = {35911670}, issn = {1664-3224}, abstract = {Oxidative stress (OS) is a key factor regulating the systemic pathophysiological effects and one of the fundamental mechanisms associated with aging and fertility deterioration. Previous studies revealed that resveratrol (RV) exhibits a preventive effect against oxidative stress in the ovary. However, it remains unknown whether gut microbiota respond to resveratrol during an OS challenge. In Exp. 1, layers received intraperitoneal injection of tert-butyl hydroperoxide (tBHP) (0 or 800 μmol/kg BW) or received resveratrol diets (0 or 600 mg/kg) for 28 days. In Exp. 2, the role of intestinal microbiota on the effects of resveratrol on tBHP-induced oxidative stress was assessed through fecal microbiota transplantation (FMT). The OS challenge reduced the egg-laying rate and exhibited lower pre-hierarchical follicles and higher atretic follicles. Oral RV supplementation ameliorated the egg-laying rate reduction and gut microbiota dysbiosis. RV also reversed the tryptphan-kynurenine pathway, upregulated nuclear factor E2-related factor 2 (Nrf2) and silent information regulator 1(SIRT1) levels, and decreased the expression of forkhead box O1 (FoxO1) and P53. These findings indicated that the intestinal microbiota-related tryptophan-kynurenine pathway is involved in the resveratrol-induced amelioration of ovary oxidative stress induced by tBHP in the layer model, while SIRT1-P53/FoxO1 and Nrf2-ARE signaling pathway were involved in this process.}, }
@article {pmid35905229, year = {2022}, author = {Huang, T and Xu, J and Wang, M and Pu, K and Li, L and Zhang, H and Liang, Y and Sun, W and Wang, Y}, title = {An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis.}, journal = {Medicine}, volume = {101}, number = {30}, pages = {e29790}, doi = {10.1097/MD.0000000000029790}, pmid = {35905229}, issn = {1536-5964}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) as a promising therapy for ulcerative colitis (UC) remains controversial. We conducted a systematic review and meta-analysis to assess the efficiency and safety of FMT as a treatment for UC.<br><br>METHODS: The target studies were identified by searching PubMed, EMBASE, the Cochrane Library, Web of Science, and ClinicalTrials and by manual supplementary retrieval. We conducted a general review and quantitative synthesis of included studies. We used the RevMan and Stata programs in the meta-analysis. The outcomes were total remission, clinical remission, steroid-free remission, and serious adverse events. We also performed subgroup analyses based on different populations.<br><br>RESULTS: A total of 34 articles were included in the general review. Only 16 articles, including 4 randomized controlled trials, 2 controlled clinical trials, and 10 cohort studies, were selected for the meta-analysis. We found that donor FMT might be more effective than placebo for attaining total remission (risk ratio [RR]: 2.77, 95% confidence interval [CI]: 1.54-4.98; P = .0007), clinical remission (RR: 0.33, 95% CI: 0.24-0.41; P < .05), and steroid-free remission (RR: 3.63, 95% CI: 1.57-8.42; P = .003), but found no statistically significant difference in the incidence of serious adverse events (RR: 0.88, 95% CI: 0.34-2.31, P = .8). The subgroup analyses revealed significant differences between the pooled clinical remission rates for different regions, degrees of severity of the disease, and patients with steroid- or nonsteroid-dependent UC.<br><br>CONCLUSIONS: FMT can achieve clinical remission and clinical response in patients with UC.}, }
@article {pmid35899275, year = {2022}, author = {Vendrik, KEW and de Meij, TGJ and Bökenkamp, A and Ooijevaar, RE and Groenewegen, B and Hendrickx, APA and Terveer, EM and Kuijper, EJ and van Prehn, J}, title = {Transmission of Antibiotic-Susceptible Escherichia coli Causing Urinary Tract Infections in a Fecal Microbiota Transplantation Recipient: Consequences for Donor Screening?.}, journal = {Open forum infectious diseases}, volume = {9}, number = {7}, pages = {ofac324}, doi = {10.1093/ofid/ofac324}, pmid = {35899275}, issn = {2328-8957}, abstract = {Fecal microbiota transplantation (FMT) has been reported to decrease the incidence of recurrent urinary tract infections (UTIs), presumably by restoring microbiome diversity and/or uropathogen competition. We report a 16-year-old female with recurrent UTIs caused by multidrug-resistant Klebsiella pneumoniae, for which frequent intravenous broad-spectrum antibiotic treatment was necessary. The patient was treated with FMT from a well-screened healthy donor without multidrug-resistant bacteria in the feces. After FMT, she developed several UTIs with an antibiotic-susceptible Escherichia coli that could be treated orally. The uropathogenic E. coli could be cultured from donor feces, and whole genome sequencing confirmed donor-to-recipient transmission. Our observation should stimulate discussion on long-term follow-up of all infections after FMT and donor fecal screening for antibiotic-susceptible Enterobacterales.}, }
@article {pmid35899041, year = {2022}, author = {Cheng, Z and Yang, L and Chu, H}, title = {The Gut Microbiota: A Novel Player in Autoimmune Hepatitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {947382}, doi = {10.3389/fcimb.2022.947382}, pmid = {35899041}, issn = {2235-2988}, abstract = {Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease distributed globally in all ethnicities with increasing prevalence. If left untreated, the disease will lead to cirrhosis, liver failure, or death. The intestinal microbiota is a complex ecosystem located in the human intestine, which extensively affects the human physiological and pathological processes. With more and more in-depth understandings of intestinal microbiota, a substantial body of studies have verified that the intestinal microbiota plays a crucial role in a variety of digestive system diseases, including alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). However, only a few studies have paid attention to evaluate the relationship between AIH and the intestinal microbiota. While AIH pathogenesis is not fully elucidated yet, some studies have indicated that intestinal microbiota putatively made significant contributions to the occurrence and the development of AIH by triggering several specific signaling pathways, altering the metabolism of intestinal microbiota, as well as modulating the immune response in the intestine and liver. By collecting the latest related literatures, this review summarized the increasing trend of the aerobic bacteria abundance in both AIH patients and AIH mice models. Moreover, the combination of specific bacteria species was found distinct to AIH patients, which could be a promising tool for diagnosing AIH. In addition, there were alterations of luminal metabolites and immune responses, including decreased short-chain fatty acids (SCFAs), increased pathogen associated molecular patterns (PAMPs), imbalanced regulatory T (Treg)/Th17 cells, follicular regulatory T (TFR)/follicular helper T (TFH) cells, and activated natural killer T (NKT) cells. These alterations participate in the onset and the progression of AIH via multiple mechanisms. Therefore, some therapeutic methods based on restoration of intestinal microbiota composition, including probiotics and fecal microbiota transplantation (FMT), as well as targeted intestinal microbiota-associated signaling pathways, confer novel insights into the treatment for AIH patients.}, }
@article {pmid35898713, year = {2022}, author = {Guo, L and Guan, Q and Duan, W and Ren, Y and Zhang, XJ and Xu, HY and Shi, JS and Wang, FZ and Lu, R and Zhang, HL and Xu, ZH and Li, H and Geng, Y}, title = {Dietary Goji Shapes the Gut Microbiota to Prevent the Liver Injury Induced by Acute Alcohol Intake.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {929776}, doi = {10.3389/fnut.2022.929776}, pmid = {35898713}, issn = {2296-861X}, abstract = {Diet is a major driver of the structure and function of the gut microbiota, which influences the host physiology. Alcohol abuse can induce liver disease and gut microbiota dysbiosis. Here, we aim to elucidate whether the well-known traditional health food Goji berry targets gut microbiota to prevent liver injury induced by acute alcohol intake. The results showed that Goji supplementation for 14 days alleviated acute liver injury as indicated by lowering serum aspartate aminotransferase, alanine aminotransferase, pro-inflammatory cytokines, as well as lipopolysaccharide content in the liver tissue. Goji maintained the integrity of the epithelial barrier and increased the levels of butyric acid in cecum contents. Furthermore, we established the causal relationship between gut microbiota and liver protection effects of Goji with the help of antibiotics treatment and fecal microbiota transplantation (FMT) experiments. Both Goji and FMT-Goji increased glutathione (GSH) in the liver and selectively enriched the butyric acid-producing gut bacterium Akkermansia and Ruminococcaceae by using 16S rRNA gene sequencing. Metabolomics analysis of cecum samples revealed that Goji and its trained microbiota could regulate retinoyl β-glucuronide, vanillic acid, and increase the level of glutamate and pyroglutamic acid, which are involved in GSH metabolism. Our study highlights the communication among Goji, gut microbiota, and liver homeostasis.}, }
@article {pmid35898289, year = {2022}, author = {Liu, Y and Zhang, S and Wu, X and Li, Q and Wang, Y and Huang, Y and Zhang, F and Cui, B and Lu, X}, title = {Instant messaging client gives the opportunity to recognize gut microbiota and dysbiosis-related disease: An investigation study on WeChat APP.}, journal = {Digital health}, volume = {8}, number = {}, pages = {20552076221115018}, doi = {10.1177/20552076221115018}, pmid = {35898289}, issn = {2055-2076}, abstract = {Objectives: Gut microbiota and dysbiosis are closely related to the occurrence and development of various diseases. It is necessary to popularize gut microbiota-related knowledge to the public. And the instant messaging client on smartphones supplies a perfect tool to achieve this goal. Hence, we will describe the current status of gut microbiota education spread by WeChat official accounts.<br><br>Methods: The keywords of "gut microbiota," "fecal microbiota transplantation (FMT)," and "probiotics" were searched in the articles published from January 2015 to August 2020 on the WeChat official accounts. And the data were analyzed based on the 10 common gut dysbiosis-related diseases.<br><br>Results: A total of 3061 WeChat official accounts have published 11,239 articles on gut microbiota dysbiosis-related diseases, with a rising trend in the total article numbers and the total pageviews. The keywords of "gut microbiota" dominate 50.61%, and the articles on inflammatory bowel disease had the largest proportion. Additionally, articles on the keyword "gut microbiota" also included cancer and obesity, articles on the keyword "FMT" mainly consist of Clostridium difficile infection and psychological disease, and the keyword "probiotics" was mainly related to obesity and irritable bowel syndrome disease. The top three total pageviews were on inflammatory bowel disease, obesity, and cancer.<br><br>Conclusion: This study indicates the current research hotspots and public concerns on the gut microbiota, and WeChat as an instant messaging client plays an important role in promoting the scientific popularization of gut microbiota.}, }
@article {pmid35889051, year = {2022}, author = {Mazzawi, T}, title = {Gut Microbiota Manipulation in Irritable Bowel Syndrome.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, doi = {10.3390/microorganisms10071332}, pmid = {35889051}, issn = {2076-2607}, abstract = {Increased knowledge suggests that disturbed gut microbiota, termed dysbiosis, might promote the development of irritable bowel syndrome (IBS) symptoms. Accordingly, gut microbiota manipulation has evolved in the last decade as a novel treatment strategy in order to improve IBS symptoms. In using different approaches, dietary management stands first in line, including dietary fiber supplements, prebiotics, and probiotics that are shown to change the composition of gut microbiota, fecal short-chain fatty acids and enteroendocrine cells densities and improve IBS symptoms. However, the exact mixture of beneficial bacteria for each individual remains to be identified. Prescribing nonabsorbable antibiotics still needs confirmation, although using rifaximin has been approved for diarrhea-predominant IBS. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and five out of seven placebo-controlled trials investigating FMT in IBS obtain promising results regarding symptom reduction and gut microbiota manipulation. However, more data, including larger cohorts and studying long-term effects, are needed before FMT can be regarded as a treatment for IBS in clinical practice.}, }
@article {pmid35889034, year = {2022}, author = {Del Vecchio, LE and Fiorani, M and Tohumcu, E and Bibbò, S and Porcari, S and Mele, MC and Pizzoferrato, M and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Risk Factors, Diagnosis, and Management of Clostridioides difficile Infection in Patients with Inflammatory Bowel Disease.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, doi = {10.3390/microorganisms10071315}, pmid = {35889034}, issn = {2076-2607}, abstract = {Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are two pathologies that share a bidirectional causal nexus, as CDI is known to have an aggravating effect on IBD and IBD is a known risk factor for CDI. The colonic involvement in IBD not only renders the host more prone to an initial CDI development but also to further recurrences. Furthermore, IBD flares, which are predominantly set off by a CDI, not only create a need for therapy escalation but also prolong hospital stay. For these reasons, adequate and comprehensive management of CDI is of paramount importance in patients with IBD. Microbiological diagnosis, correct evaluation of clinical status, and consideration of different treatment options (from antibiotics and fecal microbiota transplantation to monoclonal antibodies) carry pivotal importance. Thus, the aim of this article is to review the risk factors, diagnosis, and management of CDI in patients with IBD.}, }
@article {pmid35888994, year = {2022}, author = {Trunfio, M and Scabini, S and Rugge, W and Bonora, S and Di Perri, G and Calcagno, A}, title = {Concurrent and Subsequent Co-Infections of Clostridioides difficile Colitis in the Era of Gut Microbiota and Expanding Treatment Options.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, doi = {10.3390/microorganisms10071275}, pmid = {35888994}, issn = {2076-2607}, abstract = {We narratively reviewed the physiopathology, epidemiology, and management of co-infections in Clostridioides difficile colitis (CDI) by searching the following keywords in Embase, MedLine, and PubMed: "Clostridium/Clostridioides difficile", "co-infection", "blood-stream infection" (BSI), "fungemia", "Candida", "Cytomegalovirus", "probiotics", "microbial translocation" (MT). Bacterial BSIs (mainly by Enterobacteriaceae and Enterococcus) and fungemia (mainly by Candida albicans) may occur in up to 20% and 9% of CDI, increasing mortality and length of hospitalization. Up to 68% of the isolates are multi-drug-resistant bacteria. A pivotal role is played by gut dysbiosis, intestinal barrier leakage, and MT. Specific risk factors are represented by CDI-inducing broad-spectrum antibiotics, oral vancomycin use, and CDI severity. Probiotics administration (mainly Saccharomyces and Lactobacillus) during moderate/severe CDI may favor probiotics superinfection. Other co-infections (such as Cytomegalovirus or protozoa) can complicate limited and specific cases. There is mounting evidence that fidaxomicin, bezlotoxumab, and fecal microbiota transplantation can significantly reduce the rate of co-infections compared to historical therapies by interrupting the vicious circle between CDI, treatments, and MT. Bacterial BSIs and candidemia represent the most common co-infections in CDI. Physicians should be aware of this complication to promptly diagnose and treat it and enforce preventive strategies that include a more comprehensive consideration of newer treatment options.}, }
@article {pmid35887883, year = {2022}, author = {Biazzo, M and Deidda, G}, title = {Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases.}, journal = {Journal of clinical medicine}, volume = {11}, number = {14}, pages = {}, doi = {10.3390/jcm11144119}, pmid = {35887883}, issn = {2077-0383}, abstract = {The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota dysbiosis, thereby suggesting that the reinstatement of physiological microflora balance and composition might ameliorate the clinical symptoms. Among possible microbiota-targeted interventions, pre/pro-biotics supplementations were shown to provide effective results, but the main limitation remains in the limited microbial species available as probiotics. Differently, fecal microbiota transplantation involves the transplantation of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition aiming to confer a health benefit. Firstly used in the 4th century in traditional Chinese medicine, nowadays, it has been exploited so far to treat recurrent Clostridioides difficile infections, but accumulating data coming from a number of clinical trials clearly indicate that fecal microbiota transplantation may also carry the therapeutic potential for a number of other conditions ranging from gastrointestinal to liver diseases, from cancer to inflammatory, infectious, autoimmune diseases and brain disorders, obesity, and metabolic syndrome. In this review, we will summarize the commonly used preparation and delivery methods, comprehensively review the evidence obtained in clinical trials in different human conditions and discuss the variability in the results and the pivotal importance of donor selection. The final aim is to stimulate discussion and open new therapeutic perspectives among experts in the use of fecal microbiota transplantation not only in Clostridioides difficile infection but as one of the first strategies to be used to ameliorate a number of human conditions.}, }
@article {pmid35884093, year = {2022}, author = {Hong, AS and Tun, KM and Hong, JM and Batra, K and Ohning, G}, title = {Fecal Microbiota Transplantation in Decompensated Cirrhosis: A Systematic Review on Safety and Efficacy.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, doi = {10.3390/antibiotics11070838}, pmid = {35884093}, issn = {2079-6382}, abstract = {Background and Aims: Due to increasing knowledge of the "gut-liver axis", there has been growing interest regarding the use of fecal microbiota transplant in the management of chronic liver disease. There are limited data available and current guidelines are mostly based on expert opinions. We aim to perform the first systematic review investigating safety and efficacy of fecal microbiota transplant particularly among high-risk decompensated cirrhosis patient populations. Methods: Literature search was performed using variations of the keywords "fecal microbiota transplant" and "cirrhosis" on PubMed/Medline from inception to 3 October 2021. The resulting 116 articles were independently screened by two authors. In total, 5 qualifying studies, including 2 randomized control trials and 3 retrospective case series, were found to meet established eligibility criteria and have adequate quality of evidence to be included in this review. Results: Of the total 58 qualifying patients, there were 2 deaths post fecal microbiota transplant, 1 of which could not rule out being related (1.7%). Among the remaining 56 participants, 8 serious adverse events were reported, of which 2 could not rule out being related (3.6%). The success rate of fecal microbiota transplantation in treating recurrent Clostridioides difficile infection among patients with decompensated cirrhosis was 77.8%. The success rate when used as investigational treatment for hepatic encephalopathy was 86.7%, with multiple studies reporting clinically significant improvement in encephalopathy testing scores. Conclusions: We found a marginally higher rate of deaths and serious adverse events from fecal microbiota transplant in our patient population compared with the average immunocompetent population, where it was previously found to have 0 deaths and SAE rate of 2.83%. The efficacy when used for recurrent C.difficile infection was 77.8% and 87% in the decompensated cirrhotic and general populations, respectively. Studies on efficacy in novel treatment of hepatic encephalopathy have been promising. This study concludes that fecal microbiota transplant use in decompensated cirrhosis patients should be used with caution and preferably be limited to research purposes until better data are available.}, }
@article {pmid35882675, year = {2022}, author = {Shi, X and Ma, T and Sakandar, HA and Menghe, B and Sun, Z}, title = {Gut microbiome and aging nexus and underlying mechanism.}, journal = {Applied microbiology and biotechnology}, volume = {}, number = {}, pages = {}, pmid = {35882675}, issn = {1432-0614}, support = {No.2020ZD12//Natural Science Foundation of Inner Mongolia/ ; 2021ZD0014//Agriculture Research System of China/ ; 2018YFE0123500//Key Technologies Research and Development Program/ ; }, abstract = {According to the United Nations population profile, the number of individuals aged 60 and over in high-income nations is expected to rise from 302 million to over 366 million between 2019 and 2030, so there is an increasing emphasis on nutrition and health in older people. Numerous studies have demonstrated the crucial role that gut microbiota plays in maintaining human health. As a model of healthy aging, centenarians have different gut microbiota from ordinary elderly people. The core microbiome of centenarians in various countries has shown some common characteristics, which are worth further exploration. In this review, the significance of the human gut microbiota to health is briefly discussed, and the characteristics of the gut microbiota of long-lived senior persons of different ages and in different countries are described. Moreover, this review lists dietary interventions and fecal microbiota transplantation. In the end, it discusses the pros and cons of using probiotics to enhance the health of seniors through focused management of the gut microbiota. It aims to pave the way for further investigation into the nexus between gut microbiota, probiotics, and longevity, and then to reveal the underlying mechanism to promote longevity. KEY POINTS: • Gut microbial structure in different age groups and the characteristics of gut microbiota in centenarians. • Dietary interventions, fecal transplants, and probiotics target the modulation of gut microbiota for healthy aging.}, }
@article {pmid35879237, year = {2022}, author = {Manning, L and Gosbell, IB and Howden, B and Tong, S}, title = {The demand-supply gap for faecal microbiota transplantation in Australia and New Zealand: a survey of infectious diseases physicians.}, journal = {Internal medicine journal}, volume = {52}, number = {7}, pages = {1282-1283}, doi = {10.1111/imj.15845}, pmid = {35879237}, issn = {1445-5994}, mesh = {*Communicable Diseases ; Fecal Microbiota Transplantation ; Humans ; New Zealand ; *Physicians ; Surveys and Questionnaires ; }, }
@article {pmid35882293, year = {2022}, author = {Luo, L and Luo, J and Cai, Y and Fu, M and Li, W and Shi, L and Liu, J and Dong, R and Xu, X and Tu, L and Yang, Y}, title = {Inulin-Type Fructans Change the Gut Microbiota and Prevent the Development of Diabetic Nephropathy.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106367}, doi = {10.1016/j.phrs.2022.106367}, pmid = {35882293}, issn = {1096-1186}, abstract = {Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, and few treatment options that prevent the progressive loss of renal function are available. Studies have shown that dietary fiber intake improves kidney diseases and metabolism-related diseases, most likely through short-chain fatty acids (SCFAs). The present study aimed to examine the protective effects of inulin-type fructans (ITFs) on DN through 16S rRNA gene sequencing, gas chromatographymass spectrometry (GCMS) analysis and fecal microbiota transplantation (FMT). The results showed that ITFs supplementation protected against kidney damage in db/db mice and regulated the composition of the gut microbiota. Antibiotic treatment and FMT experiments further demonstrated a key role of the gut microbiota in mediating the beneficial effects of ITFs. The ITFs treatment-induced changes in the gut microbiota led to an enrichment of SCFA-producing bacteria, especially the genera Akkermansia and Candidatus Saccharimonas, which increased the fecal and serum acetate concentrations. Subsequently, acetate supplementation improved glomerular damage and renal fibrosis by attenuating mitochondrial dysfunction and reducing toxic glucose metabolite levels. In conclusion, ITFs play a renoprotective role by modulating the gut microbiota and increasing acetate production. Furthermore, acetate mediates renal protection by regulating glucose metabolism, decreasing glycotoxic product levels and improving mitochondrial function.}, }
@article {pmid35881124, year = {2022}, author = {Slomski, A}, title = {Durable IBS Response From Fecal Microbiota Transplant.}, journal = {JAMA}, volume = {328}, number = {4}, pages = {322}, doi = {10.1001/jama.2022.12179}, pmid = {35881124}, issn = {1538-3598}, }
@article {pmid35878341, year = {2022}, author = {Marclay, M and Dwyer, E and Suchodolski, JS and Lidbury, JA and Steiner, JM and Gaschen, FP}, title = {Recovery of Fecal Microbiome and Bile Acids in Healthy Dogs after Tylosin Administration with and without Fecal Microbiota Transplantation.}, journal = {Veterinary sciences}, volume = {9}, number = {7}, pages = {}, doi = {10.3390/vetsci9070324}, pmid = {35878341}, issn = {2306-7381}, support = {2018 IDEXX/CGS Veterinary Student Summer Scholar Award//Comparative Gastroenterology Society/ ; 2019//Hunter Retriever Club Foundation/ ; }, abstract = {Antibiotics cause gut dysbiosis and bile acid dysmetabolism in dogs. The effect of fecal microbiota transplantation (FMT) on microbiome and metabolome recovery is unknown. This prospective, randomized, placebo-controlled study included sixteen healthy purpose-bred dogs. All dogs received tylosin 20 mg/kg PO once daily (days 1-7) and were randomly assigned to either receive one FMT via enema (day 8), daily oral FMT capsules (days 8-21), or daily placebo capsules (days 8-21). Fecal samples were frozen at regular intervals until day 42. Quantitative PCR for 8 bacterial taxa was performed to calculate the fecal dysbiosis index (FDI) and fecal concentrations of unconjugated bile acids (UBA) were measured using gas chromatography-mass spectrometry. Tylosin altered the abundance of most evaluated bacteria and induced a significant decrease in secondary bile acid concentrations at day 7 in all dogs. However, most parameters returned to their baseline by day 14 in all dogs. In conclusion, tylosin markedly impacted fecal microbiota and bile acid concentrations, although return to baseline values was quick after the antibiotic was discontinued. Overall, FMT did not accelerate recovery of measured parameters. Further studies are warranted to confirm the value of FMT in accelerating microbiota recovery in antibiotic-associated dysbiosis in dogs.}, }
@article {pmid35877737, year = {2022}, author = {You, H and Deng, X and Bai, Y and He, J and Cao, H and Che, Q and Guo, J and Su, Z}, title = {The Ameliorative Effect of COST on Diet-Induced Lipid Metabolism Disorders by Regulating Intestinal Microbiota.}, journal = {Marine drugs}, volume = {20}, number = {7}, pages = {}, doi = {10.3390/md20070444}, pmid = {35877737}, issn = {1660-3397}, abstract = {BACKGROUND: Chitosan oligosaccharides, with an average molecular weight ≤ 1000 Da (COST), is a natural marine product that has the potential to improve intestinal microflora and resist lipid metabolism disorders.<br><br>METHODS: First, by establishing a mice model of lipid metabolism disorder induced by a high fat and high sugar diet, it is proven that COST can reduce lipid metabolism disorder, which may play a role in regulating intestinal microorganisms. Then, the key role of COST in the treatment of intestinal microorganisms is further confirmed through the method of COST-treated feces and fecal bacteria transplantation.<br><br>CONCLUSIONS: intestinal microbiota plays a key role in COST inhibition of lipid metabolism disorder induced by a high fat and high sugar diet. In particular, COST may play a central regulatory role in microbiota, including Bacteroides, Akkermansia, and Desulfovibrio. Taken together, our work suggests that COST may improve the composition of gut microbes, increase the abundance of beneficial bacteria, improve lipid metabolism disorders, and inhibit the development of metabolic disorders.}, }
@article {pmid35877603, year = {2022}, author = {Xian, W and Yang, S and Deng, Y and Yang, Y and Tan, Z and Li, W and Yang, R}, title = {Potential of Establishing the Corresponding Human Microbial Community in Pseudo Germ-Free Mice through Fecal Microbe Transfer from Three Urolithin Metabotypes.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c02796}, pmid = {35877603}, issn = {1520-5118}, abstract = {Three urolithin metabotypes (UMs) have been defined in the population according to final urolithins converted by gut microbiota. Currently, it is difficult to establish the cause-and-effect relationship between urolithins and microbiota in human studies. Studies on the health effects of ellagic acid (EA) in animal models rarely consider the differences in the urolithin production. Therefore, the objective of this study is to establish human microbiota-associated (HMA) mice, imitating the microbiota composition of the three UMs. Antibiotic-induced pseudo germ-free mice were gavaged with fecal bacteria of the three UM donors for four weeks. The results showed that the ability to produce corresponding urolithins was successfully transferred from the donor of the three UMs to HMA mice. The three UM HMA mice adopted a humanized microbiota profile similar to their corresponding donor. The family Eggerthellaceae and genera Eggerthella and Gordonibacter were successfully transferred and colonized from UM-A/B donors to HMA mice. Overall, the three UM HMA mouse models were successfully established, which provide a basis for exploring the health effects of EA.}, }
@article {pmid35877085, year = {2022}, author = {Thakur, PS and Aggarwal, D and Takkar, B and Shivaji, S and Das, T}, title = {Evidence Suggesting the Role of Gut Dysbiosis in Diabetic Retinopathy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {63}, number = {8}, pages = {21}, doi = {10.1167/iovs.63.8.21}, pmid = {35877085}, issn = {1552-5783}, abstract = {Purpose: Gut dysbiosis has been identified and tested in human trials for its role in diabetes mellitus (DM). The gut-retina axis could be a potential target for retardation of diabetic retinopathy (DR), a known complication of DM. This study reviews the evidence suggesting gut dysbiosis in DR.<br><br>Methods: The published literature in the past 5 years was reviewed using predetermined keywords and articles. The review intended to determine changes in gut microbiome in DR, the hypothesized mechanisms linking to the gut-retina axis, its predictive potential for progression of DR, and the possible therapeutic targets.<br><br>Results: The gut microbiota of people with DM differ from those without it, and the gut microbiota of people with DR differ from those without it. The difference is more significant in the former (DM versus no DM) and less significant in the latter (DM without DR versus DM with DR). Early research has suggested mechanisms of the gut-retina axis, but these are not different from known changes in the gut microbiome of people with DM. The current evidence on the predictive value of the gut microbiome in the occurrence and progression of DR is low. Therapeutic avenues targeting the gut-retina axis include lifestyle changes, pharmacologic inhibitors, probiotics, and fecal microbiota transplantation.<br><br>Conclusions: Investigating the therapeutic utility of the gut ecosystem for DM and its complications like DR is an emerging area of research. The gut-retina axis could be a target for retardation of DR but needs longitudinal regional studies adjusting for dietary habits.}, }
@article {pmid35876289, year = {2022}, author = {Sindhunata, DP and Meijnikman, AS and Gerdes, VEA and Nieuwdorp, M}, title = {Dietary fructose as a metabolic risk factor.}, journal = {American journal of physiology. Cell physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpcell.00439.2021}, pmid = {35876289}, issn = {1522-1563}, support = {15798//Novo Nordisk Foundation Center for Basic Metabolic Research (NovoNordisk Foundation Center for Basic Metabolic Research)/ ; 09150182010020//ZonMw (Netherlands Organisation for Health Research and Development)/ ; }, abstract = {Over the last decades, the role of the intestinal microbiota in metabolic diseases has come forward. In this regard, both composition and function of our intestinal microbiota is highly variable and influenced by multiple factors, of which diet is one of the major elements. Between 1970 and 1990 diet composition has changed and consumption of dietary sugars has increased, of which fructose intake rose by more than tenfold. This increased intake of sugars and fructose is considered as one of the major risk factors in the developments of obesity and several metabolic disturbances. In this review, we describe the association of dietary fructose intake with insulin resistance, non-alcoholic fatty liver disease (NAFLD) and lipid metabolism. Moreover, we will focus on the potential causality of this altered gut microbiota using fecal transplantation studies in human metabolic disease and whether fecal microbial transplant can reverse this phenotype.}, }
@article {pmid35874759, year = {2022}, author = {Sen, T and Thummer, RP}, title = {The Impact of Human Microbiotas in Hematopoietic Stem Cell and Organ Transplantation.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {932228}, doi = {10.3389/fimmu.2022.932228}, pmid = {35874759}, issn = {1664-3224}, abstract = {The human microbiota heavily influences most vital aspects of human physiology including organ transplantation outcomes and transplant rejection risk. A variety of organ transplantation scenarios such as lung and heart transplantation as well as hematopoietic stem cell transplantation is heavily influenced by the human microbiotas. The human microbiota refers to a rich, diverse, and complex ecosystem of bacteria, fungi, archaea, helminths, protozoans, parasites, and viruses. Research accumulating over the past decade has established the existence of complex cross-species, cross-kingdom interactions between the residents of the various human microbiotas and the human body. Since the gut microbiota is the densest, most popular, and most studied human microbiota, the impact of other human microbiotas such as the oral, lung, urinary, and genital microbiotas is often overshadowed. However, these microbiotas also provide critical and unique insights pertaining to transplantation success, rejection risk, and overall host health, across multiple different transplantation scenarios. Organ transplantation as well as the pre-, peri-, and post-transplant pharmacological regimens patients undergo is known to adversely impact the microbiotas, thereby increasing the risk of adverse patient outcomes. Over the past decade, holistic approaches to post-transplant patient care such as the administration of clinical and dietary interventions aiming at restoring deranged microbiota community structures have been gaining momentum. Examples of these include prebiotic and probiotic administration, fecal microbial transplantation, and bacteriophage-mediated multidrug-resistant bacterial decolonization. This review will discuss these perspectives and explore the role of different human microbiotas in the context of various transplantation scenarios.}, }
@article {pmid35873830, year = {2022}, author = {Sun, X and Xue, L and Wang, Z and Xie, A}, title = {Update to the Treatment of Parkinson's Disease Based on the Gut-Brain Axis Mechanism.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {878239}, doi = {10.3389/fnins.2022.878239}, pmid = {35873830}, issn = {1662-4548}, abstract = {Gastrointestinal (GI) symptoms represented by constipation were significant non-motor symptoms of Parkinson's disease (PD) and were considered early manifestations and aggravating factors of the disease. This paper reviewed the research progress of the mechanism of the gut-brain axis (GBA) in PD and discussed the roles of α-synuclein, gut microbiota, immune inflammation, neuroendocrine, mitochondrial autophagy, and environmental toxins in the mechanism of the GBA in PD. Treatment of PD based on the GBA theory has also been discussed, including (1) dietary therapy, such as probiotics, vitamin therapy, Mediterranean diet, and low-calorie diet, (2) exercise therapy, (3) drug therapy, including antibiotics; GI peptides; GI motility agents, and (4) fecal flora transplantation can improve the flora. (5) Vagotomy and appendectomy were associated but not recommended.}, }
@article {pmid35873640, year = {2022}, author = {Liu, QH and Ke, X and Xiao, C}, title = {Current Applications of Fecal Microbiota Transplantation in Functional Constipation.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2022}, number = {}, pages = {7931730}, doi = {10.1155/2022/7931730}, pmid = {35873640}, issn = {1741-427X}, abstract = {Functional constipation (FC) is a common condition that would be hard to treat in clinical practice with a prevalence incidence in the population. Pharmacotherapy is a common treatment modality. However, clinical effects are limited and patients continue to suffer from it. In recent years, with the gradual increase in research on gut microbiota, it is understood that dysbiosis of the gut microbiota is importantly associated with the development of constipation. Recent studies have shown that fecal microbiota transplantation (FMT) is an effective method for restoring gut microbiota, as well as being efficacious in the treatment of FC. This mini review explains the characteristics of gut microbiota in FC patients, the mechanism of action of FMT, treatment modalities, current efficacy, and related problems. The purpose is to provide research directions and references for the future applications of FMT in FC.}, }
@article {pmid35873168, year = {2022}, author = {Bu, F and Yao, X and Lu, Z and Yuan, X and Chen, C and Li, L and Li, Y and Jiang, F and Zhu, L and Shi, G and Chen, Y}, title = {Pathogenic or Therapeutic: The Mediating Role of Gut Microbiota in Non-Communicable Diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {906349}, doi = {10.3389/fcimb.2022.906349}, pmid = {35873168}, issn = {2235-2988}, abstract = {Noncommunicable diseases (NCDs) lead to 41 million deaths every year and account for 71% of all deaths worldwide. Increasing evidence indicates that gut microbiota disorders are closely linked to the occurrence and development of diseases. The gut microbiota, as a potential transmission medium, could play a key role in the transmission and treatment of diseases. The gut microbiota makes noncommunicable diseases communicable. New methods of the prevention and treatment of these diseases could be further explored through the gut microbiota.}, }
@article {pmid35871602, year = {2022}, author = {Li, L and Wang, M and Bao, J and Wang, N and Huang, Y and He, S and Chen, B and Yan, F}, title = {Periodontitis may impair the homeostasis of systemic bone through regulation of gut microbiota in ApoE-/- mice.}, journal = {Journal of clinical periodontology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jcpe.13708}, pmid = {35871602}, issn = {1600-051X}, abstract = {AIM: To investigate whether periodontitis impacts bone homeostasis via gut microbiota regulation.<br><br>MATERIALS AND METHODS: Experimental periodontitis was induced by ligatures (LIG group). ApoE-/- mice were employed as a model with weakened bone homeostasis. Bone turnover was evaluated through micro-CT, HE-stained sections, osteoblasts and osteoclasts biomarkers in the bone and serum. Gut microbiota was analyzed through 16S rRNA gene sequencing. Serum concentrations of cytokines were detected by ELISA. The role of gut microbiota was evaluated through their transplantation into antibiotic-treated mice.<br><br>RESULTS: Periodontitis significantly increased the number of osteoclasts and the expression of the osteoclasts biomarkers in the proximal tibia of ApoE-/- mice, with the RANKL/OPG (receptor activator of nuclear factor-κB ligand/ osteoprotegerin) ratio significantly increased, which indicated the osteoclastic activity overwhelmed osteogenesis. Meanwhile, periodontitis altered the composition of gut microbiota and induced low-grade inflammation in the colon and blood circulation. Interestingly, the concentration of circulating TNF-α, IL-6, IL-1β, IL-17A, and MCP-1 were positively correlated with fecal α1-Antitrypsin and calprotectin, as well as serum OPG and RANKL. Furthermore, transplantation of gut microbiota from mice with periodontitis to antibiotic-treated mice could partially recapitulate the phenotypes in the bone and colon.<br><br>CONCLUSION: Periodontitis may impair systemic bone homeostasis through gut microbiota.}, }
@article {pmid35871158, year = {2022}, author = {Yendrapalli, U and Edwards, J and Belk, M and Steuber, T and Hassoun, A}, title = {Efficacy and safety of commercialized fecal microbiota transplant for the treatment of recurrent Clostridioides difficile infection.}, journal = {Infection, disease &amp; health}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.idh.2022.06.002}, pmid = {35871158}, issn = {2468-0869}, }
@article {pmid35868631, year = {2022}, author = {Hamidi Nia, L and Claesen, J}, title = {Engineered Cancer Targeting Microbes and Encapsulation Devices for Human Gut Microbiome Applications.}, journal = {Biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.biochem.2c00251}, pmid = {35868631}, issn = {1520-4995}, abstract = {The gut microbiota produce specialized metabolites that are important for maintaining host health homeostasis. Hence, unstable production of these metabolites can contribute to diseases such as inflammatory bowel disease and colon cancer. While fecal transplantation or dietary modification approaches can be used to correct the gut microbial community's metabolic output, this Perspective focuses on the use of engineered bacteria. We highlight recent advances in bacterial synthetic biology approaches for the treatment of colorectal cancer and systemic tumors and discuss the functionality and biochemical properties of novel containment approaches using hydrogel-based and electronic devices. Synthetic circuitry refinement and incorporation of novel functional modules have enabled more targeted detection of colonic tumors and delivery of anticancer compounds inside the gastrointestinal (GI) tract, as well as the design of tumor-homing bacteria capable of recruiting infiltrating T cells. Engineering challenges in these applications include the stability of the genetic circuits, long-term engraftment of the chosen chassis, and containment of the synthetic microbes' activity to the diseased tissues. Hydrogels are well-suited to the encapsulationo of living organisms due to their matrix structure and tunable porosity. The matrix structure allows a dried hydrogel to collect and contain GI contents. Engineered bacteria that sense GI tract inflammation or tumors and release bioactive metabolites to the targeted area can be encapsulated. Electronic devices can be enabled with additional measuring and data processing capabilities. We expect that engineered devices will become more important in the containment and delivery of synthetic microbes for diagnostic and therapeutic applications.}, }
@article {pmid35864969, year = {2022}, author = {Liu, Z and Li, C and Liu, M and Song, Z and Moyer, MP and Su, D}, title = {The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway.}, journal = {International journal of biological sciences}, volume = {18}, number = {11}, pages = {4469-4481}, pmid = {35864969}, issn = {1449-2288}, abstract = {Our study is to explore the key molecular of Low-density lipoprotein receptor-related protein 6 (LRP6) and the related Wnt/β-catenin pathway regulated by LRP6 during the intestinal barrier dysfunction. Colorectal protein profile analysis showed that LRP6 expression was decreased in dextran sulfate sodium (DSS)-induced colitis mice, and mice received fecal bacteria transplantation from stroke patients. Mice with intestinal hypoxia and intestinal epithelial cells cultured in hypoxia showed decreased expression of LRP6. Overexpression of LPR6 or its N-terminus rescued the Wnt/β-catenin signaling pathway which was inhibited by hypoxia and endoplasmic reticulum stress. In mice overexpressing of LRP6, the expression of β-catenin and DKK1 increased, Bcl2 decreased, and Bax increased. Mice with LRP6 knockout showed an opposite trend, and the expression of Claudin2, Occludin and ZO-1 decreased. Two drugs, curcumin and auranofin could alleviate intestinal barrier damage in DSS-induced colitis mice by targeting LRP-6. Therefore, gut microbiota dysbiosis and hypoxia can inhibit the LRP6 and Wnt/β-catenin pathway, and drugs targeting LRP6 can protect the intestinal barrier.}, }
@article {pmid35862958, year = {2022}, author = {Miao, X and Jiang, Y and Kong, D and Wu, Z and Liu, H and Ye, X and Gong, W}, title = {Lactobacillus rhamnosus HN001 Ameliorates BEZ235-Induced Intestinal Dysbiosis and Prolongs Cardiac Transplant Survival.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0079422}, doi = {10.1128/spectrum.00794-22}, pmid = {35862958}, issn = {2165-0497}, abstract = {Cardiac allograft rejection remains a major factor limiting long-term engraftment after transplantation. A novel phosphoinositide 3-kinase (PI3K)/mTOR dual inhibitor, BEZ235, prolonged cardiac allograft survival by effectively suppressing activation of the PI3K/serine/threonine kinase (AKT)/mTOR pathway. However, long-term usage of pharmacological immunosuppressant drugs can cause intestinal microbiota dysbiosis. We established mouse models of allogeneic heterotopic heart transplantation with different treatments. Fecal samples were collected and subjected to 16S rRNA sequencing and targeted fecal metabolomic analysis. Graft samples were taken for immune cell detection by flow cytometry. Inflammatory cytokines in serum were quantified by enzyme-linked immunosorbent assay (ELISA). Compared to single-target approaches (IC-87114 and rapamycin), BEZ235 more efficiently prolongs cardiac transplant survival. Interestingly, BEZ235 reduces the diversity and abundance of the intestinal microbiota community. We demonstrated that Lactobacillus rhamnosus HN001 rescues the intestinal microbiota imbalance induced by BEZ235. IMPORTANCE Our data confirmed that the combination of BEZ235 and Lactobacillus rhamnosus HN001 significantly prolongs cardiac transplant survival. A main metabolic product of Lactobacillus rhamnosus HN001, propionic acid (PA), enriches regulatory T (Treg) cells and serves as a potent immunomodulatory supplement to BEZ235. Our study provides a novel and efficient therapeutic strategy for transplant recipients.}, }
@article {pmid35860380, year = {2022}, author = {Xue, L and Deng, Z and Luo, W and He, X and Chen, Y}, title = {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 = {759306}, doi = {10.3389/fcimb.2022.759306}, pmid = {35860380}, issn = {2235-2988}, abstract = {Background and Aims: The clinical efficacy of fecal microbiota transplantation (FMT) in patients with non-alcoholic fatty liver disease (NAFLD) and the variant effects of FMT on lean and obese NAFLD patients remain elusive. Our study aimed to determine the clinical efficacy and safety of FMT for patients with NAFLD, elucidating its different influences on lean and obese patients with NAFLD.<br><br>Methods: We performed a randomized and controlled clinical trial. Patients in the non-FMT group were administered oral probiotics. In the FMT group, patients were randomized to receive FMT with donor stool (heterologous) via colonoscopy, followed by three enemas over 3 days. Both groups were also required to maintain a healthy diet and keep regular exercise for more than 40 min every day. They returned to the hospital for reexamination 1 month after treatment.<br><br>Results: FMT can decrease the fat accumulation in the liver by improving the gut microbiota dysbiosis, thus attenuating fatty liver disease. Significant differences in the clinical features and gut microbiota between lean and obese NAFLD patients were unveiled. Moreover, FMT had better effects on gut microbiota reconstruction in lean NAFLD than in obese NAFLD patients.<br><br>Conclusions: FMT could successfully improve the therapeutic effects on patients with NAFLD, and its clinical efficacy was higher in lean NAFLD than in obese NAFLD patients.}, }
@article {pmid35859811, year = {2022}, author = {Cerquetella, M and Marchegiani, A and Rossi, G and Trabalza-Marinucci, M and Passamonti, F and Isidori, M and Rueca, F}, title = {Case Report: Oral Fecal Microbiota Transplantation in a Dog Suffering From Relapsing Chronic Diarrhea-Clinical Outcome and Follow-Up.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {893342}, doi = {10.3389/fvets.2022.893342}, pmid = {35859811}, issn = {2297-1769}, abstract = {The present case report describes the effects of orally administered fecal microbiota transplantation (FMT) (frozen capsules) in a dog suffering from relapsing chronic diarrhea, needing a continuous low prednisolone dose to maintain the condition under acceptable control. Through FMT, we aimed at evaluating the possibility of improving the clinical score and/or reducing/suspending steroid administration. During a first period of strict monitoring (21 days), the canine inflammatory bowel disease activity index (CIBDAI) score passed from mild to clinically insignificant disease. Furthermore, two additional gastrointestinal signs that had been reported, bloating and episodes of painful defecation, rapidly improved (bloating) or even resolved (painful defecation). The patient was then followed for 18 months (to the authors' knowledge, the longest follow-up time ever reported in a dog), during which no serious relapses occurred and no increase in prednisolone dose was necessary. No adverse clinical effects were ever reported during monitoring. The present description provides a further experience increasing those already present in the veterinary literature, in which an agreement on how to use FMT has not yet been achieved although strongly needed and recommended.}, }
@article {pmid35859583, year = {2022}, author = {Bao, P and Zhang, Z and Liang, Y and Yu, Z and Xiao, Z and Wang, Y and Yu, Y and Liu, W and Chen, X and Huang, Z and Su, Y and Chen, R and Ge, J}, title = {Role of the Gut Microbiota in Glucose Metabolism During Heart Failure.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {903316}, doi = {10.3389/fcvm.2022.903316}, pmid = {35859583}, issn = {2297-055X}, abstract = {Background: Blood glucose disorders are prevalent in heart failure, while the influence of the gut microbiota on this process remains unclear. Here, we used heart failure model mice and fecal microbiota transplantation (FMT) mice to evaluate the effect of the gut microbiota on the regulation of blood glucose during heart failure.<br><br>Methods: Thoracic aortic constriction (TAC) surgery was performed in a heart failure model, while an antibiotic cocktail was used to eliminate the microbiota to establish a germ-free (GF) model. Blood glucose, insulin, and glucagon levels were measured, and an intraperitoneal glucose tolerance test (IPGTT) was performed. 16S rRNA sequencing and metabolomics were used to evaluate the changes in gut microbiota structure and metabolism induced by TAC. Another group of FMT mice was established to observe the effect of the gut microbiota on host metabolism.<br><br>Results: After microbiota clearance, the glucagon concentration, the homeostasis model assessment for insulin resistance (HOMA-IR), and the area under the curve (AUC) of the IPGTT were decreased significantly in the TAC germ-free (TAC-GF) group in the third month as compared to the other groups. 16S rRNA sequencing indicated that TAC surgery affected the gut microbiota structure, and fecal metabolomics suggested that noradrenaline and adrenaline levels were higher in the TAC group than in the sham group. The FMT mice transplanted with the feces of the TAC (FMT-TAC) mice displayed a higher AUC of IPGTT, accompanied by a higher glucagon level, insulin level, and HOMA-IR than those of the mice in the other groups. The serum metabolomics of the FMT-TAC group showed that noradrenaline levels were significantly higher than those of the FMT-sham group.<br><br>Conclusion: The gut microbiota and its metabolism were altered during heart failure, which increased blood glucose and glucagon in the host.}, }
@article {pmid35854629, year = {2022}, author = {He, R and Li, P and Wang, J and Cui, B and Zhang, F and Zhao, F}, title = {The interplay of gut microbiota between donors and recipients determines the efficacy of fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2100197}, doi = {10.1080/19490976.2022.2100197}, pmid = {35854629}, issn = {1949-0984}, mesh = {Bacteria/genetics ; *Clostridioides difficile ; *Clostridium Infections/microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/microbiology ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising treatment for microbiota dysbiosis associated diseases, such as Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD). The engraftment of donor bacteria is essential for the effectiveness of FMT, which to some extent depends on the matching of donors and recipients. However, how different types of donor-derived bacteria affect FMT efficacy has not been fully dissected. We recruited two longitudinal IBD cohorts of 103 FMT recipients and further analyzed 1,280 microbiota datasets from 14 public CDI and IBD studies to uncover the effect of donor-derived microbiota in recipients. We found that two enterotypes, RCPT/E and RCPT/B (dominated by Enterobacteriaceae and Bacteroides, respectively), consistently exist in both CDI and IBD patients. Based on a time-course-based multi-cohort analysis of FMT fecal samples, we observed the interplay between recipient and donor-derived microbiota during FMT, in which the FMT outcome was significantly associated with the enterotype and microbiota distance between donor and recipient after FMT. We proposed a new measurement, the ratio of colonizers to residents after FMT (C2R), to quantify the engraftment of donor-derived bacteria in the recipients, and then constructed an enterotype-based statistical model for donor-recipient matching, which was validated by both cross-validation and an additional IBD FMT cohort (n = 42). We believe that with the accumulation of FMT multi-omics datasets, machine learning-based methods will be helpful for rational donor selection for improving efficacy and precision FMT practices.}, }
@article {pmid35660786, year = {2022}, author = {Rees, NP and Shaheen, W and Quince, C and Tselepis, C and Horniblow, RD and Sharma, N and Beggs, AD and Iqbal, TH and Quraishi, MN}, title = {Systematic review of donor and recipient predictive biomarkers of response to faecal microbiota transplantation in patients with ulcerative colitis.}, journal = {EBioMedicine}, volume = {81}, number = {}, pages = {104088}, doi = {10.1016/j.ebiom.2022.104088}, pmid = {35660786}, issn = {2352-3964}, mesh = {Biomarkers ; *Colitis, Ulcerative/diagnosis/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Feces ; *Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has previously been explored as a treatment for ulcerative colitis (UC) however, biomarkers that predict and / or are associated with clinical response are poorly defined. The aim of this systematic review was to identify donor and recipient clinical, microbial and metabolomic predictive biomarkers of response to FMT in UC.<br><br>METHODS: A systematic search of the relevant literature of studies exploring FMT in UC was conducted. Data on microbial diversity, taxonomic changes, metabolic changes, donor and recipient microbiota relationship and baseline predictors was examined.<br><br>FINDINGS: 2852 studies were screened, and 25 papers were included in this systematic review. Following FMT, alpha diversity was seen to increase in responders along with increases in the abundance of Clostridiales clusters (order) and Bacteroides genus. Metabolomic analysis revealed short chain fatty acid (SCFA) production as a marker of FMT success. Donors or FMT batches with higher microbial alpha diversity and a greater abundance of taxa belonging to certain Bacteroides and Clostridia clusters were associated with clinical response to FMT. Baseline clinical predictors of response in patients with UC included younger age, less severe disease and possibly shorter disease duration. Baseline recipient microbial predictors at response consisted of higher faecal species richness, greater abundance of Candida and donor microbial profile similarity.<br><br>INTERPRETATION: Distinct changes in gut microbiota profiles post-FMT indicate that certain baseline characteristics along with specific microbial and metabolomic alterations may predispose patients towards a successful therapeutic outcome. Opportunities towards a biomarker led precision medicine approach with FMT should be explored in future clinical studies.<br><br>FUNDING: There no specific funding to declare.}, }
@article {pmid35849493, year = {2022}, author = {Jin, X and Liu, Y and Yan, W and Shi, S and Liu, L and Lin, B and Guo, X and Cai, T and Wei, Y}, title = {Gut microbiota from nCAL patients promotes colon anastomotic healing by inducing collagen synthesis in epithelial cells.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15946}, pmid = {35849493}, issn = {1440-1746}, abstract = {BACKGROUND AND AIMS: Colon anastomotic leak (CAL) is considered one of the most feared and serious postoperative complications in Colorectal Cancer (CRC) patients, with no effective prevention strategies to date. Based on previous studies, gut microbiota is associated with anastomotic healing, but its ability to effectively promote anastomotic healing remains largely unknown.<br><br>METHODS: We performed a clinical study to analyze the gut microbiota profiling in CRC patients who developed CAL and those who did not (nCAL), using 16S-rRNA-based Next Generation Sequencing (NGS). To investigate these changes in an in vivo model, we performed fecal microbiota transplantation in a colon anastomosis rat experimental model to elucidate the causal-effect between gut microbiota and anastomotic healing. Notably, RNA-seq in the anastomotic tissue of the latter experimental model, was utilized to discover the potential molecular mechanism.<br><br>RESULTS: Our analysis implicated that gut microbiota profiling was profoundly different between CAL and nCAL patients. Strikingly, the rat experimental model transplanted with fecal microbiota derived from nCAL patients, demonstrated enhanced anastomotic healing properties. Moreover, collagen synthesis, EMT, and TGF-β/Smad signaling pathways were up-regulated in the same rats. Concordantly, we discovered that the better anastomotic healing profiling displayed in gut microbiota derived from nCAL patients, is dependent on the TGF-β/Smad-induced EMT in vitro and in vivo.<br><br>CONCLUSIONS: Collectively, our clinical study identified the postoperative gut microbiota profile is associated with CAL in CRC patients. On the contrary, fecal microbiota from nCAL patients promotes anastomotic healing via TGF-β/Smad-induced EMT, with subsequent collagen synthesis and enhanced anastomosis healing.}, }
@article {pmid35847121, year = {2022}, author = {Xu, X and Ying, J}, title = {Gut Microbiota and Immunotherapy.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {945887}, pmid = {35847121}, issn = {1664-302X}, abstract = {The gut microbiota is the largest microbiota in the body, which is closely related to the immune state of the body. A number of studies have shown that gut microbiota and its metabolites are involved in host immune regulation. Immune checkpoint inhibitors have become an important drug for the treatment of many malignant tumors, which can significantly improve the prognosis of tumor patients. However, a considerable number of patients cannot benefit from immune checkpoint inhibitors. At present, the known treatment methods of microbiota manipulation mainly include fecal microbiota transplantation, dietary regulation, prebiotics and so on. Therefore, this paper will discuss the possibility of improving the anti-tumor efficacy of immunotherapy from the perspectives of the gut microbiota and immunotherapy.}, }
@article {pmid35847075, year = {2022}, author = {Bilinski, J and Dziurzynski, M and Grzesiowski, P and Podsiadly, E and Stelmaszczyk-Emmel, A and Dzieciatkowski, T and Lis, K and Tyszka, M and Ozieranski, K and Dziewit, Ł and Basak, GW}, title = {Fresh Versus Frozen Stool for Fecal Microbiota Transplantation-Assessment by Multimethod Approach Combining Culturing, Flow Cytometry, and Next-Generation Sequencing.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {872735}, pmid = {35847075}, issn = {1664-302X}, abstract = {The objective of this work was to compare the quality of FMT preparations made from fresh feces with those made from feces frozen at -30°C without any pre-processing or cryopreservation additives. The research hypothesis was that such preservation protocol (frozen whole stool, then thawed and processed) is equipotent to classical fresh FMT preparation. For that, three complementary methods were applied, including: (i) culturing in aerobic and anaerobic conditions, (ii) measuring viability by flow cytometry, and (iii) next-generation sequencing. Flow cytometry with cell staining showed that the applied freezing protocol causes significant changes in all of the observed bacterial fractions. Alive cell counts dropped four times, from around 70% to 15%, while the other two fractions, dead and unknown cell counts quadrupled and doubled, with the unknown fraction becoming the dominant one, with an average contribution of 57.47% per sample. It will be very interesting to uncover what this unknown fraction is (e.g., bacterial spores), as this may change our conclusions (if these are spores, the viability could be even higher after freezing). Freezing had a huge impact on the structure of cultivable bacterial communities. The biggest drop after freezing in the number of cultivable species was observed for Actinobacteria and Bacilli. In most cases, selected biodiversity indices were slightly lower for frozen samples. PCoA visualization built using weighted UniFrac index showed no donor-wise clusters, but a clear split between fresh and frozen samples. This split can be in part attributed to the changes in the relative abundance of Bacteroidales and Clostridiales orders. Our results clearly show that whole stool freezing without any cryoprotectants has a great impact on the cultivability and biodiversity of the bacterial community, and possibly also on the viability of bacterial cells.}, }
@article {pmid35846749, year = {2022}, author = {Chen, Z and Yang, B and Wang, Z and Rong, X and Zhu, Q and Guo, J}, title = {Modulation of the Gut Microbiota by Fufang-Zhenzhu-Tiaozhi Capsule Attenuates Hypertension Induced by a High-Fructose and High-Salt Diet.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {854849}, pmid = {35846749}, issn = {2235-2988}, mesh = {Animals ; Diet ; Drugs, Chinese Herbal ; Dysbiosis ; Fructose/pharmacology ; *Gastrointestinal Microbiome ; *Hypertension/drug therapy ; RNA, Ribosomal, 16S/genetics ; Rats ; }, abstract = {Hypertension is frequently comorbid with the disorders of glucose and lipid metabolism. The increased intakes of fructose and salt contribute to the development of hypertension and related metabolic disorders, which are closely associated with gut dysbiosis. Fufang-Zhenzhu-Tiaozhi capsule (FTZ), a traditional Chinese patent medicine commonly used in clinical practice, has recently emerged as a promising drug candidate for metabolic diseases. In this study, FTZ treatment is identified as attenuating blood pressure increase and improving the metabolism of lipid and uric acid in high-fructose and high-salt (HFS) diet-fed rats. FTZ also substantially alleviated renal fibrosis and the mRNA expression of inflammation cytokines, NADPH oxidases, and the renin-angiotensin system in the renal cortex. 16S rRNA sequencing of fecal samples revealed that FTZ restored HFS-induced gut dysbiosis, seen as increased intestinal microbial richness and diversity. Furthermore, fecal microbiota transplantation also achieved similar therapeutic effects and alterations in gut microbiota profile induced by FTZ. Taken together, this study highlights the efficacy of FTZ in attenuating HFS-induced hypertension and related metabolic disorders and renal injury. The antihypertensive effect is associated with the modulation of gut microbiota.}, }
@article {pmid35846232, year = {2022}, author = {Park, SS and Kim, SH and Kim, CJ and Shin, MS and Park, YJ and Kim, TW}, title = {Effects of exercise and microbiota transplant on the memory of obesity-induced mice.}, journal = {Journal of exercise rehabilitation}, volume = {18}, number = {3}, pages = {162-170}, pmid = {35846232}, issn = {2288-176X}, abstract = {This study attempted to investigate the association between changes in the intestinal environment and the brain using a model that received aerobic exercise and microbiome transplantation. All mice were fed a diet containing 60% fat. For the obesity with nonexercise microbiome transplantation group, feces from donors that did not undergo exercise were administered. For the obesity with exercise microbiome trans-plantation group, feces from donors who underwent exercise were administered. Treadmill exercise started 16 weeks after the intake of the high fat feeding and continued for 24 weeks. The short-term memory and spatial learning memory were determined by step-down avoidance test and Morris water maze task, immunohistochemistry for glial fibrillary acidic protein, western blot analysis for brain-derived neurotrophic factor and tropomyosin receptor kinase B were performed in the hippocampus. Exercise was the most effective way to reduce obesity, improve memory function, suppress inflammation, and increase brain-derived neurotrophic factor expression. Intestinal microbiota transplantation was the second most effective after exercise. However, there was no significant difference in the fecal microbiota transplant group according to whether or not exercise was performed.}, }
@article {pmid35843456, year = {2022}, author = {Wen, S and Zhao, Y and Liu, S and Yuan, H and You, T and Xu, H}, title = {Microplastics-perturbed gut microbiota triggered the testicular disorder in male mice: Via fecal microbiota transplantation.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {119789}, doi = {10.1016/j.envpol.2022.119789}, pmid = {35843456}, issn = {1873-6424}, abstract = {Microplastics (MPs), an emerging environmental pollutant, have been clarified to induce testicular disorder in mammals. And current studies have delineated a correlation between gut microbiota and male reproduction. However, it's still unclear whether gut microbiota gets involved in MPs induced reproductive toxicity. In this work, we constructed a mouse model drinking 5 μm polystyrene-MPs (PS-MPs) at the concentrations of 100 μg/L and 1,000 μg/L for 90 days. Evident histological damage, spermatogenetic disorder and hormones synthesis inhibition were observed in PS-MPs exposed mice. With fecal microbiota transplantation (FMT) trial, the recipient mice exhibited gut microbial alteration, and elevated abundance of Bacteroides and Prevotellaceae_UCG-001 were positively correlated with testicular disorder according to spearman correlation analysis. Mechanistically, increased proportion of pro-inflammatory bacteria may drive translocation of T helper 17 (Th17) cells, resulting in overproduced interleukin (IL)-17A and downstream inflammatory response in both the mice exposed to PS-MPs and corresponding recipient mice. In summary, our findings revealed the critical role of gut microbiota in PS-MPs-induced reproductive toxicity, and tried to elucidate the underlying mechanisms of gut microbial dysregulation-mediated IL-17A signaling pathway. Furthermore, this study also provides research basis for gut microbiota-targeted treatment of male infertility in the future.}, }
@article {pmid35434820, year = {2022}, author = {Stenberg, R and Brummer, RJ and Norén, T}, title = {Faecal transplantation in a two-year-old child with therapy-resistant Clostridiodes difficileinfection.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {111}, number = {8}, pages = {1628-1629}, doi = {10.1111/apa.16363}, pmid = {35434820}, issn = {1651-2227}, mesh = {Child, Preschool ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid35842183, year = {2022}, author = {Guo, W and Zhang, Z and Li, L and Liang, X and Wu, Y and Wang, X and Ma, H and Cheng, J and Zhang, A and Tang, P and Wang, CZ and Wan, JY and Yao, H and Yuan, CS}, title = {Gut microbiota induces DNA methylation via SCFAs predisposing obesity-prone individuals to diabetes.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106355}, doi = {10.1016/j.phrs.2022.106355}, pmid = {35842183}, issn = {1096-1186}, abstract = {Obesity-prone (OP) individuals have a significant predisposition to obesity and diabetes. Previously, we have found that OP individuals, despite being normal in weight and BMI, have already exhibited diabetes-related DNA methylation signatures. However, the underlying mechanisms remain obscure. Here we determined the effects of gut microbiota on DNA methylation and investigated the underlying mechanism from microbial-derived short-chain fatty acids (SCFAs). Diabetes-related DNA methylation loci were screened and validated in a new OP cohort. Moreover, the OP group was revealed to have distinct gut microbiota compositions, and fecal microbiota transplantation (FMT) demonstrated the role of gut microbiota in inducing diabetes-related DNA methylations and glucolipid disorders. UPLC-ESI-MS/MS analysis indicated a significantly lower level of total fecal SCFAs in the OP group. The gut microbiota from OP subjects yielded markedly decreased total SCFAs, while notably enriched propionate. Additionally, propionate was also identified by variable importance in projection (VIP) score as the most symbolic SCFAs of the OP group. Further cellular experiments verified that propionate could induce hypermethylation at locus cg26345888 and subsequently inhibit the expression of the target gene DAB1, which was crucially associated with clinical vitamin D deficiency and thus may affect the development and progression of diabetes. In conclusion, our study revealed that gut microbiota-derived propionate induces specific DNA methylation, thus predisposing OP individuals to diabetes. The findings partially illuminate the mechanisms of diabetes susceptibility in OP populations, implying gut microbiota and SCFAs may serve as promising targets both for clinical treatment and medication development of diabetes.}, }
@article {pmid35841869, year = {2022}, author = {Li, X and Zhang, S and Guo, G and Han, J and Yu, J}, title = {Gut microbiome in modulating immune checkpoint inhibitors.}, journal = {EBioMedicine}, volume = {82}, number = {}, pages = {104163}, doi = {10.1016/j.ebiom.2022.104163}, pmid = {35841869}, issn = {2352-3964}, abstract = {Gut microbiome has been increasingly recognized for its influence on a diverse array of human diseases including cancer, and may also influence the outcome of cancer therapies. A prime example is seen in immunotherapy, for which gut microbes determine the therapeutic responses associated with immune checkpoint inhibitors (ICIs) in preclinical models and patient cohorts. This evidence hints that inter-individual variations in the gut microbiota may account for the significant heterogeneity in immunotherapeutic responses to ICIs. Understanding the functional role of gut microbiome in regulating not only mucosal but also systemic immunity and cancer is critical to move forward in this era of precision medicine. What's more, microbiota can be modified via several different strategies that are essential for the efforts in expanding immunotherapy efficacy. This review summarizes latest knowledge about the interactions between microbiome, host immunity and cancer, and strategies to modulate the microbiome with implications to be translated into clinic. FUNDING: This study was supported by National Key R&amp;D Program of China (No. 2020YFA0509200/2020YFA0509203), RGC Theme-based Res Scheme Hong Kong (T21-705/20-N).}, }
@article {pmid35841835, year = {2022}, author = {Gao, Y and Ma, L and Su, J}, title = {Host and microbial-derived metabolites for Clostridioides difficile infection: Contributions, mechanisms and potential applications.}, journal = {Microbiological research}, volume = {263}, number = {}, pages = {127113}, doi = {10.1016/j.micres.2022.127113}, pmid = {35841835}, issn = {1618-0623}, abstract = {Clostridioides difficile infection (CDI), which mostly occurs in hospitalized patients, is the most common and costly health care-associated disease. However, the biology of C. difficile remains incompletely understood. Current therapeutics are still challenged by the frequent recurrence of CDI. Advances in metabolomics facilitate our understanding of the etiology of CDI, which is not merely an alteration in the structure of the gut microbial community but also a dysbiosis metabolic setting promoting the germination, expansion and virulence of C. difficile. Therefore, we summarized the gut microbial and metabolic profiles for CDI under different conditions, such as those of postantibiotic treatment and postfecal microbiota transplantation. The current understanding of the role of host and gut microbial-derived metabolites as well as other nutrients in preventing or alleviating the disease symptoms of CDI will also be provided in this review. We hope that a specific nutrient-centric dietary strategy or the administration of certain nutrients to the colon could serve as an alternate line of investigation for the prophylaxis and mitigation of CDI in the future. Nevertheless, rigorously designed basic studies and randomized controlled trials need to be conducted to assess the functional mechanisms and effects of such therapeutics.}, }
@article {pmid35840468, year = {2022}, author = {Pavanello, A and Martins, IP and Tófolo, LP and Previate, C and Matiusso, CCI and Francisco, FA and Prates, KV and Alves, VS and de Almeida, DL and Ribeiro, TA and Malta, A and Mathias, PCF}, title = {Fecal Microbiota Transplantation During Lactation Programs the Metabolism of Adult Wistar Rats in a Sex-specific Way.}, journal = {Archives of medical research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.arcmed.2022.06.007}, pmid = {35840468}, issn = {1873-5487}, abstract = {BACKGROUND: The intestinal microbiota is involved in many physiological processes. However, the effects of microbiota in metabolic programming still unknow. We evaluated whether the transplantation of fecal microbiota during early life can program health or disease during adulthood in a model of lean and obese male and female Wistar rats.<br><br>METHODS: Parental obesity were induced using a small litter (SL, 3 pups/dam) model. At 90 d old, normal litter (NL, 9 pups/dam) and SL males and females (parents) from different litters were mated: NL male vs. NL female; SL male vs. SL female. After birth, male and female offspring rats were also standardized in normal litters or small litters . From the 10th until 25th d of life, the NL and SL male and female offspring received via gavage of a solution containing the diluted feces of the opposite dam (fecal microbiota, M) or saline solution (S). At 90 d of age, biometric and biochemical parameters were assessed.<br><br>RESULTS: NLM male rats transplanted with obese microbiota showed increased body weight, and fat pad deposition, hyperinsulinemia, glucose intolerance and dyslipidemia. SLM male rats transplanted with lean microbiota had decreased retroperitoneal and mesenteric fat, triglycerides and VLDL levels and improvement of glucose tolerance. Despite SLM female rats showed higher visceral fat, microbiota transplantation in female rats caused no changes in these parameters compared with control groups.<br><br>CONCLUSION: Fecal microbiota transplantation during lactation induces long-term effects on the metabolism of male Wistar rats. However, female rats were resistant to metabolic alterations caused by the treatment.}, }
@article {pmid35840401, year = {2022}, author = {Chen, Q and Xie, Q and Jiang, C and Evivie, SE and Cao, T and Wang, Z and Zhao, L and Liang, S and Li, B and Huo, G}, title = {Infant formula supplemented with 1,3-olein-2-palmitin regulated the immunity, gut microbiota, and metabolites of mice colonized by healthy infant feces.}, journal = {Journal of dairy science}, volume = {}, number = {}, pages = {}, doi = {10.3168/jds.2021-21736}, pmid = {35840401}, issn = {1525-3198}, abstract = {Infant formula is currently an important food to cope with insufficient breastfeeding. Although 1,3-olein-2-palmitin (OPO) has been used in infant formula, its effects on the immune system, gut microbiota, and metabolites for infants remain unclear. This study constructed a mouse model of colonizing healthy infant feces using antibiotic treatment and fecal microbial transplantation. Thus, the gap between the infant formula supplemented with OPO and human milk in mouse serum biochemistry, immune system, intestinal microbiota, short-chain fatty acid production, and metabolites was evaluated. Our results showed that regarding IL-9, IL-10 levels, fecal secretory IgA, and endotoxin, formula supplemented with OPO and human milk types had comparable levels. Additionally, OPO slightly increased the content of short-chain fatty acids. The 16S rRNA gene sequence analysis and metabonomics analysis demonstrated that feeding different foods affects the gut microbiota of mice; in particular, supplementing formula feeding with OPO enriched the abundance of bifidobacteria. Furthermore, feeding different foods leads to unique intestinal content of metabolites, and the gut microbiota regulates the metabolites' differences. Our results reveal a brand new perspective of OPO regarding gut microbiota and metabolites.}, }
@article {pmid35837289, year = {2022}, author = {Xue, H and Ma, J and Wang, Y and Lu, M and Wang, F and Tang, X}, title = {Shen-Ling-Bai-Zhu-San (SL) and SL Derived-Polysaccharide (PL) Ameliorate the Severity of Diarrhea-Induced by High Lactose via Modification of Colonic Fermentation.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {883355}, doi = {10.3389/fphar.2022.883355}, pmid = {35837289}, issn = {1663-9812}, abstract = {In our previous study, we demonstrated that Shen-ling-bai-zhu-san (SL), a classical Chinese herbal formula, could alleviate lactose-induced diarrhea. However, little is known about the mechanism underlying SL action or the efficacy of the polysaccharide (PL) derived from SL. In this study, we investigated the effect of SL and PL on improving the dysregulated luminal and mucosal microbiota in rats with high lactose diet using 16S rRNA analysis. The concentrations of lactose, lactic acid in cecum and short-chain fatty acids (SCFAs) in cecum and portal vein were measured, meanwhile the expression of ion transporters were ascertained. Our data suggest that the SL, PL and cecal microbiota transplantation (CMT) significantly decreased fecal water content and water intake. In the luminal microbiota there was a significant increase in Akkermansia, Bifidobacterium and Blautia and a lower abundance of Lactobacillus, Escherichia-Shigella, and Dubosiella, while the mucosal microbiota showed a significant increase in Bifidobacterium, Akkermansia, Albaculum, Bilophila, and Coriobacteriaceae_UCG-002 and a lower abundance of Enterococcus, Helicobacter, Dubosiella, and Collinsella. Furthermore, the treatments enhanced lactose fermentation and SCFA production, which may be related to the modulation of the luminal microbial community. A lower ratio of phosphorylation Na/H exchanger3/Na/H exchanger3 (pNHE3/NHE3) and a higher sodium monocarboxylate1 (sMCT1) expression were found in the treatment group than in the model group, which may be related to the changes in the mucosal microbial community. Also, the treatments may restore the impacted metabolic pathways of gut microbiota. These results provide an important foundation for mechanism of SL action and developing PL-based treatment for lactose-induced diarrhea.}, }
@article {pmid35836813, year = {2022}, author = {Cong, J and Wu, D and Dai, H and Ma, Y and Liao, C and Li, L and Ye, L and Huang, Z}, title = {Interleukin-37 exacerbates experimental colitis in an intestinal microbiome-dependent fashion.}, journal = {Theranostics}, volume = {12}, number = {11}, pages = {5204-5219}, doi = {10.7150/thno.69616}, pmid = {35836813}, issn = {1838-7640}, abstract = {Background: Inflammatory bowel disease (IBD) involves complicated crosstalk between host immunity and the gut microbiome, whereas the mechanics of how they govern intestinal inflammation remain poorly understood. In this study, we investigated the contribution of environmental factors to shaping gut microbiota composition in colitis mice that were transgenic for human IL-37, a natural anti-inflammatory cytokine possessing pathogenic and protective functions related to microbiota alterations. Methods: Mice transgenic expressing human IL-37 (IL-37tg) were housed under conventional and specific pathogen-free (SPF) conditions to develop a mouse model of dextran sulfate sodium (DSS)-induced colitis. 16S ribosomal RNA sequencing was used for analyzing fecal microbial communities. The efficacy of microbiota in the development of colitis in IL-37tg mice was investigated after antibiotic treatment and fecal microbiota transplantation (FMT). The mechanism by which IL-37 worsened colitis was studied by evaluating intestinal epithelial barrier function, immune cell infiltration, the expression of diverse cytokines and chemokines, as well as activated signaling pathways. Results: We found that IL-37 overexpression aggravated DSS-induced colitis in conventional mice but protected against colitis in SPF mice. These conflicting results from IL-37tg colitis mice are ascribed to a dysbiosis of the gut microbiota in which detrimental bacteria increased in IL-37tg conventional mice. We further identified that the outcome of IL-37-caused colon inflammation is strongly related to intestinal epithelial barrier impairment caused by pathogenic bacteria, neutrophils, and NK cells recruitment in colon lamina propria and mesenteric lymph node to enhance inflammatory responses in IL-37tg conventional mice. Conclusions: The immunoregulatory properties of IL-37 are detrimental in the face of dysbiosis of the intestinal microbiota, which contributes to exacerbated IBD occurrences that are uncontrollable by the immune system, suggesting that depleting gut pathogenic bacteria or maintaining intestinal microbial and immune homeostasis could be a promising therapeutic strategy for IBD.}, }
@article {pmid35836252, year = {2022}, author = {Zhang, X and Akhtar, M and Chen, Y and Ma, Z and Liang, Y and Shi, D and Cheng, R and Cui, L and Hu, Y and Nafady, AA and Ansari, AR and Abdel-Kafy, EM and Liu, H}, title = {Chicken jejunal microbiota improves growth performance by mitigating intestinal inflammation.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {107}, pmid = {35836252}, issn = {2049-2618}, support = {2017YFE0113700//National Key Research and Development Program of China/ ; 2017CFB514//Hubei Provincial Natural Science Foundation of China/ ; 30800808//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Intestinal inflammation is prevalent in chicken, which results in decreased growth performance and considerable economic losses. Accumulated findings established the close relationship between gut microbiota and chicken growth performance. However, whether gut microbiota impacts chicken growth performance by lessening intestinal inflammation remains elusive.<br><br>RESULTS: Seven-weeks-old male and female chickens with the highest or lowest body weights were significantly different in breast and leg muscle indices and average cross-sectional area of muscle cells. 16S rRNA gene sequencing indicated Gram-positive bacteria, such as Lactobacilli, were the predominant species in high body weight chickens. Conversely, Gram-negative bacteria, such as Comamonas, Acinetobacter, Brucella, Escherichia-Shigella, Thermus, Undibacterium, and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium were significantly abundant in low body weight chickens. Serum lipopolysaccharide (LPS) level was significantly higher in low body weight chickens (101.58 ± 5.78 ng/mL) compared with high body weight chickens (85.12 ± 4.79 ng/mL). The expression of TLR4, NF-κB, MyD88, and related inflammatory cytokines in the jejunum was significantly upregulated in low body weight chickens, which led to the damage of gut barrier integrity. Furthermore, transferring fecal microbiota from adult chickens with high body weight into 1-day-old chicks reshaped the jejunal microbiota, mitigated inflammatory response, and improved chicken growth performance.<br><br>CONCLUSIONS: Our findings suggested that jejunal microbiota could affect chicken growth performance by mitigating intestinal inflammation. Video Abstract.}, }
@article {pmid35836115, year = {2022}, author = {Hamazaki, M and Sawada, T and Yamamura, T and Maeda, K and Mizutani, Y and Ishikawa, E and Furune, S and Yamamoto, K and Ishikawa, T and Kakushima, N and Furukawa, K and Ohno, E and Honda, T and Kawashima, H and Ishigami, M and Nakamura, M and Fujishiro, M}, title = {Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan.}, journal = {BMC gastroenterology}, volume = {22}, number = {1}, pages = {342}, pmid = {35836115}, issn = {1471-230X}, support = {16K09406//the japan society for the promotion of science/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients.<br><br>METHODS: Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12 weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12 weeks after FMT. For the microbiome, we analyzed the V3-V4 region of the 16S rRNA gene.<br><br>RESULTS: IBS-SI decreased an average of 115.58 points after 12 weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. α-diversity was increased only in the responder group (p = 0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT.<br><br>CONCLUSIONS: Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased α-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects.<br><br>TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363 . The study was registered prospectively.}, }
@article {pmid35835996, year = {2022}, author = {Merli, P and Massa, M and Russo, A and Rea, F and Del Chierico, F and Galaverna, F and Del Bufalo, F and Pane, S and Algeri, M and Romeo, EF and Masucci, L and De Angelis, P and Putignani, L and Locatelli, F}, title = {Fecal microbiota transplantation for the treatment of steroid-refractory, intestinal, graft-versus-host disease in a pediatric patient.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {35835996}, issn = {1476-5365}, support = {GR-2013-02357136//Ministero della Salute (Ministry of Health, Italy)/ ; GR-2018-12368106//Ministero della Salute (Ministry of Health, Italy)/ ; }, }
@article {pmid35831743, year = {2022}, author = {Konturek, PC}, title = {[Gut microbiota and chronic inflammatory bowel disease].}, journal = {MMW Fortschritte der Medizin}, volume = {164}, number = {Suppl 7}, pages = {12-15}, doi = {10.1007/s15006-022-1230-3}, pmid = {35831743}, issn = {1613-3560}, mesh = {Diet ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {Intestinal dysbiosis remains the focus of research into the pathogenesis of chronic inflammatory bowel disease (IBD). The potential role of gut microbiota in the development of IBD includes interaction with the host genome and immune system, as well as various environmental factors, diet, drugs, industrialization, etc. Other organs are negatively affected by intestinal dysbiosis via gut-brain axis. The composition of microbiota and its metabolic activity has a significant impact on the effectiveness of anti-inflammatory therapies. Microbiome-based treatment for IBD includes the use of diet, antibiotics, pre-, pro- and synbiotics, and faecal transplantation (FMT). The development of effective therapies for IBD patients will only be possible once the interactions between the microbiota and its metabolites and the host immune system are better understood.}, }
@article {pmid35832621, year = {2022}, author = {Balaji, A and Sapoval, N and Seto, C and Leo Elworth, RA and Fu, Y and Nute, MG and Savidge, T and Segarra, S and Treangen, TJ}, title = {KOMB: K-core based de novo characterization of copy number variation in microbiomes.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {3208-3222}, doi = {10.1016/j.csbj.2022.06.019}, pmid = {35832621}, issn = {2001-0370}, abstract = {Characterizing metagenomes via kmer-based, database-dependent taxonomic classification has yielded key insights into underlying microbiome dynamics. However, novel approaches are needed to track community dynamics and genomic flux within metagenomes, particularly in response to perturbations. We describe KOMB, a novel method for tracking genome level dynamics within microbiomes. KOMB utilizes K-core decomposition to identify Structural variations (SVs), specifically, population-level Copy Number Variation (CNV) within microbiomes. K-core decomposition partitions the graph into shells containing nodes of induced degree at least K, yielding reduced computational complexity compared to prior approaches. Through validation on a synthetic community, we show that KOMB recovers and profiles repetitive genomic regions in the sample. KOMB is shown to identify functionally-important regions in Human Microbiome Project datasets, and was used to analyze longitudinal data and identify keystone taxa in Fecal Microbiota Transplantation (FMT) samples. In summary, KOMB represents a novel graph-based, taxonomy-oblivious, and reference-free approach for tracking CNV within microbiomes. KOMB is open source and available for download at https://gitlab.com/treangenlab/komb.}, }
@article {pmid35832379, year = {2022}, author = {Li, Y and Zhang, T and Sun, J and Liu, N}, title = {Fecal Microbiota Transplantation and Health Outcomes: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {899845}, doi = {10.3389/fcimb.2022.899845}, pmid = {35832379}, issn = {2235-2988}, abstract = {Background: Meta-analysis of randomized clinical trials (RCT) demonstrated several health benefits of fecal microbiota transplantation (FMT). However, there has been little comprehensive assessment of the strength and quality of evidence. We conducted an umbrella review to summarize the evidence of the association between FMT and health outcomes.<br><br>Methods: PubMed, Embase, and Cochrane library databases were searched from inception to August 6, 2021. The random-effects model was applied to recalculate the effect estimates. We used AMSTAR 2 and GRADE to assess the methodological quality and to grade the evidence.<br><br>Results: A total of 7 meta-analyses comprising 26 RCTs (median [IQR] primary study, 6 [2-7]; median [IQR] sample size, 267 [147-431] participants) were included in the current umbrella review describing 45 unique associations. There were 22 statistically significant associations (49%) demonstrating beneficial outcomes of FMT for antibiotic resistance burden, functional constipation, inflammatory bowel disease, and C. difficile infection. FMT does not appear to be associated with positive outcomes in irritable bowel syndrome and metabolic syndrome. Eight significant associations (36%) were supported by moderate-quality evidence, nine associations (41%) were supported by low-quality evidence, and the remaining associations found to be significant were supported by very low-quality evidence.<br><br>Conclusion: Although we found that FMT was positively associated with several outcomes, caution should be exercised in choosing this approach, given the insufficient number of primary studies, low methodological quality, and low quality of evidence. Further high-quality randomized controlled trials with long-term follow-up are needed to improve the strength and credibility of the evidence base.}, }
@article {pmid35821195, year = {2022}, author = {Lu, G and Wen, Q and Cui, B and Li, Q and Zhang, F}, title = {Washed microbiota transplantation stopped the deterioration of amyotrophic lateral sclerosis: the first case report and narrative review.}, journal = {Journal of biomedical research}, volume = {}, number = {}, pages = {1-8}, doi = {10.7555/JBR.36.20220088}, pmid = {35821195}, issn = {1674-8301}, abstract = {Amyotrophic lateral sclerosis (ALS) is known as a progressive paralysis disorder characterized by degeneration of upper and lower motor neurons and has an average survival time of three to five years. Growing evidence has suggested the bidirectional link between gut microbiota and neurodegeneration. Here we aimed to report one female case with ALS who benefited from washed microbiota transplantation (WMT), an improved fecal microbiota transplantation (FMT), through a transendoscopic enteral tube during a 12-month follow-up. Notedly, the accidental scalp trauma the patient suffered later was treated with prescribed antibiotics which caused ALS deterioration. The subsequent rescue WMTs successfully stopped the progression of the disease with quick improvement. The plateaus and reversals occurred during the whole course of WMT. The stool and blood samples from the first WMT to the last were collected for dynamic microbial and metabolomic analysis. We observed the microbial and metabolomic changing trend consistent with the disease status. This case report for the first time shows the direct clinical evidence on using WMT for treating ALS, indicating that WMT may be the novel treatment strategy for controlling this so-called incurable disease.}, }
@article {pmid35794639, year = {2022}, author = {Hoque, MN and Rahman, MS and Islam, T and Sultana, M and Crandall, KA and Hossain, MA}, title = {Induction of mastitis by cow-to-mouse fecal and milk microbiota transplantation causes microbiome dysbiosis and genomic functional perturbation in mice.}, journal = {Animal microbiome}, volume = {4}, number = {1}, pages = {43}, pmid = {35794639}, issn = {2524-4671}, abstract = {BACKGROUND: Mastitis pathogenesis involves a wide range of opportunistic and apparently resident microorganims including bacteria, viruses and archaea. In dairy animals, microbes reside in the host, interact with environment and evade the host immune system, providing a potential for host-tropism to favor mastitis pathogenesis. To understand the host-tropism phenomena of bovine-tropic mastitis microbiomes, we developed a cow-to-mouse mastitis model.<br><br>METHODS: A cow-to-mouse mastitis model was established by fecal microbiota transplantation (FMT) and milk microbiota transplantation (MMT) to pregnant mice to assess microbiome dysbiosis and genomic functional perturbations through shotgun whole metagenome sequencing (WMS) along with histopathological changes in mice mammary gland and colon tissues.<br><br>RESULTS: The cow-to-mouse FMT and MMT from clinical mastitis (CM) cows induced mastitis syndromes in mice as evidenced by histopathological changes in mammary gland and colon tissues. The WMS of 24 samples including six milk (CM = 3, healthy; H = 3), six fecal (CM = 4, H = 2) samples from cows, and six fecal (CM = 4, H = 2) and six mammary tissue (CM = 3, H = 3) samples from mice generating 517.14 million reads (average: 21.55 million reads/sample) mapped to 2191 bacterial, 94 viral and 54 archaeal genomes. The Kruskal-Wallis test revealed significant differences (p = 0.009) in diversity, composition, and relative abundances in microbiomes between CM- and H-metagenomes. These differences in microbiome composition were mostly represented by Pseudomonas aeruginosa, Lactobacillus crispatus, Klebsiella oxytoca, Enterococcus faecalis, Pantoea dispersa in CM-cows (feces and milk), and Muribaculum spp., Duncaniella spp., Muribaculum intestinale, Bifidobacterium animalis, Escherichia coli, Staphylococcus aureus, Massilia oculi, Ralstonia pickettii in CM-mice (feces and mammary tissues). Different species of Clostridia, Bacteroida, Actinobacteria, Flavobacteriia and Betaproteobacteria had a strong co-occurrence and positive correlation as the indicator species of murine mastitis. However, both CM cows and mice shared few mastitis-associated microbial taxa (1.14%) and functional pathways regardless of conservation of mastitis syndromes, indicating the higher discrepancy in mastitis-associated microbiomes among lactating mammals.<br><br>CONCLUSIONS: We successfully induced mastitis by FMT and MMT that resulted in microbiome dysbiosis and genomic functional perturbations in mice. This study induced mastitis in a mouse model through FMT and MMT, which might be useful for further studies- focused on pathogen(s) involved in mastitis, their cross-talk among themselves and the host.}, }
@article {pmid35709800, year = {2022}, author = {Tian, H and Zhang, S and Qin, H and Li, N and Chen, Q and , }, title = {Long-term safety of faecal microbiota transplantation for gastrointestinal diseases in China.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {8}, pages = {702-703}, doi = {10.1016/S2468-1253(22)00170-4}, pmid = {35709800}, issn = {2468-1253}, mesh = {China/epidemiology ; *Colitis, Ulcerative ; Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Diseases/therapy ; Humans ; }, }
@article {pmid35814647, year = {2022}, author = {Huang, WQ and Huang, HL and Peng, W and Liu, YD and Zhou, YL and Xu, HM and Zhang, LJ and Zhao, C and Nie, YQ}, title = {Altered Pattern of Immunoglobulin A-Targeted Microbiota in Inflammatory Bowel Disease After Fecal Transplantation.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {873018}, doi = {10.3389/fmicb.2022.873018}, pmid = {35814647}, issn = {1664-302X}, abstract = {Adaptive immune response to the gut microbiota is one of the main drivers of inflammatory bowel disease (IBD). Under inflammatory conditions, immunoglobulin (Ig)-targeted bacteria are altered. However, changes in Ig-targeted bacteria in Asian patients with IBD with ulcerative colitis (UC) remain unclear. Furthermore, changes in IgA-targeted bacteria in patients with UC treated with fecal microbiota transplantation (FMT) are unclear. Here, we analyzed fecal samples of patients with IBD and patients with UC before and after FMT by flow cytometry. We found that the percentage of IgA/G-coated bacteria can be used to assess the severity of IBD. Besides oral pharyngeal bacteria such as Streptococcus, we hypothesized that Megamonas, Acinetobacter, and, especially, Staphylococcus might play an important role in IBD pathogenesis. Moreover, we evaluated the influence of FMT on IgA-coated bacteria in patients with UC. We found that IgA-bacterial interactions were re-established in human FMT recipients and resembled those in the healthy fecal donors. Additionally, the IgA targeting was not influenced by delivery methods: gastroscopy spraying and colonic transendoscopic enteral tubing (TET). Then, we established an acute dextran sulfate sodium (DSS)-induced mouse model to explore whether FMT intervention would impact IgA/G memory B cell in the intestine. We found that after FMT, both IgA/G memory B cell and the percentage of IgA/G-targeted bacteria were restored to normal levels in DSS mice.}, }
@article {pmid35814520, year = {2022}, author = {Rajpurohit, S and Musunuri, B and Shailesh,  and Basthi Mohan, P and Shetty, S}, title = {Novel Drugs for the Management of Hepatic Encephalopathy: Still a Long Journey to Travel.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {4}, pages = {1200-1214}, doi = {10.1016/j.jceh.2022.01.012}, pmid = {35814520}, issn = {0973-6883}, abstract = {Hepatic encephalopathy (HE) is one of the reversible complications of chronic liver disease, associated with a higher mortality rate. In current clinical practice, treatment with rifaximin and lactulose/lactitol is the first line of treatment in HE. With the advance in pathophysiology, a new class of ammonia lowering drugs has been revealed to overcome the hurdle and disease burden. The mechanism of the novel agents differs significantly and includes the alteration in intestinal microbiota, intestinal endothelial integrity, oxidative stress, inflammatory markers, and modulation of neurotoxins. Most of the trials have reported promising results in the treatment and prevention of HE with fecal microbiota transplantation, albumin, probiotics, flumazenil, polyethylene glycol, AST-120, glycerol phenylbutyrate, nitazoxanide, branched-chain amino acid, naloxone, and acetyl-l-carnitine. However, their clinical use is limited due to the presence of major drawbacks in their study design, sample size, safety profile, bias, and heterogenicity. This study will discuss the novel therapeutic targets for HE in liver cirrhosis patients with supporting clinical trial data.}, }
@article {pmid35814513, year = {2022}, author = {Philips, CA and Ahamed, R and Rajesh, S and Abduljaleel, JKP and Augustine, P}, title = {Long-term Outcomes of Stool Transplant in Alcohol-associated Hepatitis-Analysis of Clinical Outcomes, Relapse, Gut Microbiota and Comparisons with Standard Care.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {4}, pages = {1124-1132}, doi = {10.1016/j.jceh.2022.01.001}, pmid = {35814513}, issn = {0973-6883}, abstract = {Background: Healthy donor fecal microbiota transplantation (FMT) was preliminarily shown to have clinical benefits in hepatic encephalopathy (HE), severe alcohol-associated hepatitis (SAH), and alcohol use disorder. However, the long-term outcomes of FMT and the gut microbiota (GM) changes in patients with SAH are unknown.<br><br>Methods: Patients with SAH who underwent FMT (N = 35) or standard of care (SoC, N = 26) from May 2017 to June 2018 were included, and their stored stool samples were analyzed prospectively. Clinical outcomes, including infections, hospitalizations, critical illness, alcohol relapse, and survival, were evaluated. Metagenomic analysis was undertaken to identify the relative abundances (Ras) and significant taxa at baseline and post-therapy (up to three years) among survivors between the two groups.<br><br>Results: At follow-up, the incidences of ascites, HE, infections, and major hospitalizations were significantly higher in the SoC than in the FMT group (P < 0.05). Alcohol relapse was lower (28.6% versus 53.8%), and the time to relapse was higher in the FMT than in the SoC group (P = 0.04). Three-year survival was higher in the FMT than in the SoC group (65.7% versus 38.5%, P = 0.052). Death due to sepsis was significantly higher in the SoC group (N = 13/16, 81.2%; P = 0.008). GM analysis showed a significant increase in the RA of Bifidobacterium and a reduction in the RA of Acinetobacter in the FMT group. Beyond one to two years, the RA of Porphyromonas was significantly higher and that of Bifidobacterium was lower in the SoC than in the FMT group.<br><br>Conclusions: In terms of treatment for patients with SAH, healthy donor FMT is associated with significantly lesser ascites, infections, encephalopathy, and alcohol relapse (with a trend toward higher survival rates) than SoC, associated with beneficial GM modulation. Larger controlled studies on FMT are an unmet need.}, }
@article {pmid35812394, year = {2022}, author = {Zhu, M and Liu, X and Ye, Y and Yan, X and Cheng, Y and Zhao, L and Chen, F and Ling, Z}, title = {Gut Microbiota: A Novel Therapeutic Target for Parkinson's Disease.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {937555}, doi = {10.3389/fimmu.2022.937555}, pmid = {35812394}, issn = {1664-3224}, abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis is involved in the occurrence, development and progression of PD. Numerous clinical trials have identified the characteristics of the changed gut microbiota profiles, and preclinical studies in PD animal models have indicated that gut dysbiosis can influence the progression and onset of PD via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels of α-synuclein fibrils, increasing oxidative stress, and decreasing neurotransmitter production. The gut microbiota can be considered promising diagnostic and therapeutic targets for PD, which can be regulated by probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, diet modifications, and Chinese medicine. This review summarizes the recent studies in PD-associated gut microbiota profiles and functions, the potential roles, and mechanisms of gut microbiota in PD, and gut microbiota-targeted interventions for PD. Deciphering the underlying roles and mechanisms of the PD-associated gut microbiota will help interpret the pathogenesis of PD from new perspectives and elucidate novel therapeutic strategies for PD.}, }
@article {pmid35812374, year = {2022}, author = {Li, P and Gao, M and Song, B and Liu, Y and Yan, S and Lei, J and Zhao, Y and Li, G and Mahmood, T and Lv, Z and Hu, Y and Guo, Y}, title = {Fecal Microbiota Transplantation Reshapes the Physiological Function of the Intestine in Antibiotic-Treated Specific Pathogen-Free Birds.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {884615}, doi = {10.3389/fimmu.2022.884615}, pmid = {35812374}, issn = {1664-3224}, abstract = {The topic about the interactions between host and intestinal microbiota has already caught the attention of many scholars. However, there is still a lack of systematic reports on the relationship between the intestinal flora and intestinal physiology of birds. Thus, this study was designed to investigate it. Antibiotic-treated specific pathogen-free (SPF) bird were used to construct an intestinal bacteria-free bird (IBF) model, and then, the differences in intestinal absorption, barrier, immune, antioxidant and metabolic functions between IBF and bacteria-bearing birds were studied. To gain further insight, the whole intestinal flora of bacteria-bearing birds was transplanted into the intestines of IBF birds to study the remodeling effect of fecal microbiota transplantation (FMT) on the intestinal physiology of IBF birds. The results showed that compared with bacteria-bearing birds, IBF birds had a lighter body weight and weaker intestinal absorption, antioxidant, barrier, immune and metabolic functions. Interestingly, FMT contributed to reshaping the abovementioned physiological functions of the intestines of IBF birds. In conclusion, the intestinal flora plays an important role in regulating the physiological functions of the intestine.}, }
@article {pmid35811664, year = {2022}, author = {Wang, X and Zhao, J and Feng, Y and Feng, Z and Ye, Y and Liu, L and Kang, G and Cao, X}, title = {Evolutionary Insights Into Microbiota Transplantation in Inflammatory Bowel Disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {916543}, doi = {10.3389/fcimb.2022.916543}, pmid = {35811664}, issn = {2235-2988}, abstract = {The intestinal microbiome plays an essential role in human health and disease status. So far, microbiota transplantation is considered a potential therapeutic approach for treating some chronic diseases, including inflammatory bowel disease (IBD). The diversity of gut microbiota is critical for maintaining resilience, and therefore, transplantation with numerous genetically diverse gut microbiota with metabolic flexibility and functional redundancy can effectively improve gut health than a single probiotic strain supplement. Studies have shown that natural fecal microbiota transplantation or washing microbiota transplantation can alleviate colitis and improve intestinal dysbiosis in IBD patients. However, unexpected adverse reactions caused by the complex and unclear composition of the flora limit its wider application. The evolving strain isolation technology and modifiable pre-existing strains are driving the development of microbiota transplantation. This review summarized the updating clinical and preclinical data of IBD treatments from fecal microbiota transplantation to washing microbiota transplantation, and then to artificial consortium transplantation. In addition, the factors considered for strain combination were reviewed. Furthermore, four types of artificial consortium transplant products were collected to analyze their combination and possible compatibility principles. The perspective on individualized microbiota transplantation was also discussed ultimately.}, }
@article {pmid35807816, year = {2022}, author = {Xu, B and Hao, K and Chen, X and Wu, E and Nie, D and Zhang, G and Si, H}, title = {Broussonetia papyrifera Polysaccharide Alleviated Acetaminophen-Induced Liver Injury by Regulating the Intestinal Flora.}, journal = {Nutrients}, volume = {14}, number = {13}, pages = {}, doi = {10.3390/nu14132636}, pmid = {35807816}, issn = {2072-6643}, support = {AB19245037//The Key Research and Development Plan of Guangxi, China/ ; 20202088//Key R &amp; D Projects in Nanning/ ; 31760746//Natural National Science Foundation of China/ ; }, abstract = {Liver injury caused by an overdose of acetaminophen (APAP) is a major public health problem. This study aimed to evaluate the effects of Broussonetia papyrifera polysaccharide (BPP) on liver injury and intestinal flora induced by APAP. The results showed that BPP could protect against APAP-induced liver injury, alleviate liver apoptosis, improve antioxidant capacity and enhance the liver's detoxification ability to APAP. At the same time, BPP improved the intestinal flora disorder caused by APAP. More importantly, we found that the hepatoprotective effect of BPP disappeared after the depletion of gut microbiota in mice. Further, we reconstructed the intestinal flora structure of mice through fecal microbiota transplantation and found that the symptoms of APAP-induced liver injury were effectively alleviated. Overall, BPP was a potential hepatoprotective drug that could protect against APAP-induced liver injury and might be mediated by intestinal flora.}, }
@article {pmid35806031, year = {2022}, author = {Rodríguez-Fernández, CA and Iglesias, MB and de Domingo, B and Conde-Pérez, K and Vallejo, JA and Rodríguez-Martínez, L and González-Barcia, M and Llorenç, V and Mondelo-Garcia, C and Poza, M and Fernández-Ferreiro, A}, title = {Microbiome in Immune-Mediated Uveitis.}, journal = {International journal of molecular sciences}, volume = {23}, number = {13}, pages = {}, doi = {10.3390/ijms23137020}, pmid = {35806031}, issn = {1422-0067}, support = {IN607D 2021//Xunta de Galicia/ ; IN607A 2020/05//Xunta de Galicia/ ; PI20/00719//Instituto de Salud Carlos III/ ; PI20/00413//Instituto de Salud Carlos III/ ; }, abstract = {In the last decades, personalized medicine has been increasing its presence in different fields of medicine, including ophthalmology. A new factor that can help us direct medicine towards the challenge of personalized treatments is the microbiome. The gut microbiome plays an important role in controlling immune response, and dysbiosis has been associated with immune-mediated diseases such as non-infectious uveitis (NIU). In this review, we gather the published evidence, both in the pre-clinical and clinical studies, that support the possible role of intestinal dysbiosis in the pathogenesis of NIU, as well as the modulation of the gut microbiota as a new possible therapeutic target. We describe the different mechanisms that have been proposed to involve dysbiosis in the causality of NIU, as well as the potential pharmacological tools that could be used to modify the microbiome (dietary supplementation, antibiotics, fecal microbiota transplantation, immunomodulators, or biologic drugs) and, consequently, in the control of the NIU. Furthermore, there is increasing scientific evidence suggesting that the treatment with anti-TNF not only restores the composition of the gut microbiota but also that the study of the composition of the gut microbiome will help predict the response of each patient to anti-TNF treatment.}, }
@article {pmid35805965, year = {2022}, author = {Elhag, DA and Kumar, M and Saadaoui, M and Akobeng, AK and Al-Mudahka, F and Elawad, M and Al Khodor, S}, title = {Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response.}, journal = {International journal of molecular sciences}, volume = {23}, number = {13}, pages = {}, doi = {10.3390/ijms23136966}, pmid = {35805965}, issn = {1422-0067}, support = {NPRP10-0125-170242//Qatar National Research Fund/ ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time. Therefore, according to the recent Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations, continuous disease monitoring from symptomatic relief to endoscopic healing along with short- and long-term therapeutic responses are critical for providing IBD patients with a tailored therapy algorithm. Moreover, considering the high unmet need for novel therapeutic approaches for IBD patients, various new modulators of cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors of cytokines (for example IL-12/IL-23, IL-22, IL-36, and IL-6 inhibitors), anti-adhesion and migration strategies (for example, β7 integrin, sphingosine 1-phosphate receptors, and stem cells), as well as microbial-based therapeutics to decolonize the bed buds (for example, fecal microbiota transplantation and bacterial inhibitors) are currently being evaluated in different phases of controlled clinical trials. This review aims to offer a comprehensive overview of available treatment options and emerging therapeutic approaches for IBD patients. Furthermore, predictive biomarkers for monitoring the therapeutic response to different IBD therapies are also discussed.}, }
@article {pmid35804021, year = {2022}, author = {Song, C and Duan, F and Ju, T and Qin, Y and Zeng, D and Shan, S and Shi, Y and Zhang, Y and Lu, W}, title = {Eleutheroside E supplementation prevents radiation-induced cognitive impairment and activates PKA signaling via gut microbiota.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {680}, pmid = {35804021}, issn = {2399-3642}, abstract = {Radiation affects not only cognitive function but also gut microbiota. Eleutheroside E (EE), a principal active compound of Acanthopanax senticosus, has a certain protective effect on the nervous system. Here, we find a four-week EE supplementation to the 60Co-γ ray irradiated mice improves the cognition and spatial memory impairments along with the protection of hippocampal neurons, remodels the gut microbiota, especially changes of Lactobacillus and Helicobacter, and altered the microbial metabolites including neurotransmitters (GABA, NE, ACH, 5-HT) as well as their precursors. Furthermore, the fecal transplantation of EE donors verifies that EE alleviated cognition and spatial memory impairments, and activates the PKA/CREB/BDNF signaling via gut microbiota. Our findings provide insight into the mechanism of EE effect on the gut-brain axis and underpin a proposed therapeutic value of EE in cognitive and memory impairments induced by radiation.}, }
@article {pmid35802940, year = {2022}, author = {Tian, Y and Zuo, L and Guan, B and Wu, H and He, Y and Xu, Z and Shen, M and Hu, J and Qian, J}, title = {Microbiota from patients with ulcerative colitis promote colorectal carcinogenesis in mice.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {102}, number = {}, pages = {111712}, doi = {10.1016/j.nut.2022.111712}, pmid = {35802940}, issn = {1873-1244}, abstract = {OBJECTIVES: Long-term ulcerative colitis (UC) is associated with both dysbiosis in intestinal microbiota and predisposition to colorectal cancer. In this study, we investigated whether microbiota from patients with UC could increase colorectal carcinogenesis in mice, generated by azoxymethane through intraperitoneal injection.<br><br>METHODS: Mice were gavaged twice per week with intestinal microbiota from patients with UC or healthy individuals. Intestinal tissues were collected from mice and compared by histology, immunohistochemistry, expression microarray, quantitative polymerase chain reaction, Western blot, and flow cytometry analyses. Quantification of bacteria in feces was performed using 16 S ribosomal RNA gene selective quantitative polymerase chain reaction.<br><br>RESULTS: Compared with mice fed microbiota from healthy controls, increased tumorigenesis was observed in mice gavaged with microbiota from patients with UC, including a higher number of colon adenoma and a significantly higher proportion of grade dysplasia. Consistent with tumorigenesis, mice gavaged with microbiota from patients with UC showed an increased expression of Ki67 and proliferating cell nuclear antigen. In addition, an increased expression of cytokines and more abundant presence of T helper cells types 1 and 17 was observed in mice receiving microbiota from patients with UC. Moreover, a decrease in the abundance of short-chain fatty acids was detected in the feces, as well as an altered intestinal microbial composition in mice fed with microbiota from patients with UC.<br><br>CONCLUSIONS: Fecal microbiota from patients with UC exacerbate tumorigenesis in mice. The disturbance of intestinal microbiota and activation of T helper cells types 1 and 17 cytokines caused by gavaging microbiota from patients with UC both contributed to intestinal carcinogenesis.}, }
@article {pmid35800791, year = {2022}, author = {Tun, KM and Hong, AS and Batra, K and Naga, Y and Ohning, G}, title = {A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplantation in the Treatment of Hepatic Encephalopathy and Clostridioides difficile Infection in Patients With Cirrhosis.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e25537}, doi = {10.7759/cureus.25537}, pmid = {35800791}, issn = {2168-8184}, abstract = {The microbiome of the human gut and liver coexists by influencing the health and disease state of each system. Fecal microbiota transplantation (FMT) has recently emerged as a potential treatment for conditions associated with cirrhosis, such as hepatic encephalopathy and recurrent/refractory Clostridioides difficile infection (rCDI). We have conducted a systematic review of the safety and efficacy of FMT in treating hepatic encephalopathy and rCDI. A literature search was performed using variations of the keywords "fecal microbiota transplant" and "cirrhosis" on PubMed/MEDLINE from inception to October 3, 2021. The resulting 116 articles were independently reviewed by two authors. Eight qualifying studies were included in the systematic review. A total of 127 cirrhotic patients received FMT. Hepatic encephalopathy was evaluated by cognitive tests, such as the Psychometric Hepatic Encephalopathy Score (PHES) and EncephalApp Stroop test. Not only was there an improvement in the cognitive performance in the FMT cohort, but the improvement was also maintained throughout long-term follow-up. In the treatment of rCDI, the FMT success rate is similar between cirrhotic patients and the general population, although more than one dose may be needed in the former. The rate of serious adverse events and adverse events in the cirrhotic cohort was slightly higher than that in the general population but was low overall. We found evidence that supports the therapeutic potential and safety profile of FMT to treat hepatic encephalopathy and rCDI in cirrhotic patients. Further research will be beneficial to better understand the role of FMT in cirrhosis.}, }
@article {pmid35799219, year = {2022}, author = {Sinha, A and Li, Y and Mirzaei, MK and Shamash, M and Samadfam, R and King, IL and Maurice, CF}, title = {Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates the severity of DSS colitis.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {105}, pmid = {35799219}, issn = {2049-2618}, support = {fellowship 170921/CAPMC/CIHR/Canada ; Innovator Award 2016-1280//Kenneth Rainin Foundation/ ; Innovator Award 2016-1280//Kenneth Rainin Foundation/ ; Innovator Award 2016-1280//Kenneth Rainin Foundation/ ; Innovator Award 2016-1280//Kenneth Rainin Foundation/ ; }, abstract = {BACKGROUND: Inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by chronic and debilitating gut inflammation. Altered bacterial communities of the intestine are strongly associated with IBD initiation and progression. The gut virome, which is primarily composed of bacterial viruses (bacteriophages, phages), is thought to be an important factor regulating and shaping microbial communities in the gut. While alterations in the gut virome have been observed in IBD patients, the contribution of these viruses to alterations in the bacterial community and heightened inflammatory responses associated with IBD patients remains largely unknown.<br><br>RESULTS: Here, we performed in vivo microbial cross-infection experiments to follow the effects of fecal virus-like particles (VLPs) isolated from UC patients and healthy controls on bacterial diversity and severity of experimental colitis in human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred to HMA mice, resulting in treatment-specific alterations in the gut virome. VLPs from healthy and UC patients also shifted gut bacterial diversity of these mice, an effect that was amplified during experimental colitis. VLPs isolated from UC patients specifically altered the relative abundance of several bacterial taxa previously implicated in IBD progression. Additionally, UC VLP administration heightened colitis severity in HMA mice, as indicated by shortened colon length and increased pro-inflammatory cytokine production. Importantly, this effect was dependent on intact VLPs.<br><br>CONCLUSIONS: Our findings build on recent literature indicating that phages are dynamic regulators of bacterial communities in the gut and implicate the intestinal virome in modulating intestinal inflammation and disease. Video Abstract.}, }
@article {pmid35797794, year = {2022}, author = {Huang, C and Yi, P and Zhu, M and Zhou, W and Zhang, B and Yi, X and Long, H and Zhang, G and Wu, H and Tsokos, GC and Zhao, M and Lu, Q}, title = {Erratum to "Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial" [J. Autoimmun. 130, June 2022, 102844].}, journal = {Journal of autoimmunity}, volume = {131}, number = {}, pages = {102862}, doi = {10.1016/j.jaut.2022.102862}, pmid = {35797794}, issn = {1095-9157}, }
@article {pmid35797768, year = {2022}, author = {Luo, Y and Zhang, Y and Han, X and Yuan, Y and Zhou, Y and Gao, Y and Yu, H and Zhang, J and Shi, Y and Duan, Y and Zhao, X and Yan, S and Hao, H and Dai, C and Zhao, S and Shi, J and Li, W and Zhang, S and Xu, W and Fang, N and Gong, Y and Li, Y}, title = {Akkermansia muciniphila prevents cold-related atrial fibrillation in rats by modulation of TMAO induced cardiac pyroptosis.}, journal = {EBioMedicine}, volume = {82}, number = {}, pages = {104087}, doi = {10.1016/j.ebiom.2022.104087}, pmid = {35797768}, issn = {2352-3964}, abstract = {BACKGROUND: Cold exposure is one of the most important risk factors for atrial fibrillation (AF), and closely related to the poor prognosis of AF patients. However, the mechanisms underlying cold-related AF are poorly understood.<br><br>METHODS: Various techniques including 16S rRNA gene sequencing, fecal microbiota transplantation, and electrophysiological examination were used to determine whether gut microbiota dysbiosis promotes cold-related AF. Metabonomics were performed to investigate changes in fecal trimethylamine (TMA) and plasma trimethylamine N-oxide (TMAO) during cold exposure. The detailed mechanism underlying cold-related AF were examined in vitro. Transgenic mice were constructed to explore the role of pyroptosis in cold-related AF. The human cohort was used to evaluate the correlation between A. muciniphila and cold-related AF.<br><br>FINDINGS: We found that cold exposure caused elevated susceptibility to AF and reduced abundance of Akkermansia muciniphila (A. muciniphila) in rats. Intriguingly, oral supplementation of A. muciniphila ameliorated the pro-AF property induced by cold exposure. Mechanistically, cold exposure disrupted the A. muciniphila, by which elevated the level of trimethylamine N-oxide (TMAO) through modulation of the microbial enzymes involved in trimethylamine (TMA) synthesis. Correspondingly, progressively increased plasma TMAO levels were validated in human subjects during cold weather. Raised TMAO enhanced the infiltration of M1 macrophages in atria and increased the expression of Casp1-p20 and cleaved-GSDMD, ultimately causing atrial structural remodeling. Furthermore, the mice with conditional deletion of caspase1 exhibited resistance to cold-related AF. More importantly, a cross-sectional clinical study revealed that the reduction of A. muciniphila abundance was an independent risk factor for cold-related AF in human subjects.<br><br>INTERPRETATION: Our findings revealed a novel causal role of aberrant gut microbiota and metabolites in pathogenesis of cold-related AF, which raises the possibility of selectively targeting microbiota and microbial metabolites as a potential therapeutic strategy for cold-related AF.<br><br>FUNDING: This work was supported by grants from the State Key Program of National Natural Science Foundation of China (No.81830012), and National Natural Science Foundation of China (No.82070336, No.81974024), Youth Program of the National Natural Science Foundation of China (No.81900374, No.81900302), and Excellent Young Medical Talents supporting project in the First Affiliated Hospital of Harbin Medical University (No. HYD2020YQ0001).}, }
@article {pmid35796402, year = {2022}, author = {Chen, C and Liang, H and Wang, J and Ren, G and Li, R and Cui, ZG and Zhang, C}, title = {Heterophyllin B an Active Cyclopeptide Alleviates Dextran Sulfate Sodium-induced Colitis by Modulating Gut Microbiota and Repairing Intestinal Mucosal Barrier via AMPK Activation.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e2101169}, doi = {10.1002/mnfr.202101169}, pmid = {35796402}, issn = {1613-4133}, abstract = {SCOPE: Advances in pathology broaden our perception of the intimate interaction between gut microbiota dysbiosis and the pathogenesis of ulcerative colitis (UC), but the potential modulating roles remain to be elucidated.<br><br>METHODS AND RESULTS: DSS-induced colitis was used to investigate the effect of Heterophyllin B (HB), a typical active cyclopeptide extracted from Pseudostellaria heterophylla, on colitis and gut microbiota. Administration of HB substantially mitigated the symptoms of UC as evidenced by increasing body weight and colon length, as well as decreased macrophages infiltration in the colon. Meanwhile, HB significantly alleviated intestinal mucosal barrier dysfunction by reducing the production of inflammatory cytokines, while all the mentioned beneficial effects were significantly eliminated by co-treatment with compound C, a selective AMPK inhibitor. In addition, 16S rDNA gene analyses and fecal microbiota transplantation also revealed that HB dramatically prevented against UC by reshaping intestinal dysbiosis, especially elevated the relative abundance of Akkermansia muciniphila.<br><br>CONCLUSION: These findings illustrated that HB prominently improved intestinal epithelial homeostasis via activating AMPK and ameliorated the colonic inflammation in a gut microbiota-dependent manner, which provide evidence for microbial contribution to UC pathogenesis and suggesting a novel approach for colitis prevention. This article is protected by copyright. All rights reserved.}, }
@article {pmid35795291, year = {2022}, author = {Tan, XY and Xie, YJ and Liu, XL and Li, XY and Jia, B}, title = {A Systematic Review and Meta-Analysis of Randomized Controlled Trials of Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2022}, number = {}, pages = {8266793}, doi = {10.1155/2022/8266793}, pmid = {35795291}, issn = {1741-427X}, abstract = {Objectives: Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the gastrointestinal tract, and its prevalence is increasing worldwide. Fecal microbiota transplantation (FMT) is an emerging therapy that modifies the patient's gut microbiota by transplanting feces from a healthy donor to achieve disease remission. However, its efficacy and safety need to be further investigated.<br><br>Methods: PubMed, the Cochrane Library, Web of Science, Embase, and Google Scholar databases (up to 8th November 2021) were searched and literature was screened by title and abstract as well as full text. The primary outcome was clinical remission, with the clinical response as a secondary outcome. Risk ratios (RR) with 95% confidence intervals (CI) were reported.<br><br>Results: A total of 14 trials were included in this study. In terms of clinical remission, FMT had a significant effect compared to placebo (RR = 1.44, 95 CI%: 1.03 to 2.02, I 2 = 38%, P=0.03), with no significant risk of study heterogeneity. Moreover, FMT led to significant results in clinical response compared to placebo with moderate between-study heterogeneity (RR = 1.34, 95 CI%: 0.92 to 1.94, I 2 = 51%, P=0.12). Subgroup analysis showed a higher clinical remission for fresh fecal FMT (40.9%) than that for frozen fecal FMT (32.2%); the efficacy of gastrointestinal (GI) pretreatment, the severity of disease, route of administration, and the donor selection remain unclear and require more extensive study. Safety analysis concluded that most adverse events were mild and self-resolving. The microbiological analysis found that the patient's gut microbiota varied in favor of the donor, with increased flora diversity and species richness.<br><br>Conclusion: FMT is a safe, effective, and well-tolerated therapy. Studies have found that fresh fecal microbiota transplant can increase clinical remission rates. However, more randomized controlled trials and long-term follow-ups are needed to assess its long-term effectiveness and safety.}, }
@article {pmid35792193, year = {2022}, author = {Avolio, E and Olivito, I and Rosina, E and Romano, L and Angelone, T and Bartolo Anna,  and Scimeca, M and Bellizzi, D and D'Aquila, P and Passarino, G and Alò, R and Maria Facciolo, R and Bagni, C and De Lorenzo, A and Canonaco, M}, title = {Modifications of behavior and inflammation in mice following transplant with fecal microbiota from children with autism.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2022.06.038}, pmid = {35792193}, issn = {1873-7544}, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder displaying the modification of complex human behaviors, characterized by social interaction impairments, stereotypical/repetitive activities and emotional dysregulation. In this study, fecal microbiota transplant (FMT) via gavage from autistic children donors to mice, leads to the colonization of ASD-like microbiota and autistic behaviors compared to the offspring of pregnant females exposed to valproic acid (VPA). Such variations seemed to be tightly associated with increased populations of Tenericutes plus a notable reduction (p<0.001) of Actinobacteria and Candidatus S. in the gastrointestinal region of FMT mice compared to controls. Indeed altered behaviors of FMT mice was reported when evaluated in the different maze tests (light dark, novel object, three chamber tests, novel cage test). Contextually, FMT accounted for elevated expression levels of the pro-inflammatory factors IL-1β, IL-6, COX-1 and TNF-α in both brain and small intestine. Villous atrophy and inflammatory infiltration (Caspase 3 and Ki67) were increased in the small intestine of FMT and VPA mice compared to controls. Moreover, the observed FMT-dependent alterations were probably due to a decrease in the methylation status. Overall, findings of the present study corroborate a key role of gut microbiota in ASD. However, further investigations are required before any possible manipulation of gut bacteria with appropriate diets or probiotics in ASD individuals.}, }
@article {pmid35791946, year = {2022}, author = {Xu, H and Wang, L and Chen, B and Zhao, L}, title = {[Fecal Microbiota Transplantation:Traditional Chinese Medicine Meets Western Medicine].}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {44}, number = {3}, pages = {472-476}, doi = {10.3881/j.issn.1000-503X.13774}, pmid = {35791946}, issn = {1000-503X}, abstract = {Fecal microbiota transplantation (FMT) is a therapy of transplanting the functional flora from the feces of a healthy donor into the gastrointestinal tract of a patient to reconstruct the normal flora.The application of FMT in western medicine dates from the 1950s.After decades of development,the efficacy of FMT has been proven in a variety of diseases.The record of FMT in traditional Chinese medicine (TCM) dates early from the 3rd century A.D.,and relevant theories have been recorded in many TCM works in the past dynasties.FMT as a therapy that has been written into guidelines has been accepted by some countries and regions such as the United States and the United Kingdom in the treatment of Clostridium difficile infection,and its clinical indications are expanding.TCM and western medicine,with different medical thoughts,meet in the application of FMT.Exploring a normative and effective FMT procedure reflects not only the patient-centered principle but also the mutual promotion of TCM and western medicine.}, }
@article {pmid35785728, year = {2022}, author = {Xu, Q and Li, D and Chen, J and Yang, J and Yan, J and Xia, Y and Zhang, F and Wang, X and Cao, H}, title = {Crosstalk between the gut microbiota and postmenopausal osteoporosis: Mechanisms and applications.}, journal = {International immunopharmacology}, volume = {110}, number = {}, pages = {108998}, doi = {10.1016/j.intimp.2022.108998}, pmid = {35785728}, issn = {1878-1705}, abstract = {Postmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. The number of people suffering from PMO has increased over the years because of the rapidly aging population worldwide. However, several pharmacological agents for the treatment of PMO have many safety risks and impose a heavy financial burden to patients and society. In recent years, the "gut-bone" axis has been proposed as a new approach in the prevention and treatment of PMO. This paper reviews the relationship between the gut microbiota and PMO, which mainly includes the underlying mechanisms between hormones, immunity, nutrient metabolism, metabolites of the gut microbiota and intestinal permeability, and explores the possible role of the gut microbiota in these processes. Finally, we discuss the therapeutic effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the gut microbiota.}, }
@article {pmid35785254, year = {2022}, author = {Xie, C and Zhu, X and Xu, B and Niu, Y and Zhang, X and Ma, L and Yan, X}, title = {Integrated analysis of multi-tissues lipidome and gut microbiome reveals microbiota-induced shifts on lipid metabolism in pigs.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {10}, number = {}, pages = {280-293}, doi = {10.1016/j.aninu.2022.04.011}, pmid = {35785254}, issn = {2405-6383}, abstract = {Lipid metabolism is very important for meat quality in pigs. Accumulating evidence shows that gut microbiota can contribute to this physiological process. However, the gut microbiota that function in lipid metabolism and adipogenesis remains unclear. Here, we compared the characteristics of fat deposition and gut microbial community between Laiwu pigs and Duroc × (Landrace × Yorkshire) (DLY) pigs. Fecal microbiota transplantation (FMT) was performed to determine the possible impact of gut microbiota on lipid metabolism in pigs. An integrated analysis of the gut microbiome and lipidome of the small intestine, plasma, and liver was conducted to investigate the effects of FMT on host lipid metabolism. The comparative analysis of the gut microbiome showed higher abundance of Bacteroidetes (P = 0.0018) while lower abundance of Firmicutes (P = 0.012) in Laiwu pigs, and the microbial composition can be transferred from Laiwu pigs into DLY pigs. Transmission electron microscope and Oil red-O staining were performed to analyze the effects of FMT on lipid deposition in liver, the main target organ for lipid metabolism. The results showed that FMT significantly increased the number of lipid droplets (P = 0.0035) and lipid accumulation (P = 0.0026) in liver. Furthermore, integrated multi-tissues lipidome analysis demonstrated that the fatty acyls and glycerophospholipids were significantly increased (P < 0.01) in intestine and liver, while glycerolipids and fatty acyls were reduced (P < 0.01) in plasma. In the small intestine, FMT increased (P < 0.01) the relative abundance of polyketides and prenol lipids but reduced (P < 0.01) the saccharolipids. Correlation analysis revealed the potential interactions between microbiota and lipid metabolites. Together, our results indicated that the gut microbiota may regulate the lipid metabolism and enhance the accumulation of lipid droplets in the liver of pigs.}, }
@article {pmid35784625, year = {2022}, author = {Vasavada, S and Panneerselvam, K and Amin, R and Varatharajalu, K and Okhuysen, PC and Oliva, ICG and Wang, J and Grivas, P and Thomas, AS and Wang, Y}, title = {Clostridioides difficile infection in cancer patients receiving immune checkpoint inhibitors.}, journal = {Annals of gastroenterology}, volume = {35}, number = {4}, pages = {393-399}, doi = {10.20524/aog.2022.0722}, pmid = {35784625}, issn = {1108-7471}, abstract = {Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but are associated with immune-mediated diarrhea and colitis (IMDC). Clostridioides difficile infection (CDI) can cause infectious diarrhea with overlapping symptoms. Thus, we sought to elucidate the characteristics of CDI in patients treated with ICI, in the context of IMDC.<br><br>Methods: We conducted a retrospective, single-center study of adult cancer patients (N=421) with ICI exposure from 2015-2020 and a positive stool nucleic acid amplification test and/or enzyme immunoassay for CDI. Baseline characteristics, treatments, and outcomes were compared between patients with and without concurrent IMDC.<br><br>Results: Forty-one eligible patients were included, 27 with concurrent IMDC and 14 without. Twenty-seven patients were taking programmed death-1 or its ligand inhibitors and 14 were taking cytotoxic T-lymphocyte-associated antigen 4 inhibitors. Patients with concurrent CDI and IMDC had a longer symptom duration (20 vs. 5 days, P=0.003) and a higher rate of grade 3-4 diarrhea (41% vs. 7%, P=0.033). Among patients with concurrent IMDC, preceding antibiotics (P=0.050) and proton pump inhibitors (PPI) (P=0.038) were used more frequently among individuals who developed CDI after immunosuppressant exposure. Thirty-eight patients received antibiotics for CDI, while 5 required fecal microbiota transplantation for concurrent CDI &amp; IMDC.<br><br>Conclusions: CDI is common in ICI-treated cancer patients, especially those with IMDC requiring immunosuppressants. Antibiotics did not alter the need for immunosuppressants in those with concurrent IMDC. Use of PPI and antibiotics while receiving immunosuppressants for IMDC was associated with a greater risk of CDI. Further large-scale studies are warranted to clarify the role of CDI, antibiotics and immunosuppression treatment in IMDC patients.}, }
@article {pmid35783604, year = {2022}, author = {Rashed, R and Valcheva, R and Dieleman, LA}, title = {Manipulation of Gut Microbiota as a Key Target for Crohn's Disease.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {887044}, doi = {10.3389/fmed.2022.887044}, pmid = {35783604}, issn = {2296-858X}, abstract = {Crohn's disease (CD) is an inflammatory bowel disease (IBD) sub-type characterized by transmural chronic inflammation of the gastrointestinal tract. Research indicates a complex CD etiology involving genetic predisposition and immune dysregulation in response to environmental triggers. The chronic mucosal inflammation has been associated with a dysregulated state, or dysbiosis, of the gut microbiome (bacteria), mycobiome (fungi), virome (bacteriophages and viruses), and archeaome (archaea) further affecting the interkingdom syntrophic relationships and host metabolism. Microbiota dysbiosis in CD is largely described by an increase in facultative anaerobic pathobionts at the expense of strict anaerobic Firmicutes, such as Faecalibacterium prausnitzii. In the mycobiome, reduced fungal diversity and fungal-bacteria interactions, along with a significantly increased abundance of Candida spp. and a decrease in Saccharomyces cerevisiae are well documented. Virome analysis also indicates a significant decrease in phage diversity, but an overall increase in phages infecting bacterial groups associated with intestinal inflammation. Finally, an increase in methanogenic archaea such as Methanosphaera stadtmanae exhibits high immunogenic potential and is associated with CD etiology. Common anti-inflammatory medications used in CD management (amino-salicylates, immunomodulators, and biologics) could also directly or indirectly affect the gut microbiome in CD. Other medications often used concomitantly in IBD, such as antibiotics, antidepressants, oral contraceptives, opioids, and proton pump inhibitors, have shown to alter the gut microbiota and account for increased susceptibility to disease onset or worsening of disease progression. In contrast, some environmental modifications through alternative therapies including fecal microbiota transplant (FMT), diet and dietary supplements with prebiotics, probiotics, and synbiotics have shown potential protective effects by reversing microbiota dysbiosis or by directly promoting beneficial microbes, together with minimal long-term adverse effects. In this review, we discuss the different approaches to modulating the global consortium of bacteria, fungi, viruses, and archaea in patients with CD through therapies that include antibiotics, probiotics, prebiotics, synbiotics, personalized diets, and FMT. We hope to provide evidence to encourage clinicians and researchers to incorporate these therapies into CD treatment options, along with making them aware of the limitations of these therapies, and indicate where more research is needed.}, }
@article {pmid35783418, year = {2022}, author = {Xiang, M and Zheng, L and Pu, D and Lin, F and Ma, X and Ye, H and Pu, D and Zhang, Y and Wang, D and Wang, X and Zou, K and Chen, L and Zhang, Y and Sun, Z and Zhang, T and Wu, G}, title = {Intestinal Microbes in Patients With Schizophrenia Undergoing Short-Term Treatment: Core Species Identification Based on Co-Occurrence Networks and Regression Analysis.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {909729}, doi = {10.3389/fmicb.2022.909729}, pmid = {35783418}, issn = {1664-302X}, abstract = {Schizophrenia, a common mental disorder, has a tremendous impact on the health and economy of people worldwide. Evidence suggests that the microbial-gut-brain axis is an important pathway for the interaction between the gut microbiome and the development of schizophrenia. What is not clear is how changes in the gut microbiota composition and structure during antipsychotic treatment improve the symptoms of schizophrenia. In this study, 25 patients with schizophrenia were recruited. Their fecal samples were collected before and after hospital treatment for 14-19 days. The composition and structure of the intestinal microbiota were evaluated by 16S rRNA sequencing analysis, and the results showed significant differences in fecal microbiota before and after treatment. Firmicutes (relative abundances of 82.60 and 86.64%) and Gemminger (relative abundances of 14.17 and 13.57%) were the first dominant species at the phylum and genus levels, respectively. The random forest algorithm and co-occurrence network analysis demonstrated that intestinal flora (especially the core species ASV57) could be used as biomarkers to distinguish different clinical states and match treatment regimens accordingly. In addition, after fecal microbiota transplantation, antibiotic-treated recipient mice showed multiple behavioral improvements. These included decreased psychomotor hyperactivity, increased social interaction, and memory. In conclusion, this study suggests that differences in the composition and structure of gut microbiota after treatment are associated with the development and severity of schizophrenia. Results may provide a potential target for the treatment of this disorder.}, }
@article {pmid35783298, year = {2022}, author = {Pan, ZY and Zhong, HJ and Huang, DN and Wu, LH and He, XX}, title = {Beneficial Effects of Repeated Washed Microbiota Transplantation in Children With Autism.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {928785}, doi = {10.3389/fped.2022.928785}, pmid = {35783298}, issn = {2296-2360}, abstract = {Objective: While fecal microbiota transplantation is demonstrated to improve symptoms of autism spectrum disorder (ASD), it remains unclear whether additional treatment courses yield better results. This study sought to evaluate the efficacy of repeated washed microbiota transplantation (WMT) in children with ASD.<br><br>Methods: Retrospective data from children who were serially treated with WMT, including ASD symptoms, sleep disorders, gastrointestinal (GI) symptoms, and white blood cell (WBC) and globulin levels were obtained. The effect of WMT on children with ASD and whether additional WMT courses led to a further improvement in symptoms were assessed.<br><br>Results: Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale, and Sleep Disturbance Scale for Children (SDSC) scores, the proportion of children with constipation and abnormal fecal forms, and WBC and globulin levels were all significantly lower in ASD children after WMT. More WMT treatment courses led to significantly lower scores on the ABC and SDSC.<br><br>Conclusion: WMT significantly improved ASD and GI symptoms and sleep disorders in children with ASD, and reduced systemic inflammation. Additional WMT courses led to more obvious improvements in ASD symptoms within three treatment courses.}, }
@article {pmid35782138, year = {2022}, author = {Zhu, Y and Xu, Y and Wang, X and Rao, L and Yan, X and Gao, R and Shen, T and Zhou, Y and Kong, C and Zhou, L}, title = {Probiotic Cocktail Alleviates Intestinal Inflammation Through Improving Gut Microbiota and Metabolites in Colitis Mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {886061}, doi = {10.3389/fcimb.2022.886061}, pmid = {35782138}, issn = {2235-2988}, abstract = {The modulation of the gut microbiome has been widely suggested as a promising therapeutic strategy for inflammatory bowel disease (IBD). Here, we established a novel probiotic cocktail to investigate its therapeutic role in acute colitis mice. During dextran sulfate sodium (DSS)-induced colitis, the mice were treated with the probiotic cocktail, fecal microbiota transplantation (FMT) from a healthy mice donor, or 5-aminosalicylic acid (5-ASA), respectively. The inflammatory responses were assessed by symptoms, serum inflammatory factors, and histological scoring. The intestinal barrier function was assessed by detecting tight junction proteins. Gut microbiota and its metabolites were further identified using 16S rDNA sequencing and a liquid chromatograph mass spectrometer (LC-MS/MS). Compared with FMT and 5-ASA treatment, the probiotic cocktail performed better in alleviating symptoms of colitis and decreasing disease activity score and mucosal inflammation. The probiotic cocktail also significantly decreased serum IL-17 level and increased JAM-1 expression in colon. The gut microbiota analysis confirmed that the beneficial effects of the probiotic cocktail were attributed to increasing anti-inflammatory bacteria Akkermansia, Bifidobacterium, and Blautia, while decreasing pro-inflammatory bacteria Parasutterella. The targeted metabolome analysis further indicated a rise in the production of Bifidobacterium-related short-chain fatty acids (SCFAs) such as propanoic acid and isobutyric acid after probiotics treatment. Taken together, the probiotic cocktail effectively alleviated intestinal inflammation through improving gut microbiota and metabolites in colitis mice, suggesting its great potential to be a novel therapeutic approach for IBD patients.}, }
@article {pmid35782123, year = {2022}, author = {Wen, L and Shi, L and Kong, XL and Li, KY and Li, H and Jiang, DX and Zhang, F and Zhou, ZG}, title = {Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {856633}, doi = {10.3389/fcimb.2022.856633}, pmid = {35782123}, issn = {2235-2988}, abstract = {Backgrounds and Purpose: The theory of "entero-pulmonary axis" proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of Pseudomonas aeruginosa pneumonia, in order to provide new insights into the treatment of pneumonia.<br><br>Methods: Pseudomonas aeruginosa and C57/BL6 mice were used to construct the acute pneumonia mouse model, and FMT was treated. Histopathological changes in lung and spleen were observed by HE staining. The expression of CD25, Foxp3 and IL-17 was observed by immunofluorescence. The proportion of Treg and Th17 cells was analyzed by flow cytometry. Serum IL-6, LPS, and IFN-γ levels were detected by ELISA. The expression of TNF-α, IFN-γ, IL-6, IL-2, Foxp3, IL-17, IL-10, and TGFβ1 in lung tissue homogenate was detected by qRT-PCR. 16S rRNA sequencing and non-targeted metabolomics were used to analyze gut microbiota and metabolism.<br><br>Results: Pseudomonas aeruginosa caused the decrease of body weight, food and water intake, lung tissue, and spleen injury in mice with pneumonia. Meanwhile, it caused lung tissue and serum inflammation, and Treg/Th17 cell imbalance in mice with pneumonia. Pseudomonas aeruginosa reduced the diversity and number of gut microbiota in pneumonia mice, resulting in metabolic disorders, superpathway of quinolone and alkylquinolone biosynthesis. It also led to the decrease of 2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis, and the enrichment of Amino sugar and nucleotide sugar metabolism. FMT with or without antibiotic intervention restored gut microbiota abundance and diversity, suppressed inflammation and tissue damage, and promoted an immunological balance of Treg/Th17 cells in mice with pneumonia. In addition, FMT inhibited the aerobactin biosynthesis, 4-hydroxyphenylacetate degradation, superpathway of lipopolysaccharide biosynthesis and L-arabinose degradation IV function of microbiota, and improved amino sugar and nucleotide sugar metabolism.<br><br>Conclusions: FMT restored the Treg/Th17 cells' balance and improved inflammation and lung injury in mice with Pseudomonas aeruginosa pneumonia by regulating gut microbiota disturbance and metabolic disorder.}, }
@article {pmid35781423, year = {2022}, author = {Ke, S and Weiss, ST and Liu, YY}, title = {Rejuvenating the human gut microbiome.}, journal = {Trends in molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molmed.2022.05.005}, pmid = {35781423}, issn = {1471-499X}, abstract = {Industrial advances have caused significant loss of diversity in our gut microbiome, potentially increasing our susceptibility to many diseases. Recently, rewilding the human gut microbiome - that is, bringing it back to an ancestral or preindustrial state (e.g., by transplanting stool material from donors in nonindustrial societies) - has been hotly debated from medical, ethical, and evolutionary perspectives. Here we propose an alternative solution: rejuvenating the human gut microbiome by stool banking and autologous fecal microbiota transplantation, that is, collecting the hosts' stool samples at a younger age when they are at optimal health, and cryopreserving the samples in a stool bank for the hosts' own future use. In this article we discuss the motivation, applications, feasibility, and challenges of this solution.}, }
@article {pmid35776638, year = {2022}, author = {Li, X and Wu, P and Zeng, X and Lang, Q and Lin, Y and Huang, H and Qian, P}, title = {Protocol for correlation analysis of the murine gut microbiome and meta-metabolome using 16S rDNA sequencing and UPLC-MS.}, journal = {STAR protocols}, volume = {3}, number = {3}, pages = {101494}, doi = {10.1016/j.xpro.2022.101494}, pmid = {35776638}, issn = {2666-1667}, abstract = {The gut microbiota and metabolites play pivotal roles in the pathobiology of various diseases. Here, we describe a protocol to profile the gut microbiome and meta-metabolome of a mouse disease model for acute graft-versus-host disease. We describe steps for fecal sample collection and processing for 16S sequencing and UPLC-MS. Finally, we detail the steps for data analysis and exhibit multi-omic associations to correlate with pathology. For complete details on the use and execution of this protocol, please refer to Li et al. (2020).}, }
@article {pmid35776086, year = {2022}, author = {Yang, J and Yang, H and Li, Y}, title = {The triple interactions between gut microbiota, mycobiota and host immunity.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-21}, doi = {10.1080/10408398.2022.2094888}, pmid = {35776086}, issn = {1549-7852}, abstract = {The gut microbiome is mainly composed of microbiota and mycobiota, both of which play important roles in the development of the host immune system, metabolic regulation, and maintenance of intestinal homeostasis. With the increasing awareness of the pathogenic essence of infectious, immunodeficiency, and tumor-related diseases, the interactions between gut bacteria, fungi, and host immunity have been shown to directly influence the disease process or final therapeutic outcome, and collaborative and antagonistic relationships are commonly found between bacteria and fungi. Interventions represented by probiotics, prebiotics, engineered probiotics, fecal microbiota transplantation (FMT), and drugs can effectively modulate the triple interactions. In particular, traditional probiotics represented by Bifidobacterium and Lactobacillus and next-generation probiotics represented by Akkermansia muciniphila and Faecalibacterium prausnitzii showed a high enrichment trend in the gut of patients with a high response to inflammation remission and tumor immunotherapy, which predicts the potential medicinal value of these beneficial microbial formulations. However, there are bottlenecks in all these interventions that need to be broken. Meanwhile, further unraveling the underlying mechanisms of the "triple interactions" model can guide precise interventions and ultimately improve the efficiency of interventions on the host gut microbiome and immune modulation, thus directly or indirectly improving anti-inflammatory and tumor immunotherapy effects.}, }
@article {pmid35774395, year = {2022}, author = {Lee, SH and Park, HK and Kang, CD and Choi, DH and Park, SC and Park, JM and Nam, SJ and Chae, GB and Lee, KY and Cho, H and Lee, SJ}, title = {High Dose Intramuscular Vitamin D3 Supplementation Impacts the Gut Microbiota of Patients With Clostridioides Difficile Infection.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {904987}, doi = {10.3389/fcimb.2022.904987}, pmid = {35774395}, issn = {2235-2988}, abstract = {Background and Aim: Current therapeutic strategies for Clostridioides difficile infections (CDI), including oral vancomycin, metronidazole and fecal microbial transplantation, have limited efficacy and treatment failure may occur in as many as one- third of cases. Recent studies have reported that lower concentrations of 25-hydroxyvitamin D are associated with CDI severity and recurrence. However, there have been no studies on microbiota composition after the administration of vitamin D in patients with CDI. Therefore, our study aimed to compare the microbiota composition between the two groups, including eight CDI-positive patients with vitamin D supplementation and ten CDI-positive patients without vitamin D supplementation by using 16S rRNA microbial profiling.<br><br>Methods: Twenty subjects were enrolled in this prospective randomized controlled study. One subject dropped out due to lack of contact with the guardian after discharge and one subject dropped out due to withdrawal of consent. Thus, 18 patients with CDI and vitamin D insufficiency (vitamin D level < 17 ng/mL) were divided into two groups: CDI with vitamin D supplementation (n = 8) and CDI without vitamin D supplementation (control: n = 10). Subjects with vitamin D insufficiency were randomized to receive 200,000 IU intramuscular cholecalciferol whereas patients in the control group received only oral vancomycin. Stool samples were obtained twice before vancomycin was administered and eight weeks after treatment; the V3-V4 16S rRNA metagenomic sequencing was performed using EzBioCloud.<br><br>Results: The alpha diversity of the gut microbiota in the recovery state was significantly higher than that in the CDI state. Analysis of bacterial relative abundance showed significantly lower Proteobacteria and higher Lachnospiraceae, Ruminococcaceae, Akkermansiaceae, and Bifidobacteriaceae in the recovery state. When comparing the control and vitamin D treatment groups after eight weeks, increase in alpha diversity and, abundance of Lachnospiraceae, and Ruminococcaceae exhibited the same trend in both groups. A significant increase in Bifidobacteriaceae and Christensenellaceae was observed in the vitamin D group; Proteobacteria abundance was significantly lower in the vitamin D treatment group after eight weeks than that in the control group.<br><br>Conclusion: Our study confirmed that the increase in the abundance of beneficial bacteria such as Bifidobacteriaceae, and Christensenellaceae were prominently evident during recovery after administration of a high dose of cholecalciferol. These findings indicate that vitamin D administration may be useful in patients with CDI, and further studies with larger sample sizes are required.}, }
@article {pmid35766805, year = {2022}, author = {El Hage Chehade, N and Ghoneim, S and Shah, S and Chahine, A and Mourad, FH and Francis, FF and Binion, DG and Farraye, FA and Hashash, JG}, title = {Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izac135}, pmid = {35766805}, issn = {1536-4844}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been investigated as a treatment option for patients with inflammatory bowel disease with controversial results.We sought to perform a systematic review and meta-analysis to evaluate the benefit of FMT in patients with ulcerative colitis.<br><br>METHODS: Double-blind randomized controlled trials (RCTs) including adult patients with active ulcerative colitis who received either FMT or placebo were eligible for inclusion. Outcomes of interest included the rate of combined clinical and endoscopic remission, endoscopic remission or response, clinical remission or response, and specific adverse events. The results were pooled together using Reviewer Manager 5.4 software. Publication bias was assessed using the Egger's test.<br><br>RESULTS: Six RCTs involving 324 patients were included. Our findings demonstrate that compared with placebo, FMT has significant benefit in inducing combined clinical and endoscopic remission (odds ratio, 4.11; 95% confidence interval, 2.19-7.72; P < .0001). Subgroup analyses of influencing factors showed no differences between pooled or single stool donors (P = .71), fresh or frozen FMT (P = .35), and different routes or frequencies of delivery (P = .80 and .48, respectively). Pre-FMT antibiotics, bowel lavage, concomitant biologic therapy, and topical rectal therapy did not affect combined remission rates (P values of .47, .38, .28, and .40, respectively). Clinical remission or response and endoscopic remission or response were significantly higher in patients who received FMT compared with placebo (P < .05) without any differences in serious or specific adverse events.<br><br>CONCLUSIONS: FMT demonstrated a clinical and endoscopic benefit in the short-term treatment of active ulcerative colitis, with a comparable safety profile to placebo. Future RCTs are required to standardize study protocols and examine data on maintenance therapy.}, }
@article {pmid35766265, year = {2022}, author = {Wang, H and Yao, J and Chen, Y and Wang, Y and Liu, Y and Liao, Y and Liang, Z and Dong, YH and Qu, M and Ge, X and Zhou, X}, title = {Gut dysbacteriosis attenuates resistance to Mycobacterium bovis infection by decreasing Cyclooxygenase 2 to inhibit endoplasmic reticulum stress.}, journal = {Emerging microbes &amp; infections}, volume = {}, number = {}, pages = {1-31}, doi = {10.1080/22221751.2022.2096486}, pmid = {35766265}, issn = {2222-1751}, abstract = {AbstractThe role of gut microbiota has been described as an important influencer of the immune system. Gut-lung axis is critical in the prevention of mycobacterium infection, but the specific mechanism by which dysbiosis affects tuberculosis have not been reported. In this study, we attempted to provide more information on how the gut-lung axis contributes to Mycobacterium bovis (M. bovis) infection. Mice pre-treated with broad-spectrum antibiotics cocktail (Abx) to induce gut dysbiosis. Interestingly, dysbiosis of microbes showed a significant increase in the bacterial burden in lungs, and inhibited the level of COX-2. After fecal transplantation, cyclooxygenase 2（COX-2） expression was restored and the inflammatory lesion in the lung was reduced. Further research found that the deficiency of COX-2 inhibited endoplasmic reticulum stress (ER-stress). This mechanism was completed by COX-2 interaction with BIP. Moreover, we found a positive feedback mechanism by which blocking ER-stress could reduce COX-2 levels via the NF-κB pathway. Taken together, we reveal for the first time gut dysbacteriosis exacerbates M. bovis disease by limiting COX-2 /ER-stress pathway. The finding strengthens the foundation of gut microbiota-targeted therapy for tuberculosis treatment.}, }
@article {pmid35765243, year = {2022}, author = {Hu, LP and Huang, W and Wang, X and Xu, C and Qin, WT and Li, D and Tian, G and Li, Q and Zhou, Y and Chen, S and Nie, HZ and Hao, Y and Song, J and Zhang, XL and Sundquist, J and Sundquist, K and Li, J and Jiang, SH and Zhang, ZG and Ji, J}, title = {Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2022.06.015}, pmid = {35765243}, issn = {1525-0024}, abstract = {Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found that they had a decreased risk of death (hazard ratio=0.50) and metastasis (hazard ratio=0.44) compared with patients without terbinafine administration. In multiple mouse models of CRC, administration of terbinafine decreased the fungal load, the fungus-induced myeloid-derived suppressor cell (MDSC) expansion, and the tumor burden. Fecal microbiota transplantation from mice without terbinafine treatment reversed MDSC infiltration and partially restored tumor proliferation. Mechanistically, terbinafine directly impaired tumor cell proliferation by reducing the ratio of nicotinamide adenine dinucleotide phosphate (NADP+) to reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suppressing the activity of glucose-6-phosphate dehydrogenase (G6PD), resulting in nucleotide synthesis disruption, deoxyribonucleotide (dNTP) starvation and cell cycle arrest. Collectively, terbinafine can inhibit CRC by reversing fungal dysbiosis, suppressing tumor cell proliferation, inhibiting fungus-induced MDSC infiltration, and restoring antitumor immune response.}, }
@article {pmid35764988, year = {2022}, author = {Ma, P and Mo, R and Liao, H and Qiu, C and Wu, G and Yang, C and Zhang, Y and Zhao, Y and Song, XJ}, title = {Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {169}, pmid = {35764988}, issn = {1742-2094}, support = {KQTD20200820113040070//Science, Technology and Innovation Commission of Shenzhen Municipality/ ; JCYJ20200109141433384//The Foundation of Shenzhen Science and Technology Innovation Committee/ ; 7191001//Natural Science Foundation of Beijing Municipality/ ; NFSC81971062//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Gut microbiota has been found involved in neuronal functions and neurological disorders. Whether and how gut microbiota impacts chronic somatic pain disorders remain elusive.<br><br>METHODS: Neuropathic pain was produced by different forms of injury or diseases, the chronic constriction injury (CCI) of the sciatic nerves, oxaliplatin (OXA) chemotherapy, and streptozocin (STZ)-induced diabetes in mice. Continuous feeding of antibiotics (ABX) cocktail was used to cause major depletion of the gut microbiota. Fecal microbiota, biochemical changes in the spinal cord and dorsal root ganglion (DRG), and the behaviorally expressed painful syndromes were assessed.<br><br>RESULTS: Under condition of gut microbiota depletion, CCI, OXA, or STZ treatment-induced thermal hyperalgesia or mechanical allodynia were prevented or completely suppressed. Gut microbiota depletion also prevented CCI or STZ treatment-induced glial cell activation in the spinal cord and inhibited cytokine production in DRG in OXA model. Interestingly, STZ treatment failed to induce the diabetic high blood glucose and painful hypersensitivity in animals with the gut microbiota depletion. ABX feeding starting simultaneously with CCI, OXA, or STZ treatment resulted in instant analgesia in all the animals. ABX feeding starting after establishment of the neuropathic pain in CCI- and STZ-, but not OXA-treated animals produced significant alleviation of the thermal hyeralgesia or mechanical allodynia. Transplantation of fecal bacteria from SPF mice to ABX-treated mice partially restored the gut microbiota and fully rescued the behaviorally expressed neuropathic pain, of which, Akkermansia, Bacteroides, and Desulfovibrionaceae phylus may play a key role.<br><br>CONCLUSION: This study demonstrates distinct roles of gut microbiota in the pathogenesis of chronic painful conditions with nerve injury, chemotherapy and diabetic neuropathy and supports the clinical significance of fecal bacteria transplantation.}, }
@article {pmid35760542, year = {2022}, author = {Hurych, J and Vejmelka, J and Hlinakova, L and Kramna, L and Larionov, V and Kulich, M and Cinek, O and Kohout, P}, title = {Protocol for faecal microbiota transplantation in irritable bowel syndrome: the MISCEAT study - a randomised, double-blind cross-over study using mixed microbiota from healthy donors.}, journal = {BMJ open}, volume = {12}, number = {6}, pages = {e056594}, doi = {10.1136/bmjopen-2021-056594}, pmid = {35760542}, issn = {2044-6055}, mesh = {Cross-Over Studies ; Diarrhea/therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/methods ; Humans ; *Irritable Bowel Syndrome/therapy ; *Microbiota ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Several studies have demonstrated dysbiosis in irritable bowel syndrome (IBS). Therefore, faecal microbiota transplantation, whose effect and safety have been proven in Clostridioides difficile infections, may hold promise in other conditions, including IBS. Our study will examine the effectiveness of stool transfer with artificially increased microbial diversity in IBS treatment.<br><br>METHODS AND ANALYSIS: A three-group, double-blind,randomised, cross-over, placebo-controlled study of two pairs of gut microbiota transfer will be conducted in 99 patients with diarrhoeal or mixed type of IBS. Patients aged 18-65 will be randomised into three equally sized groups: group A will first receive two enemas of study microbiota mixture (deep-frozen stored stool microbiota mixed from eight healthy donors); after 8 weeks, they will receive two enemas with placebo (autoclaved microbiota mixture), whereas group B will first receive placebo, then microbiota mixture. Finally, group C will receive placebos only. The IBS Severity Symptom Score (IBS-SSS) questionnaires will be collected at baseline and then at weeks 3, 5, 8, 11, 13, 32. Faecal bacteriome will be profiled before and regularly after interventions using 16S rDNA next-generation sequencing. Food records, dietary questionnaires, anthropometry, bioimpedance, biochemistry and haematology workup will be obtained at study visits during the follow-up period. The primary outcome is the change in the IBS-SSS between the baseline and 4 weeks after the intervention for each patient compared with placebo. Secondary outcomes are IBS-SSS at 2 weeks after the intervention and 32 weeks compared with placebo and changes in the number of loose stools, Bristol stool scale, abdominal pain and bloating, anthropometric parameters, psychological evaluation and the gut microbiome composition.<br><br>ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Thomayer University Hospital, Czechia (G-18-26); study results will be published in peer-reviewed journals and presented at international conferences and patient group meetings.<br><br>TRIAL REGISTRATION NUMBER: NCT04899869.}, }
@article {pmid35759305, year = {2022}, author = {Davis, BT and Chen, Z and Islam, MBAR and Timken, ME and Procissi, D and Schwulst, SJ}, title = {Fecal Microbiota Transfer Attenuates Gut Dysbiosis and Functional Deficits After Traumatic Brain Injury.}, journal = {Shock (Augusta, Ga.)}, volume = {57}, number = {6}, pages = {251-259}, doi = {10.1097/SHK.0000000000001934}, pmid = {35759305}, issn = {1540-0514}, mesh = {Animals ; *Brain Injuries, Traumatic/pathology ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Humans ; Mice ; *Neurodegenerative Diseases ; }, abstract = {BACKGROUND: Traumatic brain injury (TBI) is an underrecognized public health threat. Survivors of TBI often suffer long-term neurocognitive deficits leading to the progressive onset of neurodegenerative disease. Recent data suggests that the gut-brain axis is complicit in this process. However, no study has specifically addressed whether fecal microbiota transfer (FMT) attenuates neurologic deficits after TBI.<br><br>HYPOTHESIS: We hypothesized that fecal microbiota transfer would attenuate neurocognitive, anatomic, and pathologic deficits after TBI.<br><br>METHODS: C57Bl/6 mice were subjected to severe TBI (n = 20) or sham-injury (n = 20) via an open-head controlled cortical impact. Post-injury, this cohort of mice underwent weekly oral gavage with a slurry of healthy mouse stool or vehicle alone beginning 1 h post-TBI followed by behavioral testing and neuropathologic analysis. 16S ribosomal RNA sequencing of fecal samples was performed to characterize gut microbial community structure pre- and post-injury. Zero maze and open field testing were used to evaluate post-traumatic anxiety, exploratory behavior, and generalized activity. 3D, contrast enhanced, magnetic resonance imaging was used to determine differences in cortical volume loss and white matter connectivity. Prior to euthanasia, brains were harvested for neuropathologic analysis.<br><br>RESULTS: Fecal microbiome analysis revealed a large variance between TBI, and sham animals treated with vehicle, while FMT treated TBI mice had restoration of gut dysbiosis back to levels of control mice. Neurocognitive testing demonstrated a rescue of normal anxiety-like and exploratory behavior in TBI mice treated with FMT. FMT treated TBI mice spent a greater percentage of time (22%, P = 0.0001) in the center regions of the Open Field as compared to vehicle treated TBI mice (13%). Vehicle-treated TBI animals also spent less time (19%) in the open areas of zero maze than FMT treated TBI mice (30%, P = 0.0001). Comparing in TBI mice treated with FMT, MRI demonstrated a marked attenuation in ventriculomegaly (P < 0.002) and a significant change in fractional anisotropy (i.e., loss of white matter connectivity) (P < 0.0001). Histologic analysis of brain sections revealed a FMT- injury dependent interaction in the microglia/macrophage-specific ionized calcium-binding protein, Iba1 (P = 0.002).<br><br>CONCLUSION: These data suggest that restoring a pre-injury gut microbial community structure may be a promising therapeutic intervention after TBI.}, }
@article {pmid35731859, year = {2022}, author = {Borody, TJ and Dolai, S and Gunaratne, AW and Clancy, RL}, title = {Targeting the microbiome in Crohn's disease.}, journal = {Expert review of clinical immunology}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/1744666X.2022.2093186}, pmid = {35731859}, issn = {1744-8409}, }
@article {pmid35763604, year = {2022}, author = {Rakotonirina, A and Galperine, T and Allémann, E}, title = {Fecal microbiota transplantation: a review on current formulations in Clostridioides difficile infection and future outlooks.}, journal = {Expert opinion on biological therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14712598.2022.2095901}, pmid = {35763604}, issn = {1744-7682}, abstract = {INTRODUCTION: The role of the gut microbiota in health and the pathogenesis of several diseases has been highlighted in recent years. Even though the precise mechanisms involving the microbiome in these ailments are still unclear, microbiota-modulating therapies have been developed. Fecal microbiota transplantation (FMT) has shown significant results against Clostridioides difficile infection (CDI), and its potential has been investigated for other diseases. Unfortunately, the technical aspects of the treatment make it difficult to implement. Pharmaceutical technology approaches to encapsulate microorganisms could play an important role in providing this treatment and render the treatment modalities easier to handle.<br><br>AREAS COVERED: After an overview of CDI, this narrative review aims to discuss the current formulations for FMT and specifically addresses the technical aspects of the treatment. This review also distinguishes itself by focusing on the hurdles and emphasizing the possible improvements using pharmaceutical technologies.<br><br>EXPERT OPINION: FMT is an efficient treatment for recurrent CDI. However, its standardization is overlooked. The approach of industrial and hospital preparations of FMT are different, but both show promise in their respective methodologies. Novel FMT formulations could enable further research on dysbiotic diseases in the future.}, }
@article {pmid35762770, year = {2022}, author = {Ma, L and Shen, Q and Lyu, W and Lv, L and Wang, W and Yu, M and Yang, H and Tao, S and Xiao, Y}, title = {Clostridium butyricum and Its Derived Extracellular Vesicles Modulate Gut Homeostasis and Ameliorate Acute Experimental Colitis.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0136822}, doi = {10.1128/spectrum.01368-22}, pmid = {35762770}, issn = {2165-0497}, abstract = {Microbiological treatments are expected to have a role in the future management of inflammatory bowel disease (IBD). Clostridium butyricum (C. butyricum) is a probiotic microorganism that exhibits beneficial effects on various disease conditions. Although many studies have revealed that C. butyricum provides protective effects in mice with colitis, the way C. butyricum establishes beneficial results in the host remains unclear. In this study, we investigated the mechanisms by which C. butyricum modifies the gut microbiota, produces bacterial metabolites that may be involved, and, specifically, how microbial extracellular vesicles (EVs) positively influence IBD, using a dextran sulfate sodium (DSS)-induced colitis murine model in mice. First, we showed that C. butyricum provides a protective effect against colitis, as evidenced by the prevention of body weight loss, a reduction in the disease activity index (DAI) score, a shortened colon length, decreased histology score, and an improved gut barrier function, accompanied by reduced levels of pathogenic bacteria, including Escherichia/Shigella, and an increased relative abundance of butyrate-producing Clostridium sensu stricto-1 and Butyricicoccus. Second, we also confirmed that the gut microbiota and metabolites produced by C. butyricum played key roles in the attenuation of DSS-induced experimental colitis, as supported by the profound alleviation of colitis effects following fecal transplantation or fecal filtrate insertion supplied from C. butyricum-treated mice. Finally, C. butyricum-derived EVs protected the gut barrier function, improved gut microbiota homeostasis in ulcerative colitis, and contributed to overall colitis alleviation. IMPORTANCE This study indicated that C. butyricum provided a prevention effect against colitis mice, which involved protection of the intestinal barrier and positively regulating gut microbiota. Furthermore, we confirmed that the gut microbiota and metabolites that were induced by C. butyricum also contributed to the attenuation of DSS-induced colitis. Importantly, C. butyricum-derived EVs showed an effective impact in alleviating colitis.}, }
@article {pmid35611465, year = {2022}, author = {Gulliver, EL and Young, RB and Chonwerawong, M and D'Adamo, GL and Thomason, T and Widdop, JT and Rutten, EL and Rossetto Marcelino, V and Bryant, RV and Costello, SP and O'Brien, CL and Hold, GL and Giles, EM and Forster, SC}, title = {Review article: the future of microbiome-based therapeutics.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {56}, number = {2}, pages = {192-208}, doi = {10.1111/apt.17049}, pmid = {35611465}, issn = {1365-2036}, support = {DP190101504//Australian Research Council/ ; //Victorian Government/ ; }, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {BACKGROUND: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic.<br><br>AIM: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development.<br><br>METHODS: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'.<br><br>RESULTS: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics.<br><br>CONCLUSIONS: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.}, }
@article {pmid35759806, year = {2022}, author = {Li, Z and Ke, H and Lin, Q and Shen, Z and Chen, Y}, title = {Global trends in gut microbiota and clostridioides difficile infection research: A visualized study.}, journal = {Journal of infection and public health}, volume = {15}, number = {7}, pages = {806-815}, doi = {10.1016/j.jiph.2022.06.011}, pmid = {35759806}, issn = {1876-035X}, abstract = {BACKGROUND: Clostridioides (clostridium) difficile infection (CDI) is the most common cause of nosocomial diarrheal disease, which has become a public health problem worldwide; gut dysbiosis plays a central role in its pathophysiology. This study conducted a bibliometric analysis of publications on gut microbiota and CDI to summarize the current status of research including research hotspots.<br><br>METHODS: Relevant publications from January 2004 to February 2022 were identified from the Web of Science Core Collection. Three bibliometric tools were used to perform visualization analyses.<br><br>RESULTS: A total of 1983 publications were analyzed. Annual publications increased from 11 in 2004-237 in 2021, with the US being the leading producer (47.55 % of all papers). EG Pamer had the highest average citations per article (average citations per item = 153.03, H-index = 29). Frontiers in Microbiology published the most papers. The main research foci were "fecal microbiota transplantation," "colonization resistance," and "multidrug-resistant bacteria." The keywords with the highest frequency in recent years include: gut dysbiosis, antibiotic resistance, bile-acids, 16 s sequencing, multidrug-resistant bacteria, and short chain fatty acids.<br><br>CONCLUSIONS: Gut microbiota and CDI is likely to remain a prominent area of research in the foreseeable future. Current research hotspots ("fecal microbiota transplantation," "colonization resistance," and "multidrug-resistant bacteria") should receive even more attention in future studies.}, }
@article {pmid35759388, year = {2022}, author = {Jiang, L and Hong, Y and Xiao, P and Wang, X and Zhang, J and Liu, E and Li, H and Cai, Z}, title = {The Role of Fecal Microbiota in Liver Toxicity Induced by Perfluorooctane Sulfonate in Male and Female Mice.}, journal = {Environmental health perspectives}, volume = {130}, number = {6}, pages = {67009}, doi = {10.1289/EHP10281}, pmid = {35759388}, issn = {1552-9924}, abstract = {BACKGROUND: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that can cause hepatotoxicity. The underlying toxicological mechanism remains to be investigated. Given the critical role of fecal microbiota in liver function, it is possible that fecal microbiota may contribute to the liver toxicity induced by PFOS.<br><br>OBJECTIVES: We aimed to investigate the role of liver-fecal microbiota axis in modulating PFOS-induced liver injury in mice.<br><br>METHODS: Male and female mice were exposed to PFOS or vehicle for 14 d. In this investigation, 16S rDNA sequencing and metabolomic profiling were performed to identify the perturbed fecal microbiota and altered metabolites with PFOS exposure. In addition, antibiotic treatment, fecal microbiota transplantation, and bacterial administration were conducted to validate the causal role of fecal microbiota in mediating PFOS-induced liver injury and explore the potential underlying mechanisms.<br><br>RESULTS: Both male and female mice exposed to PFOS exhibited liver inflammation and steatosis, which were accompanied by fecal microbiota dysbiosis and the disturbance of amino acid metabolism in comparison with control groups. The hepatic lesions were fecal microbiota-dependent, as supported by antibiotic treatment and fecal microbiota transplantation. Mice with altered fecal microbiota in antibiotic treatment or fecal microbiota transplantation experiments exhibited altered arginine concentrations in the liver and feces. Notably, we observed sex-specific lower levels of key microbiota, including Lactobacillus, Enterococcus, and Akkermansia. Mice treated with specific bacteria showed lower arginine levels and lower expression of the phosphorylated mTOR and P70S6K, suggesting lower activity of the related pathway and mitigation of the pathological differences observed in PFOS-exposed mice.<br><br>CONCLUSIONS: Our study demonstrated the critical role of the fecal microbiota in PFOS-induced liver injury in mice. We also identified several critical bacteria that could protect against liver injury induced by PFOS in male and female mice. Our present research provided novel insights into the mechanism of PFOS-induced liver injury in mice. https://doi.org/10.1289/EHP10281.}, }
@article {pmid35757563, year = {2020}, author = {Soto Chervin, C and Gajewski, TF}, title = {Microbiome-based interventions: therapeutic strategies in cancer immunotherapy.}, journal = {Immuno-oncology technology}, volume = {8}, number = {}, pages = {12-20}, doi = {10.1016/j.iotech.2020.11.001}, pmid = {35757563}, issn = {2590-0188}, abstract = {The composition of the commensal microbiota has recently emerged as a key element influencing the efficacy of cancer treatments. It has become apparent that the interplay between the microbiome and immune system within the host influences the response to immunotherapy, particularly immune checkpoint inhibitor therapy. Identifying the key components of the gut microbiota that influence this response is paramount for designing therapeutic interventions to enhance the response to cancer therapy. This review will discuss strategies being considered to modulate the gut microbiota, including fecal microbiota transplantation, administration of defined bacterial isolates as well as bacterial consortia, supplementation with probiotics, and lifestyle modifications such as dietary changes. Understanding the influence of the complex variables of the human microbiota on the effectiveness of cancer therapy will help drive the clinical design of microbial-based interventions in the field of oncology.}, }
@article {pmid35756645, year = {2022}, author = {Chen, M and Liu, M and Li, C and Peng, S and Li, Y and Xu, X and Sun, M and Sun, X}, title = {Fecal Microbiota Transplantation Effectively Cures a Patient With Severe Bleeding Immune Checkpoint Inhibitor-Associated Colitis and a Short Review.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {913217}, doi = {10.3389/fonc.2022.913217}, pmid = {35756645}, issn = {2234-943X}, abstract = {Immune checkpoint inhibitors (ICIs) have opened up a new way for tumor therapy but simultaneously led to the occurrence of immune-related adverse events. We report a case of successful treatment of PD-1 inhibitor-associated colitis with fecal microbiota transplantation (FMT). The patient was a palatal malignant melanoma who developed diarrhea and hematochezia accompanied by fever, gastrointestinal bleeding, and infection after the third treatment with PD-1 (Toripalimab). The patient received general treatment unsuccessful, corticosteroid therapy after initial success but rapid loss of response, and finally successful treatment after fecal microbiota transplantation.}, }
@article {pmid35755849, year = {2022}, author = {Aira, A and Rubio, E and Ruiz, A and Vergara, A and Casals-Pascual, C and Rico, V and Suñé-Negre, JM and Soriano, A}, title = {New Procedure to Maintain Fecal Microbiota in a Dry Matrix Ready to Encapsulate.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {899257}, doi = {10.3389/fcimb.2022.899257}, pmid = {35755849}, issn = {2235-2988}, abstract = {Fecal microbiota transplantation (FMT) is one of the recommended treatments for recurrent Clostridioides difficile infection, but endoscopy and available oral formulations still have several limitations in their preparation, storage, and administration. The need for a viable oral formulation that facilitates the implementation of this highly effective therapy in different settings has led us to test the microcrystalline cellulose particles as an adsorbent of concentrated filtered fresh feces in comparison to lyophilized feces. This free-flowing material can provide protection to bacteria and results in a dried product able to maintain the viability of the microbiota for a long time. Adsorbate formulation showed a stabilizing effect in gut microbiota, maintaining bacteria viability and preserving its diversity, and is a competitive option for lyophilized capsules.}, }
@article {pmid35753395, year = {2022}, author = {Li, X and Xiao, F and Li, Y and Hu, H and Xiao, Y and Xu, Q and Li, D and Yu, G and Wang, Y and Zhang, T}, title = {Characteristics and management of children with Clostridiodes difficile infection at a tertiary pediatric hospital in China.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {}, number = {}, pages = {102380}, doi = {10.1016/j.bjid.2022.102380}, pmid = {35753395}, issn = {1678-4391}, abstract = {BACKGROUND: Clostridiodes difficile infection (CDI) is one of the most common causes of antibiotic-associated diarrhea in children. Conventional antibiotics and emerging fecal microbiota transplantation (FMT) are used to treat CDI.<br><br>METHODS: Children with CDI admitted to the Shanghai Children's Hospital, from September 2014 to September 2020, were retrospectively included to this observational study. Pediatric patients were assigned as initial CDI and recurrent CDI (RCDI), and symptoms, comorbidities, imaging findings, laboratory tests, and treatments were systematically recorded and analyzed.<br><br>RESULTS: Of 109 pediatric patients with CDI, 58 were boys (53.2%), and the median age was 5 years (range, 2-9 years). The main clinical symptoms of CDI children were diarrhea (109/109, 100%), hematochezia (55/109, 50.46%), abdominal pain (40/109, 36.70%); fever, pseudomembrane, vomit, and bloating were observed in 39 (35.78%), 33 (30.28%), and 24 (22.02%) patients, respectively. For the primary therapy with conventional antibiotics, 68 patients received metronidazole, and 41 patients received vancomycin. RCDI occurred in 48.53% (33/68) of those initially treated with metronidazole compared with 46.33% (19/41) of those initially treated with vancomycin (p=0.825). The total resolution rate of FMT for RCDI children was significantly higher than with vancomycin treatment (28/29, 96.55% vs 11/23, 47.83%, p < 0.001). There were no serious adverse events (SAEs) reported after two months of FMT.<br><br>CONCLUSIONS: The major manifestations of children with CDI were diarrhea, hematochezia, and abdominal pain. The cure rate of FMT for pediatric RCDI is superior to vancomycin treatment.}, }
@article {pmid35745257, year = {2022}, author = {Bian, J and Liebert, A and Bicknell, B and Chen, XM and Huang, C and Pollock, CA}, title = {Faecal Microbiota Transplantation and Chronic Kidney Disease.}, journal = {Nutrients}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/nu14122528}, pmid = {35745257}, issn = {2072-6643}, mesh = {*Clostridium Infections ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation/methods ; Feces ; Humans ; Renal Dialysis ; *Renal Insufficiency, Chronic/therapy ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) has attracted increasing attention as an intervention in many clinical conditions, including autoimmune, enteroendocrine, gastroenterological, and neurological diseases. For years, FMT has been an effective second-line treatment for Clostridium difficile infection (CDI) with beneficial outcomes. FMT is also promising in improving bowel diseases, such as ulcerative colitis (UC). Pre-clinical and clinical studies suggest that this microbiota-based intervention may influence the development and progression of chronic kidney disease (CKD) via modifying a dysregulated gut-kidney axis. Despite the high morbidity and mortality due to CKD, there are limited options for treatment until end-stage kidney disease occurs, which results in death, dialysis, or kidney transplantation. This imposes a significant financial and health burden on the individual, their families and careers, and the health system. Recent studies have suggested that strategies to reverse gut dysbiosis using FMT are a promising therapy in CKD. This review summarises the preclinical and clinical evidence and postulates the potential therapeutic effect of FMT in the management of CKD.}, }
@article {pmid35739018, year = {2022}, author = {Carneiro, PV and Montenegro, NA and Lana, A and Amato, AA and Santos, GM}, title = {Lipids from gut microbiota: pursuing a personalized treatment.}, journal = {Trends in molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molmed.2022.06.001}, pmid = {35739018}, issn = {1471-499X}, abstract = {The discovery of microbiome metabolites has enlivened the field of fecal transplantation for therapeutic purposes. However, the transfer of pathogenic living organisms was recently observed to limit its therapeutic potential by increasing the risk of infection. Lipids produced by gut microbiota enter the circulation and control many phenotypic changes associated with microbiota composition. Fecal lipids significantly impact the regulation of several cell signaling pathways, including inflammation. Focusing on these molecules, we review how bioactive gut microbiota-associated lipids affect cellular functioning and clinical outcome. Here, we interrogate whether the gut microbiota can be considered a cutting-edge biotechnological tool for rapid metabolic engineering of meaningful lipids to offer a novel personalized therapy.}, }
@article {pmid35751882, year = {2022}, author = {Liu, T and Li, YL and Zhou, LJ and Sun, XN and Wang, YL and Du, LJ and Liu, Y and Zhu, H and Chen, BY and Sun, JY and Liu, Y and Xu, S and Ye, HL and Huang, SJ and Wang, X and Li, B and Duan, SZ}, title = {Mineralocorticoid Receptor Deficiency in Treg Cells Ameliorates DSS-Induced Colitis in a Gut Microbiota-Dependent Manner.}, journal = {Immunology}, volume = {}, number = {}, pages = {}, doi = {10.1111/imm.13522}, pmid = {35751882}, issn = {1365-2567}, abstract = {Mineralocorticoid receptor (MR) is a classic nuclear receptor and an effective drug target in the cardiovascular system. The function of MR in immune cells such as macrophages and T cells has been increasingly appreciated. The aim of this study was to investigate the function of Treg MR in the process of inflammatory bowel disease (IBD). We treated Treg MR-deficient (MRflox/flox Foxp3YFP-Cre , KO) mice and control (Foxp3YFP-Cre , WT) mice with dextran sodium sulphate (DSS) to induce colitis and found that the severity of DSS-induced colitis was markedly alleviated in Treg MR-deficient mice, accompanied by reduced production of inflammatory cytokines, and relieved infiltration of monocytes, neutrophils and interferon γ+ T cells in colon lamina propria. Fecal microbiota of mice with colitis was analyzed by 16S rRNA gene sequencing and the composition of gut microbiota was vastly changed in Treg MR-deficient mice. Furthermore, depletion of gut microbiota by antibiotics abolished the protective effects of Treg MR deficiency and resulted in similar severity of DSS-induced colitis in WT and KO mice. Fecal microbiota transplantation from KO mice attenuated DSS-induced colitis characterized by alleviated inflammatory infiltration compared to that from WT mice. Hence, our study demonstrates that Treg MR deficiency protects against DSS-induced colitis by attenuation of colonic inflammatory infiltration. Gut microbiota is both sufficient and necessary for Treg MR deficiency to exert the beneficial effects.}, }
@article {pmid35748460, year = {2022}, author = {Catalán-Serra, I and Ricanek, P and Grimstad, T}, title = {"Out of the box" new therapeutic strategies for Crohn´s disease: moving beyond biologics.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {}, number = {}, pages = {}, doi = {10.17235/reed.2022.9010/2022}, pmid = {35748460}, issn = {1130-0108}, abstract = {New treatment options beyond immunosuppression have emerged in recent years for patients with Crohn´s disease (CD), a chronic systemic condition affecting primarily the gut with great impact in the quality of life. The cause of CD is largely unknown, and a curative treatment is not yet available. In addition, despite the growing therapeutic armamentarium in recent years almost half of the patients don´t achieve a sustained response over time. Thus, new therapeutic strategies are urgently needed. In this review, we discuss the current state of promising new "out of the box" possibilities to control chronic inflammation beyond current pharmacological treatments, including: exclusive enteral nutrition, specific diets, cell therapies using T regs, hyperbaric oxygen, fecal microbiota transplantation, phage therapy, helminths, cannabis and vagal nerve stimulation. The exploration of original and novel therapeutic modalities is key to address their potential as main or complementary treatments in selected CD populations in order to increase efficacy, minimize side effects and improve quality of life of patients.}, }
@article {pmid35745805, year = {2022}, author = {Yang, C and Sung, J and Long, D and Alghoul, Z and Merlin, D}, title = {Prevention of Ulcerative Colitis by Autologous Metabolite Transfer from Colitogenic Microbiota Treated with Lipid Nanoparticles Encapsulating an Anti-Inflammatory Drug Candidate.}, journal = {Pharmaceutics}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/pharmaceutics14061233}, pmid = {35745805}, issn = {1999-4923}, support = {RO1-DK-116306/DK/NIDDK NIH HHS/United States ; RO1-DK-107739/DK/NIDDK NIH HHS/United States ; 689659//Crohn's and Colitis Foundation/ ; BX004476//Atlanta VA Medical Center/ ; BX002526//Atlanta VA Medical Center/ ; }, abstract = {Modulating the gut microbiota composition is a potent approach to treat various chronic diseases, including obesity, metabolic syndrome, and ulcerative colitis (UC). However, the current methods, such as fecal microbiota transplantation, carry a risk of serious infections due to the transmission of multi-drug-resistant organisms. Here, we developed an organism-free strategy in which the gut microbiota is modulated ex vivo and microbiota-secreted metabolites are transferred back to the host. Using feces collected from the interleukin-10 (IL-10) knockout mouse model of chronic UC, we found that a drug candidate (M13)-loaded natural-lipid nanoparticle (M13/nLNP) modified the composition of the ex vivo-cultured inflamed gut microbiota and its secreted metabolites. Principal coordinate analysis (PCoA) showed that M13/nLNP shifted the inflamed microbiota composition toward the non-inflamed direction. This compositional modification induced significant changes in the chemical profiles of secreted metabolites, which proved to be anti-inflammatory against in vitro-cultured NF-κβ reporter cells. Further, when these metabolites were orally administered to mice, they established strong protection against the formation of chronic inflammation. Our study demonstrates that ex vivo modulation of microbiota using M13/nLNP effectively reshaped the microbial secreted metabolites and that oral transfer of these metabolites might be an effective and safe therapeutic approach for preventing chronic UC.}, }
@article {pmid35745496, year = {2022}, author = {Alam, MJ and Xie, L and Yap, YA and Marques, FZ and Robert, R}, title = {Manipulating Microbiota to Treat Atopic Dermatitis: Functions and Therapies.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, doi = {10.3390/pathogens11060642}, pmid = {35745496}, issn = {2076-0817}, support = {105663/WT_/Wellcome Trust/United Kingdom ; //Senior Medical Research Fellowship from the Sylvia and Charles Viertel Charitable Foundation/ ; //Monash Graduate Scholarship from Monash University, Australia/ ; }, abstract = {Atopic dermatitis (AD) is a globally prevalent skin inflammation with a particular impact on children. Current therapies for AD are challenged by the limited armamentarium and the high heterogeneity of the disease. A novel promising therapeutic target for AD is the microbiota. Numerous studies have highlighted the involvement of the skin and gut microbiota in the pathogenesis of AD. The resident microbiota at these two epithelial tissues can modulate skin barrier functions and host immune responses, thus regulating AD progression. For example, the pathogenic roles of Staphylococcus aureus in the skin are well-established, making this bacterium an attractive target for AD treatment. Targeting the gut microbiota is another therapeutic strategy for AD. Multiple oral supplements with prebiotics, probiotics, postbiotics, and synbiotics have demonstrated promising efficacy in both AD prevention and treatment. In this review, we summarize the association of microbiota dysbiosis in both the skin and gut with AD, and the current knowledge of the functions of commensal microbiota in AD pathogenesis. Furthermore, we discuss the existing therapies in manipulating both the skin and gut commensal microbiota to prevent or treat AD. We also propose potential novel therapies based on the cutting-edge progress in this area.}, }
@article {pmid35739196, year = {2022}, author = {Qiao, L and Zhang, X and Pi, S and Chang, J and Dou, X and Yan, S and Song, X and Chen, Y and Zeng, X and Zhu, L and Xu, C}, title = {Dietary supplementation with biogenic selenium nanoparticles alleviate oxidative stress-induced intestinal barrier dysfunction.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {30}, pmid = {35739196}, issn = {2396-8370}, support = {32072746//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Selenium (Se) is an essential micronutrient that promotes body health. Endemic Se deficiency is a major nutritional challenge worldwide. The low toxicity, high bioavailability, and unique properties of biogenic Se nanoparticles (SeNPs) allow them to be used as a therapeutic drug and Se nutritional supplement. This study was conducted to investigate the regulatory effects of dietary SeNPs supplementation on the oxidative stress-induced intestinal barrier dysfunction and its association with mitochondrial function and gut microbiota in mice. The effects of dietary SeNPs on intestinal barrier function and antioxidant capacity and its correlation with gut microbiota were further evaluated by a fecal microbiota transplantation experiment. The results showed that Se deficiency caused a redox imbalance, increased the levels of pro-inflammatory cytokines, altered the composition of the gut microbiota, and impaired mitochondrial structure and function, and intestinal barrier injury. Exogenous supplementation with biogenic SeNPs effectively alleviated diquat-induced intestinal barrier dysfunction by enhancing the antioxidant capacity, inhibiting the overproduction of reactive oxygen species (ROS), preventing the impairment of mitochondrial structure and function, regulating the immune response, maintaining intestinal microbiota homeostasis by regulating nuclear factor (erythroid-derived-2)-like 2 (Nrf2)-mediated NLR family pyrin domain containing 3 (NLRP3) signaling pathway. In addition, Se deficiency resulted in a gut microbiota phenotype that is more susceptible to diquat-induced intestinal barrier dysfunction. Supranutritional SeNPs intake can optimize the gut microbiota to protect against intestinal dysfunctions. This study demonstrates that dietary supplementation of SeNPs can prevent oxidative stress-induced intestinal barrier dysfunction through its regulation of mitochondria and gut microbiota.}, }
@article {pmid35737457, year = {2022}, author = {Rei, D and Saha, S and Haddad, M and Haider Rubio, A and Perlaza, BL and Berard, M and Ungeheuer, MN and Sokol, H and Lledo, PM}, title = {Age-associated gut microbiota impairs hippocampus-dependent memory in a vagus-dependent manner.}, journal = {JCI insight}, volume = {}, number = {}, pages = {}, doi = {10.1172/jci.insight.147700}, pmid = {35737457}, issn = {2379-3708}, abstract = {Aging is known to be associated with hippocampus-dependent memory decline, but the underlying causes of this age-related memory impairment remain yet highly debated. Here we showed that fecal microbiota transplantation (FMT) from aged, but not young, animal donors in young mice is sufficient to trigger profound hippocampal alterations including astrogliosis, decreased adult neurogenesis, decreased novelty-induced neuronal activation and impairment in hippocampus-dependent memory. Furthermore, similar alterations were reported when mice were subjected to an FMT from aged human donors. To decipher the mechanisms involved in mediating these microbiota-induced effects on brain function, we mapped the vagus nerve (VN)-related neuronal activity patterns and report that aged-mice FM transplanted animals showed a reduction in neuronal activity in the ascending VN output brain structure, whether under basal condition or after VN stimulation. Targeted pharmacogenetic manipulation of VN-ascending neurons demonstrated that the decrease in vagal activity is detrimental to hippocampal functions. In contrast, increasing vagal ascending activity alleviated the adverse effects of aged mice FMT on hippocampal functions, and had a pro-mnesic effect in aged mice. Thus, pharmacogenetic VN stimulation is a potential therapeutic strategy to lessen microbiota-dependent age-associated impairments in hippocampal functions.}, }
@article {pmid35580364, year = {2022}, author = {Thakur, S and Sheppard, JD}, title = {Gut Microbiome and Its Influence On Ocular Surface and Ocular Surface Diseases.}, journal = {Eye &amp; contact lens}, volume = {48}, number = {7}, pages = {278-282}, doi = {10.1097/ICL.0000000000000905}, pmid = {35580364}, issn = {1542-233X}, mesh = {Ecosystem ; *Eye Diseases/prevention &amp; control ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {ABSTRACT: The gut microbiome plays a substantial immunologic and pathophysiologic role in maintaining the health of the host, and dysregulation of this dynamic ecosystem has been associated with several inflammatory conditions. Many studies have explored the influence of gut microbiota on the ocular surface and whether gut microbiota impact the pathophysiology of ophthalmic conditions. These findings have highlighted the advantages of enhancing gut microbes through probiotics, prebiotics, diet, vitamin supplementations, and fecal microbial transplant in clinical practice. The purpose of this review article was to provide an up-to-date overview of the knowledge on this topic. Further exploration of this area of research is important to help guide new therapeutic targets to develop treatment and prevention of certain ocular surface diseases.}, }
@article {pmid35721102, year = {2022}, author = {Zhang, J and Guo, Y and Duan, L}, title = {Features of Gut Microbiome Associated With Responses to Fecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {773105}, doi = {10.3389/fmed.2022.773105}, pmid = {35721102}, issn = {2296-858X}, abstract = {Fecal microbiota transplantation (FMT) has been seen as a novel treatment for inflammatory bowel disease (IBD). The results on microbial alterations and their relationship to treatment efficacy are varied among studies. We performed a systematic review to explore the association between microbial features and therapy outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to November 2020. Studies that investigated the efficacy of FMT and baseline microbial features or dynamic alteration of the microbiome during FMT were included. The methodological quality of the included cohort studies and randomized controlled trials (RCTs) was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane risk of bias tool, respectively. A total of 30 studies were included in the analysis. Compared to non-responders, the microbial structure of patients who responded to FMT had a higher similarity to that of their donors after FMT. Donors of responders (R-d) and non-responders (NR-d) had different microbial taxa, but the results were inconsistent. After FMT, several beneficial short-chain fatty acids- (SCFA-) producing taxa, such as Faecalibacterium, Eubacterium, Roseburia, and species belonging to them, were enriched in responders, while pathogenic bacteria (Escherichia coli and Escherichia-Shigella) belonging to the phylum Proteobacteria were decreased. Alterations of microbial functional genes and metabolites were also observed. In conclusion, the response to FMT was associated with the gut microbiota and their metabolites. The pre-FMT microbial features of recipients, the comparison of pre- and post-FMT microbiota, and the relationship between recipients and donors at baseline should be further investigated using uniform and standardized methods.}, }
@article {pmid35719863, year = {2022}, author = {Zhang, Y and Zhang, J and Pan, Z and He, X}, title = {Effects of Washed Fecal Bacteria Transplantation in Sleep Quality, Stool Features and Autism Symptomatology: A Chinese Preliminary Observational Study.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {1165-1173}, doi = {10.2147/NDT.S355233}, pmid = {35719863}, issn = {1176-6328}, abstract = {Purpose: Autism spectrum disorder is a highly complex neurological and psychosocial disorder characterized by social dysfunction, severe reduction in speech, and a single stereotyped behavior. The treatment methods are currently limited, and children with autism generally suffer from constipation and sleep disorders. It is urgent to find an alternative psychotropic drug, given the drug dependence and adverse reactions that may occur with long-term medication.<br><br>Patients and Methods: This retrospective study included 49 children with autism at the first affiliated Hospital of Guangdong Pharmaceutical University, who received washed fecal microbiota transplantation (WMT) treatment between June 2019 and July 2021 and compared the sleep disorder scores between the constipation group, control group and blank group.<br><br>Results: Second WMT could significantly improve the sleep disorder scores in the constipation group (p=0.026) and the decrease in sleep disturbance scale for children (SDSC) score was synchronized with the increase in Bristol stool form scale (BSFS) score. However, there was no significant difference between patients without constipation (p=0.54), and the behavior of autism improved in both groups.<br><br>Conclusion: WMT could relieve constipation and improve sleep disorders in children with autism, with no deterioration in stool morphology and sleep disorders in other children. Moreover, there were no obvious serious adverse clinical events after WMT.}, }
@article {pmid35719145, year = {2022}, author = {Tan, J and Gong, J and Liu, F and Li, B and Li, Z and You, J and He, J and Wu, S}, title = {Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {918098}, doi = {10.3389/fnut.2022.918098}, pmid = {35719145}, issn = {2296-861X}, abstract = {Objective: This study aimed to evaluate the effect of an antibiotic cocktail on gut microbiota and provide a reference for establishing an available mouse model for fecal microbiota transplantation (FMT) of specific microbes.<br><br>Design: C57BL/6J mice (n = 24) had free access to an antibiotic cocktail containing vancomycin (0.5 g/L), ampicillin (1 g/L), neomycin (1 g/L), and metronidazole (1 g/L) in drinking water for 3 weeks. Fecal microbiota was characterized by 16S rDNA gene sequencing at the beginning, 1st week, and 3rd week, respectively. The mice were then treated with fecal microbiota from normal mice for 1 week to verify the efficiency of FMT.<br><br>Results: The diversity of microbiota including chao1, observed species, phylogenetic diversity (PD) whole tree, and Shannon index were decreased significantly (P < 0.05) after being treated with the antibiotic cocktail for 1 or 3 weeks. The relative abundance of Bacteroidetes, Actinobacteria, and Verrucomicrobia was decreased by 99.94, 92.09, and 100%, respectively, while Firmicutes dominated the microbiota at the phylum level after 3 weeks of treatment. Meanwhile, Lactococcus, a genus belonging to the phylum of Firmicutes dominated the microbiota at the genus level with a relative abundance of 80.63%. Further FMT experiment indicated that the fecal microbiota from the receptor mice had a similar composition to the donor mice after 1 week.<br><br>Conclusion: The antibiotic cocktail containing vancomycin, ampicillin, neomycin, and metronidazole eliminates microbes belonging to Bacteroidetes, Actinobacteria, and Verrucomicrobia, which can be recovered by FMT in mice.}, }
@article {pmid35719141, year = {2022}, author = {Zhao, HJ and Zhang, XJ and Zhang, NN and Yan, B and Xu, KK and Peng, LH and Pan, F}, title = {Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {890357}, doi = {10.3389/fnut.2022.890357}, pmid = {35719141}, issn = {2296-861X}, abstract = {Background: Gut microbiota has been identified as an imbalance in patients with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is a novel method to restore microbiota and treat IBS patients.<br><br>Objective: To conduct a meta-analysis and estimate the efficacy and safety of FMT for the treatment of IBS patients with subgroup analyses to explore the most effective way of FMT for IBS.<br><br>Methods: All eligible studies were searched from PubMed, Embase, Web of Science, and the Cochrane Library through multiple search strategies. Data were extracted from studies comprising the following criteria: double-blind, randomized controlled trials (RCTs) that compared the efficacy of FMT with placebo for adult patients (≥18 years old) with IBS. A meta-analysis was performed to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs).<br><br>Results: A total of seven RCTs comprising 489 subjects were eligible for this meta-analysis. Pooled data showed no significant improvement of global IBS symptoms in patients with FMT compared with placebo (RR = 1.34; 95% CI 0.75-2.41, p = 0.32). A significant heterogeneity was observed among the studies (I 2 = 83%, p < 0.00001). There was no significant evidence of funnel plot asymmetry (Egger's test, p = 0.719; Begg's test, p = 1.000), indicating no existence of publication bias. Subgroup analyses revealed that FMT operated by invasive routes, including gastroscope, colonoscope, and nasojejunal tube, significantly improved global IBS symptoms (RR = 1.96; 95% CI 1.23-3.11, p = 0.004) with heterogeneity (I 2 = 57%, p = 0.06) and an NNT of 3 (95% CI 2-14). However, FMT delivered via oral capsules showed a negative impact on patients with IBS (RR = 0.56; 95% CI 0.33-0.96, p = 0.03) with a low heterogeneity (I 2 = 39%, p = 0.2) and an NNH of 3 (95% CI 2-37).<br><br>Conclusion: The current evidence from RCTs with all routes of FMT does not show significant global improvement in patients with IBS. However, FMT operated by invasive routes significantly improved global IBS symptoms.}, }
@article {pmid35716734, year = {2022}, author = {Qu, Z and Tian, P and Yang, B and Zhao, J and Wang, G and Chen, W}, title = {Fecal microbiota transplantation for diseases: Therapeutic potential, methodology, risk management in clinical practice.}, journal = {Life sciences}, volume = {}, number = {}, pages = {120719}, doi = {10.1016/j.lfs.2022.120719}, pmid = {35716734}, issn = {1879-0631}, abstract = {BACKGROUND: More than 95 % of human diseases may be related to the disturbance of gut microbes. As a treatment method that extensively regulates the gut microbes, fecal microbiota transplantation (FMT) has proven to be an effective therapy for some diseases, becoming a topic of interest among clinicians, patients and scientists.<br><br>AIM: To review the latest clinical research results of FMT in the treatment of various diseases and the methodology and risk management in clinical application.<br><br>METHODS: Search PubMed and Web of Science for reliable research results of clinical treatment of FMT within 5-10 years, as well as application guidelines and risk management policies in different regions.<br><br>RESULTS: As a measure of allogeneic/autologous microbiota transplantation, FMT has been used to treat a variety of diseases. By reviewing the clinical studies of FMT in gastrointestinal diseases, metabolic diseases, neurological diseases and malignant tumors, the various mechanisms in the treatment of diseases are summarized. Such as regulation of receptor microbiota composition, specific metabolites, phage function and immune response. In addition, potential risk factors, donor stool screening indicators, recipient self-specificity and possible prognostic marker molecules in the course of FMT treatment were generalized.<br><br>CONCLUSIONS: The potential regulatory mechanisms, risk factors and targets of FMT in gastrointestinal diseases, metabolic diseases, malignancies and neurological diseases were reviewed and proposed. It provides a theoretical basis for the establishment of a standardized treatment system for FMT and a breakthrough in treatment technology.}, }
@article {pmid35711246, year = {2022}, author = {Liu, Y and Chen, M}, title = {Clostridioides difficile Infection in Liver Cirrhosis: A Concise Review.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {2022}, number = {}, pages = {4209442}, doi = {10.1155/2022/4209442}, pmid = {35711246}, issn = {2291-2797}, mesh = {*Clostridioides difficile ; *Clostridium Infections/epidemiology/prevention &amp; control ; Fecal Microbiota Transplantation/methods ; Humans ; Liver Cirrhosis/complications/therapy ; Recurrence ; Rifaximin ; Treatment Outcome ; }, abstract = {Clostridium difficile is a Gram-positive bacillus with fecal-oral transmission and is currently one of the most common nosocomial infections worldwide, which was renamed Clostridioides difficile in 2016. Clostridioides difficile infection (CDI) is a prevalent infection in cirrhosis and negatively affects prognosis. This study aimed to provide a concise review with clinical practice implications. The prevalence of CDI in cirrhotic patients increases, while the associated mortality decreases. Multiple groups of risk factors increase the likelihood of CDI in patients with cirrhosis, such as antibiotic use, the severity of cirrhosis, some comorbidities, and demographic aspects. Treatment in the general population is currently described in the latest guidelines. In patients with cirrhosis, rifaximin and lactulose have been shown to reduce CDI risk due to their modulatory effects on the intestinal flora, although conflicting results exist. Fecal microbiota transplantation (FMT) as a treatment for the second or subsequent CDI recurrences has demonstrated a good safety and efficacy in cirrhosis and CDI. Future validation in more prospective studies is needed. Screening of asymptomatic patients appears to be discouraged for the prevention currently, with strict hand hygiene and cleaning of the ward and medical equipment surfaces being the cornerstone of minimizing transmission.}, }
@article {pmid35710492, year = {2022}, author = {Zhong, W and Wu, K and Long, Z and Zhou, X and Zhong, C and Wang, S and Lai, H and Guo, Y and Lv, D and Lu, J and Mao, X}, title = {Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {94}, pmid = {35710492}, issn = {2049-2618}, support = {82173039//National Natural Science Foundation of China/ ; 81773277//National Natural Science Foundation of China/ ; 82003271//National Natural Science Foundation of China/ ; 201803010014//Science and Technology Plan Project of Guangzhou/ ; 202102010150//Science and Technology Plan Project of Guangzhou/ ; 202102080010//Science and Technology Plan Project of Guangzhou/ ; 2021A1515010659//Guangdong Province Basic and Applied Basic Research Foundation/ ; 2020A1515110922//Guangdong Province Basic and Applied Basic Research Foundation/ ; 2019A1515110033//Guangdong Province Basic and Applied Basic Research Foundation/ ; 2019M662865//China Postdoctoral Science Foundation/ ; 2019KQNCX115//Distinguished Young Talents in Higher Education Foundation of Guangdong Province/ ; ZH201908//Achievement cultivation and clinical transformation application cultivation projects of the First Affiliated Hospital of Guangzhou Medical University/ ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Docetaxel/pharmacology ; *Dysbiosis/microbiology ; Feces/microbiology ; Humans ; Interleukin-6 ; Lipopolysaccharides ; Male ; Mice ; NF-kappa B ; *Prostatic Neoplasms ; Proteobacteria/genetics ; RNA, Ribosomal, 16S/genetics ; STAT3 Transcription Factor/genetics ; }, abstract = {BACKGROUND: The gut microbiota is reportedly involved in the progression and chemoresistance of various human malignancies. However, the underlying mechanisms behind how it exerts some effect on prostate cancer, as an extra-intestinal tumor, in a contact-independent way remain elusive and deserve exploration. Antibiotic exposure, one of the various factors affecting the gut microbiota community and capable of causing gut dysbiosis, is associated with multiple disorders. This study aims to preliminarily clarify the link between gut dysbiosis and prostate cancer.<br><br>RESULTS: First, we discovered that perturbing the gut microbiota by consuming broad-spectrum antibiotics in water promoted the growth of subcutaneous and orthotopic tumors in mice. Fecal microbiota transplantation could transmit the effect of antibiotic exposure on tumor growth. Then, 16S rRNA sequencing for mouse feces indicated that the relative abundance of Proteobacteria was significantly higher after antibiotic exposure. Meanwhile, intratumoral lipopolysaccharide (LPS) profoundly increased under the elevation of gut permeability. Both in vivo and in vitro experiments revealed that the NF-κB-IL6-STAT3 axis activated by intratumoral LPS facilitated prostate cancer proliferation and docetaxel chemoresistance. Finally, 16S rRNA sequencing of patients' fecal samples revealed that Proteobacteria was enriched in patients with metastatic prostate cancer and was positively correlated with plasma IL6 level, regional lymph node metastasis status, and distant metastasis status. The receiver operating characteristic (ROC) curves showed that the relative abundance of Proteobacteria had better performance than the prostate-specific antigen (PSA) level in predicting the probability of distant metastasis in prostate cancer (area under the ROC curve, 0.860; p < 0.001).<br><br>CONCLUSION: Collectively, this research demonstrated that gut dysbiosis, characterized by the enrichment of Proteobacteria due to antibiotic exposure, resulted in the elevation of gut permeability and intratumoral LPS, promoting the development of prostate cancer via the NF-κB-IL6-STAT3 axis in mice. Considering findings from human patients, Proteobacteria might act as an intestinal biomarker for progressive prostate cancer. Video Abstract.}, }
@article {pmid35710014, year = {2022}, author = {Wen, S and Zhao, Y and Liu, S and Chen, Y and Yuan, H and Xu, H}, title = {Polystyrene microplastics exacerbated liver injury from cyclophosphamide in mice: Insight into gut microbiota.}, journal = {The Science of the total environment}, volume = {840}, number = {}, pages = {156668}, doi = {10.1016/j.scitotenv.2022.156668}, pmid = {35710014}, issn = {1879-1026}, abstract = {Microplastics (MPs) have infiltrated human food system globally, and the latent health risks have been well-described. However, the impact of pre-consumed MPs on liver resistance to foreign robust stimuli remains unclear. In this study, we developed a mouse model drinking roughly 18 and 180 μg/kg/day polystyrene MPs for 90 days, then intraperitoneally injected mice with 80 mg/kg cyclophosphamide (CTX) to investigate whether chronic pre-exposure to MPs aggravates hepatoxicity induced by CTX. Slight liver injury was found in single CTX-treated mice, while more significant liver histopathological damage, inflammation and oxidative stress elicited by CTX were observed in pre-drinking MPs mice. Moreover, chronic exposure of MPs induced remarkable colonic impairments (e.g., leaky gut, mild inflammation and repressed antioxidant activity) as well as gut microbiota perturbation, which manifested positive association with aggravated hepatotoxicity via spearman correlation analysis. Fecal microbiota transplantation (FMT) trail was conducted to ulteriorly demonstrate the critical role of MPs-altered gut bacteria in exaggerated liver susceptibility to CTX stimulation. In conclusion, our study provided an insight that the adverse impact of MPs could be best revealed when animals suffering attack from hazardous substance. It also contributes to comprehensive assessment of health risk from environmentally pervasive MPs.}, }
@article {pmid35709830, year = {2022}, author = {El-Salhy, M and Winkel, R and Casen, C and Hausken, T and Gilja, OH and Hatlebakk, JG}, title = {Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome at three years after transplantation.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2022.06.020}, pmid = {35709830}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: The long-term efficacy and possible adverse events of fecal microbiota transplantation (FMT) for IBS are unknown. This study performed a 3-year follow-up of the patients in our previous clinical trial to clarify these aspects.<br><br>METHODS: This study included 125 patients (104 females, and 21 males): 38 in a placebo group, 42 who received 30 g of donor feces, and 45 who received 60 g of donor feces. Feces was administered to the duodenum. The patients provided a fecal sample and completed five questionnaires at baseline and at 2 and 3 years after FMT. Fecal bacteria and dysbiosis index (DI) were analyzed using 16S rRNA gene PCR DNA amplification/probe hybridization covering the V3-V9 regions.<br><br>RESULTS: Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at 2 years after FMT, and 27.0%, 64.9%, and 71.8%, respectively, at 3 years after FMT. The response rates were significantly higher in the 30-g and 60-g groups than in the placebo group. Patients in the 30-g and 60-g groups had significantly fewer IBS symptoms and fatigue, and a greater quality of life both at 2 and 3 years after FMT. The DI decreased only in the active treatment groups at 2 and 3 years after FMT. Fluorescent signals of 10 bacteria had significant correlations with IBS symptoms and fatigue after FMT in the 30-g and 60-g groups. No long-term adverse events were recorded.<br><br>CONCLUSIONS: FMT performed according to our protocol resulted in high response rates and long-standing effects with only few mild self-limited adverse events.}, }
@article {pmid35709819, year = {2022}, author = {Mullish, BH and McDonald, JAK and Marchesi, JR}, title = {Intestinal microbiota transplantation: do not forget the metabolites.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {7}, pages = {594}, doi = {10.1016/S2468-1253(22)00101-7}, pmid = {35709819}, issn = {2468-1253}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid35698418, year = {2022}, author = {Zhou, W and Yang, T and Xu, W and Huang, Y and Ran, L and Yan, Y and Mi, J and Lu, L and Sun, Y and Zeng, X and Cao, Y}, title = {The polysaccharides from the fruits of Lycium barbarum L. confer anti-diabetic effect by regulating gut microbiota and intestinal barrier.}, journal = {Carbohydrate polymers}, volume = {291}, number = {}, pages = {119626}, doi = {10.1016/j.carbpol.2022.119626}, pmid = {35698418}, issn = {1879-1344}, abstract = {The antidiabetic effect and potential mechanisms of the polysaccharides from the fruits of Lycium barbarum L. (LBPs) by the mouse model of high-fat diet/streptozotocin-induced diabetes were investigated. Six-week oral administration of LBPs (200 mg/kg/day) resulted in improvement in the levels of fasting blood glucose (13.51% decrease) and glycated hemoglobin and β-cell function in diabetic mice, and simultaneously induced a 3.3-fold increment in one taxon belonging to genus Allobaculum in gut bacterial community. The experiments of fecal microbiota transplantation and antibiotics treatment confirmed that the LBPs-mediated gut microbiota participated in the glycemic control of the diabetes management. Moreover, LBPs intervention guarded the intestinal barrier function via upregulating the expression of zonula occludens 1 both in vivo (analyzing the gut permeability in diabetic mice) and in vitro (using intestinal-like Caco-2/RAW264.7 cells co-culture inflammation model). Collectively, our study showed that LBPs could confer anti-diabetic effect through modifying gut microbiota and intestinal barrier.}, }
@article {pmid35697204, year = {2022}, author = {Kattner, AA}, title = {A finger in every pie - the versatility of chemokines.}, journal = {Biomedical journal}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bj.2022.06.001}, pmid = {35697204}, issn = {2320-2890}, abstract = {In this issue of Biomedical Journal we encounter the chemokine superfamily and its clinical potential. The time course from 56 days zero COVID-19 to a resurgence in cases is presented, as well as a possible solution to overcome rejection in vascularized composite allotransplantation. We are shown the opportunity deep learning (DL) offers in the case of tracking single cells and particles, and also use of DL to bring all hands on deck to counter the current challenge of the COVID-19 pandemic. This issue contains articles about the effect of low energy shock waves in cystitis; the negative effect of high fructose on aortic valve stenosis; a study about the outcome of fecal microbiota transplantation in case of refractory Clostridioides difficile infection; a novel long non-coding RNA that could serve in treating triple-negative breast cancer; the benefits of acupressure in patients with restless leg syndrome; and Filamin A mutations in abnormal neuronal migration development. Finally, a link between jaw surgery and the psychological impact on the patient is explored; a method presented that allows identification of cervical characteristics associated with difficult embryo transfer; and a letter suggesting new parameters to evaluate the use of bone-substitute augmentation in the treatment of osteoporotic intertrochanteric fractures.}, }
@article {pmid35695221, year = {2022}, author = {Liu, T and Su, D and Lei, C and Liu, Z}, title = {Treatment of Radiation Enteritis With Fecal Transplantation.}, journal = {The American surgeon}, volume = {}, number = {}, pages = {31348221091954}, doi = {10.1177/00031348221091954}, pmid = {35695221}, issn = {1555-9823}, abstract = {Radiation enteritis (RE) is a frequent complication in patients who undergo pelvic irradiation, and this condition has been increasingly diagnosed. Fecal microbiota transplantation (FMT) is being developed in recent years, and it has remarkable curative effect for the clostridium and inflammatory bowel disease. Herein, we present a case of recurrent RE in a 59-year-old woman with RE 18 years after radiotherapy for cervical carcinoma. Fecal microbiota transplantation therapy with intestinal flora from her 18-year-old son was applied and was successful in relieving the symptoms. To the best of our knowledge, this study is the first case report of FMT in a patient with RE.}, }
@article {pmid35694271, year = {2022}, author = {Cai, M and Xiao, Y and Lin, Z and Lu, J and Wang, X and Rahman, SU and Zhu, S and Chen, X and Gu, J and Ma, Y and Chen, Z and Huo, J}, title = {Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {889181}, doi = {10.3389/fphar.2022.889181}, pmid = {35694271}, issn = {1663-9812}, abstract = {Purpose: This study aimed to investigate the relationship between gut microbiota (GM) and serum metabolism using antineoplastic Fufangchangtai (FFCT) as the model prescription in the treatment of colorectal cancer (CRC). Methods: Tumor-bearing mice and normal mice were administered different doses of FFCT. The tumor volume of tumor-bearing mice was observed. The levels of CD4+ and CD8+ T cells in the blood, spleen, and tumor of mice were determined using a flow cytometer. The bacterial microbiota in stool samples from mice and the serum metabolomics of FFCT-treated mice and fecal microbiota transplantation mice were detected using 16s RNA sequencing and liquid chromatography-mass spectrometry (LC/MS), respectively. Results: The tumor volume of mice showed no significant decrease after FFCT intervention. The levels of CD4+ and CD8+T lymphocytes showed a significant increase under the intervention of FFCT. GM of colorectal tumor-bearing mice and healthy mice were determined, and the diversity and abundance of Firmicutes, Deferribacteres, Bacteroidetes, and Proteobacteria were significantly different between the two groups. Furthermore, we found that the levels of matrine, isogingerenone B, and armillaripin were significantly decreased in tumor-bearing mice after FFCT intervention, indicating that the tumor-induced dysbiosis of gut bacteria may affect the absorption and metabolism of FFCT. Under the intervention of FFCT, serum metabolism of mice transplanted with feces from CRC patients showed less metabolites related to FFCT than that from healthy people, indicating that GM could be a single factor affecting the metabolism of FFCT. Furthermore, we found that different doses of FFCT-treated mice had higher abundance of Roseburia, Turicibacter, and Flexispira than that in the non-intervention control group. Firmicutes and Bacteroidetes in FFCT-treated groups showed a similar trend compared to the healthy group, indicating that FFCT might correct the intestinal microenvironment by modulating gut microbiota in colorectal tumor-bearing mice. Conclusion: The dysbiosis of GM in tumor-bearing mice reduced the serum metabolites related to FFCT, and FFCT could correct the disordered GM of colorectal tumor-bearing mice to exert efficacy.}, }
@article {pmid35693372, year = {2022}, author = {Gupta, K and Tappiti, M and Nazir, AM and Koganti, B and Memon, MS and Aslam Zahid, MB and Shantha Kumar, V and Mostafa, JA}, title = {Fecal Microbiota Transplant in Recurrent Clostridium Difficile Infections: A Systematic Review.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e24754}, doi = {10.7759/cureus.24754}, pmid = {35693372}, issn = {2168-8184}, abstract = {Fecal Microbiota Transplantation (FMT) is the process of transferring the fecal microbiome from a healthy donor to an individual with repeated multiple episodes of Clostridium difficile infection. It is also known as stool transplant. Fecal microbiota transplant is effective and safe in various studies, the approval from the Food and Drug Administration (FDA) remains pending. The main objective of this systemic review is to evaluate the efficacy and safety of stool transplant in studies with only treatment groups (FMT) and studies with treatment (FMT) and antibiotic (AB) groups and previous studies. Online databases PubMed, PubMed Central, Science Direct, Google Scholar, and Embase were searched for relevant articles in the last five years (2016 to 2021) using automation tools. Following the removal of duplicates, screening of eligibility criteria, titles/abstracts, and quality appraisal were done by two authors independently. In total, seven observational studies are in this review article. Out of the seven observational studies, five are retrospective and two prospective. Two of the five retrospective and one of two prospective studies have a control group. In both the prospective studies and one retrospective study, FMT efficacy of (68% to 93%) was demonstrated in the elderly population despite high index comorbidities. In the younger individuals with inflammatory bowel disease, and efficacy of 90% or above was found. The most common side effects were minor such as fever, abdominal pain, bloating, and flatulence. In one study, two cases of aspiration events occurred attributed to the gastroscopy route of donor feces delivery. There was no statistical significance in the incidence of diseases such as (allergies, autoimmune diseases, cancer, inflammatory bowel diseases, and neurological diseases like dementia and migraine). Fecal microbiota transplantation has shown to be effective and safe in recurrent Clostridium difficile infections. Since very few pragmatic studies have demonstrated its efficacy and safety, their application is not well established. Robust studies, both observation and experiment, are required in the future to well-establish its effectiveness, safety in the treatment of recurrent Clostridium difficile infection.}, }
@article {pmid35691195, year = {2022}, author = {Li, T and Tian, D and Lu, M and Wang, B and Li, J and Xu, B and Chen, H and Wu, S}, title = {Gut microbiota dysbiosis induced by polychlorinated biphenyl 126 contributes to increased brain proinflammatory cytokines: Landscapes from the gut-brain axis and fecal microbiota transplantation.}, journal = {Ecotoxicology and environmental safety}, volume = {241}, number = {}, pages = {113726}, doi = {10.1016/j.ecoenv.2022.113726}, pmid = {35691195}, issn = {1090-2414}, abstract = {The pathogenesis of brain inflammation induced by polychlorinated biphenyl 126 (PCB126) has not yet been fully illustrated. Growing evidence highlights the relevance of the microbiota-gut-brain axis in central nervous system (CNS) dysfunction. Therefore, we aimed to study the role of the gut microbiota in PCB126-induced proinflammatory cytokine increases in the mouse brain. The results showed that PCB126 exposure significantly disordered gut bacterial communities, resulting in the enrichment of gram-negative bacteria (e.g., Bacteroidetes and Proteobacteria), further leading to elevated levels of the gram-negative bacterial lipopolysaccharide (LPS). Subsequently, colonic toll-like receptor 4 (TLR-4) was activated by bacterial LPS, which promoted proinflammatory cytokine generation and inhibited tight junction (TJ) protein expression. Then, bacterial LPS translocated from the gut lumen into the blood circulation and reached the brain, triggering LPS/TLR-4-mediated increases in brain proinflammatory cytokines. Further analysis after fecal microbiota transplantation (FMT) suggested that the gut microbiota disturbance caused by PCB126 could induce elevated bacterial LPS and trigger TLR-4-mediated increases in proinflammatory cytokines in the brain. This study highlights the possibility that PCB126-induced gut microbiota disorder contributes to increased brain proinflammatory cytokines. These results provide a new perspective for identifying the toxicity mechanisms of PCB126 and open up the possibility of modulating the gut microbiota as a therapeutic target for CNS disease caused by environmental pollution.}, }
@article {pmid35690527, year = {2022}, author = {Huang, C and Yi, P and Zhu, M and Zhou, W and Zhang, B and Yi, X and Long, H and Zhang, G and Wu, H and Tsokos, GC and Zhao, M and Lu, Q}, title = {Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {102844}, doi = {10.1016/j.jaut.2022.102844}, pmid = {35690527}, issn = {1095-9157}, abstract = {Gut microbiota dysbiosis is involved in the development of systemic lupus erythematosus (SLE). The safety and efficacy of fecal microbiota transplantation (FMT) for the treatment of SLE patients has not been explored. In this 12-week, single-arm pilot clinical trial of oral encapsulated fecal microbiome from healthy donors to patients with active SLE, we aimed to evaluate the safety and efficacy of FMT in patients with SLE (ChiCTR2000036352). 20 SLE patients with SLEDAI ≥6 were recruited. FMT was administered once a week for three consecutive weeks along with standard treatment and the patients were followed for 12 weeks. Safety was evaluated throughout the trial. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. Microbiome composition, levels of short chain fatty acids (SCFAs) in the gut and of cytokines in the sera were measured along with lymphocyte phenotyping. No serious adverse events were observed after FMT. At week 12, the SRI-4 response rate was 42.12%, and significant reductions in the SLEDAI-2K scores and the level of serum anti-dsDNA antibody were observed compared to baseline. Significant enrichment of SCFAs-producing bacterial taxa and reduction of inflammation-related bacterial taxa were observed, along with increased production of SCFAs in the gut and reduced levels of IL-6 and CD4+ memory/naïve ratio in the peripheral blood. Furthermore, SRI-4 responding patients displayed specific microbiota signatures both before and after FMT. The first clinical trial of FMT in active SLE patients provide supportive evidence that FMT might be a feasible, safe, and potentially effective therapy in SLE patients by modifying the gut microbiome and its metabolic profile.}, }
@article {pmid35690329, year = {2022}, author = {Gu, Y and Wang, C and Qin, X and Zhou, B and Liu, X and Liu, T and Xie, R and Liu, J and Wang, B and Cao, H}, title = {Saccharomyces boulardii, a yeast probiotic, inhibits gut motility through upregulating intestinal serotonin transporter and modulating gut microbiota.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106291}, doi = {10.1016/j.phrs.2022.106291}, pmid = {35690329}, issn = {1096-1186}, abstract = {Saccharomyces boulardii (Sb) is a widely used fungal probiotic in treating various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of Sb relieving IBS remain unclear. The abnormal serotonin transporter (SERT) / 5-hydroxytryptamine (5-HT) system could cause disordered gastrointestinal sensation and motility, which closely related to IBS pathogenesis. The aim of this study was to explore the effects and mechanisms of Sb on regulating gut motility. Sb supernatant (SbS) was administered to intestinal epithelial cells and mice. SbS upregulated SERT expression via enhancing heparin-binding epidermal growth factor (HB-EGF) release to activate epidermal growth factor receptor (EGFR). EGFR kinase inhibitor treatment or HB-EGF siRNA transfection in cells blocked SbS upregulating SERT. Consistently, SbS-treated mice presented inhibited gut motility, and EGFR activation and SERT upregulation were found. Moreover, 16S rDNA sequence presented an evident decrease in Firmicutes / Bacteroidetes ratio in SbS group. In genus level, SbS reduced Escherichia_Shigella, Alistipes, Clostridium XlVa, and Saccharibacteria_genera_incertae_sedis, meanwhile, increased Parasutterella. The abundance of Saccharibacteria_genera_incertae_sedis positively correlated with defecation parameters and intestinal 5-HT content. Fecal microbiota transplantation showed that SbS could modulate gut microbiota to influence gut motility. Interestingly, elimination of gut microbiota with antibiotic cocktail did not entirely block SbS regulating gut motility. Furthermore, SbS administration to IBS-D mice significantly upregulated SERT and inhibited gut motility. In conclusion, SbS could upregulate SERT by EGFR activation, and modulate gut microbiota to inhibit gut motility. This finding would provide more evidence for the application of this yeast probiotic in IBS and other diarrheal disorders.}, }
@article {pmid35688268, year = {2022}, author = {Zhang, KK and Liu, JL and Chen, LJ and Li, JH and Yang, JZ and Xu, LL and Chen, YK and Zhang, QY and Li, XW and Liu, Y and Zhao, D and Xie, XL and Wang, Q}, title = {Gut microbiota mediates methamphetamine-induced hepatic inflammation via the impairment of bile acid homeostasis.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {}, number = {}, pages = {113208}, doi = {10.1016/j.fct.2022.113208}, pmid = {35688268}, issn = {1873-6351}, abstract = {Methamphetamine (Meth), an addictive psychostimulant of abuse worldwide, has been a common cause of acute toxic hepatitis in adults. Gut microbiota has emerged as a modulator of host immunity via metabolic pathways. However, the microbial mechanism of Meth-induced hepatic inflammation and effective therapeutic strategies remain unknown. Here, mice were intraperitoneally (i.p.) injected with Meth to induce hepatotoxicity. Cecal microbiome and bile acids (BAs) composition were analysed after Meth administration. Fecal microbiota transplantation (FMT) technology was utilized to investigate the role of microbiota. Additionally, the protective effects of obeticholic acid (OCA), an agonist of farnesoid X receptor (FXR), were evaluated. Results indicated that Meth administration induced hepatic cholestasis, dysfunction and aroused hepatic inflammation by stimulating the TLR4/MyD88/NF-κB pathway in mice. Meanwhile, Meth disturbed the cecal microbiome and impaired the homeostasis of BAs. Interestingly, FMT from Meth administered mice resulted in serum and hepatic BA accumulation and transferred similar phenotypic changes into the healthy recipient mice. Finally, OCA normalized Meth-induced BA accumulation in both serum and the liver, and effectively protected against Meth-induced hepatic dysfunction and inflammation by suppressing the TLR4/MyD88/NF-κB pathway. This study established the importance of microbial mechanism and its inhibition as a potential therapeutic target to treat Meth-related hepatotoxicity.}, }
@article {pmid35681702, year = {2022}, author = {Sampsell, K and Wang, W and Ohland, C and Mager, LF and Pett, N and Lowry, DE and Sales, KM and McNeely, ML and McCoy, KD and Culos-Reed, SN and Reimer, RA}, title = {Exercise and Prebiotic Fiber Provide Gut Microbiota-Driven Benefit in a Survivor to Germ-Free Mouse Translational Model of Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/cancers14112722}, pmid = {35681702}, issn = {2072-6694}, support = {VPR Catalyst Grant//University of Calgary/ ; Cancer Prevention Research Opportunity//Alberta Innovates/ ; Grant//Alberta Cancer Foundation/ ; }, abstract = {The gut microbiota plays a role in shaping overall host health and response to several cancer treatments. Factors, such as diet, exercise, and chemotherapy, can alter the gut microbiota. In the present study, the Alberta Cancer Exercise (ACE) program was investigated as a strategy to favorably modify the gut microbiota of breast cancer survivors who had received chemotherapy. Subsequently, the ability of post-exercise gut microbiota, alone or with prebiotic fiber supplementation, to influence breast cancer outcomes was interrogated using fecal microbiota transplant (FMT) in germ-free mice. While cancer survivors experienced little gut microbial change following ACE, in the mice, tumor volume trended consistently lower over time in mice colonized with post-exercise compared to pre-exercise microbiota with significant differences on days 16 and 22. Beta diversity analysis revealed that EO771 breast tumor cell injection and Paclitaxel chemotherapy altered the gut microbial communities in mice. Enrichment of potentially protective microbes was found in post-exercise microbiota groups. Tumors of mice colonized with post-exercise microbiota exhibited more favorable cytokine profiles, including decreased vascular endothelial growth factor (VEGF) levels. Beneficial microbial and molecular outcomes were augmented with prebiotic supplementation. Exercise and prebiotic fiber demonstrated adjuvant action, potentially via an enhanced anti-tumor immune response modulated by advantageous gut microbial shifts.}, }
@article {pmid35681546, year = {2022}, author = {Huang, C and Mei, Q and Lou, L and Huang, Z and Fu, Y and Fan, J and Wang, J and Yin, N and Zheng, Y and Lu, Y and Zeng, Y}, title = {Ulcerative Colitis in Response to Fecal Microbiota Transplantation via Modulation of Gut Microbiota and Th17/Treg Cell Balance.}, journal = {Cells}, volume = {11}, number = {11}, pages = {}, doi = {10.3390/cells11111851}, pmid = {35681546}, issn = {2073-4409}, support = {SHDC12017X09, SHDC2020CR2014A//Shanghai Hospital Development Center/ ; 20181813//Shanghai Jiao Tong University School of Medicine/ ; 81970555//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) may contribute to disease remission in ulcerative colitis (UC). We studied the microbiota change and its regulation on T cells after FMT.<br><br>METHODS: Patients with mild to moderately active UC were included to receive FMT. The intestinal histopathological changes and barrier function were evaluated. The fecal samples of donors and patients were analyzed by 16S rRNA gene-based microbiota analysis, and the colon Th17 and Treg cells were assessed.<br><br>RESULTS: Fifteen patients completed the 8-week-follow-up. A total of 10 patients (66.7%) were in the responders (RE) group and five in the non-responders (NR) group. The Nancy histological index and fecal calprotectin decreased (p < 0.001, p = 0.06, respectively) and Occludin and Claudin1 increased in the RE group. The abundance of Faecalibaterium increased significantly by 2.3-fold in the RE group at week 8 (p = 0.043), but it was suppressed in the NR group. Fecal calprotectin (r = -0.382, p = 0.003) and Nancy index (r = -0.497, p = 0.006) were correlated inversely with the abundance of Faecalibacterium, respectively. In the RE group the relative mRNA expression of RORγt decreased and Foxp3 increased. Significantly decreased CD4+ RORγt+ Th17 and increased CD4+ Foxp3+ Treg were also observed in the RE group. The relative abundance of Faecalibacterium correlated with CD4+ RORγt+ Th17 (r = -0.430, p = 0.018) and CD4+ Foxp3+ Treg (r = 0.571, p = 0.001).<br><br>CONCLUSIONS: The long-term Faecalibaterium colonization following FMT plays a crucial role in UC remission by alleviating intestinal inflammation. This anti-inflammatory effect of Faecalibacterium may be achieved by regulating the imbalance of Th17/Treg levels in UC.}, }
@article {pmid35680942, year = {2022}, author = {Hui, Y and Vestergaard, G and Deng, L and Kot, WP and Thymann, T and Brunse, A and Nielsen, DS}, title = {Donor-dependent fecal microbiota transplantation efficacy against necrotizing enterocolitis in preterm pigs.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {48}, pmid = {35680942}, issn = {2055-5008}, support = {8022-00188B//Det Frie Forskningsråd (Danish Council for Independent Research)/ ; 8022-00188B//Det Frie Forskningsråd (Danish Council for Independent Research)/ ; 201706350028//China Scholarship Council (CSC)/ ; }, abstract = {The development of necrotizing enterocolitis (NEC), a life-threatening inflammatory bowel disease affecting preterm infants, is connected with gut microbiota dysbiosis. Using preterm piglets as a model for preterm infants we recently showed that fecal microbiota transplantation (FMT) from healthy suckling piglet donors to newborn preterm piglets decreased the NEC risk. However, in a follow-up study using donor stool from piglets recruited from another farm, this finding could not be replicated. This allowed us to study donor-recipient microbiota dynamics in a controlled model system with a clear difference in NEC phenotype. Preterm piglets (n = 38) were randomly allocated to receive control saline (CON), or rectal FMT using either the ineffective (FMT1) or the effective donor stool (FMT2). All animals were followed for four days before necropsy and gut pathological evaluation. Donor and recipient colonic gut microbiota (GM) were analyzed by 16 S rRNA gene amplicon sequencing and shotgun metagenomics. As expected, only FMT2 recipients were protected against NEC. Both FMT groups had shifted GM composition relative to CON, but FMT2 recipients had a higher lactobacilli relative abundance compared to FMT1. Limosilactobacillus reuteri and Lactobacillus crispatus strains of FMT recipients showed high phylogenetic similarity with their respective donors, indicating engraftment. Moreover, the FMT2 group had a higher lactobacilli replication rate and harbored specific glycosaminoglycan-degrading Bacteroides. In conclusion, subtle species-level donor differences translate to major changes in engraftment dynamics and the ability to prevent NEC. This could have implications for proper donor selection in future FMT trials for NEC prevention.}, }
@article {pmid35680592, year = {2022}, author = {Tang, XW and Wu, DP}, title = {[How I treat gastrointestinal tract acute graft versus host disease with fecal microbiota transplantation].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {43}, number = {5}, pages = {365-369}, doi = {10.3760/cma.j.issn.0253-2727.2022.05.003}, pmid = {35680592}, issn = {0253-2727}, }
@article {pmid35533688, year = {2022}, author = {Joachim, A and Schwerd, T and Hölz, H and Sokollik, C and Konrad, LA and Jordan, A and Lanzersdorfer, R and Schmidt-Choudhury, A and Hünseler, C and Adam, R}, title = {[Fecal Microbiota Transfer (FMT) in Children and Adolescents - Review and statement by the GPGE microbiome working group].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {60}, number = {6}, pages = {963-969}, doi = {10.1055/a-1801-0284}, pmid = {35533688}, issn = {1439-7803}, mesh = {Adolescent ; Child ; *Clostridioides difficile ; *Clostridium Infections/complications ; Dysbiosis/complications ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {The human microbiome and especially the gastrointestinal microbiota are associated with health and disease. Disturbance in the composition or function of fecal microbiota (dysbiosis) plays a role in the development of pediatric gastrointestinal diseases. Fecal microbiota transfer (FMT) is a special intervention, where microbiota are transferred from a healthy donor.In this review we describe the current state of knowledge for FMT in pediatric patients. There is satisfactory evidence concerning FMT in patients with recurrent C. difficile infection. For inflammatory bowel disease, few studies show a potential benefit.Adverse events occurred frequently in clinical studies, but were mostly mild and transient. There are hardly any data on long-term side effects of FMT, which are particularly significant for pediatrics. In practice, there is uncertainty as to which application route, dosage or frequency should be used. Legally, donor stool is considered a drug in German-speaking countries, for which no marketing authorization exists.In conclusion, knowledge about physiology, efficacy and side effects of FMT is insufficient and legal concerns complicate its implementation. More studies on this topic are needed urgently.}, }
@article {pmid35277453, year = {2022}, author = {Ting, NL and Lau, HC and Yu, J}, title = {Cancer pharmacomicrobiomics: targeting microbiota to optimise cancer therapy outcomes.}, journal = {Gut}, volume = {71}, number = {7}, pages = {1412-1425}, doi = {10.1136/gutjnl-2021-326264}, pmid = {35277453}, issn = {1468-3288}, mesh = {Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Humans ; Immunotherapy ; *Microbiota ; *Neoplasms ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {Despite the promising advances in novel cancer therapy such as immune checkpoint inhibitors (ICIs), limitations including therapeutic resistance and toxicity remain. In recent years, the relationship between gut microbiota and cancer has been extensively studied. Accumulating evidence reveals the role of microbiota in defining cancer therapeutic efficacy and toxicity. Unlike host genetics, microbiota can be easily modified via multiple strategies, including faecal microbiota transplantation (FMT), probiotics and antibiotics. Preclinical studies have identified the mechanisms on how microbes influence cancer treatment outcomes. Clinical trials have also demonstrated the potential of microbiota modulation in cancer treatments. Herein, we review the mechanistic insights of gut microbial interactions with chemotherapy and ICIs, particularly focusing on the interplay between gut bacteria and the pharmacokinetics (eg, metabolism, enzymatic degradation) or pharmacodynamics (eg, immunomodulation) of cancer treatment. The translational potential of basic findings in clinical settings is then explored, including using microbes as predictive biomarkers and microbial modulation by antibiotics, probiotics, prebiotics, dietary modulations and FMT. We further discuss the current limitations of gut microbiota modulation in patients with cancer and suggest essential directions for future study. In the era of personalised medicine, it is crucial to understand the microbiota and its interactions with cancer. Manipulating the gut microbiota to augment cancer therapeutic responses can provide new insights into cancer treatment.}, }
@article {pmid35672382, year = {2022}, author = {Bose, D and Chatterjee, S and Older, E and Seth, R and Janulewicz, P and Saha, P and Mondal, A and Carlson, JM and Decho, AW and Sullivan, K and Klimas, N and Lasley, S and Li, J and Chatterjee, S}, title = {Host gut resistome in Gulf War chronic multisymptom illness correlates with persistent inflammation.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {552}, pmid = {35672382}, issn = {2399-3642}, support = {W81XWH-13-2-0072//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH1810374//U.S. Department of Defense (United States Department of Defense)/ ; OIA-1655740//NSF | BIO | Division of Biological Infrastructure (DBI)/ ; I01CX001923-01//U.S. Department of Veterans Affairs (Department of Veterans Affairs)/ ; }, abstract = {Chronic multisymptom illness (CMI) affects a subsection of elderly and war Veterans and is associated with systemic inflammation. Here, using a mouse model of CMI and a group of Gulf War (GW) Veterans' with CMI we show the presence of an altered host resistome. Results show that antibiotic resistance genes (ARGs) are significantly altered in the CMI group in both mice and GW Veterans when compared to control. Fecal samples from GW Veterans with persistent CMI show a significant increase of resistance to a wide class of antibiotics and exhibited an array of mobile genetic elements (MGEs) distinct from normal healthy controls. The altered resistome and gene signature is correlated with mouse serum IL-6 levels. Altered resistome in mice also is correlated strongly with intestinal inflammation, decreased synaptic plasticity, reversible with fecal microbiota transplant (FMT). The results reported might help in understanding the risks to treating hospital acquired infections in this population.}, }
@article {pmid35665355, year = {2022}, author = {Chen, Y and Zhiliang, L and Jiaqu, C and Xiaoqiong, L and Shaoyi, Z and Chunlian, M and Yinmei, Y and Bo, Y and Di, Z and Hongliang, T and Ning, L and Qiyi, C and Huanlong, Q}, title = {Fecal Microbiota and Human Intestinal Fluid Transplantation: Methodologies and Outlook.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {830004}, doi = {10.3389/fmed.2022.830004}, pmid = {35665355}, issn = {2296-858X}, abstract = {Fecal microbiota transplantation (FMT) is a therapy that involves the transplantation of healthy human fecal microorganisms into the gut of patients to rebuild or consolidate the intestinal microecology. It has been utilized in many diseases. However, FMT had a limited effect on patients with small intestinal diseases because of the unique ecological characteristics of the microorganisms. Thus, we proposed a new microecology transplantation therapy called human intestinal fluid transplantation (HIFT). Human intestinal fluid can be collected through a nasojejunal tube and be made into capsules using the freeze-dried powder method. In addition, strict standards for donor screening and management have been established. We are currently developing a high-standard HIFT preparation system and conducting high-quality clinical studies to validate the safety and efficacy of HIFT combined with FMT.}, }
@article {pmid35664229, year = {2022}, author = {Li, M and Yang, L and Mu, C and Sun, Y and Gu, Y and Chen, D and Liu, T and Cao, H}, title = {Gut microbial metabolome in inflammatory bowel disease: From association to therapeutic perspectives.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {2402-2414}, doi = {10.1016/j.csbj.2022.03.038}, pmid = {35664229}, issn = {2001-0370}, abstract = {Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a set of clinically chronic, relapsing gastrointestinal inflammatory disease and lacks of an absolute cure. Although the precise etiology is unknown, developments in high-throughput microbial genomic sequencing significantly illuminate the changes in the intestinal microbial structure and functions in patients with IBD. The application of microbial metabolomics suggests that the microbiota can influence IBD pathogenesis by producing metabolites, which are implicated as crucial mediators of host-microbial crosstalk. This review aims to elaborate the current knowledge of perturbations of the microbiome-metabolome interface in IBD with description of altered composition and metabolite profiles of gut microbiota. We emphasized and elaborated recent findings of several potentially protective metabolite classes in IBD, including fatty acids, amino acids and derivatives and bile acids. This article will facilitate a deeper understanding of the new therapeutic approach for IBD by applying metabolome-based adjunctive treatment.}, }
@article {pmid35664001, year = {2022}, author = {Liu, P and Zhou, X and Zhang, H and Wang, R and Wu, X and Jian, W and Li, W and Yuan, D and Wang, Q and Zhao, W}, title = {Danggui-Shaoyao-San Attenuates Cognitive Impairment via the Microbiota-Gut-Brain Axis With Regulation of Lipid Metabolism in Scopolamine-Induced Amnesia.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {796542}, doi = {10.3389/fimmu.2022.796542}, pmid = {35664001}, issn = {1664-3224}, abstract = {Danggui-Shaoyao-San (DSS) has a long history of being used as a traditional medicine (TCM) and has been reported to show therapeutic effects in alleviating the symptoms of cognitive impairment. The purpose of this study was to investigate whether DSS treatment attenuates cognitive impairment via the microbiota-gut-brain axis in scopolamine-induced amnesia. In this work, we first performed the Morris water maze (MWM) test and novel object recognition (NOR) test to evaluate the memory function of treated C57BL/6N mice. Then we evaluated 16S rRNA for gut microbiota analysis, as well as assessment of blood-brain barrier function and intestinal barrier function and lipid metabolism analysis on tissues from different groups. We hypothesised that DSS may affect brain function and behavior through the gut-brain axis in a bidirectional interplay with both top-down and bottom-up regulation. Furthermore, in order to confirm whether intestinal flora plays a crucial role in scopolamine-induced amnesia, C57BL/6N mice were treated with fecal microbial transplantation (FMT), and then behavioral tests were performed. The mice's feces were simultaneously evaluated by 16S rRNA analysis. The result supported that the FMT-induced improvement in cognitive function highlights the role of the gut microbiota-brain axis to mediate cognitive function and behavior. Besides theses works, more findings indicated that DSS altered lipid metabolism by activating LXR-PPAR-γ and repaired mucosal barrier dysfunction assessed with a broad range of techniques, which attenuated cognitive impairment via the microbiota-gut-brain axis.}, }
@article {pmid35662937, year = {2022}, author = {You, H and Tan, Y and Yu, D and Qiu, S and Bai, Y and He, J and Cao, H and Che, Q and Guo, J and Su, Z}, title = {The Therapeutic Effect of SCFA-Mediated Regulation of the Intestinal Environment on Obesity.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {886902}, doi = {10.3389/fnut.2022.886902}, pmid = {35662937}, issn = {2296-861X}, abstract = {Intestinal environment disorder is a potential pathological mechanism of obesity. There is increasing evidence that disorders in the homeostasis of the intestinal environment can affect various metabolic organs, such as fat and liver, and lead to metabolic diseases. However, there are few therapeutic approaches for obesity targeting the intestinal environment. In this review, on the one hand, we discuss how intestinal microbial metabolites SCFA regulate intestinal function to improve obesity and the possible mechanisms and pathways related to obesity-related pathological processes (depending on SCFA-related receptors such as GPCRs, MCT and SMCT, and through epigenetic processes). On the other hand, we discuss dietary management strategies to enrich SCFA-producing bacteria and target specific SCFA-producing bacteria and whether fecal bacteria transplantation therapy to restore the composition of the gut microbiota to regulate SCFA can help prevent or improve obesity. Finally, we believe that it will be of great significance to establish a working model of gut- SCFA- metabolic disease development in the future for the improvement this human health concern.}, }
@article {pmid35660350, year = {2022}, author = {Yan, S and Chang, J and Hao, X and Liu, J and Tan, X and Geng, Z and Wang, Z}, title = {Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {102}, number = {}, pages = {154217}, doi = {10.1016/j.phymed.2022.154217}, pmid = {35660350}, issn = {1618-095X}, abstract = {BACKGROUND: Colitis-associated cancer (CAC) is known to be a complex combination of tumor cells, non-tumor cells and a large intestinal flora. The increasing role of intestinal flora in CAC may represent a new approach to improving CAC treatment. Berberine can reduce colorectal adenoma recurrence and inhibit colorectal carcinogenesis.<br><br>PURPOSE: Berberine has demonstrated efficacy for the control and suppression of CAC. Given the low oral absorption into the blood and large intestinal excretion of berberine, intestinal flora may be one of the important targets of berberine inhibiting the occurrence of colorectal cancer (CRC). The purpose of this study was to investigate the effects of berberine on intestinal flora in CAC mice and its ability to remodel intestinal flora to improve short-chain fatty acid metabolism.<br><br>STUDY DESIGN AND METHODS: The CAC model in mice was induced by Azoxymethane/Dextran sodium sulfate (AOM/DSS). Berberine was administered daily at doses of 50 and 100 mg/kg, and aspirin was used as the positive control. The effect of berberine on colitis-associated colorectal tumorigenesis was assessed by general imaging, tumor counting, and Ki67 staining. Intestinal flora changes were detected by 16S rDNA sequencing technology. Targeted short-chain fatty acid detection was performed by GC-MS/MS, and Lipopolysaccharide (LPS) levels in feces were quantified with an ELISA kit. The signaling pathway of TLR4/NF-κB P65/IL-6/p-STAT3 was evaluated by Western blotting and immunofluorescence. The expression levels of intestinal barrier functional biomarkers Occludin and ZO-1 were detected by immunohistochemistry. Fecal flora transplantation (FMT) was used to evaluate the effect of intestinal flora in inhibiting inflammatory cancer transformation by berberine.<br><br>RESULTS: Berberine reduced the number and load of tumors in CAC mice. Berberine remodeled the composition of pathogenic and beneficial bacteria in mice with colitis-associated colorectal tumorigenesis. Berberine treatment resulted in increases in fecal butyric acid, acetic acid and propionic acid levels, but did not alter isobutyric acid, isovaleric acid, valeric acid and caproic acid. In addition, berberine reduced LPS content in feces in mice with colitis-associated colorectal tumorigenesis. Occludin and ZO-1 were upregulated, and the TLR4/p-NF-κB p65/IL-6/p-STAT3 inflammatory-cancer transformation pathway was inhibited with berberine. The FMT results further verified that the berberine-treated intestinal flora was sufficient to alleviate the occurrence of colonic tumors associated with colitis in mice.<br><br>CONCLUSION: Our study showed that berberine alleviated the colitis-associated colorectal tumorigenesis from three equilibrium levels: (1) Pathogenic and beneficial bacteria; (2) Short-chain fatty acids and LPS produced by intestinal flora; and (3) Inflammatory cancer transformation signaling and intestinal barrier function. This study provided a new approach and experimental basis for the application of berberine in the treatment of CAC in clinical practice.}, }
@article {pmid35658593, year = {2022}, author = {Fang, H and Fang, M and Wang, Y and Zhang, H and Li, J and Chen, J and Wu, Q and He, L and Xu, J and Deng, J and Liu, M and Deng, Y and Chen, C}, title = {Indole-3-Propionic Acid as a Potential Therapeutic Agent for Sepsis-Induced Gut Microbiota Disturbance.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0012522}, doi = {10.1128/spectrum.00125-22}, pmid = {35658593}, issn = {2165-0497}, abstract = {The effects of using gut microbiota metabolites instead of live microorganisms to modulate sepsis-induced gut dysbiosis remain largely unknown. We assessed the effects of microbiota metabolite indole-3-propionic acid (IPA) on gut microbiota in mice during sepsis. Sepsis models were constructed by cecal ligation and puncture (CLP) methods. Fecal microbiota composition analysis was performed to characterize the gut microbiota composition. Fecal microbiota transplantation was performed to validate the roles of gut microbiota on sepsis progression. IPA-treated mice exhibited lower serum inflammatory mediator levels and a higher survival rate than those of saline-treated mice after modeling of sepsis, which were negated in the presence of antibiotics. Compared with saline-treated mice after modeling, IPA-treated mice showed a markedly different intestinal microbiota composition, with an enrichment of Bifidobacteriaceae family and a depletion of Enterobacteriaceae family. Mice gavaged with postoperative feces from IPA-treated animals displayed better survival than mice gavaged with feces from saline-treated animals. Overall, these data suggest that IPA offers a microbe-modulated survival advantage in septic mice, indicating that some microbiota metabolites could replace live microorganisms as potential options for regulation of sepsis-induced gut dysbiosis. IMPORTANCE The role of gut microbiota in the pathophysiology of sepsis is gaining increasing attention and developing effective and safe sepsis therapies targeting intestinal microorganisms is promising. Given the safety of probiotic supplementation or fecal microbiota transplantation in critically ill patients, identifying an abiotic agent to regulate the intestinal microbiota of septic patients is of clinical significance. This study revealed that IPA, a microbiota-generated tryptophan metabolite, ameliorated sepsis-induced mortality and decreased the serum levels of proinflammatory cytokines by modulating intestinal microbiota. Although IPA did not increase the abundance and diversity of the microbiota of septic mice, it significantly decreased the number of Enterobacteriaceae family. These findings indicate that a specific microbiota metabolite (e.g., IPA) can mediate the intestinal microbiota apart from FMT or probiotics.}, }
@article {pmid35654347, year = {2022}, author = {Xu, L and Zhang, Q and Dou, X and Wang, Y and Wang, J and Zhou, Y and Liu, X and Li, J}, title = {Fecal microbiota transplantation from young donor mice improves ovarian function in aged mice.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgg.2022.05.006}, pmid = {35654347}, issn = {1673-8527}, abstract = {Advanced maternal age is characterized by declines in the quantity and quality of oocytes in the ovaries, and the aging process is accompanied by changes in gut microbiota composition. However, little is known about the relationship between gut microbiota and ovarian aging. By using fecal microbiota transplantation (FMT) to transplant material from young (5-week-old) into aged (42-week-old) mice, we find that the composition of gut microbiota in FMT-treated mice presents a "younger-like phenotype" and an increase of commensal bacteria, such as Bifidobacterium and Ruminococcaceae. Moreover, the FMT-treated mice show increased anti-inflammatory cytokine IL-4 and decreased pro-inflammatory cytokine IFN-γ. Fertility tests for assessing ovarian function reveal that the first litter size of female FMT-treated mice is significantly higher than that of the non-FMT group. Morphology analysis demonstrates a dramatic decrease in follicle atresia and apoptosis as well as an increase in cellular proliferation in the ovaries of the FMT-treated mice. Our results also show that FMT improves the immune microenvironment in aged ovaries, with decreased macrophages and macrophage-derived multinucleated giant cells (MNGCs). These results suggest that FMT from young donors could be a good choice for delaying ovarian aging.}, }
@article {pmid35653887, year = {2022}, author = {Duan, S and Li, X and Fan, G and Liu, R}, title = {Targeting bile acid signaling for the treatment of liver diseases: From bench to bed.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {152}, number = {}, pages = {113154}, doi = {10.1016/j.biopha.2022.113154}, pmid = {35653887}, issn = {1950-6007}, abstract = {Liver diseases and related complications have become one of the leading causes of morbidity and mortality worldwide, yet effective medicine or approved treatment approach is still limited. Thus, novel therapy is urgently required to prevent or at least slow down the growing burden of liver transplantation or even death caused by malignant liver diseases. As the irreplaceable modulator of hepatic and intestinal signaling cascades, bile acids (BAs) play complex physiological as well as pathological roles in regulating energy and immune homeostasis in various liver diseases, including but not limited to metabolic diseases and cholangiopathies, making them highly attractive therapeutic targets. In the current review, recent progress in the research of enterohepatic circulation of BAs and potential therapeutic targets of BAs signaling, especially the development of currently available treatments, including agonizts of FXR and TGR5, analogs of FGF19, inhibitors of ASBT, and the regulation of gut microbiome through fecal microbiota transplantation were extensively summarized. Their protective effects, molecular mechanisms, and outcomes of clinical trials were highlighted. The structural features of these candidates and perspectives for their future development were further discussed. In conclusion, we believe that pharmacological therapies targeting BAs signaling represent promising and efficient strategies for the treatment of complex and multifactorial liver disorders.}, }
@article {pmid35650202, year = {2022}, author = {Pu, Y and Zhang, Q and Tang, Z and Lu, C and Wu, L and Zhong, Y and Chen, Y and Hashimoto, K and Luo, Y and Liu, Y}, title = {Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation.}, journal = {Translational psychiatry}, volume = {12}, number = {1}, pages = {223}, pmid = {35650202}, issn = {2158-3188}, support = {21H00184//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05612//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 82101616//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81973540//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Depression is common in patients with rheumatoid arthritis (RA); however, the precise mechanisms underlying a link between depression and RA remain unclear. Accumulating evidence suggests the role of gut-microbiota-brain axis in depression. In this study, we investigated whether collagen-induced arthritis (CIA) mice produce depression-like behaviors and abnormal composition of gut microbiota. Furthermore, we investigated whether fecal microbiota transplantation (FMT) from RA patients causes depression-like phenotypes in antibiotic cocktail (ABX)-treated mice. CIA mice displayed depression-like behaviors, increased blood levels of pro-inflammatory cytokine interleukin-6 (IL-6), decreased expression of synaptic proteins in the prefrontal cortex (PFC), and abnormal composition of gut microbiota. Furthermore, FMT from RA patients caused depression-like phenotypes, alterations of gut microbiota composition, increased levels of IL-6 and tumor necrosis factor-α (TNF-α), and downregulation of synaptic proteins in the PFC compared to FMT from healthy controls. There were correlations between relative abundance of microbiota and plasma cytokines, expression of synaptic proteins in the PFC or depression-like behaviors. Interestingly, FMT from RA patients induced T cells differentiation in Peyer's patches and spleen. Reduced percentage of Treg cells with an increase of Th1/Th2 index was observed in the mice after FMT from RA patients. These findings suggest that CIA mice exhibit depression-like behaviors, systemic inflammation, and abnormal composition of gut microbiota, and that FMT from RA patients produces depression-like behaviors in ABX-treated mice via T cells differentiation. Therefore, abnormalities in gut microbiota in RA patients may contribute to depression via gut-microbiota-brain axis.}, }
@article {pmid35647000, year = {2022}, author = {Zhi, W and Song, W and Abdi Saed, Y and Wang, Y and Li, Y}, title = {Fecal Capsule as a Therapeutic Strategy in IgA Nephropathy: A Brief Report.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {914250}, doi = {10.3389/fmed.2022.914250}, pmid = {35647000}, issn = {2296-858X}, abstract = {In this brief report, we reported an IgA nephropathy (IgAN) patient who presented in November 2020 with an acute exacerbation with massive proteinuria and diarrhea. He had the earliest onset in 2018 when his IgAN was diagnosed by renal biopsy. He has been treated with active ACEI/ARB drugs for more than 90 days, intermittent steroid therapy, combined with anti-infective therapy. Although his acute symptoms resolved with each episode, he became increasingly severe as the interval between episodes shortened. Accordingly, the immunosuppressive drugs were administered under the KDIGO guidelines and related guidelines. However, the patient and his family refused this treatment. We pondered over the possible pathogenesis of IgAN, and after a full discussion with the patient and his family, FMT was administered to him after obtaining his informed consent. During the FMT procedure, one healthy volunteer (the doctor himself) also took the FMT capsules. In the end, the patient's urine protein dropped significantly and even turned negative after treatment. Neither the patient nor the healthy volunteer experienced any serious adverse effects during the use of the capsules and the subsequent 6-month follow-up period. We also used metagenomic sequencing to analyze the intestinal flora of patients before and after treatment, and a gradual increase stood out in the abundance of the patient's intestinal flora after drug administration.}, }
@article {pmid35646285, year = {2022}, author = {Said, I and Ahad, H and Said, A}, title = {Gut microbiome in non-alcoholic fatty liver disease associated hepatocellular carcinoma: Current knowledge and potential for therapeutics.}, journal = {World journal of gastrointestinal oncology}, volume = {14}, number = {5}, pages = {947-958}, doi = {10.4251/wjgo.v14.i5.947}, pmid = {35646285}, issn = {1948-5204}, abstract = {Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). The gut microbiome is closely connected to the liver via the portal vein, and has recently been identified as a predictor of liver disease state. Studies in NAFLD, cirrhosis and HCC have identified certain microbial signatures associated with these diseases, with the disease-associated microbiome changes collectively referred to as dysbiosis. The pathophysiologic underpinnings of these observations are an area of ongoing investigation, with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability (leaky gut) and activation of the innate immune system. In the innate immune system, pathogen recognition receptors (Toll like receptors) on resident liver cells and macrophages cause liver inflammation, fibrosis, hepatocyte proliferation and reduced antitumor immunity, leading to chronic liver disease and carcinogenesis. Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR (nuclear receptor), which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease. Longitudinal experimental and clinical studies are needed in different populations to examine these questions further. The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet, probiotics, fecal microbiota transplantation and prebiotics in improving liver disease in experimental models. Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis. The microbial profile is different in responders to cancer immunotherapy including liver cancer, but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.}, }
@article {pmid35646276, year = {2022}, author = {Hoilat, GJ and Suhail, FK and Adhami, T and John, S}, title = {Evidence-based approach to management of hepatic encephalopathy in adults.}, journal = {World journal of hepatology}, volume = {14}, number = {4}, pages = {670-681}, doi = {10.4254/wjh.v14.i4.670}, pmid = {35646276}, issn = {1948-5182}, abstract = {Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function and represents one of the many complications of portal hypertension and decompensated liver disease. Although ammonia is clearly implicated in the pathogenesis of HE, the pathogenesis of HE is multifactorial with numerous mechanisms that results in functional impairment of neuronal cells. The initial management of HE focuses on supportive care and stabilization which includes providing appropriate nutritional support. Thereafter, focus should be on identifying and treating the precipitating factors. There are many therapeutic agents available for the management of HE, most of which are directed towards lowering the gut nitrogen load and thus the serum ammonia level. This review aims to provide an update on the conventional and emerging treatment options for HE.}, }
@article {pmid35643532, year = {2022}, author = {He, Z and Ma, Y and Yang, S and Zhang, S and Liu, S and Xiao, J and Wang, Y and Wang, W and Yang, H and Li, S and Cao, Z}, title = {Gut microbiota-derived ursodeoxycholic acid from neonatal dairy calves improves intestinal homeostasis and colitis to attenuate extended-spectrum β-lactamase-producing enteroaggregative Escherichia coli infection.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {79}, pmid = {35643532}, issn = {2049-2618}, support = {2021YFF1000703-03//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: Antimicrobials are often used to prevent and treat diarrhea induced by enteroaggregative Escherichia coli (EAEC) in young ruminants. However, drug overuse or misuse accelerates the spread of multidrug-resistant extended-spectrum β-lactamase (ESBL)-producing E. coli. Thus, supplementary foods as alternatives to antibiotics are needed to prevent colibacillus diarrhea in neonatal dairy calves. Ursodeoxycholic acid (UDCA), a therapeutic bile acid, helps alleviate colitis. However, how UDCA helps alleviate ESBL-EAEC-induced clinical symptoms and colitis remains unclear.<br><br>RESULTS: We investigated the microbial profiles and metabolites of healthy and diarrheic neonatal calves to determine microbial and metabolite biomarkers in early-life development. Both the gut microbiota communities and their associated metabolites differed between healthy and diarrheic calves. Commensal Butyricicoccus, Faecalibacterium, Ruminococcus, Collinsella, and Coriobacterium were key microbial markers that distinguished healthy and diarrheic gut microbiomes. Random forest machine-learning algorithm and Spearman correlation results indicated that enriched UDCA, short-chain fatty acids (SCFAs), and other prebiotics were strongly positively correlated with these five bacterial genera. We explored the effect of ursodiol on bacterial growth, cell adherence, and lipopolysaccharide-treated Caco-2 cells. Adding ursodiol induced direct antibacterial effects, suppressed proinflammatory effects, and reduced cell integrity damage. Oral ursodiol delivery to neonatal mice exhibited significant antibacterial effects and helped maintain colonic barrier integrity in mouse models of peritonitis sepsis and oral infection. UDCA supplementation attenuated colitis and recovered colonic SCFA production. To validate this, we performed fecal microbiota transplantations to inoculate ESBL-EAEC-infected neonatal mice. Microbiotas from UDCA-treated neonatal mice ameliorated colitis and hindgut commensal bacterial damage compared with that of the microbiotas from the control and placebo mice, as evidenced by colonization of abundant bacteria, including Oscillospiraceae, Ruminococcaceae, Lachnospiraceae, and Clostridia_UCG-014, and upregulated SCFA production.<br><br>CONCLUSIONS: This study provided the first evidence that UDCA could confer diarrhea resistance in ESBL-EAEC-infected newborn dairy calves. UDCA blocked bacterial growth and invasion both in vitro and in vivo, alleviated commensal bacterial dysbiosis during ESBL-EAEC infection in neonatal mouse models of sepsis and colitis via the TGR5-NF-κB axis, and upregulated SCFA production in the hindgut digesta. Our findings provide insight into the UDCA-mediated remission of ESBL-EAEC infections and the potential role of UDCA as an antibiotic alternative. Video abstract.}, }
@article {pmid35642928, year = {2022}, author = {Liu, Q and Zuo, T and Lu, W and Yeoh, YK and Su, Q and Xu, Z and Tang, W and Yang, K and Zhang, F and Lau, LHS and Lui, RNS and Chin, ML and Wong, R and Cheung, CP and Zhu, W and Chan, PKS and Chan, FKL and Lui, GC and Ng, SC}, title = {Longitudinal Evaluation of Gut Bacteriomes and Viromes after Fecal Microbiota Transplantation for Eradication of Carbapenem-Resistant Enterobacteriaceae.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0151021}, doi = {10.1128/msystems.01510-21}, pmid = {35642928}, issn = {2379-5077}, abstract = {Understanding the role of fecal microbiota transplantation (FMT) in the decolonization of multidrug-resistant organisms (MDRO) is critical. Specifically, little is known about virome changes in MDRO-infected subjects treated with FMT. Using shotgun metagenomic sequencing, we characterized longitudinal dynamics of the gut virome and bacteriome in three recipients who successfully decolonized carbapenem-resistant Enterobacteriaceae (CRE), including Klebsiella spp. and Escherichia coli, after FMT. We observed large shifts of the fecal bacterial microbiota resembling a donor-like community after transfer of a fecal microbiota dominated by the genus Ruminococcus. We found a substantial expansion of Klebsiella phages after FMT with a concordant decrease of Klebsiella spp. and striking increase of Escherichia phages in CRE E. coli carriers after FMT. We also observed the CRE elimination and similar evolution of Klebsiella phage in mice, which may play a role in the collapse of the Klebsiella population after FMT. In summary, our pilot study documented bacteriome and virome alterations after FMT which mediate many of the effects of FMT on the gut microbiome community. IMPORTANCE Fecal microbiota transplantation (FMT) is an effective treatment for multidrug-resistant organisms; however, introducing a complex mixture of microbes also has unknown consequences for landscape features of gut microbiome. We sought to understand bacteriome and virome alterations in patients undergoing FMT to treat infection with carbapenem-resistant Enterobacteriaceae. This finding indicates that transkingdom interactions between the virome and bacteriome communities may have evolved in part to support efficient FMT for treating CRE.}, }
@article {pmid35642838, year = {2022}, author = {Fang, H and Wang, Y and Deng, J and Zhang, H and Wu, Q and He, L and Xu, J and Shao, X and Ouyang, X and He, Z and Zhou, Q and Wang, H and Deng, Y and Chen, C}, title = {Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0139921}, doi = {10.1128/msystems.01399-21}, pmid = {35642838}, issn = {2379-5077}, abstract = {Sepsis-associated encephalopathy (SAE) is common in septic patients and is associated with adverse outcomes. The gut microbiota has been recognized as a key mediator of neurological disease development. However, the exact role of the gut microbiota in regulating SAE remains elusive. Here, we investigated the role of the gut microbiota in SAE and its underlying mechanisms. Cecal ligation and puncture (CLP) was conducted to induce sepsis in mice. Neurological scores were recorded to distinguish SAE-resistant (SER) (score of >6 at 36 h postoperatively) from SAE-susceptible (SES) (score of ≤6 at 36 h postoperatively) mice. 16S rRNA gene sequencing and metabolomics analyses were used to characterize the gut microbiota in the two groups. Fecal microbiota transplantation was performed to validate the role of the gut microbiota in SAE progression. The gut microbiota was more severely disrupted in SES mice than in SER mice after sepsis modeling. Interestingly, mice receiving postoperative feces from SES mice exhibited more severe cortical inflammation than mice receiving feces from SER mice. Indole-3-propionic acid (IPA), a neuroprotective molecule, was more enriched in feces from SER mice than in feces from SES mice. IPA alleviated CLP-induced anxiety and spatial memory impairment in septic mice. Moreover, IPA markedly inhibited NLRP3 inflammasome activation and interleukin-1β (IL-1β) secretion in lipopolysaccharide-stimulated microglia. These responses were attenuated after antagonizing the aryl hydrocarbon receptor. Our study indicates that the variability in sepsis-induced gut dysbiosis mediates the differential susceptibility to SAE in CLP-induced experimental sepsis mice, and microbially derived IPA is possibly involved in SAE development as a neuroprotective compound. IMPORTANCE The bidirectional interactions between the gut microbiota and sepsis-associated encephalopathy (SAE) are not well characterized. We found that the gut microbiota was more severely disturbed in SAE-susceptible (SES) mice than in SAE-resistant (SER) mice after sepsis modeling. Mice gavaged with postoperative feces from SES mice exhibited more severe neuroinflammation than mice gavaged with feces from SER mice. The gut microbiota from SER mice enriched a neuroprotective metabolite, IPA, which appeared to protect mice from SAE. The potential underlying mechanism of the protective effect of IPA may be mediated via the inhibition of NLRP3 inflammasome activation and IL-1β secretion in microglia. These anti-inflammatory effects of IPA may be regulated by aryl hydrocarbon receptors. These results enhance our understanding of the role of the intestinal microbiota in sepsis. In particular, gut microbiota-derived IPA may serve as a potential therapeutic agent to prevent neuroinflammation in SAE.}, }
@article {pmid35635005, year = {2022}, author = {Li, WJ and Zhang, L and Wu, HX and Li, M and Wang, T and Zhang, WB and Du, ZY and Zhang, ML}, title = {Intestinal Microbiota Mediates Gossypol-Induced Intestinal Inflammation, Oxidative Stress, and Apoptosis in Fish.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c01263}, pmid = {35635005}, issn = {1520-5118}, abstract = {Gossypol, the main antinutritional factor in cottonseed protein concentrate (CPC), could affect the growth conditions of fish, but the underlying mechanism remains unclear. In this study, an 8-week feeding trial was carried out to investigate the effects of gossypol on Nile tilapia (Oreochromis niloticus). Three experimental diets were designed, including control diet (CON), control diet supplemented with 150 mg/kg gossypol (ML), and 300 mg/kg gossypol (MH). 16S rRNA gene sequencing showed that gossypol significantly reduced the richness and diversity of the gut microbiota. Untargeted metabolite analysis revealed that most metabolites were down-regulated by gossypol, and riboflavin was the key metabolite with significant difference between CON-treated and gossypol-treated groups. Gossypol caused intestinal inflammation, oxidative stress, and apoptosis. Through fecal bacteria transplantation experiments, we demonstrated that intestinal microbiota mediated gossypol-induced negative effects, suggesting that intestinal microbiota and its metabolite may account for the harmful effects of gossypol.}, }
@article {pmid35634716, year = {2022}, author = {González-Dávila, P and Schwalbe, M and Danewalia, A and Wardenaar, R and Dalile, B and Verbeke, K and Mahata, SK and El Aidy, S}, title = {Gut microbiota transplantation drives the adoptive transfer of colonic genotype-phenotype characteristics between mice lacking catestatin and their wild type counterparts.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2081476}, doi = {10.1080/19490976.2022.2081476}, pmid = {35634716}, issn = {1949-0984}, abstract = {The gut microbiota is in continuous interaction with the intestinal mucosa via metabolic, neuro-immunological, and neuroendocrine pathways. Disruption in levels of antimicrobial peptides produced by the enteroendocrine cells, such as catestatin, has been associated with changes in the gut microbiota and imbalance in intestinal homeostasis. However, whether the changes in the gut microbiota have a causational role in intestinal dyshomeostasis has remained elusive. To this end, we performed reciprocal fecal microbial transplantation in wild-type mice and mice with a knockout in the catestatin coding region of the chromogranin-A gene (CST-KO mice). Combined microbiota phylogenetic profiling, RNA sequencing, and transmission electron microscopy were employed. Fecal microbiota transplantation from mice deficient in catestatin (CST-KO) to microbiota-depleted wild-type mice induced transcriptional and physiological features characteristic of a distorted colon in the recipient animals, including impairment in tight junctions, as well as an increased collagen area fraction indicating colonic fibrosis. In contrast, fecal microbiota transplantation from wild-type mice to microbiota-depleted CST-KO mice reduced collagen fibrotic area, restored disrupted tight junction morphology, and altered fatty acid metabolism in recipient CST-KO mice. This study provides a comprehensive overview of the murine metabolic- and immune-related cellular pathways and processes that are co-mediated by the fecal microbiota transplantation and supports a prominent role for the gut microbiota in the colonic distortion associated with the lack of catestatin in mice. Overall, the data show that the gut microbiota may play a causal role in the development of features of intestinal inflammation and metabolic disorders, known to be associated with altered levels of catestatin and may, thus, provide a tractable target in the treatment and prevention of these disorders.}, }
@article {pmid35634319, year = {2022}, author = {Xia, Y and Shi, H and Qian, C and Han, H and Lu, K and Tao, R and Gu, R and Zhao, Y and Wei, Z and Lu, Y}, title = {Modulation of Gut Microbiota by Magnesium Isoglycyrrhizinate Mediates Enhancement of Intestinal Barrier Function and Amelioration of Methotrexate-Induced Liver Injury.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {874878}, doi = {10.3389/fimmu.2022.874878}, pmid = {35634319}, issn = {1664-3224}, abstract = {Background: The gut-liver axis plays a crucial role in various liver diseases. Therefore, targeting this crosstalk may provide a new treatment strategy for liver diseases. However, the exact mechanism underlying this crosstalk and its impact on drug-induced liver injury (DILI) requires clarification.<br><br>Aim: This study aimed to investigate the potential mechanism and therapeutic effect of MgIG on MTX-induced liver injury, which is associated with the gut-liver axis and gut microbiota.<br><br>Methods: An MTX-induced liver injury model was generated after 20-mg/kg/3d MTX application for 30 days. Meanwhile, the treatment group was treated with 40-mg/kg MgIG daily. Histological examination, aminotransferase, and aspartate aminotransferase enzyme levels were estimated to evaluate liver function. Immune cells infiltration and inflammatory cytokines were detected to indicate inflammation levels. Colon histological score, intestinal barrier leakage, and expression of tight junctions were employed to assess the intestinal injury. Bacterial translocation was observed using fluorescent in situ hybridisation, colony-forming unit counting, and lipopolysaccharide detection. Alterations in gut microbial composition were analysed using 16s rDNA sequencing and relative quantitative polymerase chain reaction. Short-chain-fatty-acids and lactic acid concentrations were then utilized to validate changes in metabolites of specific bacteria. Lactobacillus sp. supplement and fecal microbiota transplantation were used to evaluate gut microbiota contribution.<br><br>Results: MTX-induced intestinal and liver injuries were significantly alleviated using MgIG treatment. Bacterial translocation resulting from the intestinal barrier disruption was considered a crucial cause of MTX-induced liver injury and the therapeutic target of MgIG. Moreover, MgIG was speculated to have changed the gut microbial composition by up-regulating probiotic Lactobacillus and down-regulating Muribaculaceae, thereby remodelling the intestinal barrier and inhibiting bacterial translocation.<br><br>Conclusion: The MTX-induced intestinal barrier was protected owing to MgIG administration, which reshaped the gut microbial composition and inhibited bacterial translocation into the liver, thus attenuating MTX-related DILI.}, }
@article {pmid35631220, year = {2022}, author = {Yoo, JW and Shin, YJ and Ma, X and Son, YH and Jang, HM and Lee, CK and Kim, DH}, title = {The Alleviation of Gut Microbiota-Induced Depression and Colitis in Mice by Anti-Inflammatory Probiotics NK151, NK173, and NK175.}, journal = {Nutrients}, volume = {14}, number = {10}, pages = {}, doi = {10.3390/nu14102080}, pmid = {35631220}, issn = {2072-6643}, support = {2017R1A5A2014768//National Research Foundation of Korea/ ; }, abstract = {Gut microbiota dysbiosis is strongly associated with psychiatric disorders and inflammatory bowel disease (IBD). Herein, we examined whether the fecal microbiota of IBD patients with depression (IBDD) and their gut microbiota culture (iGm) could cause depression and colitis in mice and anti-inflammatory probiotics could mitigate depression in iGm-transplanted or immobilization stress (IS)-exposed mice. Fecal microbiota transplantation (FMT) from IBDD patients, which exhibited Enterobacteriaceae-rich gut microbiota, and its gut microbiota culture (iGm) increased depression-like behaviors in mice. Their treatments heightened the blood lipopolysaccharide (LPS) level and colonic IL-1β and IL-6 expression. However, FMT from healthy volunteers or sulfasalazine treatment alleviated cGm-induced depressive-like behaviors and hippocampal and colonic inflammation in mice. Moreover, oral administration of Lactobacillus plantarum NK151, Bifidobacterium longum NK173, and Bifidobacterium bifidum NK175, which inhibited LPS-induced IL-6 expression in macrophages, alleviated cGm-induced depression-like behaviors, hippocampal NF-κB+Iba1+ cell numbers and IL-1β and IL-6 expression, blood LPS, IL-6, and creatinine levels, and colonic NF-κB+CD11c+ number and IL-1β and IL-6 expression in mice. Treatment with NK151, NK173, or NK175 mitigated immobilization stress (IS)-induced depressive-like behaviors, neuroinflammation, and gut inflammation in mice. NK151, NK173, or NK175 also decreased IS-induced blood LPS, IL-6, and creatinine levels. The transplantation of Enterobacteriaceae-rich gut microbiota can cause depression and colitis, as IS exposure, and anti-inflammatory NK151, NK173, and NK175, may alleviate stress-induced fatigue, depression, and colitis by regulating the expression of proinflammatory and anti-inflammatory cytokines through the suppression of gut bacterial LPS.}, }
@article {pmid35631150, year = {2022}, author = {Wang, P and Ma, Y and Wang, D and Zhao, W and Hu, X and Chen, F and Zhao, X}, title = {Protective Effects of Dietary Resveratrol against Chronic Low-Grade Inflammation Mediated through the Gut Microbiota in High-Fat Diet Mice.}, journal = {Nutrients}, volume = {14}, number = {10}, pages = {}, doi = {10.3390/nu14101994}, pmid = {35631150}, issn = {2072-6643}, support = {32101959//National Natural Science Foundation of China/ ; 202244/WT_/Wellcome Trust/United Kingdom ; KJCX201915//the Collaborative Innovation Center of Beijing Academy of Agricultural and Forestry Sciences/ ; KJCX20200208//Scientific and Technological Innovation Ability Foundation of Beijing Academy of Agricultural and Forestry Sciences/ ; CARS-23//China Agriculture Research System of MOF and MRAR/ ; }, abstract = {Resveratrol (RSV), a natural polyphenol, has been shown to exert activity against obesity and related chronic inflammation. However, due to the poor bioavailability of RSV, the mechanisms of RSV against inflammation in obesity models remain unclear. In this study, we aimed to investigate the relationship between the gut bacteria and the anti-inflammation effects of RSV in HFD-fed mice. We found that RSV supplementation reduced fat accumulation and improved systemic inflammation in HFD-fed mice. Meanwhile, RSV attenuated HFD-induced changes in the gut microbiota's structure, which were associated with inflammatory parameters. A fecal microbiota transplantation (FMT) experiment proved that the anti-inflammation effects of RSV largely rely on the gut microbiota. Moreover, the microbiota-genera-changing trend in the FMT experiment was similar to that in the oral RSV-feeding experiment. Thus, these results demonstrate that modulation of the gut bacteria induced by RSV treatment has a therapeutic effect on chronic low-grade inflammation in HFD-fed mice.}, }
@article {pmid35630496, year = {2022}, author = {Gan, L and Bo, T and Liu, W and Wang, D}, title = {The Gut Microbiota May Affect Personality in Mongolian Gerbils.}, journal = {Microorganisms}, volume = {10}, number = {5}, pages = {}, doi = {10.3390/microorganisms10051054}, pmid = {35630496}, issn = {2076-2607}, support = {31872232//National Natural Science Foundation of China/ ; 32090024//State Natural Sciences Foundation Monumental Projects/ ; XDPB16//Strategic Priority Research Program of Chinese Academy of Sciences/ ; 2021M693158//Postdoctoral Research Foundation of China/ ; }, abstract = {The "gut-microbiota-brain axis" reveals that gut microbiota plays a critical role in the orchestrating behavior of the host. However, the correlation between the host personalities and the gut microbiota is still rarely known. To investigate whether the gut microbiota of Mongolian gerbils (Meriones unguiculatus) differs between bold and shy personalities, we compared the gut microbiota of bold and shy gerbils, and then we transplanted the gut microbiota of bold and shy gerbils into middle group gerbils (individuals with less bold and shy personalities). We found a significant overall correlation between host boldness and gut microbiota. Even though there were no significant differences in alpha diversity and beta diversity of gut microbiota between bold and shy gerbils, the Firmicutes/Bacteroidetes phyla and Odoribacter and Blautia genus were higher in bold gerbils, and Escherichia_shigella genus was lower. Furthermore, the fecal microbiota transplantation showed that changes in gut microbiota could not evidently cause the increase or decrease in the gerbil's boldness score, but it increased the part of boldness behaviors by gavaging the "bold fecal microbiota". Overall, these data demonstrated that gut microbiota were significantly correlated with the personalities of the hosts, and alteration of microbiota could alter host boldness to a certain extent.}, }
@article {pmid35630347, year = {2022}, author = {Shang, L and Tu, J and Dai, Z and Zeng, X and Qiao, S}, title = {Microbiota Transplantation in an Antibiotic-Induced Bacterial Depletion Mouse Model: Reproducible Establishment, Analysis, and Application.}, journal = {Microorganisms}, volume = {10}, number = {5}, pages = {}, doi = {10.3390/microorganisms10050902}, pmid = {35630347}, issn = {2076-2607}, support = {32030105//National Key Research and Development Program of China/ ; cstc2019ngzx0019//Chongqing Rongchang Agricultural and Animal Husbandry High-tech Industry Research and Development Project/ ; }, abstract = {The fecal bacteria transplantation (FMT) technique is indispensable when exploring the pathogenesis and potential treatments for microbiota-related diseases. For FMT clinical treatments, there are already systematic guidelines for donor selection, fecal bacterial separation, FMT frequency, and infusion methods. However, only a few studies have demonstrated the use of standardized FMT procedures for animal models used in theoretical research, creating difficulties for many new researchers in this field. In the present paper, we provide a brief overview of FMT and discuss its contribution to the current understanding of disease mechanisms that relate to microbiota. This protocol can be used to generate a commonly used FMT mouse model and provides a literature reference of customizable steps.}, }
@article {pmid35625513, year = {2022}, author = {Ugrayová, S and Švec, P and Hric, I and Šardzíková, S and Kubáňová, L and Penesová, A and Adamčáková, J and Pačesová, P and Horáková, J and Kolenová, A and Šoltys, K and Kolisek, M and Bielik, V}, title = {Gut Microbiome Suffers from Hematopoietic Stem Cell Transplantation in Childhood and Its Characteristics Are Positively Associated with Intra-Hospital Physical Exercise.}, journal = {Biology}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/biology11050785}, pmid = {35625513}, issn = {2079-7737}, support = {APVV-17-0099//Slovak Research and Development Agency/ ; APVV-19-0222//Slovak Research and Development Agency/ ; No. MAGDG2000059//Grant program for the development of sport and education in the capital of the Slovak Republic in Bratislava/ ; UK/38/20//Comenius University/ ; UK/112/2021//Comenius University/ ; VEGA 1/0260/21//Vedecká grantová agentúra MŠVVaŠ SR a SAV (VEGA)/ ; }, abstract = {Gut microbiome impairment is a serious side effect of cancer treatment. The aim of this study was to identify the effects of hematopoietic stem cell transplantation (HSCT) treatment on gut microbiota composition in children with acute lymphoblastic leukemia (ALL). Fecal microbiotas were categorized using specific primers targeting the V1-V3 region of 16S rDNA in eligible pediatric ALL patients after HSCT (n = 16) and in healthy controls (Ctrl, n = 13). An intra-hospital exercise program was also organized for child patients during HSCT treatment. Significant differences in gut microbiota composition were observed between ALL HSCT and Ctrl with further negative effects. Plasma C-reactive protein correlated positively with the pathogenic bacteria Enterococcus spp. and negatively with beneficial bacteria Butyriccocus spp. or Akkermansia spp., respectively (rs = 0.511, p = 0.05; rs = -0.541, p = 0.04; rs = -0.738, p = 0.02). Bacterial alpha diversity correlated with the exercise training characteristics. Therefore, specific changes in the microbiota of children were associated with systemic inflammation or the ability to exercise physically during HSCT treatment.}, }
@article {pmid35625485, year = {2022}, author = {Dey, P and Ray Chaudhuri, S}, title = {Cancer-Associated Microbiota: From Mechanisms of Disease Causation to Microbiota-Centric Anti-Cancer Approaches.}, journal = {Biology}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/biology11050757}, pmid = {35625485}, issn = {2079-7737}, support = {SRG/2021/000082//Science and Engineering Research Board/ ; }, abstract = {Helicobacter pylori infection is the only well-established bacterial cause of cancer. However, due to the integral role of tissue-resident commensals in maintaining tissue-specific immunometabolic homeostasis, accumulated evidence suggests that an imbalance of tissue-resident microbiota that are otherwise considered as commensals, can also promote various types of cancers. Therefore, the present review discusses compelling evidence linking tissue-resident microbiota (especially gut bacteria) with cancer initiation and progression. Experimental evidence supporting the cancer-causing role of gut commensal through the modulation of host-specific processes (e.g., bile acid metabolism, hormonal effects) or by direct DNA damage and toxicity has been discussed. The opportunistic role of commensal through pathoadaptive mutation and overcoming colonization resistance is discussed, and how chronic inflammation triggered by microbiota could be an intermediate in cancer-causing infections has been discussed. Finally, we discuss microbiota-centric strategies, including fecal microbiota transplantation, proven to be beneficial in preventing and treating cancers. Collectively, this review provides a comprehensive understanding of the role of tissue-resident microbiota, their cancer-promoting potentials, and how beneficial bacteria can be used against cancers.}, }
@article {pmid35624084, year = {2022}, author = {Jee, JJ and Lim, J and Park, S and Koh, H and Lee, HW}, title = {The gut microbial community differentially characterizes patients with nonalcoholic fatty liver disease.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15903}, pmid = {35624084}, issn = {1440-1746}, abstract = {BACKGROUND AND AIM: Discordant reports of the signature gut microbes involved in nonalcoholic fatty liver disease (NAFLD) have hampered understanding of the pathogenesis of the disease, and thus its diagnosis. Thus, we investigated diagnostic factors and the potential mechanisms for heterogenous NAFLD based on the gut environment, including microbes and functional pathways.<br><br>METHODS: Stools from 16 biopsy-proven NAFLD patients were analyzed for bacterial taxonomy and functional pathways based on 16s rRNA gene sequencing. Data from the physical examination, serum biochemistry, and the gut environment were subjected to a decision tree classifier to identify diagnostic markers.<br><br>RESULTS: We identified two NAFLD subpopulations: those with and without a gut microbiota similar to health controls (HCs), defined as PHC-like and P patients, respectively. Stools of PHC-like patients were significantly populated with Enterobacteriaceae and were inferred to be rich in metabolites degraded from dicarboxylic acid sugars. Significant colonization of Prevotella was observed in the stools of P patients, in parallel with enrichment of metabolites from heme b biosynthesis and sulfate reduction. As a potential mechanism, we suggest that protoporphyrin IX and/or protoheme from Prevotella participates in hepatic injury, and that endogenous hydrogen sulfide increases serum IL-6 level in P patients. However, endotoxin-producing Enterobacteriaceae are thought to produce glycerate, triggering a peroxisome proliferator- activated receptor-alpha-mediated decrease in IL-6 level and fat accumulation in PHC-like patients.<br><br>CONCLUSIONS: Heterogenous NAFLD subpopulations were identified, defined according to gut microbial composition and their potential underlying pathogenic mechanisms; our results raise the possibility of personalized treatment for NALFD patients.}, }
@article {pmid35623598, year = {2022}, author = {Pane, K and Boccella, S and Guida, F and Franzese, M and Maione, S and Salvatore, M}, title = {Role of gut microbiota in neuropathy and neuropathic pain states: A systematic preclinical review.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {105773}, doi = {10.1016/j.nbd.2022.105773}, pmid = {35623598}, issn = {1095-953X}, abstract = {Gut microbiota has implications in Central Nervous System (CNS) disorders. Our study systematically identified preclinical studies aimed to investigate the possible gut microbiota contribution in neuropathy and neuropathic pain. The systematic review is reported in accordance with PRISMA checklist and guidelines outlined updated to 2020. We included research articles reporting neuropathy-related behavioral evaluations and/or neurological scores coupled to gut microbiota analysis performed by high-throughput technologies in the last ten years. Two investigators performed a search through 3 electronic bibliographic databases for full-text articles (PubMed, Scopus, and EMBASE) and three registries (Prospero, SyRF, and bioRxiv), cross-references, and linear searches. We assessed the methodological quality via the CAMARADES checklist and appraised the heterogeneous body of evidence by narrative synthesis. In total, there were 19 eligible studies. The most of these reports showed significant changes in gut microbiota setting in neuropathy conditions. The major gut microbiome remodeling was through fecal microbiome transplantation. Mechanistic proof of the gut-CNS communication was achieved by measuring inflammatory mediators, metabolic products, or neurotransmitters. As a limitation, we found considerable heterogeneity across eligible studies. We conclude that the current understanding of preclinical findings suggested an association between neuropathy and/or neuropathic pain and gut microbiota modifications. Our analysis provides the basis for further studies targeting microbiota for managing symptoms of neuropathy or other neuroinflammation-based CNS disorders. The systematic review protocol was registered on the international database Prospero under the registration number (# 257628).}, }
@article {pmid35620724, year = {2022}, author = {Hu, Y and Ye, Z and Wu, M and She, Y and Li, L and Xu, Y and Qin, K and Hu, Z and Yang, M and Lu, F and Ye, Q}, title = {Corrigendum: The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {886105}, doi = {10.3389/fmed.2022.886105}, pmid = {35620724}, issn = {2296-858X}, abstract = {[This corrects the article DOI: 10.3389/fmed.2021.766126.].}, }
@article {pmid35619714, year = {2022}, author = {Zhang, B and Chen, T and Cao, M and Yuan, C and Reiter, RJ and Zhao, Z and Zhao, Y and Chen, L and Fan, W and Wang, X and Zhou, X and Li, C}, title = {Gut Microbiota Dysbiosis Induced by Decreasing Endogenous Melatonin Mediates the Pathogenesis of Alzheimer's Disease and Obesity.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {900132}, doi = {10.3389/fimmu.2022.900132}, pmid = {35619714}, issn = {1664-3224}, abstract = {Lifestyle choices, external environment, aging, and other factors influence the synthesis of melatonin. Although the physiological functions of melatonin have been widely studied in relation to specific organs, the systemic effects of endogenous melatonin reduction has not been reported. This study evaluates the systemic changes and possible pathogenic risks in an endogenous melatonin reduction (EMR) mouse model deficient in the rate limiting enzyme in melatonin production, arylalkylamine N-acetyltransferase (Aanat) gene. Using this model, we identified a new relationship between melatonin, Alzheimer's disease (AD), and gut microbiota. Systematic changes were evaluated using multi-omics analysis. Fecal microbiota transplantation (FMT) was performed to examine the role of gut microbiota in the pathogenic risks of EMR. EMR mice exhibited a pan-metabolic disorder, with significant transcriptome changes in 11 organs, serum metabolome alterations as well as microbiota dysbiosis. Microbiota dysbiosis was accompanied by increased gut permeability along with gut and systemic inflammation. Correlation analysis revealed that systemic inflammation may be related to the increase of Ruminiclostridium_5 relative abundance. 8-month-old EMR mice had AD-like phenotypes, including Iba-1 activation, A β protein deposition and decreased spatial memory ability. Moreover, EMR mice showed decreased anti stress ability, under high-fat diet, EMR mice had greater body weight and more obvious hepatic steatosis compared with WT group. FMT improved gut permeability, systemic inflammation, and AD-related phenotypes, while reducing obesity in EMR mice. Our findings suggest EMR causes systemic changes mediated by gut microbiota dysbiosis, which may be a pathogenic factor for AD and obesity, we further proved the gut microbiota is a potential target for the prevention and treatment of AD and obesity.}, }
@article {pmid35616308, year = {2022}, author = {Yan, X and Zhai, Y and Zhou, W and Qiao, Y and Guan, L and Liu, H and Jiang, J and Peng, L}, title = {Intestinal Flora Mediates Antiobesity Effect of Rutin in High-Fat-Diet Mice.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e2100948}, doi = {10.1002/mnfr.202100948}, pmid = {35616308}, issn = {1613-4133}, abstract = {SCOPE: Intestinal flora plays a critical role in the development of diet-induced obesity and related metabolic complications. Rutin is a natural flavonoid with potential prebiotic effects on regulating the intestinal flora composition that is beneficial for host health. Therefore, we hypothesized that rutin supplementation has beneficial effects on high-fat-diet (HFD)-induced obesity and metabolic disorder through the modulation of intestinal flora in mice.<br><br>METHODS AND RESULTS: We investigated the obesity-alleviating property of rutin using 6-week-old C57BL/6J male mice fed on HFD with or without rutin supplementation for 16 weeks. Rutin supplementation effectively reduced body-weight gain, insulin resistance, and acted favorably on the intestinal barrier, thereby reducing endotoxemia and systemic inflammation. Sequencing of 16S rRNA genes from fecal samples indicated that rutin exerted modulatory effects on HFD-induced intestinal flora disorders (e.g., rutin decreased Firmicutes abundance and increased Bacteroidetes and Verrucomicrobia abundance). Antibiotic treatment and fecal microbiota transplantation further demonstrated that the salutary effects of rutin on obesity control were strongly dependent on the intestinal flora.<br><br>CONCLUSION: Rutin can be considered as a prebiotic agent for improving intestinal flora disorders and obesity-associated metabolic perturbations in obese individuals. This article is protected by copyright. All rights reserved.}, }
@article {pmid35613492, year = {2022}, author = {Fu, Y and Hu, J and Erasmus, MA and Johnson, TA and Cheng, HW}, title = {Effects of early-life cecal microbiota transplantation from divergently selected inbred chicken lines on growth, gut serotonin, and immune parameters in recipient chickens.}, journal = {Poultry science}, volume = {101}, number = {7}, pages = {101925}, doi = {10.1016/j.psj.2022.101925}, pmid = {35613492}, issn = {1525-3171}, abstract = {Recent studies have revealed that fecal microbiota transplantation exerts beneficial effects on modulating stress-related inflammation and gastrointestinal health of the host. The aim of this study was to examine if cecal microbiota transplantation (CMT) presents similar efficiency in improving the health status of egg-laying strain chickens. Chicken lines 63 and 72 divergently selected for resistance or susceptibility to Marek's disease were used as CMT donors. Eighty-four d-old male recipient chicks (a commercial DeKalb XL layer strain) were randomly assigned into 3 treatments with 7 replicates per treatment and 4 birds per replicate (n = 7): saline (control, CTRL), cecal solution of line 63 (63-CMT), and cecal solution of line 72 (72-CMT) for a 16-wk trial. Cecal transplant gavage was conducted once daily from d 1 to d 10, then boosted once weekly from wk 3 to wk 5. The results indicated that 72-CMT birds had the highest body weight and ileal villus/crypt ratio among the treatments at wk 5 (P ≤ 0.05); and higher heterophil/lymphocyte ratios than that of 63-CMT birds at wk 16 (P < 0.05). 72-CMT birds also had higher levels of plasma natural IgG and Interleukin (IL)-6 at wk 16, while 63-CMT birds had higher concentrations of ileal mucosal secretory IgA at wk 5 and plasma IL-10 at wk 16 (P < 0.05), with a tendency for lower mRNA abundance of splenic IL-6 and tumor necrosis factor (TNF)-α at wk 16 (P = 0.08 and 0.07, respectively). In addition, 72-CMT birds tended to have the lowest serotonin concentrations (P = 0.07) with the highest serotonin turnover in the ileum at wk 5 (P < 0.05). There were no treatment effects on the levels of plasma corticosterone and testosterone at wk 16 (P > 0.05). In conclusion, early postnatal CMT from different donors led to different patterns of growth and health status through the regulation of ileal morphological structures, gut-derived serotonergic activities, peripheral cytokines, and antibody production in recipient chickens.}, }
@article {pmid35610004, year = {2022}, author = {Zeyue, YU and Liyu, H and Zongyuan, LI and Jianhui, S and Hongying, C and Hairu, H and Xiaoqin, LI and Zhongchao, S and Hongmei, LI}, title = {Correlation between slow transit constipation and spleen deficiency, and gut microbiota: a pilot study.}, journal = {Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan}, volume = {42}, number = {3}, pages = {353-363}, doi = {10.19852/j.cnki.jtcm.20220408.002}, pmid = {35610004}, issn = {2589-451X}, support = {Z2021022//Fundamental Scientific Research Business Fees of Central Public Welfare Scientific Research Institutes of China Academy of Chinese Medical Sciences/ ; 81891010//National Natural Science Foundation Project: Study on the Authenticity of Traditional Chinese Medicine/ ; CI2021A04605//Science and Technology Innovation Project of China Academy of Chinese Medical Sciences: Efficacy Evaluation and Mechanism Exploration of Huashi Baidu Granule based on "multi-link and multi-target" in the Prevention and Treatment of Influenza Virus Infection/ ; ZZ15-WT-04//Basic Scientific Research Business Fee Project of Central Public Welfare Scientific Research Institutes of the Chinese Academy of Chinese Medical Sciences: Study on the Novel Coronavirus Pneumonia Mech-anism of Yiqi Zeng Fang and Huashi Baidu Granules/ ; }, abstract = {OBJECTIVE: To investigate the effect of slow transit constipation (STC) and spleen deficiency on gut microbiota, and the mechanism underlying the action that the positive drug Maren Runchang (MR) alleviates STC.<br><br>METHODS: STC was induced, using the cathartic method of Senna and the hunger-fullness disorder method, in ICR mice; one group of model mice was treated with MR (6.24 g/kg). The changes in the general condition, fecal parameters, D-xylose content in the serum, intestinal propulsion rate, and histopathology of the colon were assessed after STC induction in the control, model, and MR groups. Fecal microbiota transplantation (FMT) was performed from STC mice into pseudo germ-free mice. Changes in the contents of substance P (SP), vasoactive intestinal peptide (VIP), and gut microbiota in STC mice and pseudo germ-free mice were assessed after FMT.<br><br>RESULTS: Compared with the control group, the model mice showed the following results: the time of the first black stool was significantly longer (0.01), the number and weight of black stools were significantly reduced within 6 h (0.05), the D-xylose content in the serum was significantly reduced (< 0.05), the intestinal propulsion rate decreased (< 0.01), the content of VIP in colon tissue significantly increased (< 0.05), and SP content in the colon tissue significantly decreased (< 0.01); moreover, the colon showed significant inflame-mation and injury. Furthermore, the abundance of Firmicutes was increased, the abundance of Bacteroides decreased, and the abundance of decreased, while the abundance of the conditional pathogenic bacteria and Klebsiella increased. However, after treatment with MR, the time of the first black stool decreased (0.01), the number of black stools within 6 h increased, and the intestinal propulsion rate increased (< 0.05). Moreover, the content of D-xylose in the serum and the content of VIP in colon tissue significantly decreased (< 0.05), the content of SP in colon tissue significantly increased (< 0.01), and colon inflammation significantly improved. Additionally, the abundance of Firmicutes decreased, and the abundance of Bacteroides increased. The abundance of increased, and the abundance of decreased. In the model + FMT group, compared with control + FMT group, the content of VIP in colon tissue decreased (< 0.05), the content of SP in colon tissue significantly increased (< 0.01), and the abundance of probiotics, such as , decreased. In the MR + FMT group, compared with the model + FMT group, the content of VIP in colon tissue increased, the content of SP in colon tissue significantly decreased (< 0.01), and the abundance of probiotics increased.<br><br>CONCLUSIONS: STC mice with spleen deficiency show a decreased abundance of beneficial bacteria, such as , and an increased abundance of the conditional pathogenic bacteria . Furthermore, the mechanism of action of MR in treating STC may involve the regulation of intestinal movement, reduction of intestinal inflammation, elevation of intestinal absorption, and regulation of gut microbiota.}, }
@article {pmid35609771, year = {2022}, author = {Li, M and Guo, W and Dong, Y and Wang, W and Tian, C and Zhang, Z and Yu, T and Zhou, H and Gui, Y and Xue, K and Li, J and Jiang, F and Sarapultsev, A and Wang, H and Zhang, G and Luo, S and Fan, H and Hu, D}, title = {Beneficial effects of celastrol on immune balance by modulating gut microbiota in experimental ulcerative colitis.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gpb.2022.05.002}, pmid = {35609771}, issn = {2210-3244}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and the mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR in treating UC with histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight, colon length, and the decreased disease activity index (DAI) score, as well as intestinal permeability. Meanwhile, CSR down-regulated the secretion of pro-inflammatory cytokines, up-regulated the anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. It's worth noting that all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and composition, and changed the metabolic productions, which was probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provided the strong evidence that CSR may be a promising therapeutic drug for UC.}, }
@article {pmid35606800, year = {2022}, author = {Sun, Y and Sun, P and Hu, Y and Shan, L and Geng, Q and Gong, Y and Fan, H and Zhang, T and Zhou, Y}, title = {Elevated testicular apoptosis is associated with elevated sphingosine driven by gut microbiota in prediabetic sheep.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {121}, pmid = {35606800}, issn = {1741-7007}, support = {31900595//National Natural Science Foundation of China/ ; 32000582//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Men with prediabetes often exhibit concomitant low-quality sperm production or even infertility, problems which urgently require improved therapeutic options. In this study, we have established a sheep model of diet-induced prediabetes that is associated with spermatogenic defects and have explored the possible underlying metabolic causes.<br><br>RESULTS: We compared male sheep fed a normal diet with those in which prediabetes was induced by a rich diet and with a third group in which the rich diet was supplemented by melatonin. Only the rich diet group had symptoms of prediabetes, and in these sheep, we found impaired spermatogenesis characterized by a block in the development of round spermatids and an increased quantity of testicular apoptotic cells. Comparing the gut microbiomes and intestinal digest metabolomes of the three groups revealed a distinctive difference in the taxonomic composition of the microbiota in prediabetic sheep, and an altered metabolome, whose most significant feature was altered sphingosine metabolism; elevated sphingosine was also found in blood and testes. Administration of melatonin alleviated the symptoms of prediabetes, including those of impaired spermatogenesis, while restoring a more normal microbiota and metabolic levels of sphingosine. Fecal microbiota transplantation from prediabetic sheep induced elevated sphingosine levels and impaired spermatogenesis in recipient mice, indicating a causal role of gut microbiota in these phenotypes.<br><br>CONCLUSIONS: Our results point to a key role of sphingosine in the disruption of spermatogenesis in prediabetic sheep and suggest it could be a useful disease marker; furthermore, melatonin represents a potential prebiotic agent for the treatment of male infertility caused by prediabetes.}, }
@article {pmid35604764, year = {2022}, author = {Benítez-Páez, A and Hartstra, AV and Nieuwdorp, M and Sanz, Y}, title = {Species- and strain-level assessment using rrn long-amplicons suggests donor's influence on gut microbial transference via fecal transplants in metabolic syndrome subjects.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2078621}, doi = {10.1080/19490976.2022.2078621}, pmid = {35604764}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation (FMT) is currently used for treating Clostridium difficile infection and explored for other clinical applications in experimental trials. However, the effectiveness of this therapy could vary, and partly depend on the donor's bacterial species engraftment, whose evaluation is challenging because there are no cost-effective strategies for accurately tracking the microbe transference. In this regard, the precise identification of bacterial species inhabiting the human gut is essential to define their role in human health unambiguously. We used Nanopore-based device to sequence bacterial rrn operons (16S-ITS-23S) and to reveal species-level abundance changes in the human gut microbiota of a FMT trial. By assessing the donor and recipient microbiota before and after FMT, we further evaluated whether this molecular approach reveals strain-level genetic variation to demonstrate microbe transfer and engraftment. Strict control over sequencing data quality and major microbiota covariates was critical for accurately estimating the changes in gut microbial species abundance in the recipients after FMT. We detected strain-level variation via single-nucleotide variants (SNVs) at rrn regions in a species-specific manner. We showed that it was possible to explore successfully the donor-bacterial strain (e.g., Parabacteroides merdae) engraftment in recipients of the FMT by assessing the nucleotide frequencies at rrn-associated SNVs. Our findings indicate that the engraftment of donors' microbiota is to some extent correlated with the improvement of metabolic health in recipients and that parameters such as the baseline gut microbiota configuration, sex, and age of donors should be considered to ensure the success of FMT in humans. The study was prospectively registered at the Dutch Trial registry - NTR4488 (https://www.trialregister.nl/trial/4488).}, }
@article {pmid35601099, year = {2022}, author = {Wang, J and Zhou, X and Li, X and Guo, W and Zhu, Q and Zhu, B and Lu, Y and Zheng, X and Yang, D and Wang, B}, title = {Fecal Microbiota Transplantation Alters the Outcome of Hepatitis B Virus Infection in Mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {844132}, doi = {10.3389/fcimb.2022.844132}, pmid = {35601099}, issn = {2235-2988}, abstract = {The susceptibility of mice to hepatitis B virus (HBV) infection depends on their genetic background. The gut microbiota modulates the antiviral immune response in the liver and plays a protective role against HBV infection. However, whether HBV infection outcomes depend on the gut microbiota remains unclear. In this study, we assessed the gut microbiota composition in naïve BALB/c and C57BL/6 mice using 16S rRNA gene sequencing. The gut microbiota in BALB/c mice was depleted using broad-spectrum antibiotics (ABX) and then reconstituted with fecal microbiota from naïve BALB/c or C57BL/6 mice to evaluate the effect of fecal microbiota transplantation (FMT) on the outcomes of and immune response to HBV infection. We found that HBV infection outcomes and the gut microbiota composition differed between BALB/c and C57BL/6 mice. Commensal bacteria from the fecal microbiota selectively colonized the guts of ABX-treated BALB/c mice. Mice receiving fecal microbiota from BALB/c or C57BL/6 mice displayed different HBV infection outcomes. The fecal microbiota from C57BL/6 mice induced immune tolerance in the liver and prolonged HBV infection. In conclusion, HBV infection outcomes in mice are determined by the host genetic background and gut microbiota composition. Reconstitution of the gut microbiota by FMT can alter the susceptibility to HBV infection in mice.}, }
@article {pmid35600753, year = {2022}, author = {Singh, R and Stogios, N and Smith, E and Lee, J and Maksyutynsk, K and Au, E and Wright, DC and De Palma, G and Graff-Guerrero, A and Gerretsen, P and Müller, DJ and Remington, G and Hahn, M and Agarwal, SM}, title = {Gut microbiome in schizophrenia and antipsychotic-induced metabolic alterations: a scoping review.}, journal = {Therapeutic advances in psychopharmacology}, volume = {12}, number = {}, pages = {20451253221096525}, doi = {10.1177/20451253221096525}, pmid = {35600753}, issn = {2045-1253}, abstract = {Schizophrenia (SCZ) is a severe mental disorder with high morbidity and lifetime disability rates. Patients with SCZ have a higher risk of developing metabolic comorbidities such as obesity and diabetes mellitus, leading to increased mortality. Antipsychotics (APs), which are the mainstay in the treatment of SCZ, increase the risk of these metabolic perturbations. Despite extensive research, the mechanism underlying SCZ pathophysiology and associated metabolic comorbidities remains unclear. In recent years, gut microbiota (GMB) has been regarded as a 'chamber of secrets', particularly in the context of severe mental illnesses such as SCZ, depression, and bipolar disorder. In this scoping review, we aimed to investigate the underlying role of GMB in the pathophysiology of SCZ and metabolic alterations associated with APs. Furthermore, we also explored the therapeutic benefits of prebiotic and probiotic formulations in managing SCZ and AP-induced metabolic alterations. A systematic literature search yielded 46 studies from both preclinical and clinical settings that met inclusion criteria for qualitative synthesis. Preliminary evidence from preclinical and clinical studies indicates that GMB composition changes are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Fecal microbiota transplantation from SCZ patients to mice has been shown to induce SCZ-like behavioral phenotypes, further supporting the plausible role of GMB in SCZ pathogenesis. This scoping review recapitulates the preclinical and clinical evidence suggesting the role of GMB in SCZ symptomatology and metabolic adverse effects associated with APs. Moreover, this scoping review also discusses the therapeutic potentials of prebiotic/probiotic formulations in improving SCZ symptoms and attenuating metabolic alterations related to APs.}, }
@article {pmid35598286, year = {2022}, author = {Batra, M and Bhatnager, R and Kumar, A and Suneja, P and Dang, AS}, title = {Interplay between PCOS and Microbiome: The road less travelled.}, journal = {American journal of reproductive immunology (New York, N.Y. : 1989)}, volume = {}, number = {}, pages = {}, doi = {10.1111/aji.13580}, pmid = {35598286}, issn = {1600-0897}, abstract = {: Polycystic ovarian syndrome (PCOS) is a complicated neuro-endocrinal, reproductive, and metabolic condition. It encompasses patterns such as hyperandrogenism, recurrent cysts triggered by steroidogenic functional aberrations in the ovaries, overweight, chronic inflammation, and more. The underlying cause of this heterogeneous illness is obscure, although it is suspected to be driven by a blend of environmental and hereditary factors. In recent years, the connection between the microbiome and PCOS has been acknowledged and is thought to be involved in the genesis of the syndrome's emergence. Microbiota vary in different pathological features of PCOS, and fundamental pathways linked to their involvement in the commencement of diverse clinical presentations in PCOS open up a new avenue for its management . Prebiotic, probiotic, synbiotic, and fecal-microbiota-transplant, by promoting eubiosis and nullifying the effect caused by the altered microbial profile in PCOS women, can aid in management of diverse phenotypes associated with the syndrome. These microbiota-mediated treatments improve PCOS women's metabolic, inflammatory, and hormonal profiles. However, more studies are needed to elucidate the mechanisms that drive this positive effect . This article is protected by copyright. All rights reserved.}, }
@article {pmid35596224, year = {2022}, author = {Chen, H and Ye, C and Cai, B and Zhang, F and Wang, X and Zhang, J and Zhang, Z and Guo, Y and Yao, Q}, title = {Berberine inhibits intestinal carcinogenesis by suppressing intestinal pro-inflammatory genes and oncogenic factors through modulating gut microbiota.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {566}, pmid = {35596224}, issn = {1471-2407}, support = {LY21H290001//Natural Science Foundation of Zhejiang Province/ ; Z20H290002//Natural Science Foundation of Zhejiang Province/ ; 2021KY569//Medical and Health Platform Program of Zhejiang Province/ ; 2017-XK-A09//Zhejiang Provincial Project for the key discipline of Traditional Chinese Medicine/ ; 82074201//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The role of Berberine (BBR) in colorectal cancer (CRC) and gut microbiota has begun to appreciate. However, there was no direct evidence confirm that the gut microbiota regulated by BBR could inhibit CRC. This report investigated the effect of stool from BBR treated subjects and its effect on CRC.<br><br>METHODS: A mouse model for CRC was developed using azoxymethane (AOM) and dextran sulfate sodium (DSS). Intestinal tissue from affected mice were used to determine the efficacy of BBR against CRC. Stool samples were collected for the 16s rRNA gene sequencing and fecal microbiota transplantation (FMT). Finally, the mechanism of gut microbiota from BBR treated mice on CRC was explored using immunohistochemistry, RNA-Sequencing, quantitative RT-PCR, and western blot analyses.<br><br>RESULTS: BBR significantly reduced intestinal tumor development. The richness of gut microbiota were notably decreased by BBR. Specifically, the relative abundance of beneficial bacteria (Roseburia, Eubacterium, Ruminococcaceae, and Firmicutes_unclassified) was increased while the level of bacteria (Odoribacter, Muribaculum, Mucispirillum, and Parasutterella) was decreased by BBR treatment. FMT experiment determined that the mice fed with stool from BBR treated AOM/DSS mice demonstrated a relatively lower abundance of macroscopic polyps and a significantly lower expression of β-catenin, and PCNA in intestinal tissue than mice fed with stool from AOM/DSS mice. Mechanistically, intestinal tissue obtained from mice fed with stool from BBR treated AOM/DSS mice demonstrated a decreased expression of inflammatory cytokines including interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), C-C motif chemokine 1 (Ccl1), Ccl6, and C-X-C motif ligand (Cxcl9). In addition, the NF-κB expression was greatly suppressed in mice fed with stool from BBR treated AOM/DSS mice. Real-time PCR arrays revealed a down-regulation of genes involved in cell proliferation, angiogenesis, invasiveness, and metastasis in mice fed with stool from BBR treated AOM/DSS mice.<br><br>CONCLUSIONS: Stool obtained from BBR treated AOM/DSS mice was able to increase colon length while simultaneously decreasing the density of macroscopic polyps, cell proliferation, inflammatory modulators and the expression of NF-κB. Therefore, it was concluded that suppression of pro-inflammatory genes and carcinogens factors by modulating gut microbiota was an important pathway for BBR to inhibit tumor growth in conventional mice.}, }
@article {pmid35595837, year = {2022}, author = {Quaranta, G and Mandrioli, J and Bibbò, S and Guarnaccia, A and Fancello, G and Simonini, C and Amedei, A and Niccolai, E and Nannini, G and Cammarota, G and Sanguinetti, M and Masucci, L}, title = {Rummeliibacillus suwonensis: First Time Isolation from Human Feces by Culturomics.}, journal = {Current microbiology}, volume = {79}, number = {7}, pages = {197}, pmid = {35595837}, issn = {1432-0991}, support = {RF-2016-02361616.//italian ministry of health/ ; }, abstract = {Gut microbiota is a complex ecosystem composed by trillions of microorganisms that are crucial for human health or disease status. Currently, there are two methodological options to explore its complexity: metagenomics and culturomics. Culturomics is an approach that uses multiple culture conditions (days of incubation, enrichment factors and growth temperature) and MALDI-TOF mass spectrometry for the identification of bacterial species and sequencing when this method fails. In this paper, we describe how Colturomic's protocol has allowed the first isolation in human sample of Rummeliibacillus suwonensis, a Gram positive, facultative anaerobe bacterium. The bacterium was isolated from feces of a 69 years old male with amyotrophic lateral sclerosis (ALS) recruited for a clinical trial assessing safety and efficacy of fecal microbiota transplantation in ALS. The first isolation of the microorganism dates back to 2013 from the soil of a South Korean mountain area. In this report, morphological description, biochemical characterization and antibiotic susceptibility tests were performed to outline the bacterial properties.}, }
@article {pmid35593345, year = {2022}, author = {Bashir, R and Wani, IA and Ganie, MA}, title = {Insights into new therapeutic approaches for the treatment and management of polycystic ovary syndrome: An updated review.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/1381612828666220518150754}, pmid = {35593345}, issn = {1873-4286}, abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is a long-term, highly prevalent, complex heterogeneous, polygenic endocrine disorder characterized by both metabolic and reproductive disorders. It affects 6-23% of reproductive age women globally.<br><br>OBJECTIVE: This review aims to facilitate an understanding of novel PCOS management approaches and highlights the results from relevant interventional studies from animal and human studies.<br><br>METHODS: Manual search on PubMed, Cochrane, Scopus databases was performed for relevant articles, preclinical and clinical trials based on related keywords.<br><br>RESULTS: According to a multitude of studies, PCOS has evolved over time, but a substantial lag remains in management approaches. New insights into the cross-talk between muscle, brain, fat, and ovaries pointed out new therapeutic targets. This review has highlighted the efficacy of a wide spectrum of novel therapeutic agents [Phosphodiesterase-4 Inhibitors, Glucagon-like peptide-1 receptor agonists, nutritional supplements (Vitamins D and K, omega-3, prebiotics, probiotics and synbiotics), fecal microbiota transplantation (FMT) and intestinal cytokine IL-22] as PCOS therapeutic options. These novel therapies combine anti-inflammatory, insulin sensitizing, anti-obesity, and restoration of the gut microbiota and thus hold the potential to address the basic pathogenic mechanisms of PCOS.<br><br>CONCLUSION: Exhaustive, multicentric and multiethnic studies are vital to generate a network of normative data to better figure out the PCOS trajectory and change prognostic outcomes. Preclinical and clinical data is warranted to corroborate the new therapeutics and direct health care resources accordingly.}, }
@article {pmid34992261, year = {2022}, author = {Sorbara, MT and Pamer, EG}, title = {Microbiome-based therapeutics.}, journal = {Nature reviews. Microbiology}, volume = {20}, number = {6}, pages = {365-380}, pmid = {34992261}, issn = {1740-1534}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Health Promotion ; Humans ; *Microbiota ; }, abstract = {Symbiotic microorganisms inhabiting the gastrointestinal tract promote health by decreasing susceptibility to infection and enhancing resistance to a range of diseases. In this Review, we discuss our increasing understanding of the impact of the microbiome on the mammalian host and recent efforts to culture and characterize intestinal symbiotic microorganisms that produce or modify metabolites that impact disease pathology. Manipulation of the intestinal microbiome has great potential to reduce the incidence and/or severity of a wide range of human conditions and diseases, and the biomedical research community now faces the challenge of translating our understanding of the microbiome into beneficial medical therapies. Our increasing understanding of symbiotic microbial species and the application of ecological principles and machine learning are providing exciting opportunities for microbiome-based therapeutics to progress from faecal microbiota transplantation to the administration of precisely defined and clinically validated symbiotic microbial consortia that optimize disease resistance.}, }
@article {pmid35589257, year = {2022}, author = {Bajaj, JS and Ng, SC and Schnabl, B}, title = {Promises of microbiome-based therapies.}, journal = {Journal of hepatology}, volume = {76}, number = {6}, pages = {1379-1391}, doi = {10.1016/j.jhep.2021.12.003}, pmid = {35589257}, issn = {1600-0641}, abstract = {Humans harbour large quantities of microbes, including bacteria, fungi, viruses and archaea, in the gut. Patients with liver disease exhibit changes in the intestinal microbiota and gut barrier dysfunction. Preclinical models demonstrate the importance of the gut microbiota in the pathogenesis of various liver diseases. In this review, we discuss how manipulation of the gut microbiota can be used as a novel treatment approach for liver disease. We summarise current data on untargeted approaches, including probiotics and faecal microbiota transplantation, and precision microbiome-centered therapies, including engineered bacteria, postbiotics and phages, for the treatment of liver diseases.}, }
@article {pmid35587527, year = {2022}, author = {Yan, S and Chen, J and Zhu, L and Guo, T and Qin, D and Hu, Z and Han, S and Zhou, Y and Akan, OD and Wang, J and Luo, F and Lin, Q}, title = {Oryzanol Attenuates High Fat and Cholesterol Diet-Induced Hyperlipidemia by Regulating the Gut Microbiome and Amino Acid Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c00885}, pmid = {35587527}, issn = {1520-5118}, abstract = {Hyperlipidemia is intricately associated with the dysregulation of gut microbiota and host metabolomes. This study explored the antihyperlipidemic function of oryzanol and investigated whether the function of oryzanol affected the gut microbiome and its related metabolites. Hamsters were fed a standard diet (Control) and a high fat and cholesterol (HFCD) diet with or without oryzanol, separately. Our results showed that oryzanol significantly decreased HFCD-induced fat accumulation, serum total cholesterol, low-density lipoprotein cholesterol (LDL-c), LDL-c/HDL-c ratio, triglyceride, and liver steatohepatitis, attenuated HFCD-induced gut microbiota alterations, and altered amino acid concentrations in feces and the liver. We investigated the role of the gut microbiota in the observed beneficial effects; the protective effects of oryzanol were partly diminished by suppressing the gut bacteria of hamsters after using antibiotics. A fecal microbiota transplantation experiment was carried out by transplanting the feces from HFCD group hamsters or hamsters given oryzanol supplementation (as a donor hamster). Our results showed that administering the fecal liquid from oryzanol-treated hamsters attenuated HFCD-induced hyperlipidemia, significantly decreased the abundance of norank_f__Erysipelotrichaceae, norank_f__Eubacteriaceae, and norank_f__Oscillospiraceae and the concentration of tyrosine. These outcomes are significantly positively correlated with serum lipid concentration. This study illustrated that gut microbiota is the target of oryzanol in the antihyperlipidemic effect.}, }
@article {pmid35585088, year = {2022}, author = {Yan, J and Liao, C and Taylor, BP and Fontana, E and Amoretti, LA and Wright, RJ and Littmann, ER and Dai, A and Waters, N and Peled, JU and Taur, Y and Perales, MA and Siranosian, BA and Bhatt, AS and van den Brink, MRM and Pamer, EG and Schluter, J and Xavier, JB}, title = {A compilation of fecal microbiome shotgun metagenomics from hematopoietic cell transplantation patients.}, journal = {Scientific data}, volume = {9}, number = {1}, pages = {219}, pmid = {35585088}, issn = {2052-4463}, support = {R01 AI137269/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, abstract = {Hospitalized patients receiving hematopoietic cell transplants provide a unique opportunity to study the human gut microbiome. We previously compiled a large-scale longitudinal dataset of fecal microbiota and associated metadata, but we had limited that analysis to taxonomic composition of bacteria from 16S rRNA gene sequencing. Here we augment those data with shotgun metagenomics. The compilation amounts to a nested subset of 395 samples compiled from different studies at Memorial Sloan Kettering. Shotgun metagenomics describes the microbiome at the functional level, particularly in antimicrobial resistances and virulence factors. We provide accession numbers that link each sample to the paired-end sequencing files deposited in a public repository, which can be directly accessed by the online services of PATRIC to be analyzed without the users having to download or transfer the files. Then, we show how shotgun sequencing enables the assembly of genomes from metagenomic data. The new data, combined with the metadata published previously, enables new functional studies of the microbiomes of patients with cancer receiving bone marrow transplantation.}, }
@article {pmid35584163, year = {2022}, author = {Benech, N and Galperine, T and Sokol, H and , }, title = {SER-109 for Recurrent Clostridioides difficile Infection.}, journal = {The New England journal of medicine}, volume = {386}, number = {20}, pages = {1956-1957}, doi = {10.1056/NEJMc2202493}, pmid = {35584163}, issn = {1533-4406}, }
@article {pmid35579462, year = {2022}, author = {Renu, S and Deblais, L and Patil, V and Schrock, J and Kathayat, D and Srivastava, V and Feliciano-Ruiz, N and Han, Y and Ramesh, A and Lakshmanappa, YS and Ghimire, S and Dhakal, S and Rajashekara, G and Renukaradhya, GJ}, title = {Gut Microbiota of Obese Children Influences Inflammatory Mucosal Immune Pathways in the Respiratory Tract to Influenza Virus Infection: Optimization of an Ideal Duration of Microbial Colonization in a Gnotobiotic Pig Model.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0267421}, doi = {10.1128/spectrum.02674-21}, pmid = {35579462}, issn = {2165-0497}, abstract = {The impact of obesity on the human microbiota, immune maturation, and influenza virus infection has not been yet established in natural host animal models of influenza. In this study, gnotobiotic (Gn) pigs were colonized with human fecal microbiota (HFM) of obese (oHFM) or healthy lean (hHFM) children and infected at different periods (2-, 3-, and 5-weeks post-transplantation) using a zoonotic influenza virus strain. The infected oHFM pigs were characterized by lower levels of Firmicutes (Lactococcus, Lactobacillus, Turicibacter, and Streptococcus) and Actinobacteria (Bifidobacterium), which was associated with higher levels of Proteobacteria (Klebsiella), Bacteroidetes, and Verrucomicrobia (Akkermansia) compared with the infected hHFM group (P < 0.01). Furthermore, these genera significantly correlated with the expression of immune effectors, immune regulators, and inflammatory mediators, and displayed opposite trends between oHFM and hHFM groups (P < 0.01). The lymphoid and myeloid immune cell frequencies were differently modulated by the oHFM and hHFM colonization, especially apparent in the 5-weeks HFM colonized piglets. In addition, oHFM group had higher pro-inflammatory cytokines (IL-6, IL-12, TNF-α, and IFNγ) gene expression in the respiratory tract compared with the hHFM colonized pigs was detected. In conclusion, pigs colonized for longer duration, established oHFM increased the immune maturation favoring the activation of inflammatory mediators, however, the influenza virus load remained comparable with the hHFM group. Further, a longer duration of microbial colonization (5 weeks) may be required to reveal the impact of microbiome on the host immune maturation and susceptibility to influenza virus infection in the humanized Gn pig model. IMPORTANCE The diversity of gut microbiome of obese people differs markedly from that of lean healthy individuals which, in turn, influences the severity of inflammatory diseases because of differential maturation of immune system. The mouse model provides crucial insights into the mechanism(s) regulating the immune systems mediated by the gut microbiota but its applicability to humans is questionable because immune cells in mice are poorly activated in microbiota humanized mice. Several important strains of Bifidobacterium, Lactobacillus, and Clostridium fails to colonize the murine gut. Thus, understanding the role of certain important commensal gut bacterial species influences upon health and disease, a suitable large animal model like pig that supports the growth and colonization of most of the important human gut bacteria and possess comparable immunology and physiology to humans is beneficial to improve health.}, }
@article {pmid35577712, year = {2022}, author = {Piawah, S and Walker, EJ and Van Blarigan, EL and Atreya, CE}, title = {The Gut Microbiome in Colorectal Cancer.}, journal = {Hematology/oncology clinics of North America}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.hoc.2022.03.001}, pmid = {35577712}, issn = {1558-1977}, abstract = {The gut microbiome is important in human health and disease. Recent studies have begun to elucidate its specific role in colorectal cancer. The gut microbiome seems to play an integral role in colorectal cancer initiation and progression, and oncologic drug metabolism and toxicity. This review examines the associations between the gut microbiome and colorectal cancer initiation, progression, and oncologic drug metabolism, highlighting proposed mechanisms and landmark publications in this field. It also discusses potential methods of modulating the gut microbiome, underscoring the gaps in current understanding, and ends with a clinically relevant overview of microbiome research considerations and study design.}, }
@article {pmid35574751, year = {2022}, author = {Yan, Y and Peng, X and Chen, Y}, title = {[Fecal microbiota transplantation in the treatment of acute intestinal pseudo obstruction secondary to intracerebral hemorrhage: a case report and literature review].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {34}, number = {3}, pages = {306-310}, doi = {10.3760/cma.j.cn121430-20220225-00179}, pmid = {35574751}, issn = {2095-4352}, abstract = {OBJECTIVE: To analyze the clinical effects of fecal microbiota transplantation (FMT) on the treatment of acute intestinal pseudo obstruction (AIPO) secondary to intracerebral hemorrhage.<br><br>METHODS: The clinical data of a patient with AIPO secondary to intracerebral hemorrhage who was admitted to Nanfang Hospital of Southern Medical University was analyzed. The flora compositon between donor and patient was compared, finding the changes of intestinal flora before and after FMT (day 0 and day 25).<br><br>RESULTS: The main clinical findings in the patient were serious bloating, expansion of the intestinal canal and intra-abdominal hypertension. A week of conventional therapy was not effective, and the symptoms became progressively worse, affecting respiratory function.The result of fecal flora suggested the intestinal microbiota dybiosis, so FMT was attempted. After FMT, the patient's gastrointestinal symptoms were significantly relieved, and there were no further episodes within 25 days. The new result of fecal flora showed that the flora colonizing the intestine was dominated by Akkermansia and Bifidobacterium, with a significant decrease in potential pro-inflammatory and gas-producing bacteria and an increased gut microbiota diversity. The results trended to be partly consistent with the donor at 25 days after FMT: at the phylum level, the relative abundance of Bacterioidetes, Vereucomicrobia, Firmicutes and Actinobacteria were increased while Proteobacteria was decreased; at the class level, the relative abundance of Verrucomicrobiae, Bacterioidia, Actinobacteria, Coriobacteriia and Clostridia were increased and Gammaproteobacteria was decreased; at the order level, the relative abundance of Bacterioidales, Verrucomicrobiales, Clostridiale, Coriobacteriales were increased and Betaproteobacteriales, Enterobacteriales were decreased; at the family level, the relative abundance of Bifidobacteriaceae, Akkermansiaceae, Ruminococcaceae were increased and Enterobacteriaceae was decreased; at the genus level, the relative abundance of Akkermansia, Bifidobacterium were increased and Escherichia-Shigella, Klebsiella were decreased. At 1-year follow-up, the patient lived with self-care and scored 5 points in Glasgow outcome scale (GOS).<br><br>CONCLUSIONS: FMT may provide clinical benefit in treated patients with AIPO secondary to intracerebral hemorrhage, probably by regulating the intestinal microflora, and re-establishing proper intestinal barrier, to maintain intestinal homeostasis.}, }
@article {pmid35572534, year = {2022}, author = {Zhao, H and Lyu, Y and Zhai, R and Sun, G and Ding, X}, title = {Metformin Mitigates Sepsis-Related Neuroinflammation via Modulating Gut Microbiota and Metabolites.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {797312}, doi = {10.3389/fimmu.2022.797312}, pmid = {35572534}, issn = {1664-3224}, abstract = {Gut microbiota affects the functions of brains. However, its mechanism in sepsis remains unclear. This study evaluated the effect of metformin on ameliorating sepsis-related neurodamage by regulating gut microbiota and metabolites in septic rats. Cecal ligation and puncture (CLP) was used to establish the sepsis-related neurodamage animal models. Metformin therapy by gavage at 1 h after CLP administration was followed by fecal microbiota transplantation (FMT) to ensure the efficacy and safety of metformin on the sepsis-related neurodamage by regulating gut microbiota. The gut microbiota and metabolites were conducted by 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry metabolomic analysis. The brain tissue inflammation response was analyzed by histopathology and reverse transcription-polymerase chain reaction (RT-PCR). This study reported brain inflammatory response, hemorrhage in sepsis-related neurodamage rats compared with the control group (C group). Surprisingly, the abundance of gut microbiota slightly increased in sepsis-related neurodamage rats than C group. The ratio of Firmicutes/Bacteroidetes was significantly increased in the CLP group than the C group. However, no difference was observed between the CLP and the metformin-treated rats (MET group). Interestingly, the abundance of Escherichia_Shigella increased in the MET group than the C and CLP groups, while Lactobacillaceae abundance decreased. Furthermore, Prevotella_9, Muribaculaceae, and Alloprevotella related to short-chain fatty acids production increased in the sepsis-related neurodamage of metformin-treated rats. Additionally, Prevotella_9 and Muribaculaceae correlated positively to 29 metabolites that might affect the inflammatory factors in the brain. The FMT assay showed that metformin improved sepsis-related neurodamage by regulating the gut microbiota and metabolites in septic rats. The findings suggest that metformin improves the sepsis-related neurodamage through modulating the gut microbiota and metabolites in septic rats, which may be an effective therapy for patients with sepsis-related neurodamage.}, }
@article {pmid35572528, year = {2022}, author = {Kawasoe, J and Uchida, Y and Kawamoto, H and Miyauchi, T and Watanabe, T and Saga, K and Tanaka, K and Ueda, S and Terajima, H and Taura, K and Hatano, E}, title = {Propionic Acid, Induced in Gut by an Inulin Diet, Suppresses Inflammation and Ameliorates Liver Ischemia and Reperfusion Injury in Mice.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {862503}, doi = {10.3389/fimmu.2022.862503}, pmid = {35572528}, issn = {1664-3224}, abstract = {Liver ischemia and reperfusion injury (IRI) is one of the obstacles in liver surgery such as liver resection and transplantation. In this study, we investigated the preventive effect on mouse liver IRI by feeding mice with inulin, which is a heterogeneous blend of indigestible fructose polymer. Mice were fed either a control ordinary diet (CD) or an inulin diet (ID) containing 5% inulin in the CD, for 14 days before the ischemia and reperfusion (IR) maneuver. IR induced-liver damages were significantly ameliorated in the ID group, compared with those in the CD group. Feeding mice with an ID, but not a CD, elevated levels of Bacteroidetes among gut microbiota, and especially increased Bacteroides acidifaciens in mouse feces, which resulted in significant elevation of short-chain fatty acids (SCFAs) in the portal vein of mice. Among SCFAs, propionic acid (PA) was most significantly increased. The microbial gene functions related to PA biosynthesis were much higher in the fecal microbiome of the ID group compared to the CD. However, the action of PA on liver IRI has not been yet clarified. Direct intraperitoneal administration of PA alone prior to the ischemia strongly suppressed liver cell damages as well as inflammatory responses caused by liver IR. Furthermore, PA suppressed the secretion of inflammatory cytokines from peritoneal macrophages stimulated in vitro through TLR-4 with high-mobility group box 1 protein (HMGB-1), known to be released from apoptotic liver cells during the IR insult. The present study shows that PA may play a key role in the inulin-induced amelioration of mouse liver IRI.}, }
@article {pmid35571974, year = {2022}, author = {Al, KF and Craven, LJ and Gibbons, S and Parvathy, SN and Wing, AC and Graf, C and Parham, KA and Kerfoot, SM and Wilcox, H and Burton, JP and Kremenchutzky, M and Morrow, SA and Casserly, C and Meddings, J and Sharma, M and Silverman, MS}, title = {Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: A pilot randomized controlled trial.}, journal = {Multiple sclerosis journal - experimental, translational and clinical}, volume = {8}, number = {2}, pages = {20552173221086662}, doi = {10.1177/20552173221086662}, pmid = {35571974}, issn = {2055-2173}, abstract = {Background: Patients with MS have an altered gut microbiota compared to healthy individuals, as well as elevated small intestinal permeability, which may be contributing to the development and progression of the disease.<br><br>Objective: We sought to investigate if fecal microbiota transplantation was safe and tolerable in MS patients and if it could improve abnormal intestinal permeability.<br><br>Methods: Nine patients with MS were recruited and provided monthly FMTs for up to six months. The primary outcome investigated was change in peripheral blood cytokine concentrations. The secondary outcomes were gut microbiota composition, intestinal permeability, and safety (assessed with EDSS and MRI).<br><br>Results: The study was terminated early and was subsequently underpowered to assess whether peripheral blood cytokines were altered following FMTs. FMTs were safe in this group of patients. Two of five patients had elevated small intestinal permeability at baseline that improved to normal values following FMTs. Significant, donor-specific, beneficial alterations to the MS patient gut microbiota were observed following FMT.<br><br>Conclusion: FMT was safe and tolerable in this cohort of RRMS patients, may improve elevated small intestinal permeability, and has the potential to enrich for an MS-protective microbiota. Further studies with longer follow-up and larger sample sizes are required to determine if FMT is a suitable therapy for MS.}, }
@article {pmid35568180, year = {2022}, author = {Chatterjee, G and Negi, S and Basu, S and Faintuch, J and O'Donovan, A and Shukla, P}, title = {Microbiome systems biology advancements for natural well-being.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {155915}, doi = {10.1016/j.scitotenv.2022.155915}, pmid = {35568180}, issn = {1879-1026}, abstract = {Over the course of years all data from epidemiological, physiological and omics have suggested that the microbial communities play a considerable role in modulating human health. These set of microorganisms residing in the human intestine collectively known as microbiota presents a genetic repertoire that is higher in magnitude than the human genome. They play an essential role in host immunity and neuronal signaling. Rapid enhancement of sequence based screening and humanized gnotobiotic model has sparked a great deal of interest among scientists to interact the dynamic interactions of the commensal bacteria. This review focuses on systemic analysis of the gut microbiome to decipher the complexity of the host-microbe intercommunication and gives a special emphasis on the evolution of targeted precision medicine through microbiome engineering. In addition, we have also provided a comprehensive understanding of how interconnection between metabolism and biochemical reactions in a specific organism can be obtained from a metabolic network or a flux balance analysis and can help in the identification of a particular metabolite, by combining multiple datasets. The review highlights on how the genetic modification of the critical components and programming the resident microflora can be employed for targeted precision medicine. Inspite of the ongoing debate on the utility of gut microbiome we have explored on the probable new therapeutic avenues like FMT (Fecal microbiota transplant) can be utilized. This review also recapitulates integrating human-relevant 3D cellular models coupled with computational models and the metadata obtained from interventional and epidemiological studies may decipher the complex interactome of diet-microbiota-disease pathophysiology. In addition, it will also open new avenues for the development of therapeutics derived from microbiome or implementation of personalized nutrition. In addition, the identification of biomarkers can also help towards the development of new diagnostic tools and eventually will lead to strategic management of the disease.}, }
@article {pmid35563189, year = {2022}, author = {Fan, Z and Zhang, X and Shang, Y and Zou, M and Zhou, M and E, Q and Fei, S and Chen, W and Li, J and Zhang, X and Liu, X}, title = {Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries.}, journal = {International journal of molecular sciences}, volume = {23}, number = {9}, pages = {}, doi = {10.3390/ijms23094797}, pmid = {35563189}, issn = {1422-0067}, abstract = {Obesity induced by a high-fat diet (HFD) leads to the excessive consumption of primordial follicles (PFs) in the ovaries. There is systemic chronic inflammation under HFD conditions, but no previous studies have explored whether there is a certain causal relationship between HFD-induced chronic inflammation and the overactivation of PFs. Here, we showed that HFD causes disorders of intestinal microflora in mice, with five Gram-negative bacteria showing the most profound increase at the genus level compared to the normal diet (ND) groups and contributes to the production of endotoxin. Endotoxin promotes M1 macrophage infiltration in the ovaries, where they exhibit proinflammatory actions by secreting cytokines IL-6, IL-8, and TNFα. These cytokines then boost the activation of PFs by activating Signal Transducer and Activator of Transcription 3 (STAT3) signaling in follicles. Interestingly, transplantation of the HFD intestinal microflora to the ND mice partly replicates ovarian macrophage infiltration, proinflammation, and the overactivation of PFs. Conversely, transplanting the ND fecal microbiota to the HFD mice can alleviate ovarian inflammation and rescue the excessive consumption of PFs. Our findings uncover a novel and critical function of gut microbes in the process of PF overactivation under HFD conditions, and may provide a new theoretical basis for the microbial treatment of patients with premature ovarian insufficiency caused by HFD.}, }
@article {pmid35562867, year = {2022}, author = {Soriano, S and Curry, K and Wang, Q and Chow, E and Treangen, TJ and Villapol, S}, title = {Fecal Microbiota Transplantation Derived from Alzheimer's Disease Mice Worsens Brain Trauma Outcomes in Wild-Type Controls.}, journal = {International journal of molecular sciences}, volume = {23}, number = {9}, pages = {}, doi = {10.3390/ijms23094476}, pmid = {35562867}, issn = {1422-0067}, support = {R21NS106640/NH/NIH HHS/United States ; }, abstract = {Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration, both of which increase the risk and accelerate the progression of Alzheimer's disease (AD). The gut microbiome is an essential modulator of the immune system, impacting the brain. AD has been related with reduced diversity and alterations in the community composition of the gut microbiota. This study aimed to determine whether the gut microbiota from AD mice exacerbates neurological deficits after TBI in control mice. We prepared fecal microbiota transplants from 18 to 24 month old 3×Tg-AD (FMT-AD) and from healthy control (FMT-young) mice. FMTs were administered orally to young control C57BL/6 (wild-type, WT) mice after they underwent controlled cortical impact (CCI) injury, as a model of TBI. Then, we characterized the microbiota composition of the fecal samples by full-length 16S rRNA gene sequencing analysis. We collected the blood, brain, and gut tissues for protein and immunohistochemical analysis. Our results showed that FMT-AD administration stimulates a higher relative abundance of the genus Muribaculum and a decrease in Lactobacillus johnsonii compared to FMT-young in WT mice. Furthermore, WT mice exhibited larger lesion, increased activated microglia/macrophages, and reduced motor recovery after FMT-AD compared to FMT-young one day after TBI. In summary, we observed gut microbiota from AD mice to have a detrimental effect and aggravate the neuroinflammatory response and neurological outcomes after TBI in young WT mice.}, }
@article {pmid35561601, year = {2022}, author = {Wang, X and Wu, X and Cong, X and Ren, J and Li, J and Zhu, J and Dai, M and Hrabchenko, N and Du, Y and Qi, J}, title = {The functional role of fecal microbiota transplantation on Salmonella Enteritidis infection in chicks.}, journal = {Veterinary microbiology}, volume = {269}, number = {}, pages = {109449}, doi = {10.1016/j.vetmic.2022.109449}, pmid = {35561601}, issn = {1873-2542}, abstract = {The intestinal microbiota plays important roles in animal health and growth. We investigated the efficacy and mechanisms of fecal microbiota transplantation (FMT) from adult SPF chickens against Salmonella Enteritidis (SE) infection in chicks. We transplanted 160 recipient SPF chicks (1-day-old) that were randomly divided into four groups, Ca (challenge), Cb (non-challenge), Fa (FMT and challenge) and Fb (FMT without challenge). The experiment lasted 40 days. We found that FMT reduced mortality as well as liver inflammatory lesions, promoted weight gain, improved immunity, ameliorated the digestion and absorption ability and inhibited SE colonization in the liver of challenged chicks. 16S rRNA gene high-throughput sequencing indicated that SE challenge caused a significant increase in the relative abundance of Parasutterella in the cecal microbiota of the recipient chicks (P < 0.05). FMT led to the maturation of the intestinal flora of recipients and the relative abundance of the Bacteroides, Rikenellaceae_ RC9_ gut_ group, Prevotellaceae_ UCG_ 001, Prevotellaceae_ Ga6A1_ group and Parabacteroides was significantly increased (P < 0.05). FMT from adult SPF chickens regulated the intestinal microbiota of chicks and increased resistance to SE infection.}, }
@article {pmid35560552, year = {2022}, author = {Hermanson, JB and Fei, N and Miyoshi, S and Miyoshi, J and Hawkins, M and Xie, B and Sulakhe, D and Hart, J and Chang, EB and Leone, VA and Charlton, M}, title = {Dietary Cholesterol-Induced Gut Microbes Drive Nonalcoholic Fatty Liver Disease Pathogenesis in a Murine Model.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {36 Suppl 1}, number = {}, pages = {}, doi = {10.1096/fasebj.2022.36.S1.0R748}, pmid = {35560552}, issn = {1530-6860}, abstract = {Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of metabolic syndrome and major indications for liver transplantation. Western diet contributes to disease pathogenesis, partially mediated through the gut microbiome, yet mechanisms remain elusive. Human epidemiological studies identified high dietary cholesterol intake as a NAFLD risk factor and it is essential to drive disease in murine models, yet little is known about its role in reshaping gut microbiota. Using the fast food (FF) diet murine model in germ-free (GF) mice completely devoid of all microbes and their conventionally-raised (control) counterparts harboring complex microbiomes, we hypothesized high dietary cholesterol-induced gut microbiota impact NAFLD onset, progression, and severity. Male C57Bl/6 age-matched GF and control mice were fed 1 of 4 semi-purified diets: low-fat (LF); high fat (HF); FF + 0.2% high cholesterol (FFHC); FF + 2% very high cholesterol (FFVHC) for 8 or 24 weeks. Fecal gut microbiota profiles were tracked over time via Illumina MiSeq 16S rRNA gene amplicon sequencing. Serum alanine transaminase (ALT) and lipopolysaccharide binding protein (LBP, an indicator of gut barrier function) were measured throughout the study. Livers were collected for histology and Illumina NovaSeq RNA-sequencing. Despite equal caloric intake between GF and controls across diets, significant weight gain and increased liver weight to body weight ratios (P<0.05) were observed only in control mice fed FF diets. GF mice were largely protected from disease, with no elevation in plasma ALT, LBP, or histology-based NAFLD activity score (NAS) regardless of treatment. Conversely, FFVHC control mice exhibited significantly elevated plasma ALT after 8 weeks on diet, which was exacerbated at 24 weeks relative to LF control and all GF groups. FF diets significantly increased (FFHC: P<0.05; FFVHC: P<0.01) plasma LBP after 24 weeks. Control mice fed FF diets exhibited severe steatosis, where FFVHC significantly increased NAS at 8 (P<0.05) and 24 (P<0.001) weeks relative to LF control and all GF groups. Microbiota profiling revealed no change in α-diversity regardless of diet in control mice. β-diversity analysis showed HF and FF diets, particularly FFVHC, rapidly shifted gut microbiota community membership after only 4 weeks, preceding disease onset and was further exacerbated over time. Liver RNA-seq revealed FFVHC diet in control, but not GF, mice significantly enriched genes involved in the KEGG pathway, "antigen processing and presentation" (Bonferroni P<0.001) relative to HF-fed counterparts at 24 weeks. Taken together, FF diet-induced shifts in gut microbes are both a prerequisite for and precede NAFLD/NASH disease onset, which is exacerbated by increased dietary cholesterol, driving liver inflammation. These data provide unique insights into how Western diet components impact host-microbe interactions in complex liver diseases, which may aid in identifying novel therapeutic interventions.}, }
@article {pmid35548572, year = {2022}, author = {Inczefi, O and Bacsur, P and Resál, T and Keresztes, C and Molnár, T}, title = {The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {718710}, doi = {10.3389/fnut.2022.718710}, pmid = {35548572}, issn = {2296-861X}, abstract = {The leakage of the intestinal barrier and the disruption of the gut microbiome are increasingly recognized as key factors in different pathophysiological conditions, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), chronic liver diseases, obesity, diabetes mellitus, types of cancer, and neuropsychiatric disorders. In this study, the mechanisms leading to dysbiosis and "leaky gut" are reviewed, and a short summary of the current knowledge regarding different diseases is provided. The simplest way to restore intestinal permeability and the microbiota could be ideal nutrition. Further therapeutic options are also available, such as the administration of probiotics or postbiotics or fecal microbiota transplantation.}, }
@article {pmid35548562, year = {2022}, author = {Lei, J and Dong, Y and Hou, Q and He, Y and Lai, Y and Liao, C and Kawamura, Y and Li, J and Zhang, B}, title = {Intestinal Microbiota Regulate Certain Meat Quality Parameters in Chicken.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {747705}, doi = {10.3389/fnut.2022.747705}, pmid = {35548562}, issn = {2296-861X}, abstract = {Growing evidence of intestinal microbiota-muscle axis provides a possibility to improve meat quality of broilers through regulating intestinal microbiota. Water-holding capacity is a crucial factor to evaluate the meat quality. High quality of water-holding capacity is usually described as a low drip-losing rate. This study aimed to explore the relationship between intestinal microbiota and water-holding capacity of muscle in broilers. According to our results, two native breeds of broilers (the Arbor Acres broilers and the Beijing-You broilers) exhibited remarkable differences in microbiota composition. However, the regular of gut bacteria compositions gradually became similar when the two breeds of broiler were raised in a same feeding environment. Therefore, this similar regular of intestinal microbiota induced similar water-holding capacity of the muscle from the two breeds. In subsequent fecal microbiota transplantation (FMT) experiments, the intestinal microbiota community of the Arbor Acres broilers was remodeling by oral gavage of bacterial suspension that was derived from the Beijing-You broilers. Then, not only body weight and abdominal fat rate were increased, but also drip loss of muscle was decreased in the Arbor Acres broilers. Additionally, muscle fiber diameter of biceps femoris muscle and expression of MyoD1 were notably enlarged. Muscle fiber diameter and related genes were deemed as important elements for water-holding capacity of muscle. Simultaneously, we screened typical intestinal bacteria in both the two native breeds of broilers by 16S rDNA sequencing. Lachnoclostridium was the only bacteria genus associated with drip-losing rate, meat fiber diameter, body weight, and abdominal fat rate.<br><br>Importance: Higher body weight and superior meat quality in livestock imply an adequate source of protein and substantial commercial value. Regulating the intestinal microbiota of broilers is a promising approach to optimize commercial phenotypes. Our results indicate that the intestinal microbiota profile could be reconstructed by external factors, leading to advantageous changes in muscle characteristics. The cecum microbiota of native broilers have the ability to improve certain meat quality and production performance. The population of Lachnoclostridium spp. could be used to regulate body weight and drip-losing rate in broilers, but more study is needed.}, }
@article {pmid35545183, year = {2022}, author = {Ouyang, ZR and Niu, XR and Wang, WG and Zhao, JH}, title = {The role of short-chain fatty acids in Clostridioides difficile infection: A review.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {102585}, doi = {10.1016/j.anaerobe.2022.102585}, pmid = {35545183}, issn = {1095-8274}, abstract = {Clostridioides difficile is a Gram-positive, obligate anaerobic, spore-producing intestinal opportunistic pathogen. CDI outbreaks in Europe and the Americas in recent years are a major health concern. Intestinal short-chain fatty acids (SCFAs) are an important energy source for colonic epithelial cells, and the roles of SCFAs in reducing intestinal inflammation, inhibiting intestinal tumours, and regulating gut microbial homeostasis are being actively researched. Furthermore, SCFAs attenuate CDI or directly inhibit C. difficile growth through different pathways in vivo and in vitro. This review assesses the role of SCFAs in CDI and discusses the potential use of these molecules as therapeutic targets for CDI.}, }
@article {pmid35539874, year = {2018}, author = {Diao, H and Yan, HL and Xiao, Y and Yu, B and Zheng, P and He, J and Yu, J and Mao, XB and Chen, DW}, title = {Modulation of intestine development by fecal microbiota transplantation in suckling pigs.}, journal = {RSC advances}, volume = {8}, number = {16}, pages = {8709-8720}, doi = {10.1039/c7ra11234c}, pmid = {35539874}, issn = {2046-2069}, abstract = {The present study was conducted to investigate the effects of early fecal microbiota transplantation on gut development in sucking piglets. A total of 24 3 day-old DLY sucking piglets (2.11 ± 0.15) kg were randomly divided into four groups (TMP, YMP, RMP and control group (CON)), which were transplanted with intact fecal microbiota of Tibetan pig (TP), Yorkshire pig (YP), Rongchang pig (RP), and without transplantation, respectively. The whole trial lasted for 56 d. The results are as follows: when compared with the YMP and RMP treatments, TMP and CON had a lower diarrhea index (P < 0.05), TMP and CON had higher GLP-2 and ANG4 mRNA abundances in the ileum (P < 0.05), and the TMP had a higher jejunal villus height: crypt depth and a higher colonic GLP-2 mRNA abundance (P < 0.05). Moreover, when compared with the YMP and RMP treatments, TMP had an enhanced DMT1 mRNA abundance in the duodenum (P < 0.05), TMP and CON had a greater lactase activity and a higher DMT1 mRNA abundance in the jejunum (P < 0.05), and CON had a higher γ-GT activity in the jejunum (P < 0.05). The jejunal Ca2+, Mg2+-ATPase activity in TMP was higher than that in CON, and the jejunal Na+, K+-ATPase activity in TMP was higher than that in the other three treatments (P < 0.05). Besides, when compared with the YMP and RMP treatments, TMP had a lower MDA content and a higher MUC1 mRNA abundance in the jejunum (P < 0.05); CON had a higher SOD activity in the jejunum (P < 0.05), whereas TMP and CON had a higher butyric acid concentration in the colon and a lower LPS content in the serum (P < 0.05). Finally, when compared with the TMP treatment, the other three treatments had an enhanced IL-10 mRNA abundance in the colon (P < 0.05), YMP and CON had higher counts of Escherichia coli in the colonic digesta (P < 0.05), and the CON had lower counts of Lactobacillus spp in the cecal and colonic digesta (P < 0.05). These data indicated that early transplantation of the fecal microbiota from the Yorkshire pigs and Rongchang pigs to DLY suckling piglets would destroy the gut microbiota balance and thus damage intestinal health.}, }
@article {pmid35538082, year = {2022}, author = {Shin, J and Noh, JR and Choe, D and Lee, N and Song, Y and Cho, S and Kang, EJ and Go, MJ and Ha, SK and Kim, JH and Kim, YH and Kim, KS and Kim, BC and Lee, CH and Cho, BK}, title = {Comprehensive 16S rRNA and metagenomic data from the gut microbiome of aging and rejuvenation mouse models.}, journal = {Scientific data}, volume = {9}, number = {1}, pages = {197}, pmid = {35538082}, issn = {2052-4463}, support = {2019M3A9F3065867//National Research Foundation of Korea (NRF)/ ; 2018M3A9H3024759//National Research Foundation of Korea (NRF)/ ; }, abstract = {The gut microbiota is associated with the health and longevity of the host. A few methods, such as fecal microbiota transplantation and oral administration of probiotics, have been applied to alter the gut microbiome and promote healthy aging. The changes in host microbiomes still remain poorly understood. Here, we characterized both the changes in gut microbial communities and their functional potential derived from colon samples in mouse models during aging. We achieved this through four procedures including co-housing, serum injection, parabiosis, and oral administration of Akkermansia muciniphila as probiotics using bacterial 16 S rRNA sequencing and shotgun metagenomic sequencing. The dataset comprised 16 S rRNA sequencing (36,249,200 paired-end reads, 107 sequencing data) and metagenomic sequencing data (307,194,369 paired-end reads, 109 sequencing data), characterizing the taxonomy of bacterial communities and their functional potential during aging and rejuvenation. The generated data expand the resources of the gut microbiome related to aging and rejuvenation and provide a useful dataset for research on developing therapeutic strategies to achieve healthy active aging.}, }
@article {pmid35535879, year = {2022}, author = {Alsegiani, AS and Shah, ZA}, title = {The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline.}, journal = {Neural regeneration research}, volume = {17}, number = {11}, pages = {2407-2412}, doi = {10.4103/1673-5374.335837}, pmid = {35535879}, issn = {1673-5374}, abstract = {Recent emerging research on intestinal microbiota and its contribution to the central nervous system during health and disease has attracted significant attention. Age-related intestinal microbiota changes initiate brain aging and age-related neurodegenerative disorders. Aging is one of the critical predisposing risk factors for the development of neurodegenerative diseases. Maintaining a healthy gut microbiota is essential for a healthy body and aging, but dysbiosis could initiate many chronic diseases. Understanding the underlying mechanisms of gut microbiota alterations/dysbiosis will help identify biomarkers for aging-related chronic conditions. This review summarizes recent advances in microbiota-neurodegenerative disease research and will enhance our understanding of gut microbiota dysbiosis and its effects on brain aging.}, }
@article {pmid35535069, year = {2022}, author = {Philips, CA and Augustine, P}, title = {Gut Barrier and Microbiota in Cirrhosis.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {2}, pages = {625-638}, doi = {10.1016/j.jceh.2021.08.027}, pmid = {35535069}, issn = {0973-6883}, abstract = {Gut microbiota and their homeostatic functions are central to the maintenance of the intestinal mucosal barrier. The gut barrier functions as a structural, biological, and immunological barrier, preventing local and systemic invasion and inflammation of pathogenic taxa, resulting in the propagation or causation of organ-specific (liver disease) or systemic diseases (sepsis) in the host. In health, commensal bacteria are involved in regulating pathogenic bacteria, sinister bacterial products, and antigens; and help control and kill pathogenic organisms by secreting antimicrobial metabolites. Gut microbiota also participates in the extraction, synthesis, and absorption of nutrient metabolites, maintains intestinal epithelial integrity and regulates the development, homeostasis, and function of innate and adaptive immune cells. Cirrhosis is associated with local and systemic immune, vascular, and inflammatory changes directly or indirectly linked to perturbations in quality and quantity of intestinal microbiota and intestinal mucosal integrity. Dysbiosis and gut barrier dysfunction are directly involved in the pathogenesis of compensated cirrhosis and the type and severity of complications in decompensated cirrhosis, such as bacterial infections, encephalopathy, extrahepatic organ failure, and progression to acute on chronic liver failure. This paper reviews the normal gut barrier, gut barrier dysfunction, and dysbiosis-associated clinical events in patients with cirrhosis. The role of dietary interventions, antibiotics, prebiotics, probiotics, synbiotics, and healthy donor fecal microbiota transplantation (FMT) to modulate the gut microbiota for improving patient outcomes is further discussed.}, }
@article {pmid35530905, year = {2022}, author = {Alabdaljabar, MS and Aslam, HM and Veeraballi, S and Faizee, FA and Husain, BH and Iqbal, SM and Hashmi, SK}, title = {Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e23873}, doi = {10.7759/cureus.23873}, pmid = {35530905}, issn = {2168-8184}, abstract = {A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion.}, }
@article {pmid35530507, year = {2022}, author = {Lai, Z and Chen, Z and Zhang, A and Niu, Z and Cheng, M and Huo, C and Xu, J}, title = {The Gut Microbiota in Liver Transplantation Recipients During the Perioperative Period.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {854017}, doi = {10.3389/fphys.2022.854017}, pmid = {35530507}, issn = {1664-042X}, abstract = {Background: Chronic liver disease is a global problem, and an increasing number of patients receive a liver transplant yearly. The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients during the perioperative. Methods: We studied gut fecal microbial community signatures in 37 Chinese adults using 16S rRNA sequencing targeting V3-V4 hypervariable regions, with a total of 69 fecal samples. We analyzed the Alpha and Beta diversities of various groups. Then we compared the abundance of bacteria in groups at the phylum, family, and genus levels. Results: The healthy gut microbiota predominantly consisted of the phyla Firmicutes and Bacteroidestes, followed by Proteobacteria and Actinobacteria. Compared with healthy people, due to the dominant bacteria in patients with chronic liver disease losing their advantages in the gut, the antagonistic effect on the inferior bacteria was reduced. The inferior bacteria multiplied in large numbers during this process. Some of these significant changes were observed in bacterial species belonging to Enterococcus, Klebsiella, and Enterobacter, which increased in patients' intestines. There were low abundances of signature genes such as Bacteroides, Prevotella, and Ruminococcus. Blautia and Bifidobacterium (considered probiotics) almost disappeared after liver transplantation. Conclusion: There is an altered microbial composition in liver transplantation patients and a distinct signature of microbiota associated with the perioperative period.}, }
@article {pmid35528013, year = {2022}, author = {Liang, F and Lu, X and Deng, Z and Zhong, HJ and Zhang, W and Li, Q and Zhou, HH and Liou, YL and He, XX}, title = {Effect of Washed Microbiota Transplantation on Patients With Dyslipidemia in South China.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {827107}, doi = {10.3389/fendo.2022.827107}, pmid = {35528013}, issn = {1664-2392}, abstract = {Background and Aims: Although the manual crude fecal microbiota transplantation (FMT) reduces blood lipids in animal models of hyperlipidemia, its clinical effect on blood lipid metabolism in patients with hyperlipidemia and hypolipidemia remains unclear, especially in the Chinese population. It was reported that washed microbiota transplantation (WMT) was safer, more precise, and more quality-controllable than the crude FMT by manual. This study aimed to investigate the feasibility and effectiveness of WMT on lipid metabolism in the Chinese population.<br><br>Methods: Clinical data of patients with various indications who received WMT for 1-3 treatment procedures were collected. Changes in blood lipids before and after WMT, namely, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), liver fat attenuation, and liver stiffness measurement, were compared.<br><br>Results: A total of 177 patients (40 cases of hyperlipidemia, 87 cases with normal blood lipids, and 50 cases of hypolipidemia) were enrolled in the First Affiliated Hospital of Guangdong Pharmaceutical University. WMT has a significant therapeutic effect in reducing blood lipid levels (TC and TG) in the short- and medium term in patients with hyperlipidemia (p <0.05). Hyper blood lipid decreased to normal in the short-term (35.14%; p <0.001), and LDL-C changed to normal in the medium term (33.33%; p = 0.013). In the hypolipidemia group, 36.36% and 47.06% changed to normal in the short-term (p = 0.006) and medium term (p = 0.005) of therapeutic effects based on blood lipid levels. In the normal blood lipid group and the low-risk group of atherosclerotic cardiovascular disease (ASCVD), the change was not statistically significant, indicating that WMT does not increase the risk of blood lipid and ASCVD in the long-term.<br><br>Conclusions: WMT treatment changes blood lipids in patients with hyperlipidemia and hypolipidemia without serious adverse events, with no risk for increasing blood lipids and ASCVD in the long-term. There were significant decreased TC, TG, and LDL-C levels in the medium term of WMT treatment for hyperlipidemia. Therefore, the regulation of gut microbiota by WMT may indicate a new clinical method for the treatment of dyslipidemia.}, }
@article {pmid35526726, year = {2022}, author = {Kinoshita, Y and Niwa, H and Uchida-Fujii, E and Nukada, T and Ueno, T}, title = {Simultaneous daily fecal microbiota transplantation fails to prevent metronidazole-induced dysbiosis of equine gut microbiota.}, journal = {Journal of equine veterinary science}, volume = {}, number = {}, pages = {104004}, doi = {10.1016/j.jevs.2022.104004}, pmid = {35526726}, issn = {0737-0806}, abstract = {Antimicrobial administration can lead to imbalances of gastrointestinal microbiota, called dysbiosis. Dysbiosis sometimes results in diarrhea and enteritis in horses. Fecal microbiota transplantation (FMT) is used to treat affected horses, but whether it is effective as a prophylactic approach for dysbiosis in horses receiving antimicrobials remains unknown. The aim of this study was to assess the efficacy of simultaneous FMT against metronidazole-induced dysbiosis in horses. Changes in the ratios of bacterial families, determined by metagenomic analysis, were similar between the metronidazole-treated group and the simultaneous metronidazole- and FMT-treated group, notably in the Clostridiaceae, Ruminococcaceae, and Enterobacteriaceae. Differences in fecal bacterial compositions were due mainly to metronidazole administration (P = 0.0003), but not to FMT (P = 0.3136). Simultaneous FMT at 500 g of donor feces in 1 L of suspension once a day did not inhibit metronidazole-induced dysbiosis. The results show that the FMT protocol needs to be improved to prevent metronidazole-induced gut dysbiosis in horses.}, }
@article {pmid35332832, year = {2022}, author = {Crits-Christoph, A and Hallowell, HA and Koutouvalis, K and Suez, J}, title = {Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2055944}, pmid = {35332832}, issn = {1949-0984}, support = {DP5 OD029603/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Drug Resistance, Bacterial/genetics ; *Gastrointestinal Microbiome/genetics ; Genes, Bacterial ; Humans ; Metagenomics ; *Microbiota/genetics ; }, abstract = {A global rise in antimicrobial resistance among pathogenic bacteria has proved to be a major public health threat, with the rate of multidrug-resistant bacterial infections increasing over time. The gut microbiome has been studied as a reservoir of antibiotic resistance genes (ARGs) that can be transferred to bacterial pathogens via horizontal gene transfer (HGT) of conjugative plasmids and mobile genetic elements (the gut resistome). Advances in metagenomic sequencing have facilitated the identification of resistome modulators, including live microbial therapeutics such as probiotics and fecal microbiome transplantation that can either expand or reduce the abundances of ARG-carrying bacteria in the gut. While many different gut microbes encode for ARGs, they are not uniformly distributed across, or transmitted by, various members of the microbiome, and not all are of equal clinical relevance. Both experimental and theoretical approaches in microbial ecology have been applied to understand differing frequencies of ARG horizontal transfer between commensal microbes as well as between commensals and pathogens. In this commentary, we assess the evidence for the role of commensal gut microbes in encoding antimicrobial resistance genes, the degree to which they are shared both with other commensals and with pathogens, and the host and environmental factors that can impact resistome dynamics. We further discuss novel sequencing-based approaches for identifying ARGs and predicting future transfer events of clinically relevant ARGs from commensals to pathogens.}, }
@article {pmid33785557, year = {2022}, author = {Ng, SC and Xu, Z and Mak, JWY and Yang, K and Liu, Q and Zuo, T and Tang, W and Lau, L and Lui, RN and Wong, SH and Tse, YK and Li, AYL and Cheung, K and Ching, JYL and Wong, VWS and Kong, APS and Ma, RCW and Chow, EYK and Wong, SKH and Ho, ICH and Chan, PKS and Chan, FKL}, title = {Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial.}, journal = {Gut}, volume = {71}, number = {4}, pages = {716-723}, doi = {10.1136/gutjnl-2020-323617}, pmid = {33785557}, issn = {1468-3288}, mesh = {*Diabetes Mellitus, Type 2/complications/therapy ; Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Obesity/complications/microbiology/therapy ; Treatment Outcome ; }, abstract = {OBJECTIVE: The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).<br><br>DESIGN: In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.<br><br>RESULTS: Proportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05).<br><br>CONCLUSION: Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients' microbiota and improvement in lipid profile and liver stiffness.<br><br>TRIAL REGISTRATION NUMBER: NCT03127696.}, }
@article {pmid35525320, year = {2022}, author = {Ianiro, G}, title = {An artificial microbiome consortium prevents recurrence of C. difficile infection: paving the way for fecal microbiota transplantation 2.0.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2022.05.002}, pmid = {35525320}, issn = {1528-0012}, }
@article {pmid35517805, year = {2022}, author = {Liu, D and Zhao, R and Wu, Y and Wang, Y and Yang, R and Ke, X}, title = {Variation in the Efficacy of Anti-Ulcerative Colitis Treatments Reveals the Conflict Between Precipitating Compatibility of Traditional Chinese Medicine and Modern Technology: A Case of Scutellaria-Coptis.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {819851}, doi = {10.3389/fphar.2022.819851}, pmid = {35517805}, issn = {1663-9812}, abstract = {Scutellariae and Coptidis compose a classical drug pair applied in clinical practice to dispel heat, dryness, and dampness, and they are also precipitation compatible drug pairs. With modern technology, Scutellaria-Coptis is mostly prepared by decocting its components separately, while in the traditional method, it is predominantly prepared as a combined decoction. The present study investigated the effects and mechanisms of separate and combined application of Scutellaria-Coptis decoction on ulcerative colitis (UC) in mice induced by the administration of dextran sulfate sodium (DSS). Changes in body weight, colon length, and Disease Activity Index scores were also evaluated. Hematoxylin and eosin staining and other methods were used to evaluate the overall condition of animals in each group. Intestinal microflora was analyzed using 16S rRNA sequencing, while colon inflammation and antioxidant capacity were evaluated based on the levels of interleukin-6 (IL-6), IL-10, IL-1β, tumor necrosis factor-α, superoxide dismutase, malondialdehyde, and reduced glutathione. The results revealed that Scutellaria-Coptis significantly relieved colon inflammation in mice, and the combined decoction of Scutellaria-Coptis exerted a significant effect on UC. Notably, the protective effect of Scutellaria-Coptis against colon inflammation was weakened when the antibiotic mixture was partially consumed by the gut microbiota. The results of 16S rRNA sequencing showed that the group treated with combined decoction of Scutellaria-Coptis exhibited a higher intestinal microbial diversity and intestinal flora composition than the separated decoction group. Treatment of mice with UC by administering Scutellaria-Coptis decoction through intestinal flora removal (ABX) and fecal microbial transplantation (FMT) was closely associated with intestinal flora composition. In conclusion, Scutellaria-Coptis can relieve UC with an excellent effect especially when taken as a combined decoction, alleviating colon inflammation incurred by intestinal microbes to a certain extent.}, }
@article {pmid35510325, year = {2022}, author = {Cheng, F and Huang, Z and Li, Z and Wei, W}, title = {Efficacy and safety of fecal microbiota transplant for recurrent Clostridium difficile infection in inflammatory bowel disease patients: a systematic review and meta-analysis.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {}, number = {}, pages = {}, doi = {10.17235/reed.2022.8814/2022}, pmid = {35510325}, issn = {1130-0108}, abstract = {OBJECTIVES: The objective of this systematic review and meta-analysis was to evaluate the outcomes of fecal microbiota transplantation (FMT) therapy for recurrent Clostridium difficile infection (C) among inflammatory bowel disease (IBD) patients.<br><br>METHODS: Electronic databases were searched for studies that reported efficacy and/or safety of FMT therapy for recurrent CDI among IBD. We used the meta-prop command of the meta package in R to assess the efficacy and safety. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes.<br><br>RESULTS: 11 trials were included in our study. Pooled analysis showed that the initial cure rate of recurrent CDI among IBD patients was 80% (95% CI 0.76, 0.84), and the overall cure rate after two or more FMT procedures was 90% (95% CI 0.84, 0.94). The recurrence rate post FMT therapy was 25% (95% CI: 0.20, 0.32). Sub-analyses suggested that the initial cure rate of CDI in ulcerative colitis (UC) patients was higher than that in Crohn's disease (CD) patients (85% vs. 79%), with no statistically significant differences (P >0.05). No serious adverse events were noted in any of the patients post-FMT.<br><br>CONCLUSIONS: FMT is an effective and safe treatment for recurrent CDI in patients with IBD. FMT should be considered early in cases of recurrent or refractory CDI. Multiple FMT procedures can improve the cure rate of CDI.}, }
@article {pmid35506083, year = {2022}, author = {Oliveira, AC and Yang, T and Li, J and Sharma, RK and Karas, MK and Bryant, AJ and de Kloet, AD and Krause, EG and Joe, B and Richards, EM and Raizada, MK}, title = {Fecal matter transplant from Ace2 overexpressing mice counteracts chronic hypoxia-induced pulmonary hypertension.}, journal = {Pulmonary circulation}, volume = {12}, number = {1}, pages = {e12015}, doi = {10.1002/pul2.12015}, pmid = {35506083}, issn = {2045-8932}, abstract = {Recent evidence suggests pulmonary hypertension (PH), a disease of the pulmonary vasculature actually has multiorgan pathophysiology and perhaps etiology. Herein, we demonstrated that fecal matter transplantation from angiotensin-converting enzyme 2 overexpressing mice counteracted the effects of chronic hypoxia to prevent pulmonary hypertension, neuroinflammation, and gut dysbiosis in wild type recipients.}, }
@article {pmid35501923, year = {2022}, author = {Parker, A and Romano, S and Ansorge, R and Aboelnour, A and Le Gall, G and Savva, GM and Pontifex, MG and Telatin, A and Baker, D and Jones, E and Vauzour, D and Rudder, S and Blackshaw, LA and Jeffery, G and Carding, SR}, title = {Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {68}, pmid = {35501923}, issn = {2049-2618}, abstract = {BACKGROUND: Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina.<br><br>METHODS: Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing.<br><br>RESULTS: We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota.<br><br>CONCLUSIONS: These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut-brain and gut-retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. Video abstract.}, }
@article {pmid35493741, year = {2022}, author = {Xing, J and Liao, Y and Zhang, H and Zhang, W and Zhang, Z and Zhang, J and Wang, D and Tang, D}, title = {Impacts of MicroRNAs Induced by the Gut Microbiome on Regulating the Development of Colorectal Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {804689}, pmid = {35493741}, issn = {2235-2988}, mesh = {*Colorectal Neoplasms/microbiology ; Faecalibacterium prausnitzii ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; *MicroRNAs/genetics ; }, abstract = {Although a dysfunctional gut microbiome is strongly linked to colorectal cancer (CRC), our knowledge of the mediators between CRC and the microbiome is limited. MicroRNAs (miRNAs) affect critical cellular processes, such as apoptosis, proliferation, and differentiation, and contribute to the regulation of CRC progression. Increasingly, studies found that miRNAs can significantly mediate bidirectional interactions between the host and the microbiome. Notably, miRNA expression is regulated by the gut microbiome, which subsequently affects the host transcriptome, thereby influencing the development of CRC. This study typically focuses on the specific functions of the microbiome in CRC and their effect on CRC-related miRNA production and reviews the role of several bacteria on miRNA, including Fusobacterium nucleatum, Escherichia coli, enterotoxigenic Bacteroides fragilis, and Faecalibacterium prausnitzii. Based on the important roles of miRNAs and the gut microbiome in CRC, strategies for modulating miRNA expression and regulating the gut microbiome composition need to be applied, such as bioactive dietary components and fecal microorganism transplantation.}, }
@article {pmid35500802, year = {2022}, author = {Li, X and Zhao, W and Xiao, M and Yu, L and Chen, Q and Hu, X and Zhao, Y and Xiong, L and Chen, X and Wang, X and Ba, Y and Guo, Q and Wu, X}, title = {Penthorum chinense Pursh. extract attenuates non-alcholic fatty liver disease by regulating gut microbiota and bile acid metabolism in mice.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {115333}, doi = {10.1016/j.jep.2022.115333}, pmid = {35500802}, issn = {1872-7573}, abstract = {Penthorum chinense Pursh. (PCP) is commonly used as a Miao ethno-medicine and health food for liver protection in China. Gansukeli (WS3-B-2526-97) is made from the extract of PCP (PCPE) for the treatment of viral hepatitis. In recent years, PCPE has been reported in the treatment of non-alcoholic fatty liver disease (NAFLD), however its potential mechanism is not fully elucidated.<br><br>AIM OF THE STUDY: To investigate the ameliorating effect of PCPE on high-fat diet (HFD)-induced NAFLD mice and demonstrate whether its protective effect is gut microbiota dependent and associated with bile acid (BA) metabolism.<br><br>MATERIALS AND METHODS: The alleviating effect of PCPE on NAFLD was conducted on male C57BL/6J mice fed an HFD for 16 weeks, and this effect associated with gut microbiota dependent was demonstrated by pseudo-germfree mice treated with antibiotics and fecal microbiota transplantation (FMT). The composition of the gut microbiota in the cecum contents was analyzed by 16S rRNA sequencing, and the levels of BAs in liver and fecal samples were determined by UPLC/MS-MS.<br><br>RESULTS: The results showed that administration of PCPE for 8 weeks could potently ameliorate HFD-induced NAFLD and alleviate dyslipidemia and insulin resistance. Moreover, PCPE treatment alleviated gut dysbiosis, especially reducing the relative abundance of bile salt hydrolase (BSH)-producing bacteria. Furthermore, PCPE significantly increased the levels of taurine-conjugated BAs in feces, such as tauro-β-muricholic acid (T-βMCA), tauroursodesoxycholic acid (TUDCA), and taurochenodeoxycholic acid (TCDCA), and increased hepatic chenodeoxycholic acid (CDCA). The protein and mRNA expression of farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were decreased in intestine, increased taurine-conjugated BAs inhibited the intestinal signaling pathway, which was associated with increased genes expression of enzymes in the alternative BA synthesis pathway that reduced the levels of cholesterol. The increased CDCA produced via the alternative BA synthesis pathway promoted hepatic FXR activation and BA excretion.<br><br>CONCLUSION: Our study is the first time to demonstrate that PCPE could ameliorate NAFLD in HFD-induced mice by regulating the gut microbiota and BA metabolism, and from a novel view, to understand the mechanism of PCPE in NAFLD.}, }
@article {pmid35499059, year = {2022}, author = {Shen, Q and Huang, Z and Yao, J and Jin, Y}, title = {Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease.}, journal = {Journal of advanced research}, volume = {37}, number = {}, pages = {221-233}, doi = {10.1016/j.jare.2021.07.002}, pmid = {35499059}, issn = {2090-1224}, abstract = {Background: The intestinal tract is a complicated ecosystem with dynamic homeostasis via interaction of intestine and microbiota. Inflammatory bowel disease (IBD) is chronic intestinal inflammation involving dysbiosis of intestinal microenvironment. Extracellular vesicles (EVs), as vital characteristics of cell-cell and cell-organism communication, contribute to homeostasis in intestine. Recently, EVs showed excellent potential for clinical applications in disease diagnoses and therapies.<br><br>Aim of Review: Our current review discusses the modulatory functions of EVs derived from different sources in intestine, especially their effects and applications in IBD clinical therapy. EV-mediated interaction systems between host intestine and microbiota were established to describe possible mechanisms of IBD pathogenesis and its cure.<br><br>EVs are excellent vehicles for delivering molecules containing genetic information to recipient cells. Multiple pieces of evidence have illustrated that EVs participate the interaction between host and microbiota in intestinal microenvironment. In inflammatory intestine with dysbiosis of microbiota, EVs as regulators target promoting immune response and microbial reconstruction. EVs-based immunotherapy could be a promising therapeutic approach for the treatment of IBD in the near future.}, }
@article {pmid35499044, year = {2022}, author = {Wu, C and Zhao, Y and Zhang, Y and Yang, Y and Su, W and Yang, Y and Sun, L and Zhang, F and Yu, J and Wang, Y and Guo, P and Zhu, B and Wu, S}, title = {Gut microbiota specifically mediates the anti-hypercholesterolemic effect of berberine (BBR) and facilitates to predict BBR's cholesterol-decreasing efficacy in patients.}, journal = {Journal of advanced research}, volume = {37}, number = {}, pages = {197-208}, doi = {10.1016/j.jare.2021.07.011}, pmid = {35499044}, issn = {2090-1224}, abstract = {Introduction: Gut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)'s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation.<br><br>Objectives: This study aims to confirm the causal role of the gut microbiota in BBR's anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness.<br><br>Methods: The correlation between gut microbiota and BBR's inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR's anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis.<br><br>Results: Three-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy.<br><br>Conclusion: The gut microbiota is necessary and sufficient for BBR's hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy.}, }
@article {pmid35498721, year = {2022}, author = {Liu, T and Guo, Y and Lu, C and Cai, C and Gao, P and Cao, G and Li, B and Guo, X and Yang, Y}, title = {Effect of Different Pig Fecal Microbiota Transplantation on Mice Intestinal Function and Microbiota Changes During Cold Exposure.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {805815}, doi = {10.3389/fvets.2022.805815}, pmid = {35498721}, issn = {2297-1769}, abstract = {Cold stress influences intestinal processes, causing physiological and immunological responses in animals. Intestinal microbiota participates in maintaining the stability of the intestinal environment. However, phenotypic characteristics and the effects of porcine microbiota changes under cold conditions remain poorly understood. Here, the fecal microbiota of cold tolerant breed (Mashen) and cold sensitive breed (Duroc-Landrace-Yorkshire) was transferred to germ-free mice, respectively. After a cold exposure (4°C) for 21 days, intestinal function and microbe changes of mice were explored. The results showed that Mashen pigs microbiota transplantation made the body temperature of the mice stable, in which the fat weight and expression of uncoupling protein 1 (UCP1), carnitine palmitoyltransferase 1B (Cpt1b), and Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) were significantly higher (P < 0.05) than those of the control group. The results of intestinal structure and expression of serum inflammatory factors showed that fecal microbiota transplantation (FMT) mice have more intact intestinal structure and high expression of proinflammatory factor such as interleukin-4 (IL-4). The study of mice fecal microbiome characterized via 16S rRNA sequencing found that pig microbiota transplantation changed the abundance of Firmicutes. In addition, it identified discriminative features of Firmicutes in the microbiota between two breeds of pig, in which Clostridiaceae were enriched in the microbiota community of Mashen pig and Coriobacteriales were significantly (P < 0.05) enriched in the Duroc-Landrace-Yorkshire pig microbiota transplantation group based on linear discriminant analysis effect size (LEfSe) analysis. Finally, we found that the content of propionic acid and butyric acid in rectal contents significantly changed and the abundances of Clostridium and Lachnospira showed significant correlations with changes in short-chain fatty acids. The results suggest that pig fecal microbiota transplantation can alleviate the changes in physiological and biochemical indicators in mice caused by cold exposure. Mice have gut microbes altered and improved gut barrier function via fecal microbiota transplantation in pigs.}, }
@article {pmid35496818, year = {2021}, author = {Wang, Q and Wang, X and Lv, Y and Yang, C and Zhou, C and Wang, L}, title = {Changes in Rats' Gut Microbiota Composition Caused by Induced Chronic Myocardial Infarction Lead to Depression-Like Behavior.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {641084}, doi = {10.3389/fmicb.2021.641084}, pmid = {35496818}, issn = {1664-302X}, abstract = {Depression is common among patients who have chronic myocardial infarction (CMI). Despite their frequency, depression and CMI are bidirectional related conditions, each is a risk for the other, and they often co-exist, suggesting shared or interacting pathomechanisms. Accumulating data revealed the effects of gut microbiota in terms of regulating depression via the gut-brain axis. Thus, we investigated the role of gut microbial dysbiosis in CMI-induced depression-like behavior. Hierarchical cluster analysis of sucrose preference test (SPT) results was adopted to classify the CMI rats into depression-like behavior (CMI + Dep) or non-depression-like behavior (CMI + Non-Dep) phenotypes. First, 16S ribosomal RNA sequencing analysis showed both β-diversity and relative abundance of several gut bacteria significantly differed between the CMI + Dep and CMI + Non-Dep rats. Next, transplantation of fecal microbiota from CMI + Dep rats visibly altered the relative abundance of gut microbiota and also induced depression-like behavior in the antibiotics-treated pseudo-germ-free rats. In conclusion, these findings suggested that dysbiosis in gut microbial composition contributed to the onset of CMI-induced depression-like behavior and that exogenous regulation of gut microbiota composition could be a potential therapeutic strategy for CMI and related depression-like behavior.}, }
@article {pmid35495114, year = {2022}, author = {Xu, P and Lv, T and Dong, S and Cui, Z and Luo, X and Jia, B and Jeon, CO and Zhang, J}, title = {Association between intestinal microbiome and inflammatory bowel disease: Insights from bibliometric analysis.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {1716-1725}, doi = {10.1016/j.csbj.2022.04.006}, pmid = {35495114}, issn = {2001-0370}, abstract = {The gut microbiome is highly linked to inflammatory bowel disease (IBD). A total of 3890 publications related to the two terms from 2000 to 2020 were extracted from the Web of Science Core Collection to study the association from a bibliometric perspective. Publications on this topic have grown rapidly since 2008. The United States and Harvard University are the country and institution with the largest number of publications, respectively. Inflammatory Bowel Diseases is the most productive journal with 211 published articles. The most influential journal in this field is Gut with 13,359 citations. The co-citation analysis of references showed that the IBD-related topics with the highest focus are "gut microbiota," "metagenomics," "bacterial community," "fecal microbiota transplantation," "probiotics," and "colitis-associated colorectal cancer." Keyword cluster and keyword burst analyses showed that "gut microbiota," "metagenomics," and "fecal microbiota transplantation" are currently the most researched topics in the field of IBD. The literature in this field is mainly distributed between alterations of the intestinal microbiota, microbial metabolites, and related host signaling pathways. Probiotic treatment also frequently appears in literature. This bibliometric analysis can guide future research and promote the development of the field of gut microbiome and IBD.}, }
@article {pmid33687943, year = {2022}, author = {Lai, HC and Lin, TL and Chen, TW and Kuo, YL and Chang, CJ and Wu, TR and Shu, CC and Tsai, YH and Swift, S and Lu, CC}, title = {Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide.}, journal = {Gut}, volume = {71}, number = {2}, pages = {309-321}, doi = {10.1136/gutjnl-2020-322599}, pmid = {33687943}, issn = {1468-3288}, mesh = {Animals ; Bacteroidetes/*isolation &amp; purification ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Lipopolysaccharides/metabolism ; Mice ; Mice, Inbred C57BL ; Pulmonary Disease, Chronic Obstructive/*etiology/metabolism/pathology ; Smoking ; }, abstract = {OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.<br><br>DESIGN: A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.<br><br>RESULTS: Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.<br><br>CONCLUSION: The gut microbiota-lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.}, }
@article {pmid35489181, year = {2022}, author = {Ezquer, F and Quintanilla, ME and Morales, P and Santapau, D and Munita, JM and Moya-Flores, F and Ezquer, M and Herrera-Marschitz, M and Israel, Y}, title = {A dual treatment blocks alcohol binge-drinking relapse: Microbiota as a new player.}, journal = {Drug and alcohol dependence}, volume = {236}, number = {}, pages = {109466}, doi = {10.1016/j.drugalcdep.2022.109466}, pmid = {35489181}, issn = {1879-0046}, abstract = {RATIONALE: Gut microbiota communicates information to the brain. Some animals are born with a gut microbiota that predisposes to high alcohol consumption, and transplantation of fecal material from alcoholics to mice increases animal preference for ethanol. Alcohol-use-disorders are chronic conditions where relapse is the hallmark. A predictive animal model of relapse is the "alcohol deprivation effect" where ethanol re-access is allowed following chronic alcohol intake and a long alcohol deprivation. The present study evaluates the effect of gut microbiota modification on relapse, as an adjunct to N-acetylcysteine + Acetylsalicylic acid administration, which inhibits the alcohol-induced hyper-glutamatergic condition.<br><br>METHODS: Rats bred as heavy alcohol consumers (UChB) were allowed ethanol intake for one month, were deprived of alcohol for two-weeks and subsequently offered re-access to ethanol. Prior to ethanol re-access animals received orally either (i) vehicle-control, (ii) Lactobacillus-rhamnosus-GG after antibiotic treatment (LGG); (iii) N-acetylcysteine+Acetylsalicylic acid (NAC/ASA) or (iv) both treatments: LGG+ (NAC/ASA).<br><br>RESULTS: Marked binge drinking (1.75 g ethanol/kg in 60 min) and blood alcohol levels exceeding 80 mg/dl were observed in the control group upon ethanol-re-access. Lactobacillus-GG or (NAC+ASA) treatments inhibited alcohol intake by 66-80%. The combination of both treatments virtually suppressed (inhibition of 90%) the re-access binge-like drinking, showing additive effects. Treatment with NAC+ASA increased the levels of glutamate transporters xCT and GLT-1 in nucleus accumbens, while Lactobacillus-GG administration increased those of the dopamine transporter (DAT).<br><br>CONCLUSIONS: The administration of a well-accepted probiotic may be of value as an adjunct in the treatment of alcohol-use-disorders.}, }
@article {pmid35488243, year = {2022}, author = {Lu, Y and Yuan, X and Wang, M and He, Z and Li, H and Wang, J and Li, Q}, title = {Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies.}, journal = {Journal of hematology &amp; oncology}, volume = {15}, number = {1}, pages = {47}, pmid = {35488243}, issn = {1756-8722}, support = {Grant NO. 81973715//the General program of National Natural Science Foundation of China/ ; Grant NO. ZYYCXTD-C-202001//the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine/ ; Grant NO. 81301912//National Natural Science Foundation of China/ ; Grant NO. BHTPP202008//the Beijing Municipal Health and Scientific and Technological Achievements and Appropriate Technology Promotion Project/ ; Grant NO. yyzscq202003//the "High-value Patent Cultivation" project of the Beijing Friendship Hospital Affiliated to the Capital Medical University/ ; Grant NO. yyqdkt2019-40//the Research Foundation of Beijing Friendship Hospital/ ; }, abstract = {The gut microbiota have long been recognized to play a key role in human health and disease. Currently, several lines of evidence from preclinical to clinical research have gradually established that the gut microbiota can modulate antitumor immunity and affect the efficacy of cancer immunotherapies, especially immune checkpoint inhibitors (ICIs). Deciphering the underlying mechanisms reveals that the gut microbiota reprogram the immunity of the tumor microenvironment (TME) by engaging innate and/or adaptive immune cells. Notably, one of the primary modes by which the gut microbiota modulate antitumor immunity is by means of metabolites, which are small molecules that could spread from their initial location of the gut and impact local and systemic antitumor immune response to promote ICI efficiency. Mechanistic exploration provides novel insights for developing rational microbiota-based therapeutic strategies by manipulating gut microbiota, such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites, to augment the efficacy of ICI and advance the age utilization of microbiota precision medicine.}, }
@article {pmid35487886, year = {2022}, author = {Wang, B and Zhang, L and Wang, Y and Dai, T and Qin, Z and Zhou, F and Zhang, L}, title = {Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {143}, pmid = {35487886}, issn = {2059-3635}, support = {31871405 and 31571460//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31925013, 31671457 and 91753139//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The global coronavirus disease 2019 (COVID-19) pandemic is currently ongoing. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high proportion of COVID-19 patients exhibit gastrointestinal manifestations such as diarrhea, nausea, or vomiting. Moreover, the respiratory and gastrointestinal tracts are the primary habitats of human microbiota and targets for SARS-CoV-2 infection as they express angiotensin-converting enzyme-2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) at high levels. There is accumulating evidence that the microbiota are significantly altered in patients with COVID-19 and post-acute COVID-19 syndrome (PACS). Microbiota are powerful immunomodulatory factors in various human diseases, such as diabetes, obesity, cancers, ulcerative colitis, Crohn's disease, and certain viral infections. In the present review, we explore the associations between host microbiota and COVID-19 in terms of their clinical relevance. Microbiota-derived metabolites or components are the main mediators of microbiota-host interactions that influence host immunity. Hence, we discuss the potential mechanisms by which microbiota-derived metabolites or components modulate the host immune responses to SARS-CoV-2 infection. Finally, we review and discuss a variety of possible microbiota-based prophylaxes and therapies for COVID-19 and PACS, including fecal microbiota transplantation (FMT), probiotics, prebiotics, microbiota-derived metabolites, and engineered symbiotic bacteria. This treatment strategy could modulate host microbiota and mitigate virus-induced inflammation.}, }
@article {pmid35486073, year = {2022}, author = {El-Salhy, M and Mazzawi, T and Hausken, T and Hatlebakk, JG}, title = {The fecal microbiota transplantation response differs between patients with severe and moderate irritable bowel symptoms.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/00365521.2022.2064725}, pmid = {35486073}, issn = {1502-7708}, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is a promising intervention for patients with irritable bowel syndrome (IBS). The present study aimed to identify any differences in FMT response between patients with severe and moderate IBS symptoms.<br><br>MATERIALS AND METHOD: The study included the 164 patients who participated in our previous study, of which 96 (58.5%) and 68 (41.5%) had severe (S-IBS-S) and moderate (Mo-IBS-S) IBS, respectively. The patients were randomly divided into a placebo group (own feces) and 30-g and 60-g (donor feces) FMT groups. Patients completed three questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT, and provided fecal samples before and 1 month after FMT. The fecal bacteria were analyzed using the 16S rRNA gene in PCR DNA amplification covering the V3-V9 variable genes.<br><br>RESULTS: Response rates of the placebo group did not differ between S-IBS-S and Mo-IBS-S patients at 2 weeks, 1 month and 3 months after FMT. The response rates in the active treatment group were higher in S-IBS-S patients than in Mo-IBS-S patients at each observation time. FMT reduced abdominal symptoms and fatigue and improved the quality of life in patients with both severe and moderate IBS. Patients with S-IBS-S had higher levels of Eubacterium siraeum, and lower levels of Eubacterium rectale than Mo-IBS-S, after FMT.<br><br>CONCLUSION: Patients with S-IBS-S have a higher response rate to FMT and a marked improvement in fatigue and in quality of life compared with those with Mo-IBS-S. The clinical trial registration number is NCT03822299 and is available at www.clinicaltrials.gov.}, }
@article {pmid35481834, year = {2022}, author = {Zou, YT and Zhou, J and Zhu, JH and Wu, CY and Shen, H and Zhang, W and Zhou, SS and Xu, JD and Mao, Q and Zhang, YQ and Long, F and Li, SL}, title = {Gut Microbiota Mediates the Protective Effects of Traditional Chinese Medicine Formula Qiong-Yu-Gao against Cisplatin-Induced Acute Kidney Injury.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0075922}, doi = {10.1128/spectrum.00759-22}, pmid = {35481834}, issn = {2165-0497}, abstract = {Our previous study found that Qiong-Yu-Gao (QYG), a traditional Chinese medicine formula derived from Rehmanniae Radix, Poria, and Ginseng Radix, has protective effects against cisplatin-induced acute kidney injury (AKI), but the underlying mechanisms remain unknown. In the present study, the potential role of gut microbiota in the nephroprotective effects of QYG was investigated. We found that QYG treatment significantly attenuated cisplatin-induced AKI and gut dysbiosis, altered the levels of bacterial metabolites, with short-chain fatty acids (SCFAs) such as acetic acid and butyric acid increasing and uremic toxins such as indoxyl sulfate and p-cresyl sulfate reducing, and suppressed histone deacetylase expression and activity. Spearman's correlation analysis found that QYG-enriched fecal bacterial genera Akkermansia, Faecalibaculum, Bifidobacterium, and Lachnospiraceae_NK4A136_group were correlated with the altered metabolites, and these metabolites were also correlated with the biomarkers of AKI, as well as the indicators of fibrosis and inflammation. The essential role of gut microbiota was further verified by both the diminished protective effects with antibiotics-induced gut microbiota depletion and the transferable renal protection with fecal microbiota transplantation. All these results suggested that gut microbiota mediates the nephroprotective effects of QYG against cisplatin-induced AKI, potentially via increasing the production of SCFAs, thus suppressing histone deacetylase expression and activity, and reducing the accumulation of uremic toxins, thereby alleviating fibrosis, inflammation, and apoptosis in renal tissue. IMPORTANCE Cisplatin-induced acute kidney injury is the main limiting factor restricting cisplatin's clinical application. Accumulating evidence indicated the important role of gut microbiota in pathogenesis of acute kidney injury. In the present study, we have demonstrated that gut microbiota mediates the protective effects of traditional Chinese medicine formula Qiong-Yu-Gao against cisplatin-induced acute kidney injury. The outputs of this study would provide scientific basis for future clinical applications of QYG as prebiotics to treat cisplatin-induced acute kidney injury, and gut microbiota may be a promising therapeutic target for chemotherapy-induced nephrotoxicity.}, }
@article {pmid35481347, 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 = {Effects of 'Healthy' Fecal Microbiota Transplantation against the Deterioration of Depression in Fawn-Hooded Rats.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0021822}, doi = {10.1128/msystems.00218-22}, pmid = {35481347}, issn = {2379-5077}, abstract = {Depression is a recurrent, heterogeneous mood disorder occurring in more than 260 million people worldwide. Gut microbiome dysbiosis is associated with the development of depressive-like behaviors by modulating neuro-biochemical metabolism through the microbiome-gut-brain (MGB) axis. Fecal microbiota transplantation (FMT) has been proposed as a potential therapeutic solution for depression, but the therapeutic efficiency and mechanism are unknown. Here, we performed an FMT from Sprague-Dawley (SD) rats ('healthy' controls) to Fawn-hooded (FH) rats (depression model). Pre-FMT, the FH rats exhibited significantly elevated depressive-like behaviors and distinct neurotransmitter and cytokine levels compared with SD rats. Post-FMT, FH recipients receiving FH fecal microbiota (FH-FH rats) showed aggravated depressive-like behaviors, while the ones receiving SD microbiota (FH-SD rats) had significantly alleviated depressive symptoms, a significant increase in hippocampal neurotransmitters, and a significant decrease of some hippocampal cytokines than FH-FH rats. SD-FMT resulted in the FH-SD rats' gut microbiome resembling the SD donors, and a significant shift in the serum metabolome but not the hippocampal metabolome. Co-occurrence analysis suggests that SD-FMT prevented recipients' depression development via the significant decrease of gut microbial species such as Dialister sp., which led to the recipients' metabolic modulation in serum and hippocampus through the enteric nervous system, the intestinal barrier, and the blood-brain barrier. Our results provided new data pointing to multiple mechanisms of interaction for the impact of gut microbiome modulation on depression therapy. IMPORTANCE Depression is a chronic, recurrent mental disease, which could make the patients commit suicide in severe cases. Considering that gut microbiome dysbiosis could cause depressive symptoms in animals through the MGB axis, the modification of gut microbiota is expected to be a potential therapy for depression, but the daily administration of probiotics is invalid or transient. In this study, we demonstrated that the gut microbiome transferred from a healthy rat model to a depressive rat model could regulate the recipient's neurobiology and behavior via the systematic alternation of the depressive gut microbiota followed by the serum and hippocampal metabolism. These results underline the significance of understanding the impact of gut microbiota on mental disorders and suggest that 'healthy' microbiota transplantation with the function to solve the host's cerebral inflammation may serve as a novel therapeutic strategy for depression.}, }
@article {pmid35479587, year = {2022}, author = {Rapoport, EA and Baig, M and Puli, SR}, title = {Adverse events in fecal microbiota transplantation: a systematic review and meta-analysis.}, journal = {Annals of gastroenterology}, volume = {35}, number = {2}, pages = {150-163}, doi = {10.20524/aog.2022.0695}, pmid = {35479587}, issn = {1108-7471}, abstract = {Background: Fecal microbiota transplantation (FMT) is a highly efficacious procedure used most commonly for the treatment of recurrent Clostridioides difficile infection (CDI). Despite the high value of incorporating FMT into practice, there remain concerns about its safety. To the best of our knowledge, there has not been an updated meta-analysis reporting pooled rates of adverse events in FMT for CDI.<br><br>Methods: A search for studies of FMT in patients with CDI was performed with the rate of serious adverse events (SAEs) related to FMT evaluated as the primary outcome. Secondary outcomes included SAEs unrelated to FMT and minor adverse events associated with FMT. A pooled analysis was then performed.<br><br>Results: Initial search identified 378 reference articles. Data were extracted from the 61 of these studies that met the inclusion criteria, comprising 5099 patients. Pooled analysis showed that SAEs related to FMT developed in less than 1% of patients. The pooled rate of SAEs not related to FMT was higher at 2.9%. The pooled rate of minor adverse events also showed infrequent self-limited gastrointestinal and systemic discomfort.<br><br>Conclusions: This meta-analysis supports FMT as a safe option for treating recurrent CDI. Future randomized trials are needed to improve our current understanding of FMT safety and further examine the improvements in the quality of life of patients treated with FMT compared to standard therapy of antibiotics.}, }
@article {pmid35271353, year = {2022}, author = {Fobofou, SA and Savidge, T}, title = {Microbial metabolites: cause or consequence in gastrointestinal disease?.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {322}, number = {6}, pages = {G535-G552}, doi = {10.1152/ajpgi.00008.2022}, pmid = {35271353}, issn = {1522-1547}, support = {P30-DK56338//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; R01DK130517//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; U01-AI24290//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID)/ ; P01-AI152999//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID)/ ; R01-NR013497//HHS | NIH | National Institute of Nursing Research (NINR)/ ; }, mesh = {*COVID-19 ; Dysbiosis/microbiology ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Systems biology studies have established that changes in gastrointestinal microbiome composition and function can adversely impact host physiology. Notable diseases synonymously associated with dysbiosis include inflammatory bowel diseases, cancer, metabolic disorders, and opportunistic and recurrent pathogen infections. However, there is a scarcity of mechanistic data that advances our understanding of taxonomic correlations with pathophysiological host-microbiome interactions. Generally, to survive a hostile gut environment, microbes are highly metabolically active and produce trans-kingdom signaling molecules to interact with competing microorganisms and the host. These specialized metabolites likely play important homeostatic roles, and identifying disease-specific taxa and their effector pathways can provide better strategies for diagnosis, treatment, and prevention, as well as the discovery of innovative therapeutics. The signaling role of microbial biotransformation products such as bile acids, short-chain fatty acids, polysaccharides, and dietary tryptophan is increasingly recognized, but little is known about the identity and function of metabolites that are synthesized by microbial biosynthetic gene clusters, including ribosomally synthesized and posttranslationally modified peptides (RiPPs), nonribosomal peptides (NRPs), polyketides (PKs), PK-NRP hybrids, and terpenes. Here we consider how bioactive natural products directly encoded by the human microbiome can contribute to the pathophysiology of gastrointestinal disease, cancer, autoimmune, antimicrobial-resistant bacterial and viral infections (including COVID-19). We also present strategies used to discover these compounds and the biological activities they exhibit, with consideration of therapeutic interventions that could emerge from understanding molecular causation in gut microbiome research.}, }
@article {pmid35475976, year = {2022}, author = {Li, S and Zhao, X and Lin, F and Ni, X and Liu, X and Kong, C and Yao, X and Mo, Y and Dai, Q and Wang, J}, title = {Gut Flora Mediates the Rapid Tolerance of Electroacupuncture on Ischemic Stroke by Activating Melatonin Receptor through Regulating Indole-3-Propionic Acid.}, journal = {The American journal of Chinese medicine}, volume = {}, number = {}, pages = {1-28}, doi = {10.1142/S0192415X22500409}, pmid = {35475976}, issn = {1793-6853}, abstract = {Electroacupuncture (EA) is commonly used to treat cerebrovascular diseases. This study aimed to clarify the mechanisms of action of treatments of cerebral ischemic stroke from the perspective of gut microecology. We used a mouse model and cell cultures to investigate the effects of EA on the intestinal microflora in mice models of middle cerebral artery occlusion (MCAO) and the mechanisms underlying the antioxidant activities of metabolites. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota. Metabolomic analysis was performed to characterize the metabolic profile differences between the mice in the EA + MCAO and MCAO groups. Gavaging with feces relieved brain damage in mice that received EA (EA mice) more than in mice that did not (non-EA [NEA] mice). The gut microbial composition and metabolic profiles of the EA and NEA mice were different. In particular, the microbiota from the mice in the EA or EA-FMT groups generated more indole-3-propionic acid (IPA) than the microbiota from the mice in the MCAO or NEA-FMT groups. We confirmed that IPA binds to specific melatonin receptors (MTRs) in target cells and exerts antioxidant effects by adding MTR inhibitors or knocking out the MTR1 gene in vivo and in the oxygen and glucose deprivation/reperfusion models of N2a cell experiments. EA can prevent ischemic stroke by improving the composition of intestinal microbiota in MCAO mice. Moreover, this study reveals a new mechanism of intestinal flora regulation of stroke that differs from inflammation/immunity, namely gut microbiota regulates stroke by affecting IPA levels.}, }
@article {pmid35474500, year = {2022}, author = {Kumar, P and Brazel, D and DeRogatis, J and Valerin, JBG and Whiteson, K and Chow, WA and Tinoco, R and Moyers, JT}, title = {The cure from within? a review of the microbiome and diet in melanoma.}, journal = {Cancer metastasis reviews}, volume = {}, number = {}, pages = {}, pmid = {35474500}, issn = {1573-7233}, abstract = {Therapy for cutaneous melanoma, the deadliest of the skin cancers, is inextricably linked to the immune system. Once thought impossible, cures for metastatic melanoma with immune checkpoint inhibitors have been developed within the last decade and now occur regularly in the clinic. Unfortunately, half of tumors do not respond to checkpoint inhibitors and efforts to further exploit the immune system are needed. Tantalizing associations with immune health and gut microbiome composition suggest we can improve the success rate of immunotherapy. The gut contains over half of the immune cells in our bodies and increasingly, evidence is linking the immune system within our gut to melanoma development and treatment. In this review, we discuss the importance the skin and gut microbiome may play in the development of melanoma. We examine the differences in the microbial populations which inhabit the gut of those who develop melanoma and subsequently respond to immunotherapeutics. We discuss the role of dietary intake on the development and treatment of melanoma. And finally, we review the landscape of published and registered clinical trials therapeutically targeting the microbiome in melanoma through dietary supplements, fecal microbiota transplant, and microbial supplementation.}, }
@article {pmid35472435, year = {2022}, author = {Zhu, L and Ye, C and Hu, B and Xia, H and Bian, Q and Liu, Y and Kong, M and Zhou, S and Liu, H}, title = {Regulation of gut microbiota and intestinal metabolites by Poria cocos oligosaccharides improves glycolipid metabolism disturbance in high-fat diet-fed mice.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109019}, doi = {10.1016/j.jnutbio.2022.109019}, pmid = {35472435}, issn = {1873-4847}, abstract = {In this study, we aimed to explore the effect of Poria cocos oligosaccharides (PCO) on glucolipid metabolism disorder. Based on a high-fat diet (HFD)-induced obese mouse model, we demonstrated that PCO ameliorated glucose intolerance and insulin resistance, decreased the levels of blood glucose (187.8 ± 19.8 mg/dL) and insulin (566.3 ± 53.34 ng/L) in HFD-fed mice compared to the Ctrl group (140.4 ± 7.942 mg/dL for glucose, 423.2 ± 19.56 ng/L for insulin). Moreover, PCO treatment suppressed the mRNA expressions of fatty acid synthesis regulators (decreases of 68.8%, 62.8%, and 32.0% for G6Pase, FASN, and DGAT, respectively, vs HFD group) and pro-inflammatory cytokines in epididymal fat (decreases of 71.9%, 81.5%, 76.0%, 29.3%, and 63.9% for TNF-α, IL-1β, IL-6, COX-5b, and MCP-1, respectively, vs HFD group). Also, PCO treatment alleviated damage to the intestinal barrier of HFD-fed mice. By 16S rDNA gene sequencing, PCO partly restored the imbalance of gut microbiota in HFD-fed mice, accompanied by the reversal of several intestinal metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and tryptophan metabolites. By Spearman's correlation analysis, we found that the changed gut microbiota and their metabolites were significantly correlated with the alteration of metabolic markers. Finally, the significance of gut microbiota in PCO-mediated improvement on glucolipid metabolism disorder was confirmed by an antibiotic depletion experiment and fecal microbiota transplantation. In summary, PCO may be used as a novel prebiotic in the treatment of glucolipid disorders by reshaping intestinal bacteria structure. Our studies also point towards the potential of Poria cocos as a healthy food in the clinical application to metabolic diseases in the future.}, }
@article {pmid35468731, year = {2022}, author = {Hao, Y and Feng, Y and Yan, X and Chen, L and Zhong, R and Tang, X and Shen, W and Sun, Q and Sun, Z and Ren, Y and Zhang, H and Zhao, Y}, title = {Gut microbiota-testis axis: FMT improves systemic and testicular micro-environment to increase semen quality in type 1 diabetes.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {28}, number = {1}, pages = {45}, pmid = {35468731}, issn = {1528-3658}, support = {31772408//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Clinical data suggest that male reproductive dysfunction especially infertility is a critical issue for type 1 diabetic patient (T1D) because most of them are at the reproductive age. Gut dysbiosis is involved in T1D related male infertility. However, the improved gut microbiota can be used to boost spermatogenesis and male fertility in T1D remains incompletely understood.<br><br>METHODS: T1D was established in ICR (CD1) mice with streptozotocin. Alginate oligosaccharide (AOS) improved gut microbiota (fecal microbiota transplantation (FMT) from AOS improved gut microbiota; A10-FMT) was transplanted into the T1D mice by oral administration. Semen quality, gut microbiota, blood metabolism, liver, and spleen tissues were determined to investigate the beneficial effects of A10-FMT on spermatogenesis and underlying mechanisms.<br><br>RESULTS: We found that A10-FMT significantly decreased blood glucose and glycogen, and increased semen quality in streptozotocin-induced T1D subjects. A10-FMT improved T1D-disturbed gut microbiota, especially the increase in small intestinal lactobacillus, and blood and testicular metabolome to produce n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to ameliorate spermatogenesis and semen quality. Moreover, A10-FMT can improve spleen and liver functions to strengthen the systemic environment for sperm development. FMT from gut microbiota of control animals (Con-FMT) produced some beneficial effects; however, to a smaller extent.<br><br>CONCLUSIONS: AOS-improved gut microbiota (specific microbes) may serve as a novel, promising therapeutic approach for the improvement of semen quality and male fertility in T1D patients via gut microbiota-testis axis.}, }
@article {pmid35467645, year = {2022}, author = {Xiao, Y and Zhong, XS and Liu, X and Li, Q}, title = {Therapeutic Evaluation of Fecal Microbiota Transplantation in an Interleukin 10-deficient Mouse Model.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {182}, pages = {}, doi = {10.3791/63350}, pmid = {35467645}, issn = {1940-087X}, abstract = {With the development of microecology in recent years, the relationship between intestinal bacteria and inflammatory bowel disease (IBD) has attracted considerable attention. Accumulating evidence suggests that dysbiotic microbiota plays an active role in triggering or worsening the inflammatory process in IBD and that fecal microbiota transplantation (FMT) is an attractive therapeutic strategy since transferring a healthy microbiota to IBD patient could restore the appropriate host-microbiota communication. However, the molecular mechanisms are unclear, and the efficacy of FMT has not been very well established. Thus, further studies in animal models of IBD are necessary. In this method, we applied FMT from wild-type C57BL/6J mice to IL-10 deficient mice, a widely used mouse model of colitis. The study elaborates on collecting fecal pellets from the donor mice, making the fecal solution/suspension, administering the fecal solution, and monitoring the disease. We found that FMT significantly mitigated the cardiac impairment in IL-10 knockout mice, underlining its therapeutic potential for IBD management.}, }
@article {pmid35467388, year = {2022}, author = {Jing, Y and Bai, F and Wang, L and Yang, D and Yan, Y and Wang, Q and Zhu, Y and Yu, Y and Chen, Z}, title = {Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0017722}, doi = {10.1128/spectrum.00177-22}, pmid = {35467388}, issn = {2165-0497}, abstract = {The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including β-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of β-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that β-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord. IMPORTANCE FMT treatment shows a profound impact on the microenvironment that involves microcirculation, blood-spinal cord-barrier, activation of immune cells, and secretion of neurotrophic factors. Analysis of metabolic profiles reveals around 22 differentially detected metabolites between the groups, and β-alanine was further chosen for functional validation experiments. Supplementation of SCI mice with β-alanine significantly improves neuronal survival, and the integrity of blood-spinal cord-barrier at the lesion site, suggesting that β-alanine might be one of the mediators following FMT that has contributed to the recovery.}, }
@article {pmid35465162, year = {2022}, author = {Feng, T and Liu, Y}, title = {Microorganisms in the reproductive system and probiotic's regulatory effects on reproductive health.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {1541-1553}, doi = {10.1016/j.csbj.2022.03.017}, pmid = {35465162}, issn = {2001-0370}, abstract = {The presence of microbial communities in the reproductive tract has been revealed, and this resident microbiota is involved in the maintenance of health. Intentional modulation via probiotics has been proposed as a possible strategy to enhance reproductive health and reduce the risk of diseases. The male seminal microbiota has been suggested as an important factor that influences a couple's health, pregnancy outcomes, and offspring health. Probiotics have been reported to play a role in male fertility and to affect the health of mothers and offspring. While the female reproductive microbiota is more complicated and has been identified in both the upper and lower reproductive systems, they together contribute to health maintenance. Probiotics have shown regulatory effects on the female reproductive tract, thereby contributing to homeostasis of the tract and influencing the health of offspring. Further, through transmission of bacteria or through other indirect mechanisms, the parent's reproductive microbiota and probiotic intervention influence infant gut colonization and immunity development, with potential health consequences. In vitro and in vivo studies have explored the mechanisms underlying the benefits of probiotic administration and intervention, and an array of positive results, such as modulation of microbiota composition, regulation of metabolism, promotion of the epithelial barrier, and improvement of immune function, have been observed. Herein, we review the state of the art in reproductive system microbiota and its role in health and reproduction, as well as the beneficial effects of probiotics on reproductive health and their contributions to the prevention of associated diseases.}, }
@article {pmid35463939, year = {2022}, author = {Hammeken, LH and Baunwall, SMD and Dahlerup, JF and Hvas, CL and Ehlers, LH}, title = {Health-related quality of life in patients with recurrent Clostridioides difficile infections.}, journal = {Therapeutic advances in gastroenterology}, volume = {15}, number = {}, pages = {17562848221078441}, doi = {10.1177/17562848221078441}, pmid = {35463939}, issn = {1756-283X}, abstract = {Background: The health-related quality of life (HrQoL) can be substantially affected in patients with recurrent Clostridioides difficile infection (rCDI) but the impact of effective treatment of the infection remains unclear. This study aimed to evaluate the HrQoL in patients with rCDI and estimate the gain in HrQoL associated with effective treatment of rCDI.<br><br>Methods: Patients' HrQoL was estimated based on EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaires obtained from a Danish randomised controlled trial (RCT). In the RCT, 64 patients with rCDI were randomised to receive either vancomycin (n = 16), fidaxomicin (n = 24) or faecal microbiota transplantation (FMT) preceded by vancomycin (n = 24). The primary outcome in the RCT was rCDI resolution. Patients were closely monitored during the RCT, and rescue FMT was offered to those who failed their primary treatment. Patients' HrQoL was measured at baseline and at 8- and 26-weeks follow-up. Linear regression analyses conditional on the differences between baseline and follow-up measurements were used to assess statistical significance (p < 0.05).<br><br>Results: Within 26 weeks of follow-up, 13 (81%) patients treated with vancomycin, 12 (50%) patients treated with fidaxomicin, and 3 (13%) patients treated with FMT had a subsequent recurrence and received a rescue FMT. The average HrQoL for untreated patients with rCDI was 0.675. After receiving effective treatment, this value increased by 0.139 to 0.813 (p < 0.001) at week 8 and by 0.098 to 0.773 (p = 0.003) at week 26 of follow-up compared with baseline.<br><br>Conclusion: The HrQoL was adversely affected in patients with an active episode of rCDI but increased substantially after receiving an effective treatment algorithm in which rescue FMT was provided in case of a primary treatment failure.<br><br>Trial registration: The RCT was preregistered at EudraCT (j.no. 2015-003004-24, https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003004-24/results) and at ClinicalTrials.gov (study identifier NCT02743234, https://clinicaltrials.gov/ct2/show/NCT02743234).}, }
@article {pmid35462505, year = {2022}, author = {Zhou, Y and Li, YY and Liu, Y}, title = {[Effect of fecal microbiota transplantation on type 1 diabetes mellitus in non-obese diabetic mice and its underlying mechanism].}, journal = {Zhonghua yi xue za zhi}, volume = {102}, number = {16}, pages = {1224-1231}, doi = {10.3760/cma.j.cn112137-20210907-02043}, pmid = {35462505}, issn = {0376-2491}, support = {82070849, 81770778, 81800735//National Natural Science Foundation of China/ ; 20182015//Innovation and Entrepreneurship Team Project in Jiangsu Province/ ; }, abstract = {Objective: To investigate the effects of fecal microbiota transplantation (FMT) on non-obese diabetic (NOD) mice of type 1 diabetes mellitus (T1DM) and its underlying mechanisms. Methods: A total of 8-9 week-female NOD mice were randomly divided into control (n=36) and FMT groups (n=36) according to the random number table. Fecal microbiota from C57BL/6 mice were transplanted into FMT group, and control group were transplanted with microbiota from themselves, once every two days for 5 times. The insulitis score and incidence of T1DM were compared between two groups;16S rRNA gene sequencing was used to evaluate the structure of fecal bacteria in NOD mice. The expressions of intestinal barrier related genes were detected by real-time quantitative PCR. The proportions of regulatory T cells (Tregs), helper T cell (Th)-1 and Th17 in the enteric-pancreatic immune axis were detected by flow cytometry. Amino acid in serum was measured by amino acid metabolomics. Results: Incidence of T1DM in NOD mice from FMT group was 40.9% (9/22), lower than 72.7% (13/22) from control group at 26 weeks of age (P=0.034). FMT promoted colonization of probiotics such as Lactobacillus, Clostridium_sp_ND2, Candidatus_Arthromitus and Clostridiaceae_1; mRNA of intestinal barrier related genes were up-regulated in FMT group [ mucins(Muc)-1: 0.93±0.29 vs 2.97±0.79, P=0.036; Muc2: 0.72±0.39 vs 10.70±3.54, P=0.019;Muc3: 1.79±0.69 vs 10.97±2.78, P=0.009;Muc4: 1.01±0.23 vs 2.42±0.49, P=0.029;Occludin(Ocln): 0.96±0.08 vs 1.81±0.36, P=0.045; Claudin(Cldn)-1:0.94±0.17 vs 2.20±0.43, P=0.022] compared to control. The proportions of Treg in mesenteric lymphoid node, pancreatic lymph node and peyer's patches of FMT group [(6.10±0.49)% vs (7.54±0.27)%, P=0.020;(5.28±0.39)% vs (6.42±0.34)%, P=0.048;(6.78±0.42)% vs (7.88±0.13)%, P=0.029] were increased compared to control,while proportions of Th1 [(1.02±0.06)% vs (0.83±0.06)%, P=0.040;(0.82±0.10)% vs (0.56±0.05)%, P=0.038;(1.28±0.12) vs (0.85±0.07), P=0.012] and proportions of Th17 [(0.40±0.01)% vs (0.30±0.02)%, P=0.004;(0.40±0.02)% vs (0.31±0.02)%, P=0.008;(0.51±0.06) vs (0.36±0.02), P=0.027] were decreased. The contents of leucine [(92.86±7.32) vs (91.87±12.62) μmol/L, P=0.027], valine [(162.74±15.97) vs (155.89±25.70) μmol/L, P=0.046] and isoleucine [(75.65±5.59) vs (73.61±9.67) μmol/L, P=0.048] in serum were decreased in FMT group. Conclusions: FMT can alleviate insulitis and T1DM occurrence in NOD mice, of which mechanism may be related to remodeling gut microbiota and improving intestinal barrier function, affecting immune response of enteric-pancreatic immune axis, correcting amino acid metabolism disorder and reducing the accumulation of branch chain amino acids in NOD mice.}, }
@article {pmid35461908, year = {2022}, author = {Macareño-Castro, J and Solano-Salazar, A and Dong, LT and Mohiuddin, M and Espinoza, JL}, title = {Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review.}, journal = {The Journal of infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jinf.2022.04.028}, pmid = {35461908}, issn = {1532-2742}, abstract = {The prevalence of Carbapenem-resistant Enterobacteriaceae (CRE) has increased dramatically in recent years and has become a global public health issue. Since carbapenems are considered the last drugs of choice, infections caused by these pathogens are difficult to treat and carry a high risk of mortality. Several antibiotic combination regimens have been utilized for the management of CRE infections or to eradicate colonization in CRE carriers with variable clinical responses. In addition, recent studies have explored the use of fecal microbiota transplantation (FMT) to eradicate CRE infections. Here, we conducted a systematic review of publications in which FMT was used to eliminate CRE colonization in infected individuals. We searched the PubMed, Cochrane, and Medline databases up to November 30, 2021. Ten studies (209 patients) met the inclusion criteria for this review with three articles describing retrospective cohorts (n = 53 patients) and seven reporting prospective data (n = 156 patients), including one randomized open-label clinical trial. All studies were published between 2017 and 2021 with eight studies from Europe and two from South Korea. There were substantial variations in terms of outcome measurements and study endpoint among these studies. Among the 112 FMT recipients with confirmed CRE colonization, CRE decolonization was reported in 55/90 cases at one month after FMT and at the end of the study follow-up (6-12 months), decolonization was documented in 74/94 (78.7%) patients. The predominant CRE strains reported were Klebsiella pneumoniae and Escherichia coli and the most frequently documented carbapenemases were KPC, OXA-48, and NDM. In general, FMT was well tolerated, with no severe complications reported even in immunosuppressed patients and in those with multiple underlying conditions. In conclusion, FMT appears to be safe and effective in eradicating CRE colonization, however, more studies, especially randomized trials, are needed to validate the safety and clinical utility of FMT for CRE eradication.}, }
@article {pmid35461318, year = {2022}, author = {Hou, K and Wu, ZX and Chen, XY and Wang, JQ and Zhang, D and Xiao, C and Zhu, D and Koya, JB and Wei, L and Li, J and Chen, ZS}, title = {Microbiota in health and diseases.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {135}, pmid = {35461318}, issn = {2059-3635}, abstract = {The role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, microbiota can be classified into gut, oral, respiratory, and skin microbiota. The microbial communities are in symbiosis with the host, contributing to homeostasis and regulating immune function. However, microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases (CVDs), cancers, respiratory diseases, etc. In this review, we discuss the current knowledge of how microbiota links to host health or pathogenesis. We first summarize the research of microbiota in healthy conditions, including the gut-brain axis, colonization resistance and immune modulation. Then, we highlight the pathogenesis of microbiota dysbiosis in disease development and progression, primarily associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Finally, we introduce the clinical approaches that utilize microbiota for disease treatment, such as microbiota modulation and fecal microbial transplantation.}, }
@article {pmid35458209, year = {2022}, author = {Thye, AY and Law, JW and Tan, LT and Thurairajasingam, S and Chan, KG and Letchumanan, V and Lee, LH}, title = {Exploring the Gut Microbiome in Myasthenia Gravis.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/nu14081647}, pmid = {35458209}, issn = {2072-6643}, support = {FRGS/1/2019/SKK08/MUSM/02/7//Fundamental Research Grant Scheme/ ; STG-000051//Jeffrey Cheah School of Medicine and Health Sciences Strategic Grant 2021/ ; }, abstract = {The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host's antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota's relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG's clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.}, }
@article {pmid35458198, year = {2022}, author = {Liu, X and Hu, G and Wang, A and Long, G and Yang, Y and Wang, D and Zhong, N and Jia, J}, title = {Black Tea Reduces Diet-Induced Obesity in Mice via Modulation of Gut Microbiota and Gene Expression in Host Tissues.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/nu14081635}, pmid = {35458198}, issn = {2072-6643}, abstract = {Black tea was reported to alter the microbiome populations and metabolites in diet-induced obese mice and displays properties that prevent obesity, but the underlying mechanism of the preventative effect of black tea on high-fat diet (HFD) induced obesity has not been elucidated. Epigenetic studies are a useful tool for determining the relationship between obesity and environment. Here, we show that the water extract of black tea (Lapsang souchong, LS) reverses HFD-induced gut dysbiosis, alters the tissue gene expression, changes the level of a major epigenetic modification (DNA methylation), and prevents obesity in HFD feeding mice. The anti-obesity properties of black tea are due to alkaloids, which are the principal active components. Our data indicate that the anti-obesity benefits of black tea are transmitted via fecal transplantation, and the change of tissue gene expression and the preventative effects on HFD-induced obesity in mice of black tea are dependent on the gut microbiota. We further show that black tea could regulate the DNA methylation of imprinted genes in the spermatozoa of high-fat diet mice. Our results show a mechanistic link between black tea, changes in the gut microbiota, epigenetic processes, and tissue gene expression in the modulation of diet-induced metabolic dysfunction.}, }
@article {pmid35456788, year = {2022}, author = {van Thiel, IAM and Rahman, S and Hakvoort, TBM and Davids, M and Verseijden, C and van Hamersveld, PHP and Bénard, MV and Lodders, MH and Boekhout, T and van den Wijngaard, RM and Heinsbroek, SEM and Ponsioen, CY and de Jonge, WJ}, title = {Fecal Filobasidium Is Associated with Clinical Remission and Endoscopic Response following Fecal Microbiota Transplantation in Mild-to-Moderate Ulcerative Colitis.}, journal = {Microorganisms}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/microorganisms10040737}, pmid = {35456788}, issn = {2076-2607}, support = {LSHM17028//Health Holland/ ; LSHM20085//Health Holland/ ; }, abstract = {Fecal microbiota transplantation (FMT) has the potential to restore (bacterial and fungal) microbial imbalance in ulcerative colitis (UC) patients and contribute to disease remission. Here, we aimed to identify fecal fungal species associated with the induction of clinical remission and endoscopic response to FMT for patients with mild-to-moderate ulcerative colitis. We analyzed the internal transcribed spacer 1 (ITS1)-based mycobiota composition in fecal samples from patients (n = 31) and donors (n = 7) that participated previously in a double-blinded randomized control trial evaluating the efficacy of two infusions of donor FMT compared with autologous FMT. The abundance of the yeast genus Filobasidium in fecal material used for transplantation was shown to correlate with clinical remission following FMT, irrespective of its presence in the material of donor or autologous fecal microbiota transfer. The amplified sequence variants within the genus Filobasidium most closely resembled Filobasidium magnum. Monocyte-derived macrophages and HT29 epithelial cells were stimulated with fungal species. Especially Filobasidium floriforme elicited an IL10 response in monocyte-derived macrophages, along with secretion of other cytokines following stimulation with other Filobasidium species. No effect of Filobasidium spp. was seen on epithelial wound healing in scratch assays. In conclusion, the enriched presence of Filobasidium spp. in donor feces is associated with the positive response to FMT for patients with UC and hence it may serve as a predictive fungal biomarker for successful FMT.}, }
@article {pmid35456735, year = {2022}, author = {Monteiro, RC and Rafeh, D and Gleeson, PJ}, title = {Is There a Role for Gut Microbiome Dysbiosis in IgA Nephropathy?.}, journal = {Microorganisms}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/microorganisms10040683}, pmid = {35456735}, issn = {2076-2607}, support = {11-IDEX-0005-02//Agence Nationale de la Recherche/ ; EQU201903007816//Fondation pour la Recherche Stratégique/ ; }, abstract = {Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and one of the leading causes of renal failure worldwide. The pathophysiology of IgAN involves nephrotoxic IgA1-immune complexes. These complexes are formed by galactose-deficient (Gd) IgA1 with autoantibodies against the hinge region of Gd-IgA1 as well as soluble CD89, an immune complex amplifier with an affinity for mesangial cells. These multiple molecular interactions result in the induction of the mesangial IgA receptor, CD71, injuring the kidney and causing disease. This review features recent immunological and microbiome studies that bring new microbiota-dependent mechanisms developing the disease based on data from IgAN patients and a humanized mouse model of IgAN. Dysbiosis of the microbiota in IgAN patients is also discussed in detail. Highlights of this review underscore that nephrotoxic IgA1 in the humanized mice originates from mucosal surfaces. Fecal microbiota transplantation (FMT) experiments in mice using stools from patients reveal a possible microbiota dysbiosis in IgAN with the capacity to induce progression of the disease whereas FMT from healthy hosts has beneficial effects in mice. The continual growth of knowledge in IgAN patients and models can lead to the development of new therapeutic strategies targeting the microbiota to treat this disease.}, }
@article {pmid35456041, year = {2022}, author = {Sonali, S and Ray, B and Ahmed Tousif, H and Rathipriya, AG and Sunanda, T and Mahalakshmi, AM and Rungratanawanich, W and Essa, MM and Qoronfleh, MW and Chidambaram, SB and Song, BJ}, title = {Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review.}, journal = {Cells}, volume = {11}, number = {8}, pages = {}, doi = {10.3390/cells11081362}, pmid = {35456041}, issn = {2073-4409}, abstract = {Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus-pituitary-adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut-brain axis (GBA) for the effective management of depressive behavior and anxiety.}, }
@article {pmid35455639, year = {2022}, author = {Di Domenico, M and Ballini, A and Boccellino, M and Scacco, S and Lovero, R and Charitos, IA and Santacroce, L}, title = {The Intestinal Microbiota May Be a Potential Theranostic Tool for Personalized Medicine.}, journal = {Journal of personalized medicine}, volume = {12}, number = {4}, pages = {}, doi = {10.3390/jpm12040523}, pmid = {35455639}, issn = {2075-4426}, abstract = {The human intestine is colonized by a huge number of microorganisms from the moment of birth. This set of microorganisms found throughout the human body, is called the microbiota; the microbiome indicates the totality of genes that the microbiota can express, i.e., its genetic heritage. Thus, microbiota participates in and influences the proper functioning of the organism. The microbiota is unique for each person; it differs in the types of microorganisms it contains, the number of each microorganism, and the ratio between them, but mainly it changes over time and under the influence of many factors. Therefore, the correct functioning of the human body depends not only on the expression of its genes but also on the expression of the genes of the microorganisms it coexists with. This fact makes clear the enormous interest of community science in studying the relationship of the human microbiota with human health and the incidence of disease. The microbiota is like a unique personalized "mold" for each person; it differs quantitatively and qualitatively for the microorganisms it contains together with the relationship between them, and it changes over time and under the influence of many factors. We are attempting to modulate the microbial components in the human intestinal microbiota over time to provide positive feedback on the health of the host, from intestinal diseases to cancer. These interventions to modulate the intestinal microbiota as well as to identify the relative microbiome (genetic analysis) can range from dietary (with adjuvant prebiotics or probiotics) to fecal transplantation. This article researches the recent advances in these strategies by exploring their advantages and limitations. Furthermore, we aim to understand the relationship between intestinal dysbiosis and pathologies, through the research of resident microbiota, that would allow the personalization of the therapeutic antibiotic strategy.}, }
@article {pmid35453611, year = {2022}, author = {Lian, WS and Wang, FS and Chen, YS and Tsai, MH and Chao, HR and Jahr, H and Wu, RW and Ko, JY}, title = {Gut Microbiota Ecosystem Governance of Host Inflammation, Mitochondrial Respiration and Skeletal Homeostasis.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/biomedicines10040860}, pmid = {35453611}, issn = {2227-9059}, support = {NHRI-EX110-11029SI//National Health Research Institutes/ ; CORPG8L0361, and CMRPG8K0041-43//Chang Gung Memorial Hospital/ ; }, abstract = {Osteoporosis and osteoarthritis account for the leading causes of musculoskeletal dysfunction in older adults. Senescent chondrocyte overburden, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability are prominent features of these age-mediated skeletal diseases. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Dysregulation of gut microflora correlates with development of osteoarthritis and osteoporosis in humans and rodents. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes and bone cells to regulate joint and bone tissue homeostasis. Modulating the abundance of Lactobacillus and Bifidobacterium, or the ratio of Firmicutes and Bacteroidetes, in the gut microenvironment by probiotics or fecal microbiota transplantation is advantageous to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue. Supplementation with gut microbiota-derived metabolites potentially slows down development of osteoarthritis and osteoporosis. This review provides latest molecular and cellular insights into the biological significance of gut microorganisms and primary and secondary metabolites important to cartilage and bone integrity. It further highlights treatment options with probiotics or metabolites for modulating the progression of these two common skeletal disorders.}, }
@article {pmid35453587, year = {2022}, author = {Biliński, J and Jasiński, M and Basak, GW}, title = {The Role of Fecal Microbiota Transplantation in the Treatment of Acute Graft-versus-Host Disease.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/biomedicines10040837}, pmid = {35453587}, issn = {2227-9059}, abstract = {The number of allogeneic hematopoietic stem cell transplantations conducted worldwide is constantly rising. Together with that, the absolute number of complications after the procedure is increasing, with graft-versus-host disease (GvHD) being one of the most common. The standard treatment is steroid administration, but only 40-60% of patients will respond to the therapy and some others will be steroid-dependent. There is still no consensus regarding the best second-line option, but fecal microbiota transplantation (FMT) has shown encouraging preliminary and first clinically relevant results in recent years and seems to offer great hope for patients. The reason for treatment of steroid-resistant acute GvHD using this method derives from studies showing the significant immunomodulatory role played by the intestinal microbiota in the pathogenesis of GvHD. Depletion of commensal microbes is accountable for aggravation of the disease and is associated with decreased overall survival. In this review, we present the pathogenesis of GvHD, with special focus on the special role of the gut microbiota and its crosstalk with immune cells. Moreover, we show the results of studies and case reports to date regarding the use of FMT in the treatment of steroid-resistant acute GvHD.}, }
@article {pmid35451337, year = {2022}, author = {Caira-Chuquineyra, B and Fernandez-Guzman, D and Soriano-Moreno, DR and Fernandez-Morales, J and Flores-Lovon, K and Medina-Ramirez, SA and Gonzales-Uribe, AG and Pelayo-Luis, IP and Gonzales-Zamora, JA and Huaringa-Marcelo, J}, title = {Fecal microbiota transplantation for people living with HIV: A scoping review.}, journal = {AIDS research and human retroviruses}, volume = {}, number = {}, pages = {}, doi = {10.1089/AID.2022.0016}, pmid = {35451337}, issn = {1931-8405}, abstract = {The aim of the present scoping review was to determine the characteristics of studies evaluating fecal microbiota transplantation (FMT), as well as its effects and safety as a therapeutic intervention for people living with HIV. We conducted a scoping review following the methodology of the Joanna Briggs Institute. We searched the following databases: PubMed, Web of Science, Scopus, Embase, Cochrane Library, and Medline until September 19, 2021. Studies that used FMT in people living with HIV and explored its effects on the health of these people were included. Two randomized and two uncontrolled clinical trials with a total of 55 participants were included. Participants were well-controlled HIV infected people. Regarding microbiota changes, three studies found significant post-FMT increases in Fusobacterium, Prevotella, α-diversity, Chao-index, and/or Shannon-index, and/or decreases in Bacteroides. Regarding markers of intestinal damage, one study found a decrease in intestinal fatty-acid binding protein post- FMT, and another study found an increase in zonulin. Other outcomes evaluated by the studies were: markers of immune and inflammatory activation, markers of immunocompetence (CD4+, and CD8+ T lymphocytes), and HIV viral load; however, none showed significant changes. Clinical outcomes were not evaluated by these studies. Regarding the safety of FMT, only mild adverse events were appreciated. No serious adverse events were reported. The clinical evidence for FMT in people living with HIV is sparse. FMT appears to have good tolerability and, no serious adverse events have been reported so far. Further clinical trials and evaluation of clinically important biomedical outcomes for FMT in people living with HIV are needed.}, }
@article {pmid35449107, year = {2022}, author = {Wang, Y and Li, H}, title = {Gut microbiota modulation: a tool for the management of colorectal cancer.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {178}, pmid = {35449107}, issn = {1479-5876}, abstract = {Colorectal cancer (CRC) is the second cause of cancer death and the third most frequently diagnosed cancer. Besides the lifestyle, genetic and epigenetic alterations, and environmental factors, gut microbiota also plays a vital role in CRC development. The interruption of the commensal relationship between gut microbiota and the host could lead to an imbalance in the bacteria population, in which the pathogenic bacteria become the predominant population in the gut. Different therapeutic strategies have been developed to modify the gut immune system, prevent pathogen colonization, and alter the activity and composition of gut microbiota, such as prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). Even though the employed strategies exhibit promising results, their translation into the clinic requires evaluating potential implications and risks, as well as assessment of their long-term effects. This study was set to review the gut microbiota imbalances and their relationship with CRC and their effects on CRC therapy, including chemotherapy and immunotherapy. More importantly, we reviewed the strategies that have been used to modulate gut microbiota, their impact on the treatment of CRC, and the challenges of each strategy.}, }
@article {pmid35446385, year = {2022}, author = {}, title = {Eshel A, Sharon I, Nagler A, et al. Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis. Blood Adv. 2022;6(2):568-573.}, journal = {Blood advances}, volume = {6}, number = {8}, pages = {2578-2580}, doi = {10.1182/bloodadvances.2022007476}, pmid = {35446385}, issn = {2473-9537}, }
@article {pmid35446112, year = {2022}, author = {Hao, Y and Feng, Y and Yan, X and Chen, L and Ma, X and Tang, X and Zhong, R and Sun, Z and Agarwal, M and Zhang, H and Zhao, Y}, title = {Gut Microbiota-Testis Axis: FMT Mitigates High-Fat Diet-Diminished Male Fertility via Improving Systemic and Testicular Metabolome.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0002822}, doi = {10.1128/spectrum.00028-22}, pmid = {35446112}, issn = {2165-0497}, abstract = {High-fat diet (HFD)-induced obesity is known to be associated with reduced male fertility and decreased semen quality in humans. HFD-related male infertility is a growing issue worldwide, and it is crucial to overcome this problem to ameliorate the distress of infertile couples. For the first time, we discovered that fecal microbiota transplantation (FMT) of alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) ameliorated HFD-decreased semen quality (sperm concentration: 286.1 ± 14.1 versus 217.9 ± 17.4 million/mL; sperm motility: 40.1 ± 0.7% versus 29.0 ± 0.9%), and male fertility (pregnancy rate: 87.4 ± 1.1% versus 70.2 ± 6.1%) by benefiting blood and testicular metabolome. A10-FMT improved HFD-disturbed gut microbiota by increasing gut Bacteroides (colon: 24.9 ± 1.1% versus 8.3 ± 0.6%; cecum: 10.2 ± 0.7% versus 3.6 ± 0.7%) and decreasing Mucispirillum (colon: 0.3 ± 0.1% versus 2.8 ± 0.4%; cecum: 2.3 ± 0.5% versus 6.6 ± 0.7%). A10-FMT benefited gut microbiota to improve liver function by adjusting lipid metabolism to produce n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (blood: 55.5 ± 18.7 versus 20.3 ± 2.4) and docosahexaenoic acid (testis: 121.2 ± 6.2 versus 89.4 ± 6.7), thus ameliorating HFD-impaired testicular microenvironment to rescue spermatogenesis and increase semen quality and fertility. The findings indicated that AOS-improved gut microbiota may be a promising strategy to treat obesity or metabolic issues-related male infertility in the future. IMPORTANCE HFD decreases male fertility via upsetting gut microbiota and transplantation of AOS-benefited gut microbiota (A10-FMT) improves gut microbiota to ameliorate HFD-reduced male fertility. Moreover, A10-FMT improved liver function to benefit the blood metabolome and simultaneously ameliorated the testicular microenvironment to turn the spermatogenesis process on. We demonstrated that AOS-benefited gut microbiota could be applied to treat infertile males with obesity and metabolic issues induced by HFD.}, }
@article {pmid35444617, year = {2022}, author = {Zhang, WH and Jin, ZY and Yang, ZH and Zhang, JY and Ma, XH and Guan, J and Sun, BL and Chen, X}, title = {Fecal Microbiota Transplantation Ameliorates Active Ulcerative Colitis by Downregulating Pro-inflammatory Cytokines in Mucosa and Serum.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {818111}, doi = {10.3389/fmicb.2022.818111}, pmid = {35444617}, issn = {1664-302X}, abstract = {Background: Ulcerative colitis (UC) is a multi-factor disease characterized by alternating remission periods and repeated occurrence. It has been shown that fecal microbiota transplantation (FMT) is an emerging and effective approach for UC treatment. Since most existing studies chose adults as donors for fecal microbiota, we conducted this study to determine the long-term efficacy and safety of the microbiota from young UC patient donors and illustrate its specific physiological effects.<br><br>Methods: Thirty active UC patients were enrolled and FMT were administered with the first colonoscopy and two subsequent enema/transendoscopic enteral tubing (TET) practical regimens in The First Affiliated Hospital of Anhui Medical University in China. Disease activity and inflammatory biomarkers were assessed 6 weeks/over 1 year after treatment. The occurrence of adverse events was also recorded. The samples from blood and mucosa were collected to detect the changes of inflammatory biomarkers and cytokines. The composition of gut and oral microbiota were also sampled and sequenced to confirm the alteration of microbial composition.<br><br>Results: Twenty-seven patients completed the treatment, among which 16 (59.3%) achieved efficacious clinical response and 11 (40.7%) clinical remission. Full Mayo score and calprotectin dropped significantly and remained stable over 1 year. FMT also significantly reduced the levels of C-reactive protein (CRP), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). The gut microbiota altered significantly with increased bacterial diversity and decreased metabolic diversity in responsive patients. The pro-inflammatory enterobacteria decreased after FMT and the abundance of Collinsella increased. Accordingly, the altered metabolic functions, including antigen synthesis, amino acids metabolism, short chain fatty acid production, and vitamin K synthesis of microbiota, were also corrected by FMT.<br><br>Conclusion: Fecal microbiota transplantation seems to be safe and effective for active UC patients who are nonresponsive to mesalazine or prednisone in the long-term. FMT could efficiently downregulate pro-inflammatory cytokines to ameliorate the inflammation.}, }
@article {pmid35278396, year = {2022}, author = {Haifer, C and Paramsothy, S and Kaakoush, NO and Leong, RW}, title = {Oral faecal microbiota transplantation in ulcerative colitis - Authors' reply.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {4}, pages = {286-287}, doi = {10.1016/S2468-1253(22)00045-0}, pmid = {35278396}, issn = {2468-1253}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid35278395, year = {2022}, author = {Yuan, TY and Rajesh, R and Tan, M}, title = {Oral faecal microbiota transplantation in ulcerative colitis.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {4}, pages = {286}, doi = {10.1016/S2468-1253(21)00469-6}, pmid = {35278395}, issn = {2468-1253}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid34393197, year = {2022}, author = {Lucarini, E and Di Pilato, V and Parisio, C and Micheli, L and Toti, A and Pacini, A and Bartolucci, G and Baldi, S and Niccolai, E and Amedei, A and Rossolini, GM and Nicoletti, C and Cryan, JF and O'Mahony, SM and Ghelardini, C and Di Cesare Mannelli, L}, title = {Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence.}, journal = {Pain}, volume = {163}, number = {5}, pages = {861-877}, doi = {10.1097/j.pain.0000000000002438}, pmid = {34393197}, issn = {1872-6623}, mesh = {Animals ; Bacteria ; Colon/pathology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Mice ; Rats ; *Visceral Pain/drug therapy ; }, abstract = {ABSTRACT: Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing postinflammatory visceral pain persistence. Colitis was induced in mice by intrarectally injecting 2,4-dinitrobenzenesulfonic acid (DNBS). The effect of faecal microbiota transplantation from viscerally hypersensitive DNBS-treated and naive donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. Faecal microbiota transplantation from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition of gut microbiota and short chain fatty acids. By contrast, no significant alterations of colon histology, permeability, and monoamines levels were detected. Finally, by manipulating the gut microbiota of DNBS-treated animals, a counteraction of persistent visceral pain was achieved. The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota-targeted interventions.}, }
@article {pmid35435504, year = {2022}, author = {Deng, L and Wojciech, L and Png, CW and Koh, EY and Aung, TT and Kioh, DYQ and Chan, ECY and Malleret, B and Zhang, Y and Peng, G and Gascoigne, NRJ and Tan, KSW}, title = {Experimental colonization with Blastocystis ST4 is associated with protective immune responses and modulation of gut microbiome in a DSS-induced colitis mouse model.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {79}, number = {5}, pages = {245}, pmid = {35435504}, issn = {1420-9071}, support = {R-571-000-037-114//NUHS Seed Grant/ ; R-571-000-061-114//NUHS Seed Grant/ ; R-148-000-277-114//NUS Research Grant/ ; CPF2017-12//Chengdu Giant Panda Breeding Research Foundation/ ; }, abstract = {BACKGROUND: Blastocystis is a common gut protistan parasite in humans and animals worldwide, but its interrelationship with the host gut microbiota and mucosal immune responses remains poorly understood. Different murine models of Blastocystis colonization were used to examine the effect of a common Blastocystis subtype (ST4) on host gut microbial community and adaptive immune system.<br><br>RESULTS: Blastocystis ST4-colonized normal healthy mice and Rag1-/- mice asymptomatically and was able to alter the microbial community composition, mainly leading to increases in the proportion of Clostridia vadinBB60 group and Lachnospiraceae NK4A136 group, respectively. Blastocystis ST4 colonization promoted T helper 2 (Th2) response defined by interleukin (IL)-5 and IL-13 cytokine production, and T regulatory (Treg) induction from colonic lamina propria in normal healthy mice. Additionally, we observed that Blastocystis ST4 colonization can maintain the stability of bacterial community composition and induce Th2 and Treg immune responses to promote faster recovery from experimentally induced colitis. Furthermore, fecal microbiota transplantation of Blastocystis ST4-altered gut microbiome to colitis mice reduced the severity of colitis, which was associated with increased production of short-chain fat acids (SCFAs) and anti-inflammatory cytokine IL-10.<br><br>CONCLUSIONS: The data confirm our hypothesis that Blastocystis ST4 is a beneficial commensal, and the beneficial effects of Blastocystis ST4 colonization is mediated through modulating of the host gut bacterial composition, SCFAs production, and Th2 and Treg responses in different murine colonization models.}, }
@article {pmid35435140, year = {2022}, author = {Debédat, J and Le Roy, T and Voland, L and Belda, E and Alili, R and Adriouch, S and Bel Lassen, P and Kasahara, K and Hutchison, E and Genser, L and Torres, L and Gamblin, C and Rouault, C and Zucker, JD and Kapel, N and Poitou, C and Marcelin, G and Rey, FE and Aron-Wisnewsky, J and Clément, K}, title = {The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2050635}, doi = {10.1080/19490976.2022.2050635}, pmid = {35435140}, issn = {1949-0984}, abstract = {Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.}, }
@article {pmid35432306, year = {2022}, author = {Jasiński, M and Biliński, J and Basak, GW}, title = {The Role of the Crosstalk Between Gut Microbiota and Immune Cells in the Pathogenesis and Treatment of Multiple Myeloma.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {853540}, doi = {10.3389/fimmu.2022.853540}, pmid = {35432306}, issn = {1664-3224}, abstract = {Around 10% of all hematologic malignancies are classified as multiple myeloma (MM), the second most common malignancy within that group. Although massive progress in developing of new drugs against MM has been made in recent years, MM is still an incurable disease, and every patient eventually has relapse refractory to any known treatment. That is why further and non-conventional research elucidating the role of new factors in MM pathogenesis is needed, facilitating discoveries of the new drugs. One of these factors is the gut microbiota, whose role in health and disease is still being explored. This review presents the continuous changes in the gut microbiota composition during our whole life with a particular focus on its impact on our immune system. Additionally, it mainly focuses on the chronic antigenic stimulation of B-cells as the leading mechanism responsible for MM promotion. The sophisticated interactions between microorganisms colonizing our gut, immune cells (dendritic cells, macrophages, neutrophils, T/B cells, plasma cells), and intestinal epithelial cells will be shown. That article summarizes the current knowledge about the initiation of MM cells, emphasizing the role of microorganisms in that process.}, }
@article {pmid35432269, year = {2022}, author = {Qu, L and Cheng, Q and Wang, Y and Mu, H and Zhang, Y}, title = {COPD and Gut-Lung Axis: How Microbiota and Host Inflammasome Influence COPD and Related Therapeutics.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {868086}, doi = {10.3389/fmicb.2022.868086}, pmid = {35432269}, issn = {1664-302X}, abstract = {The exact pathogenesis of chronic obstructive pulmonary disease (COPD) remains largely unknown. While current management strategies are effective at stabilizing the disease or relief the symptoms, new approaches are required to target underlying disease process and reverse lung function deterioration. Recent research showed that pneumonia bacteria is critical in disease progression and gut microbiome is likely perturbed in COPD, which is usually accompanied by a decreased intestinal microbial diversity and a disturbance in immune system, contributing to a chronic inflammation. The cross-talk between gut microbes and lungs, termed as the "gut-lung axis," is known to impact immune response and homeostasis in the airway. Although the gut and respiratory microbiota exhibit compositional differences, the gut and lung showed similarities in the origin of epithelia of both gastrointestinal and respiratory tracts, the anatomical structure, and early-life microbial colonization. Evidence showed that respiratory infection might be prevented, or at least dampened by regulating gut microbial ecosystem; thus, a promising yet understudied area of COPD management is nutrition-based preventive strategies. COPD patient is often deficient in nutrient such as antioxidant, vitamins, and fiber intake. However, further larger-scale randomized clinical trials (RCTs) are required to establish the role of these nutrition-based diet in COPD management. In this review, we highlight the important and complex interaction of microbiota and immune response on gut-lung axis. Further research into the modification and improvement of the gut microbiota and new interventions through diet, probiotics, vitamins, and fecal microbiota transplantation is extreme critical to provide new preventive therapies for COPD.}, }
@article {pmid35431512, year = {2022}, author = {Hong, Y and Zhao, J and Chen, YR and Huang, ZH and Hou, LD and Shen, B and Xin, Y}, title = {Spinal anesthesia alleviates dextran sodium sulfate-induced colitis by modulating the gut microbiota.}, journal = {World journal of gastroenterology}, volume = {28}, number = {12}, pages = {1239-1256}, doi = {10.3748/wjg.v28.i12.1239}, pmid = {35431512}, issn = {2219-2840}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease with recurrent intestinal inflammation. Although the exact etiology of IBD remains unknown, the accepted hypothesis of the pathogenesis to date is that abnormal immune responses to the gut microbiota are caused by environmental factors. The role of the gut microbiota, particularly the bidirectional interaction between the brain and gut microbiota, has gradually attracted more attention.<br><br>AIM: To investigate the potential effect of spinal anesthesia on dextran sodium sulfate (DSS)-induced colitis mice and to detect whether alterations in the gut microbiota would be crucial for IBD.<br><br>METHODS: A DSS-induced colitis mice model was established. Spinal anesthesia was administered on colitis mice in combination with the methods of cohousing and fecal microbiota transplantation (FMT) to explore the role of spinal anesthesia in IBD and identify the potential mechanisms involved.<br><br>RESULTS: We demonstrated that spinal anesthesia had protective effects against DSS-induced colitis by alleviating clinical symptoms, including reduced body weight loss, decreased disease activity index score, improved intestinal permeability and colonic morphology, decreased inflammatory response, and enhanced intestinal barrier functions. Moreover, spinal anesthesia significantly increased the abundance of Bacteroidetes, which was suppressed in the gut microbiota of colitis mice. Interestingly, cohousing with spinal anesthetic mice and FMT from spinal anesthetic mice can also alleviate DSS-induced colitis by upregulating the abundance of Bacteroidetes. We further showed that spinal anesthesia can reduce the increase in noradrenaline levels induced by DSS, which might affect the gut microbiota.<br><br>CONCLUSION: These data suggest that microbiota dysbiosis may contribute to IBD and provide evidence supporting the protective effects of spinal anesthesia on IBD by modulating the gut microbiota, which highlights a novel approach for the treatment of IBD.}, }
@article {pmid35430804, year = {2022}, author = {Xiao, W and Su, J and Gao, X and Yang, H and Weng, R and Ni, W and Gu, Y}, title = {The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {62}, pmid = {35430804}, issn = {2049-2618}, support = {82171313//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 81870917//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 81771237//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82101397//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 2016YFC1301704//Ministry of Human Resources and Social Security/ ; 2018SHZDZX01//Science and Technology Commission of Shanghai Municipality/ ; }, abstract = {BACKGROUND: Chronic cerebral hypoperfusion (CCH) underlies secondary brain injury following certain metabolic disorders and central nervous system (CNS) diseases. Dysregulation of the microbiota-gut-brain axis can exacerbate various CNS disorders through aberrantly expressed metabolites such as short-chain fatty acids (SCFAs). Yet, its relationship with CCH remains to be demonstrated. And if so, it is of interest to explore whether restoring gut microbiota to maintain SCFA metabolism could protect against CCH.<br><br>RESULTS: Rats subjected to bilateral common carotid artery occlusion (BCCAO) as a model of CCH exhibited cognitive impairment, depressive-like behaviors, decreased gut motility, and compromised gut barrier functions. The 16S ribosomal RNA gene sequencing revealed an abnormal gut microbiota profile and decreased relative abundance of some representative SCFA producers, with the decreased hippocampal SCFAs as the further evidence. Using fecal microbiota transplantation (FMT), rats recolonized with a balanced gut microbiome acquired a higher level of hippocampal SCFAs, as well as decreased neuroinflammation when exposed to lipopolysaccharide. Healthy FMT promoted gut motility and gut barrier functions, and improved cognitive decline and depressive-like behaviors by inhibiting hippocampal neuronal apoptosis in BCCAO rats. Long-term SCFA supplementation further confirmed its neuroprotective effect in terms of relieving inflammatory response and hippocampal neuronal apoptosis following BCCAO.<br><br>CONCLUSION: Our results demonstrate that modulating the gut microbiome via FMT can ameliorate BCCAO-induced gut dysbiosis, cognitive decline, and depressive-like behaviors, possibly by enhancing the relative abundance of SCFA-producing floras and subsequently increasing SCFA levels. Video abstract.}, }
@article {pmid35426646, year = {2022}, author = {Adams, SM and Close, ED and Shreenath, AP}, title = {Ulcerative Colitis: Rapid Evidence Review.}, journal = {American family physician}, volume = {105}, number = {4}, pages = {406-411}, pmid = {35426646}, issn = {1532-0650}, abstract = {Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and a family history of ulcerative colitis. Diagnosis is suspected based on symptoms of urgency, tenesmus, and hematochezia and is confirmed with endoscopic findings of continuous inflammation from the rectum to more proximal colon, depending on the extent of disease. Fecal calprotectin may be used to assess disease activity and relapse. Medications available to treat the inflammation include 5-aminosalicylic acid, corticosteroids, tumor necrosis factor-alpha antibodies, anti-integrin antibodies, anti-interleukin-12 and -23 antibodies, and Janus kinase inhibitors. Choice of medication and method of delivery depend on the location and severity of mucosal inflammation. Other treatments such as fecal microbiota transplantation are considered experimental, and complementary therapies such as probiotics and curcumin have mixed data. Surgical treatment may be needed for fulminant or refractory disease. Increased risk of colorectal cancer and use of immunosuppressive therapies affect the preventive care needs for these patients.}, }
@article {pmid35421334, year = {2022}, author = {Severyn, CJ}, title = {Find a little help from my (microbial) friends.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {4}, pages = {420-422}, doi = {10.1016/j.chom.2022.03.024}, pmid = {35421334}, issn = {1934-6069}, mesh = {*Clostridioides difficile ; *Clostridium Infections/prevention &amp; control ; Fecal Microbiota Transplantation ; Friends ; Humans ; *Microbiota ; }, abstract = {Modulation of the microbiota to improve clinical outcomes remains challenging partially because of the large variability in biotherapeutic composition. In this issue of Cell Host &amp; Microbe, Dsouza and colleagues present the phase 1 study results of a defined microbial consortia developed for the prevention of recurrent Clostridioides difficile infection (CDI).}, }
@article {pmid34797954, year = {2022}, author = {Cheng, J and Li, W and Wang, Y and Cao, Q and Ni, Y and Zhang, W and Guo, J and Chen, B and Zang, Y and Zhu, Y}, title = {Electroacupuncture modulates the intestinal microecology to improve intestinal motility in spinal cord injury rats.}, journal = {Microbial biotechnology}, volume = {15}, number = {3}, pages = {862-873}, pmid = {34797954}, issn = {1751-7915}, mesh = {Animals ; *Electroacupuncture ; Fecal Microbiota Transplantation ; Gastrointestinal Motility ; Rats ; Serotonin ; *Spinal Cord Injuries/metabolism/pathology/therapy ; }, abstract = {Spinal cord injury (SCI) is a disease involving gastrointestinal disorders. The underlying mechanisms of the potential protective effects of electroacupuncture (EA) and 5-hydroxytryptamine (5-HT) system on SCI remain unknown. We investigated whether EA improves gut microbial dysbiosis in SCI and regulates the 5-HT system. 16S rDNA gene sequencing was applied to investigate alterations in the gut microbiome of the rats. Faecal metabolites and the expression of the 5-HT system were detected. EA and faecal microbiota transplantation (FMT) treatment facilitated intestinal transmission functional recovery and restored the colon morphology of SCI rats. The composition of the intestinal microbiota, including numbers of phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea, were amplified in SCI rats, and EA and FMT significantly reshaped the intestinal microbiota. SCI resulted in disturbed metabolic conditions in rats, and the EA and FMT group showed increased amounts of catechin compared with SCI rats. SCI inhibited 5-HT system expression in the colon, which was significantly reversed by EA and FMT treatment. Therefore, EA may ameliorate SCI by modulating microbiota and metabolites and regulate the 5-HT system. Our study provides new insights into the pathogenesis and therapy of SCI from the perspective of microbiota and 5-HT regulation.}, }
@article {pmid35421353, year = {2022}, author = {Dsouza, M and Menon, R and Crossette, E and Bhattarai, SK and Schneider, J and Kim, YG and Reddy, S and Caballero, S and Felix, C and Cornacchione, L and Hendrickson, J and Watson, AR and Minot, SS and Greenfield, N and Schopf, L and Szabady, R and Patarroyo, J and Smith, W and Harrison, P and Kuijper, EJ and Kelly, CP and Olle, B and Bobilev, D and Silber, JL and Bucci, V and Roberts, B and Faith, J and Norman, JM}, title = {Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {4}, pages = {583-598.e8}, doi = {10.1016/j.chom.2022.03.016}, pmid = {35421353}, issn = {1934-6069}, abstract = {Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance.}, }
@article {pmid35421277, year = {2022}, author = {Asadi, A and Shadab Mehr, N and Mohamadi, MH and Shokri, F and Heidary, M and Sadeghifard, N and Khoshnood, S}, title = {Obesity and gut-microbiota-brain axis: A narrative review.}, journal = {Journal of clinical laboratory analysis}, volume = {}, number = {}, pages = {e24420}, doi = {10.1002/jcla.24420}, pmid = {35421277}, issn = {1098-2825}, abstract = {INTRODUCTION: Obesity is a major health problem that is associated with many physiological and mental disorders, such as diabetes, stroke, and depression. Gut microbiota has been affirmed to interact with various organs, including the brain. Intestinal microbiota and their metabolites might target the brain directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms, and they can regulate metabolism, adiposity, homoeostasis and energy balance, and central appetite and food reward signaling, which together have crucial roles in obesity. Studies support the concept of bidirectional signaling within the gut-brain axis (GBA) in the pathophysiology of obesity, mediated by metabolic, endocrine, neural, and immune system mechanisms.<br><br>MATERIALS AND METHODS: Scopus, PubMed, Google Scholar, and Web of Science databases were searched to find relevant studies.<br><br>RESULTS: The gut-brain axis (GBA), a bidirectional connection between the gut microbiota and brain, influences physiological function and behavior through three different pathways. Neural pathway mainly consists of the enteric nervous system (ENS) and vagus nerve. Endocrine pathway, however, affects the neuroendocrine system of the brain, particularly the hypothalamus-pituitary-adrenal (HPA) axis and immunological pathway. Several alterations in the gut microbiome can lead to obesity, by modulating metabolic pathways and eating behaviors of the host through GBA. Therefore, novel therapies targeting the gut microbiome, i.e., fecal microbiota transplantation and supplementation with probiotics and prebiotics, can be a potential treatment for obesity.<br><br>CONCLUSION: This study corroborates the effect of gut microbiome on physiological function and body weight. The results show that the gut microbiota is becoming a target for new antiobesity therapies.}, }
@article {pmid35418976, year = {2022}, author = {Wang, J and Zhang, H and He, J and Xiong, X}, title = {The Role of the Gut Microbiota in the Development of Ischemic Stroke.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {845243}, doi = {10.3389/fimmu.2022.845243}, pmid = {35418976}, issn = {1664-3224}, abstract = {An increasing number of studies have focused on the gut microbiota and its relationship with various neurological diseases. The gut microbiota can affect the metabolic status of the body, in addition to having an important impact on blood pressure, blood glucose, and atherosclerosis, all of which are risk factors for ischemic stroke. In this review, we summarized studies that included the physiological function of the gut microbiota and gut microbiota disorders related to the central nervous system, thus providing novel ideas for the prevention and treatment of ischemic stroke.}, }
@article {pmid35409202, year = {2022}, author = {Bastos, RMC and Simplício-Filho, A and Sávio-Silva, C and Oliveira, LFV and Cruz, GNF and Sousa, EH and Noronha, IL and Mangueira, CLP and Quaglierini-Ribeiro, H and Josefi-Rocha, GR and Rangel, ÉB}, title = {Fecal Microbiota Transplant in a Pre-Clinical Model of Type 2 Diabetes Mellitus, Obesity and Diabetic Kidney Disease.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, doi = {10.3390/ijms23073842}, pmid = {35409202}, issn = {1422-0067}, support = {2013/19560-6; 2017/23195-2; 2017/18072-9; 2016/26263-6//São Paulo Research Foundation/ ; 2016-5/423320//National Council for Scientific and Technological Development/ ; 2015//European Foundation for the Study of Diabetes/Sanofi/ ; }, abstract = {Diabetes mellitus (DM) burden encompasses diabetic kidney disease (DKD), the leading cause of end-stage renal disease worldwide. Despite compelling evidence indicating that pharmacological intervention curtails DKD progression, the search for non-pharmacological strategies can identify novel targets for drug development against metabolic diseases. One of those emergent strategies comprises the modulation of the intestinal microbiota through fecal transplant from healthy donors. This study sought to investigate the benefits of fecal microbiota transplant (FMT) on functional and morphological parameters in a preclinical model of type 2 DM, obesity, and DKD using BTBRob/ob mice. These animals develop hyperglycemia and albuminuria in a time-dependent manner, mimicking DKD in humans. Our main findings unveiled that FMT prevented body weight gain, reduced albuminuria and tumor necrosis factor-α (TNF-α) levels within the ileum and ascending colon, and potentially ameliorated insulin resistance in BTBRob/ob mice. Intestinal structural integrity was maintained. Notably, FMT was associated with the abundance of the succinate-consuming Odoribacteraceae bacteria family throughout the intestine. Collectively, our data pointed out the safety and efficacy of FMT in a preclinical model of type 2 DM, obesity, and DKD. These findings provide a basis for translational research on intestinal microbiota modulation and testing its therapeutic potential combined with current treatment for DM.}, }
@article {pmid35276080, year = {2022}, author = {Lam, S and Bai, X and Shkoporov, AN and Park, H and Wu, X and Lan, P and Zuo, T}, title = {Roles of the gut virome and mycobiome in faecal microbiota transplantation.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {5}, pages = {472-484}, doi = {10.1016/S2468-1253(21)00303-4}, pmid = {35276080}, issn = {2468-1253}, mesh = {Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; *Mycobiome ; Virome ; }, abstract = {Faecal microbiota transplantation (FMT) is an innovative approach to treat diseases that are associated with gut dysbiosis, by transferring a healthy stool microbiota to a recipient with disease. Beyond the bacteriome, the human gut also harbours diverse communities of viruses and fungi, collectively known as the virome and the mycobiome. The effect of the virome and the mycobiome on the success of FMT therapy has not been appreciated until recently. In this Review, we summarise the current literature on the effects of the gut virome and mycobiome on the treatment of various diseases with FMT. We discuss the beneficial effects and health concerns of viral and fungal transfer during FMT, and highlight the roles of bacteriophages and Candida species in FMT efficacy. We also summarise the intricate relationships between the gut virome, mycobiome, bacteriome, and host immunity underlying FMT effectiveness. Future efforts should be devoted to understanding the versatile roles and the therapeutic mechanisms of viral and fungal lineages, and their combinations, in different diseases. Harnessing the gut virome, mycobiome, and bacteriome in combination is a promising prospect for the future of FMT and microbiota-based therapies.}, }
@article {pmid35402293, year = {2022}, author = {Ding, D and Yong, H and You, N and Lu, W and Yang, X and Ye, X and Wang, Y and Cai, T and Zheng, X and Chen, H and Cui, B and Zhang, F and Liu, X and Mao, JH and Lu, Y and Chang, H}, title = {Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {820367}, doi = {10.3389/fcimb.2022.820367}, pmid = {35402293}, issn = {2235-2988}, abstract = {Background: Increasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown.<br><br>Methods: We enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment.<br><br>Results: We found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 ± 0.148 to 7.190 ± 0.210, p<0.01), blood glucose (from 8.483 ± 0.497 to 7.286 ± 0.454 mmol/L, p<0.01), and uric acid (from 309.4 ± 21.5 to 259.1 ± 15.8 µmol/L, p<0.01) while a significant increase in postprandial C-peptide (from 4.503 ± 0.600 to 5.471 ± 0.728 ng/ml, p<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family Rikenellaceae and the genus Anaerotruncus (family Ruminococcaceae) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83.<br><br>Conclusion: Our findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of Rikenellaceae and Anaerotruncus in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.}, }
@article {pmid35401492, year = {2022}, author = {Gao, JM and Rao, JH and Wei, ZY and Xia, SY and Huang, L and Tang, MT and Hide, G and Zheng, TT and Li, JH and Zhao, GA and Sun, YX and Chen, JH}, title = {Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {876043}, doi = {10.3389/fmicb.2022.876043}, pmid = {35401492}, issn = {1664-302X}, abstract = {Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.}, }
@article {pmid35400819, year = {2022}, author = {Fukushima, S and Shiotani, A and Matsumoto, H and Handa, O and Handa, Y and Osawa, M and Murao, T and Umegaki, E and Kawano, M and Inoue, R and Naito, Y}, title = {Comparison of mucosa-associated microbiota in Crohn's disease patients with and without anti-tumor necrosis factor-α therapy.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {70}, number = {2}, pages = {182-188}, doi = {10.3164/jcbn.21-41}, pmid = {35400819}, issn = {0912-0009}, abstract = {Most studies on the gut microbiome of Crohn's disease have been conducted using feces, instead of intestinal mucus to analyze the mucosa-associated microbiota. To investigate the characteristics of mucosa-associated microbiota in Crohn's disease patients and the effect of anti-tumor necrosis factor (TNF)-α therapy on mucosa-associated microbiota, we analyzed microbiota in Crohn's disease patients using brushing samples taken from terminal ileum. The recruited subjects were 18 Crohn's disease patients and 13 controls. There were 10 patients with anti-TNF-α therapy in Crohn's disease group. Crohn's disease patients had significantly reduced α-diversity in Shannon index compared to the controls. The comparative analysis of the taxonomic composition at the genus level between the Crohn's disease group and the controls indicated that butyrate-producing bacteria were less abundant in the Crohn's disease group compared to the controls. There were no differences in the diversity between the patients taking anti-TNF-α therapy and the patients without. The comparative analysis of the taxonomic composition at the genus level between the two groups indicated that some of anti-inflammatory bacteria were less abundant in the anti-TNF-α therapy group than the other. Reduction of specific bacteria producing anti-inflammatory molecules, especially butyrate-producing bacteria may play important roles in the pathophysiology of Crohn's disease.}, }
@article {pmid35399688, year = {2022}, author = {He, Z and Ma, Y and Chen, X and Liu, S and Xiao, J and Wang, Y and Wang, W and Yang, H and Li, S and Cao, Z}, title = {Protective Effects of Intestinal Gallic Acid in Neonatal Dairy Calves Against Extended-Spectrum β-lactamase Producing Enteroaggregative Escherichia coli Infection: Modulating Intestinal Homeostasis and Colitis.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {864080}, doi = {10.3389/fnut.2022.864080}, pmid = {35399688}, issn = {2296-861X}, abstract = {Calf diarrhea induced by enteroaggregative E. coli (EAEC) spreads fast among young ruminants, causing continuous hazard to dairy industry. Antimicrobial drug abuse aggravates the incidence rate of multi-drug resistant (MDR) extended-spectrum β-lactamase-producing E. coli (ESBL-EC). However, knowledge of detection and significance of disease-related biomarkers in neonatal female calves are still limited. Gallic acid (GA), a natural secondary metabolite mostly derived from plants, has attracted increasing attention for its excellent anti-inflammatory and anti-oxidative properties. However, it is vague how GA engenders amelioration effects on clinical symptoms and colitis induced by ESBL-EAEC infection in neonatal animals. Here, differentiated gut microbiome and fecal metabolome discerned from neonatal calves were analyzed to ascertain biomarkers in their early lives. Commensal Collinsella and Coriobacterium acted as key microbial markers mediating colonization resistance. In addition, there exists a strongly positive relation between GA, short-chain fatty acid (SCFA) or other prebiotics, and those commensals using random forest machine learning algorithm and Spearman correlation analyses. The protective effect of GA pretreatment on bacterial growth, cell adherence, and ESBL-EAEC-lipopolysaccharide (LPS)-treated Caco-2 cells were first assessed, and results revealed direct antibacterial effects and diminished colonic cell inflammation. Then, oral GA mediated colitis attenuation and recovery of colonic short-chain fatty acid (SCFA) productions on neonatal mice peritonitis sepsis or oral infection model. To corroborate this phenomenon, fecal microbiota transplantation (FMT) method was adopted to remedy the bacterial infection. Of note, FMT from GA-treated neonatal mice achieved profound remission of clinical symptoms and colitis over the other groups as demonstrated by antibacterial capability and prominent anti-inflammatory abilities, revealing improved hindgut microbiota structure with enriched Clostridia_UCG-014, Lachnospiraceae, Oscillospiraceae, and Enterococcaceae, and upregulation of SCFA productions. Collectively, our findings provided the direct evidence of hindgut microbiota and intestinal metabolites, discriminating the health status of neonatal calves post ESBL-EAEC infection. The data provided novel insights into GA-mediated remission of colitis via amelioration of hindgut commensal structure and upregulation of SCFA productions. In addition, its eminent role as potential antibiotic alternative or synergist for future clinic ESBL-EAEC control in livestock.}, }
@article {pmid35399089, year = {2022}, author = {Wang, X and Tsai, T and Zuo, B and Wei, X and Deng, F and Li, Y and Maxwell, CV and Yang, H and Xiao, Y and Zhao, J}, title = {Donor age and body weight determine the effects of fecal microbiota transplantation on growth performance, and fecal microbiota development in recipient pigs.}, journal = {Journal of animal science and biotechnology}, volume = {13}, number = {1}, pages = {49}, pmid = {35399089}, issn = {1674-9782}, support = {2018-67015-27479//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: The application of fecal microbiota transplantation (FMT) to improve swine growth performance has been sporadically studied. Most of these studies used a single microbiota source and thus the effect of donor characteristics on recipient pigs' fecal microbiota development and growth performance is largely unknown.<br><br>RESULTS: In this study, we collected feces from six donors with heavy (H) or light (L) body weight and different ages (d 42, nursery; d 96, growing; and d 170, finisher) to evaluate their effects on the growth performance and fecal microbiota development of recipient pigs. Generally, recipients that received two doses of FMT from nursery and finisher stages donor at weaning (21 ± 2 days of age) inherited the donor's growth pattern, while the pigs gavaged with grower stage material exerted a numerically greater weight gain than the control pigs regardless of donor BW. FMT from heavier donors (NH, GH, and FH) led to the recipients to have numerically increased growth compared to their lighter counterparts (NL, GL, and FL, respectively) throughout the growing and most finishing stages. This benefit could be attributed to the enrichment of ASV25 Faecalibacterium, ASV61 Faecalibacterium, ASV438 Coriobacteriaceae_unclassified, ASV144 Bulleidia, and ASV129 Oribacterium and decrease of ASV13 Escherichia during nursery stage. Fecal microbiota transplantation from growing and finishing donors influenced the microbial community significantly in recipient pigs during the nursery stage. FMT of older donors' gut microbiota expedited recipients' microbiota maturity on d 35 and 49, indicated by increased estimated microbiota ages. The age-associated bacterial taxa included ASV206 Ruminococcaceae, ASV211 Butyrivibrio, ASV416 Bacteroides, ASV2 Streptococcus, and ASV291 Veillonellaceae. The body weight differences between GL and GH pigs on d 104 were associated with the increased synthesis of the essential amino acid, lysine and methionine, mixed acid fermentation, expedited glycolysis, and sucrose/galactose degradation.<br><br>CONCLUSIONS: Overall, our study provided insights into how donor age and body weight affect FMT outcomes regarding growth performance, microbiota community shifts, and lower GI tract metabolic potentials. This study also provided guidance to select qualified donors for future fecal microbiota transplantation.}, }
@article {pmid35398345, year = {2022}, author = {Osman, M and Budree, S and Kelly, CR and Panchal, P and Allegretti, JR and Kassam, Z and ,  and Olesen, SW and Ramakrishna, B and Dubois, N and O'Brien, K and Fischer, M and Stollman, N and Hays, RA and Kelly, CP and Amaratunga, K and Qazi, T and Crothers, JW and Abend, A and Bougas, M and Burns, L and Decaille-Hodge, I and Dickens, M and Edelstein, C and Gabdrakhmanova, D and Landry, R and Ling, K and Martin, D and Medina, G and Mendolia, G and Muñoz, R and Rao, S and Seng, M and Smith, M and Stehler, L and Yoder, K and Zellmer, C}, title = {Effectiveness and safety of fecal microbiota transplantation for Clostridioides difficile infection: Results from a 5,344 patient cohort study.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2022.03.051}, pmid = {35398345}, issn = {1528-0012}, }
@article {pmid35393390, year = {2022}, author = {Segovia-Rodríguez, L and Echeverry-Alzate, V and Rincón-Pérez, I and Calleja-Conde, J and Bühler, KM and Giné, E and Albert, J and Hinojosa, JA and Huertas, E and Gómez-Gallego, F and Bressa, C and Rodríguez de Fonseca, F and López-Moreno, JA}, title = {Gut microbiota and voluntary alcohol consumption.}, journal = {Translational psychiatry}, volume = {12}, number = {1}, pages = {146}, pmid = {35393390}, issn = {2158-3188}, abstract = {Alcohol is part of the usual diet of millions of individuals worldwide. However, not all individuals who drink alcohol experience the same effects, nor will everyone develop an alcohol use disorder. Here we propose that the intestinal microbiota (IMB) helps explain the different consumption patterns of alcohol among individuals. 507 humans participated in this study and alcohol consumption and IMB composition were analyzed. On the other hand, in 80 adult male Wistar rats, behavioral tests, alcohol intoxication, fecal transplantation, administration of antibiotics and collection of fecal samples were performed. For identification and relative quantification of bacterial taxa was used the bacterial 16 S ribosomal RNA gene. In humans, we found that heavy episodic drinking is associated with a specific stool type phenotype (type 1, according to Bristol Stool Scale; p < 0.05) and with an increase in the abundance of Actinobacteria (p < 0.05). Next, using rats, we demonstrate that the transfer of IMB from alcohol-intoxicated animals causes an increase in voluntary alcohol consumption in transplant-recipient animals (p < 0.001). The relative quantification data indicate that the genus Porphyromonas could be associated with the effect on voluntary alcohol consumption. We also show that gut microbiota depletion by antibiotics administration causes a reduction in alcohol consumption (p < 0.001) and altered the relative abundance of relevant phyla such as Firmicutes, Bacteroidetes or Cyanobacteria (p < 0.05), among others. Benjamini-Hochberg false discovery rate (FDR) correction was performed for multiple comparisons. These studies reveal some of the consequences of alcohol on the IMB and provide evidence that manipulation of IMB may alter voluntary alcohol consumption.}, }
@article {pmid35387830, year = {2022}, author = {Pérez-Nadales, E and Cano, Á and Recio, M and Artacho, MJ and Guzmán-Puche, J and Doblas, A and Vidal, E and Natera, C and Martínez-Martínez, L and Torre-Cisneros, J and Castón, JJ}, title = {Randomised, double-blind, placebo-controlled, phase 2, superiority trial to demonstrate the effectiveness of faecal microbiota transplantation for selective intestinal decolonisation of patients colonised by carbapenemase-producing Klebsiella pneumoniae (KAPEDIS).}, journal = {BMJ open}, volume = {12}, number = {4}, pages = {e058124}, doi = {10.1136/bmjopen-2021-058124}, pmid = {35387830}, issn = {2044-6055}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Proteins ; *Carbapenem-Resistant Enterobacteriaceae ; Fecal Microbiota Transplantation/methods ; Humans ; *Klebsiella Infections/drug therapy ; Klebsiella pneumoniae ; beta-Lactamases ; }, abstract = {INTRODUCTION: Infections caused by carbapenemase-producing Enterobacterales are frequent and associated with high rates of mortality. Intestinal carriers are at increased risk of infection by these microorganisms. Decolonisation strategies with antibiotics have not obtained conclusive results. Faecal microbiota transplantation (FMT) could be an effective and safe strategy to decolonise intestinal carriers of KPC-producing Klebsiella pneumoniae (KPC-Kp) but this hypothesis needs evaluation in appropriate clinical trials.<br><br>METHODS AND ANALYSIS: The KAPEDIS trial is a single-centre, randomised, double-blind, placebo-controlled, phase 2, superiority clinical trial of FMT for eradication of intestinal colonisation by KPC-Kp. One hundred and twenty patients with rectal colonisation by KPC-Kp will be randomised 1:1 to receive encapsulated lyophilised FMT or placebo. The primary outcome is KPC-Kp eradication at 30 days. Secondary outcomes are: (1) frequency of adverse events; (2) changes in KPC-Kp relative load within the intestinal microbiota at 7, 30 and 90 days, estimated by real-time quantitative PCR analysis of rectal swab samples and (3) rates of persistent eradication, KPC-Kp infection and crude mortality at 90 days. Participants will be monitored for adverse effects throughout the intervention.<br><br>ETHICS AND DISSEMINATION: Ethical approval was obtained from Reina Sofía University Hospital Institutional Review Board (approval reference number: 2019-003808-13). Trial results will be published in peer-reviewed journals and disseminated at national and international conferences.<br><br>TRIAL REGISTRATION NUMBER: NCT04760665.}, }
@article {pmid35159245, year = {2022}, author = {Cold, F and Svensson, CK and Petersen, AM and Hansen, LH and Helms, M}, title = {Long-Term Safety Following Faecal Microbiota Transplantation as a Treatment for Recurrent Clostridioides difficile Infection Compared with Patients Treated with a Fixed Bacterial Mixture: Results from a Retrospective Cohort Study.}, journal = {Cells}, volume = {11}, number = {3}, pages = {}, pmid = {35159245}, issn = {2073-4409}, support = {7076-00129B//Danish Innovation Fund/ ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; Humans ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) is the recommended treatment for recurrent C. difficile infection (rCDI) following a second recurrence. FMT is considered safe in the short term when procedures for the screening of donors and transferred material are followed. However, the long-term safety profile of FMT treatment is largely unknown. In a retrospective cohort study, we assessed the long-term safety of patients treated for rCDI with FMT or a fixed bacterial mixture, rectal bacteriotherapy (RBT). The overall survival, risk of hospital admission, onset of certain pre-specified diseases (cancer, diabetes mellitus, hypertension and inflammatory bowel disease) and risk of being diagnosed with a multidrug-resistant organism were assessed by undertaking a review of the treated patients' medical records for up to five years following treatment. A total of 280 patients were treated for rCDI with FMT (n = 145) or RBT (n = 135) between 2016 and 2020. In the five years following treatment, there were no differences in survival (adjusted hazard ratio (aHR) 1.03; 95% CI 0.68-1.56), p = 0.89), risk of hospital admission ((aHR 0.92; 95% CI 0.72-1.18), p = 0.5) or onset of any of the analysed diseases. In conclusion, FMT was not associated with increased mortality, risk of hospital admission or onset of disease following treatment when compared with RBT.}, }
@article {pmid35390687, year = {2022}, author = {Huang, C and Wu, D and Zhang, K and Khan, FA and Pandupuspitasari, NS and Wang, Y and Huo, L and Sun, F}, title = {Perfluorooctanoic acid alters the developmental trajectory of female germ cells and embryos in rodents and its potential mechanism.}, journal = {Ecotoxicology and environmental safety}, volume = {236}, number = {}, pages = {113467}, doi = {10.1016/j.ecoenv.2022.113467}, pmid = {35390687}, issn = {1090-2414}, abstract = {The epidemiological studies regarding perfluorooctanoic acid (PFOA) suggests that its exposure causes reproductive health issues, the underlying mechanisms of which are still in its infancy. Here, we report that PFOA deteriorates female reproduction at multiple development stages. Oocyte meiosis and preimplantation development are severely impaired by PFOA with oxidative stress being a contributor. Supplementing with antioxidant melatonin partially rescues oocyte meiotic maturation and non-apoptotic demise. The attenuation in ovarian follicle development however can be improved by metformin but not melatonin. Importantly, metformin blunts PFOA-induced fetal growth retardation (FGR) and such protective effect could be recapitulated by transplantation of fecal material and pharmacological activation of AMPK. Mechanistically, PFOA causes gut microbiota dysbiosis, which might thereby rewire host metabolism of L-phenylalanine, histamine and L-palmitoylcarnitine that triggers hyperphenylalaninaemia, inflammation and ferroptosis to initiate FGR. Deregulated serine metabolism by the gut microbe constitutes an alternative mechanism underlying PFOA-induced FGR in that modulation of serine in dam's diet phenocopied the FGR. Our study expands the understanding of risk factors that impair human reproductive health, and proposes restoration of gut microbiota diversity and intervention of metabolism as therapeutics mitigating health risks predisposed by environmental perturbation.}, }
@article {pmid35388189, year = {2022}, author = {Aggarwala, V and Mogno, I and Li, Z and Yang, C and Britton, GJ and Chen-Liaw, A and Mitcham, J and Bongers, G and Gevers, D and Clemente, JC and Colombel, JF and Grinspan, A and Faith, J}, title = {Author Correction: Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41564-022-01118-8}, pmid = {35388189}, issn = {2058-5276}, support = {650451//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; 580924//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; }, }
@article {pmid35387936, year = {2022}, author = {Tamura, S and Ishida, H and Shimizu, T and Imaeda, H and Nishida, A and Bamba, S and Andoh, A and Iwasa, Y and Kuroda, H}, title = {[Fecal microbiota transplantation for refractory Clostridioides difficile infection with Crohn's disease in an allogeneic bone marrow transplant recipient].}, journal = {[Rinsho ketsueki] The Japanese journal of clinical hematology}, volume = {63}, number = {3}, pages = {217-223}, doi = {10.11406/rinketsu.63.217}, pmid = {35387936}, issn = {0485-1439}, abstract = {We report a case of a 15-year-old girl who developed refractory Clostridioides difficile infection (CDI) after allogeneic bone marrow transplantation (BMT). She was treated successfully with fecal microbiota transplantation (FMT). The patient who had aplastic anemia underwent allogeneic BMT from an HLA 1-locus-mismatched unrelated donor. Four months later, she developed gastrointestinal graft-versus-host disease (GVHD), and immunosuppressive treatment improved the GVHD. However, she developed CDI 5 months after BMT and experienced recurrence after that. Fifteen months after transplant, CDI relapsed despite discontinuation of immunosuppressive treatment; thus, she underwent FMT. Colonoscopy at the time of FMT revealed round aphthae, mainly in the ileocecum, and colonic biopsy revealed inflammatory cell infiltration and noncaseating epithelioid granuloma, which fulfilled the diagnostic criteria for Crohn's disease. Following FMT for CDI, she was treated with enteric budesonide and intravenous methotrexate for Crohn's disease. These interventions resulted in a marked improvement in both CDI and Crohn's disease. Twenty-eight months after FMT, both CDI and Crohn's disease remained in remission with oral mesalamine monotherapy.}, }
@article {pmid35386224, year = {2022}, author = {Zhang, H and Xu, J and Wu, Q and Fang, H and Shao, X and Ouyang, X and He, Z and Deng, Y and Chen, C}, title = {Gut Microbiota Mediates the Susceptibility of Mice to Sepsis-Associated Encephalopathy by Butyric Acid.}, journal = {Journal of inflammation research}, volume = {15}, number = {}, pages = {2103-2119}, doi = {10.2147/JIR.S350566}, pmid = {35386224}, issn = {1178-7031}, abstract = {Purpose: Neuroinflammation plays an important part in the pathophysiology of sepsis-associated encephalopathy (SAE). Gut microbiota and gut brain axis are considered as important mediators in the development of neurological diseases. The aim of this study was to investigate the role of intestinal microbiota in sepsis-related brain injury and to explore the underlying mechanisms.<br><br>Methods: Mouse model of SAE was established using cecal ligation and puncture (CLP). Based on the mouse mortality and the associated time of death, light SAE (LSAE) and severe SAE (SSAE) were classified. Fecal microbiota transplantation (FMT) was performed to verify the role of intestinal microbiota. Feces of mice in the two groups which collected before operation were sequenced for 16S and targeted short chain fatty acids.<br><br>Results: Intestinal microbiota from SSAE and LSAE mice displayed diverse functions. Interestingly, LSAE mice produced more butyric acid compared with SSAE mice. In the in vivo experiments, sodium butyrate (NaB) reduced the high oxidative stress levels in mice hippocampus and conferred a marked survival superiority to sepsis mice. In addition, NaB prevented the increase in intracellular reactive oxygen species (ROS) generation and inducible nitric-oxide synthase expression in LPS-stimulated primary microglia. The GPR109A/Nrf2/HO-1 signaling pathway was found to be involved in the activation of antioxidant response of primary microglia induced by sodium butyrate.<br><br>Conclusion: Our findings indicate a crucial role of gut microbiota in the susceptibility to SAE. Butyrate, a metabolite of intestinal microbiota, may have a neuroprotective effect in the process of sepsis by GPR109A/Nrf2/HO-1 pathway.}, }
@article {pmid35084496, year = {2022}, author = {Stapleton, TE and Kohl, KD and Dearing, MD}, title = {Plant secondary compound- and antibiotic-induced community disturbances improve the establishment of foreign gut microbiota.}, journal = {FEMS microbiology ecology}, volume = {98}, number = {1}, pages = {}, doi = {10.1093/femsec/fiac005}, pmid = {35084496}, issn = {1574-6941}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Fecal transplants are a powerful tool for manipulating the gut microbial community, but how these non-native communities establish in the presence of an intact host gut microbiome is poorly understood. We explored the microbiome of desert woodrats (Neotoma lepida) to determine whether disrupting existing microbial communities using plant secondary compounds (PSCs) or antibiotics increases the establishment of foreign microbes. We administered two fecal transplants between natural populations of adult woodrats that harbor distinct gut microbiota and have different natural dietary exposure to PSCs. First, we administered fecal transplants to recipients given creosote resin, a toxin found in the natural diet of our "donor" population, and compared the gut microbial communities to animals given fecal transplants and control diet using 16S rRNA gene sequencing. Second, we disrupted the gut microbial community of the same recipients with an antibiotic prior to fecal transplants. We found that gut microbial communities of woodrats disrupted with PSCs or antibiotics resembled that of donors more closely than control groups. PSC treatment also enriched microbes associated with metabolizing dietary toxins in transplant recipients. These results demonstrate that microbial community disturbances by PSCs or antibiotics are sufficient to facilitate establishment of foreign microbes in animals with intact microbiomes.}, }
@article {pmid34896249, year = {2022}, author = {Kang, Y and Kang, X and Yang, H and Liu, H and Yang, X and Liu, Q and Tian, H and Xue, Y and Ren, P and Kuang, X and Cai, Y and Tong, M and Li, L and Fan, W}, title = {Lactobacillus acidophilus ameliorates obesity in mice through modulation of gut microbiota dysbiosis and intestinal permeability.}, journal = {Pharmacological research}, volume = {175}, number = {}, pages = {106020}, doi = {10.1016/j.phrs.2021.106020}, pmid = {34896249}, issn = {1096-1186}, mesh = {Adipose Tissue, Brown ; Animals ; Endotoxemia/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gene Expression ; Insulin Resistance ; Intestinal Mucosa/metabolism ; *Lactobacillus acidophilus ; Lipid Metabolism/genetics ; Male ; Mice, Inbred C57BL ; Obesity/metabolism/microbiology/*therapy ; Permeability ; Probiotics/*therapeutic use ; }, abstract = {Obesity associated with low-grade chronic inflammation and intestinal dysbiosis is considered as a worldwide public health crisis. In the meanwhile, different probiotics have demonstrated beneficial effects on this condition, thus increasing the interest in the development of probiotic treatments. In this context, the aim of this study is to investigate the anti-obesity effects of potential probiotic Lactobacillus acidophilus isolated from the porcine gut. Then, it is found that L. acidophilus reduces body weight, fat mass, inflammation and insulin resistance in mice fed with a high-fat diet (HFD), accompanied by activation in brown adipose tissue (BAT) as well as improvements of energy, glucose and lipid metabolism. Besides, our data indicate that L. acidophilus not only reverses HFD-induced gut dysbiosis, as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin bearing Gram-negative bacteria levels, but also maintains intestinal barrier integrity, reduces metabolic endotoxemia, and inhibits the TLR4 / NF- κB signaling pathway. In addition, the results of microbiome phenotype prediction by BugBase and bacterial functional potential prediction using PICRUSt show that L. acidophilus treatment improves the gut microbiota functions involving metabolism, immune response, and pathopoiesia. Furthermore, the anti-obesity effect is transmissible via horizontal faeces transfer from L. acidophilus-treated mice to HFD-fed mice. According to our data, it is seen that L. acidophilus could be a good candidate for probiotic of ameliorating obesity and associated diseases such as hyperlipidemia, nonalcoholic fatty liver diseases, and insulin resistance through its anti-inflammatory properties and alleviation of endothelial dysfunction and gut dysbiosis.}, }
@article {pmid35384688, year = {2022}, author = {Cruz, N and Abernathy, GA and Dichosa, AEK and Kumar, A}, title = {The Age of Next-Generation Therapeutic-Microbe Discovery: Exploiting Microbe-Microbe and Host-Microbe Interactions for Disease Prevention.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0058921}, doi = {10.1128/iai.00589-21}, pmid = {35384688}, issn = {1098-5522}, abstract = {Humans are considered "superorganisms," harboring a diverse microbial collective that outnumbers human cells 10 to 1. Complex and gravely understudied host- and microbe-microbe interactions-the product of millions of years of host-microbe coevolution-govern the superorganism in almost every aspect of life functions and overall well-being. Abruptly disrupting these interactions via extrinsic factors has undesirable consequences for the host. On the other hand, supplementing commensal or beneficial microbes may mitigate perturbed interactions or enhance the interactive relationships that ultimately benefit all parties. Hence, immense efforts have focused on dissecting the innumerable host- and microbe-microbe relationships to characterize if a "positive" or "negative" interaction is at play and to exploit such behavior for broader implications. For example, microbiome research has worked to identify and isolate naturally antipathogenic microbes that may offer therapeutic potential either in a direct, one-on-one application or by leveraging its unique metabolic properties. However, the discovery and isolation of such desired therapeutic microbes from complex microbiota have proven challenging. Currently, there is no conventional technique to universally and functionally screen for these microbes. With this said, we first describe in this review the historical (probiotics) and current (fecal microbiota or defined consortia) perspectives on therapeutic microbes, present the discoveries of therapeutic microbes through exploiting microbe-microbe and host-microbe interactions, and detail our team's efforts in discovering therapeutic microbes via our novel microbiome screening platform. We conclude this minireview by briefly discussing challenges and possible solutions with therapeutic microbes' applications and paths ahead for discovery.}, }
@article {pmid35384391, year = {2022}, author = {Bloom, PP and Donlan, J and Torres Soto, M and Daidone, M and Hohmann, E and Chung, RT}, title = {Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient.}, journal = {Hepatology communications}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep4.1950}, pmid = {35384391}, issn = {2471-254X}, support = {Clinical Research Award//American College of Gastroenterology/ ; }, abstract = {Early data suggest fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics are unknown. We assessed the safety and efficacy of FMT in patients with prior overt HE, comparing five FMT donors. We performed an open-label study of FMT capsules, administered 5 times over 3 weeks. Primary outcomes were change in psychometric HE score (PHES) and serious adverse events (SAEs). Serial stool samples underwent shallow shotgun metagenomic sequencing. Ten patients completed FMT administration and 6-month follow-up. Model for End-Stage Liver Disease (MELD) score did not change after FMT (14 versus 14, p = 0.51). Thirteen minor adverse events and three serious adverse events (two unrelated to FMT) were reported. One SAE was extended-spectrum beta-lactamase Escherichia coli bacteremia. The PHES improved after three doses of FMT (+2.1, p < 0.05), after five doses of FMT (+2.9, p = 0.007), and 4 weeks after the fifth dose of FMT (+3.1, p = 0.02). Mean change in the PHES ranged from -1 to +6 by donor. Two taxa were identified by random forest analysis and confirmed by linear regression to predict the PHES- Bifidobacterium adolescentis (adjusted R2 = 0.27) and B. angulatum (adjusted R2 = 0.25)-both short-chain fatty acid (SCFA) producers. Patients who responded to FMT had higher levels of Bifidobacterium as well as other known beneficial taxa at baseline and throughout the study. The FMT donor with poorest cognitive outcomes in recipients had the lowest fecal SCFA levels. Conclusion: FMT capsules improved cognition in HE, with an effect varying by donor and recipient factors (NCT03420482).}, }
@article {pmid35382170, year = {2022}, author = {Eriksen, LL and Baunwall, SMD and Eriksen, PL and Bak-Fredslund, KP and Nielsen, JE and Dahlerup, JF and Thomsen, KL and Vilstrup, H and Hvas, CL}, title = {Deep hyperammonemic hepatic encephalopathy precipitated by fecal microbiota transplantation for fulminant Clostridioides difficile infection.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goab043}, doi = {10.1093/gastro/goab043}, pmid = {35382170}, issn = {2052-0034}, }
@article {pmid35382160, year = {2022}, author = {Burstiner, LS and Silver, J and Burstiner, LJ and Teymoorian, A and Pallav, K and Jones, D and Owings, A and Glover, S}, title = {Escherichia coli O157: H7 sepsis following fecal microbiota transplant in an IgA-deficient inflammatory bowel disease patient.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goab041}, doi = {10.1093/gastro/goab041}, pmid = {35382160}, issn = {2052-0034}, }
@article {pmid35278334, year = {2022}, author = {Donoso, F and Cryan, JF and Olavarría-Ramírez, L and Nolan, YM and Clarke, G}, title = {Inflammation, Lifestyle Factors, and the Microbiome-Gut-Brain Axis: Relevance to Depression and Antidepressant Action.}, journal = {Clinical pharmacology and therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1002/cpt.2581}, pmid = {35278334}, issn = {1532-6535}, support = {SFI/FFP/6820//Science Foundation Ireland Investigator Award/ ; //Reta Lila Weston Trust Award/ ; }, abstract = {Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss the role of the microbiota-gut-brain axis as a possible mediator for the adjunctive therapies for depression through inflammatory mechanisms. Finally, we review existing and future adjunctive strategies to manipulate the gut microbiota with potential use for depression, including physical exercise, dietary interventions, prebiotics/probiotics, and fecal microbiota transplantation.}, }
@article {pmid35151729, year = {2022}, author = {Hu, C and Sun, B and Liu, M and Yu, J and Zhou, X and Chen, L}, title = {Fecal transplantation from young zebrafish donors efficiently ameliorates the lipid metabolism disorder of aged recipients exposed to perfluorobutanesulfonate.}, journal = {The Science of the total environment}, volume = {823}, number = {}, pages = {153758}, doi = {10.1016/j.scitotenv.2022.153758}, pmid = {35151729}, issn = {1879-1026}, mesh = {Animals ; Fecal Microbiota Transplantation ; Female ; Fluorocarbons ; Lipid Metabolism ; *Lipid Metabolism Disorders ; *Probiotics/pharmacology ; Sulfonic Acids ; Zebrafish ; }, abstract = {Aging is a biological process that is accompanied by the gradual loss of physiological functions. Under the context of ubiquitous and persistent environmental pollution, the elderly will be more vulnerable to the detrimental effects of toxic pollutants than the young. With objectives to explore effective measures to ameliorate the double stress of aging and toxicants, the present study transplanted the feces from young zebrafish donors to aged recipients, which were concurrently exposed to perfluorobutanesulfonate (PFBS), an emerging environmental pollutant of international concern. After exposure, growth, hepatic structural organization, and lipid metabolism were examined. The results showed that, irrespective of PFBS toxicity, transplantation of young feces significantly enhanced the growth of the aged. In the livers of aged and PFBS-exposed zebrafish, vacuolization symptom was prevalently observed, while young fecal transplantation alleviated the structural defects in aged livers. In the gut of the elderly, digestive activity of lipids was promoted after the transplantation of young feces. The blood of the aged females accumulated significantly higher concentration of triglyceride (TG) than the young counterparts (2.6-fold), implying that the elderly were at high risk of cardiovascular diseases. PFBS treatment of the aged further increased blood TG levels by 2.0-fold relative to the aged control group, pointing to the aggravation of the health of the elderly by environmental pollution. However, it is intriguing that young fecal transplantation efficiently inhibited the metabolic toxicity of PFBS and restored the normal level of blood TG, which provided more evidence about the benefit of young fecal transplant to improve the health of the aged individuals. In the aged livers transplanted with young feces, mitochondrial β-oxidation of fatty acids was consistently activated. Overall, the present study verified the efficacy of young fecal transplantation to mitigate the metabolic disorders resulting from aging and an environmental pollutant.}, }
@article {pmid35379265, year = {2022}, author = {Wang, H and Zhang, M and Li, J and Liang, J and Yang, M and Xia, G and Ren, Y and Zhou, H and Wu, Q and He, Y and Yin, J}, title = {Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {76}, pmid = {35379265}, issn = {1742-2094}, support = {NSFC81870936//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Poststroke cognitive impairment (PSCI) is prevalent in stroke patients. The etiology of PSCI remains largely unknown. We previously found that stroke induces gut microbiota dysbiosis which affects brain injury. Hereby, we aimed to investigate whether the gut microbiota contributes to the pathogenesis of PSCI.<br><br>METHODS: 83 stroke patients were recruited and their cognitive function were measured by Montreal Cognitive Assessment (MoCA) scores 3 months after stroke onset. The peripheral inflammatory factor levels and gut microbiota compositions of the patients were analyzed. Fecal microbiota transplantation from patients to stroke mice was performed to examine the causal relationship between the gut microbiota and PSCI. The cognitive function of mice was evaluated by Morris water maze test.<br><br>RESULTS: 34 and 49 stroke patients were classified as PSCI and non-PSCI, respectively. Compared with non-PSCI patients, PSCI patients showed significantly higher levels of gut Enterobacteriaceae, lipopolysaccharide (LPS) and peripheral inflammation markers. Consistently, stroke mice that received microbiota from PSCI patients (PSCI mice) presented a higher level of Enterobacteriaceae, intestinal Toll-like receptor-4 (TLR4) expression, circulating LPS, LPS-binding protein (LBP) and inflammatory cytokines, and a lower level of fecal butyrate, severer intestine destruction and cognitive impairment than mice that received microbiota from nPSCI patients (nPSCI mice). In addition, we observed exacerbations in blood-brain barrier (BBB) integrity, microglial activation, neuronal apoptosis in the CA1 region of the hippocampus, and Aβ deposition in the thalamus of PSCI mice in comparison with nPSCI mice. Intraperitoneal injection of LPS after stroke caused similar pathology to those seen in PSCI mice. Supplementation with sodium butyrate (NaB) via drinking water rescued these detrimental changes in PSCI mice.<br><br>CONCLUSIONS: Our data indicate a cause-effect relationship between gut microbiota and PSCI for the first time, which is likely mediated by inflammation-regulating metabolites including LPS and butyrate.}, }
@article {pmid34826617, year = {2022}, author = {Ghani, R and Mullish, BH and Davies, FJ and Marchesi, JR}, title = {How to adapt an intestinal microbiota transplantation programme to reduce the risk of invasive multidrug-resistant infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {4}, pages = {502-512}, doi = {10.1016/j.cmi.2021.11.006}, pmid = {34826617}, issn = {1469-0691}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; MR/T005254/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19 ; Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Vulnerable patients with intestinal colonization of multidrug-resistant organisms (MDROs) are recognized to be at increased risk of invasive MDRO-driven infection. Intestinal microbiota transplantation (IMT, also called faecal microbiota transplant) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection.<br><br>OBJECTIVES: To describe how to establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimizing administration and assessment of endpoints.<br><br>SOURCES: Expert guidelines and peer-reviewed clinical studies are encompassed and discussed.<br><br>CONTENT: IMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) and take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT is timed for when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least 2 weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonization as a binary outcome. Repeat IMT is considered case by case.<br><br>IMPLICATIONS: Future research areas should include randomized studies that consider clinical outcomes and cost-effectiveness, and better understanding of mechanisms to identify markers of treatment success and functional microbiome components that could be used therapeutically.}, }
@article {pmid35372517, year = {2022}, author = {Baquero, F and Del Campo, R and Martínez, JL}, title = {Interventions in Nicotinamide Adenine Dinucleotide Metabolism, the Intestinal Microbiota and Microcin Peptide Antimicrobials.}, journal = {Frontiers in molecular biosciences}, volume = {9}, number = {}, pages = {861603}, doi = {10.3389/fmolb.2022.861603}, pmid = {35372517}, issn = {2296-889X}, abstract = {A proper NADH/NAD + balance allows for the flow of metabolic and catabolic activities determining cellular growth. In Escherichia coli, more than 80 NAD + dependent enzymes are involved in all major metabolic pathways, including the post-transcriptional build-up of thiazole and oxazole rings from small linear peptides, which is a critical step for the antibiotic activity of some microcins. In recent years, NAD metabolism boosting drugs have been explored, mostly precursors of NAD + synthesis in human cells, with beneficial effects on the aging process and in preventing oncological and neurological diseases. These compounds also enhance NAD + metabolism in the human microbiota, which contributes to these beneficial effects. On the other hand, inhibition of NAD + metabolism has been proposed as a therapeutic approach to reduce the growth and propagation of tumor cells and mitigating inflammatory bowel diseases; in this case, the activity of the microbiota might mitigate therapeutic efficacy. Antibiotics, which reduce the effect of microbiota, should synergize with NAD + metabolism inhibitors, but these drugs might increase the proportion of antibiotic persistent populations. Conversely, antibiotics might have a stronger killing effect on bacteria with active NAD + production and reduce the cooperation of NAD + producing bacteria with tumoral cells. The use of NADH/NAD + modulators should take into consideration the use of antibiotics and the population structure of the microbiota.}, }
@article {pmid35372103, year = {2022}, author = {Halaweish, HF and Boatman, S and Staley, C}, title = {Encapsulated Fecal Microbiota Transplantation: Development, Efficacy, and Clinical Application.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {826114}, doi = {10.3389/fcimb.2022.826114}, pmid = {35372103}, issn = {2235-2988}, abstract = {Fecal microbiota transplantation (FMT) has been established as a highly restorative therapeutic approach for treating recurrent Clostridioides difficile infection (rCDI). Recently, the use of capsule-based fecal microbiota transplantation (cFMT) has been shown to be a clinically effective approach to restore intestinal microbiota composition. This convenient, oral delivery provides an easy route of administration and a newfound flexibility for clinicians and patients. In this review, we discuss the development of cFMT, paying particular attention to lyophilized cFMT products. We review the available published clinical studies comparing cFMT with lower endoscopic FMT (eFMT) or placebo. We further discuss the pharmacokinetics of FMT, which should be understood in a framework of microbial ecology that considers the complex and dynamic interactions of gut microbiota with host factors and other microorganisms. Promisingly, the results of multiple trials investigating cFMT vs. eFMT in rCDI show cFMT to be as effective as eFMT at preventing rCDI. However, its efficacy in non-rCDI conditions, including obesity and metabolic syndrome, inflammatory bowel disease, HIV, and neurologic conditions, is less clear and more research is needed in these areas. Standardization of formulation, dose, and timing of administration to ensure optimal microbiota engraftment and clinical response is also a challenge to be addressed. Overall, cFMT is a practical method for fecal microbiota transplantation, with similar efficacy to eFMT in the resolution of rCDI, that holds therapeutic potential in a variety of other diseases.}, }
@article {pmid35371048, year = {2022}, author = {Brevi, A and Cogrossi, LL and Lorenzoni, M and Mattorre, B and Bellone, M}, title = {The Insider: Impact of the Gut Microbiota on Cancer Immunity and Response to Therapies in Multiple Myeloma.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {845422}, doi = {10.3389/fimmu.2022.845422}, pmid = {35371048}, issn = {1664-3224}, abstract = {The human microbiota is a unique set of microorganisms colonizing the human body and evolving within it from the very beginning. Acting as an insider, the microbiota provides nutrients, and mutualistically interacts with the host's immune system, thus contributing to the generation of barriers against pathogens. While a strong link has been documented between intestinal dysbiosis (i.e., disruption to the microbiota homeostasis) and diseases, the mechanisms by which commensal bacteria impact a wide spectrum of mucosal and extramucosal human disorders have only partially been deciphered. This is particularly puzzling for multiple myeloma (MM), a treatable but incurable neoplasia of plasma cells that accumulate in the bone marrow and lead to end-organ damage. Here we revise the most recent literature on data from both the bench and the bedside that show how the gut microbiota modulates cancer immunity, potentially impacting the progression of asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM) to full blown MM. We also explore the effect of the gut microbiome on hematopoietic stem cell transplantation, chemotherapy, immunomodulating therapy and cancer immunotherapy in MM patients. Additionally, we identify the most cogent area of investigation that have the highest chance to delineate microbiota-related and pathobiology-based parameters for patient risk stratification. Lastly, we highlight microbiota-modulating strategies (i.e., diet, prebiotics, probiotics, fecal microbiota transplantation and postbiotics) that may reduce treatment-related toxicity in patients affected by MM as well as the rates of undertreatment of SMM patients.}, }
@article {pmid35370847, year = {2022}, author = {Huang, HL and Xu, HM and Liu, YD and Shou, DW and Chen, HT and Nie, YQ and Li, YQ and Zhou, YJ}, title = {First Application of Fecal Microbiota Transplantation in Adult Asperger Syndrome With Digestive Symptoms-A Case Report.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {695481}, doi = {10.3389/fpsyt.2022.695481}, pmid = {35370847}, issn = {1664-0640}, abstract = {Asperger syndrome (AS) is a chronic neurodevelopmental disorder. Although all of the clinically diagnosed cases display normal intelligence and speech functions, barriers in social interaction and communication seriously affect mental health and psychological function. In addition to traditional psychological/behavioral training and symptomatic medication, in-depth studies of intestinal microbiota and mental health have indicated that probiotics (e.g., Lactobacillus rhamnosus) can effectively reduce the occurrence of AS. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe the first case of adult AS treated with FMT. The patient suffered from diarrhea-predominant irritable bowel syndrome for 6 years with symptoms of diarrhea and abdominal pain. After three rounds of FMT, the diarrhea and abdominal pain were significantly improved. Moreover, the symptoms of AS were also significantly ameliorated. We found that FMT changed the structure of the intestinal microbiota as well as the patient's serum metabolites, and these changes were consistent with the patient's symptoms. The metabolites may affect signaling pathways, as revealed by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The changes in microbial metabolites following FMT may affect other regions (e.g., the nervous system) via the circulatory system, such that the bacteria-gut-blood-brain axis may be the means through which FMT mitigates AS.}, }
@article {pmid35370631, year = {2022}, author = {Huang, Y and Xin, W and Xiong, J and Yao, M and Zhang, B and Zhao, J}, title = {The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {837500}, doi = {10.3389/fphar.2022.837500}, pmid = {35370631}, issn = {1663-9812}, abstract = {Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients.}, }
@article {pmid35081663, year = {2022}, author = {Shehata, E and Parker, A and Suzuki, T and Swann, JR and Suez, J and Kroon, PA and Day-Walsh, P}, title = {Microbiomes in physiology: insights into 21st-century global medical challenges.}, journal = {Experimental physiology}, volume = {107}, number = {4}, pages = {257-264}, doi = {10.1113/EP090226}, pmid = {35081663}, issn = {1469-445X}, support = {//Newton-Mosharafa Scholarship Fund from the Egyptian Ministry of Higher Education (Cultural Affairs and Mission sector), the British Council and the British Embassy in Egypt/ ; //National Institute for Health Research (Leicester Biomedical Research Centre)/ ; //Medical Research Council (MRC) UK Consortium on MetAbolic Phenotyping (MAP/UK)/ ; BB/R012512/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10343/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10346/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10347/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {NEW FINDINGS: What is the topic of this review? The role of the gut microbiome in physiology and how it can be targeted as an effective strategy against two of the most important global medical challenges of our time, namely, metabolic diseases and antibacterial resistance. What advances does it highlight? The critical roles of the microbiome in regulating host physiology and how microbiome analysis is useful for disease stratification to enable informed clinical decisions and develop interventions such as faecal microbiota transplantation, prebiotics and probiotics. Also, the limitations of microbiome modulation, including the potential for probiotics to enhance antimicrobial resistance gene reservoirs, and that currently a 'healthy microbiome' that can be used as a biobank for transplantation is yet to be defined.<br><br>ABSTRACT: The human gut microbiome is a key factor in the development of metabolic diseases and antimicrobial resistance, which are among the greatest global medical challenges of the 21st century. A recent symposium aimed to highlight state-of-the-art evidence for the role of the gut microbiome in physiology, from childhood to adulthood, and the impact this has on global disease outcomes, ageing and antimicrobial resistance. Although the gut microbiome is established early in life, over time the microbiome and its components including metabolites can become perturbed due to changes such as dietary habits, use of antibiotics and age. As gut microbial metabolites, including short-chain fatty acids, secondary bile acids and trimethylamine-N-oxide, can interact with host receptors including G protein-coupled receptors and can alter host metabolic fluxes, they can significantly affect physiological homoeostasis leading to metabolic diseases. These metabolites can be used to stratify disease phenotypes such as irritable bowel syndrome and adverse events after heart failure and allow informed decisions on clinical management and treatment. While strategies such as use of probiotics, prebiotics and faecal microbiota transplantation have been proposed as interventions to treat and prevent metabolic diseases and antimicrobial resistance, caution must be exercised, first due to the potential of probiotics to enhance antimicrobial resistance gene reservoirs, and second, a 'healthy gut microbiome' that can be used as a biobank for transplantation is yet to be defined. We highlight that sampling other parts of the gastrointestinal tract may produce more representative data than the faecal microbiome alone.}, }
@article {pmid35365713, year = {2022}, author = {Smith, BJ and Piceno, Y and Zydek, M and Zhang, B and Syriani, LA and Terdiman, JP and Kassam, Z and Ma, A and Lynch, SV and Pollard, KS and El-Nachef, N}, title = {Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {5517}, pmid = {35365713}, issn = {2045-2322}, support = {1563159//National Science Foundation (NSF)/ ; 5T32DK007007//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; 5T32DK007007//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; 1563159//National Science Foundation (NSF)/ ; }, abstract = {Fecal microbiota transplant is a promising therapy for ulcerative colitis. Parameters maximizing effectiveness and tolerability are not yet clear, and it is not known how import the transmission of donor microbes to patients is. Here (clinicaltrails.gov: NCT03006809) we have tested the effects of antibiotic pretreatment and compared two modes of maintenance dose delivery, capsules versus enema, in a randomized, pilot, open-label, 2 × 2 factorial design with 22 patients analyzed with mild to moderate UC. Clinically, the treatment was well-tolerated with favorable safety profile. Of patients who received antibiotic pretreatment, 6 of 11 experienced remission after 6 weeks of treatment, versus 2 of 11 non-pretreated patients (log odds ratio: 1.69, 95% confidence interval: -0.25 to 3.62). No significant differences were found between maintenance dosing via capsules versus enema. In exploratory analyses, microbiome turnover at both the species and strain levels was extensive and significantly more pronounced in the pretreated patients. Associations were also revealed between taxonomic turnover and changes in the composition of primary and secondary bile acids. Together these findings suggest that antibiotic pretreatment contributes to microbiome engraftment and possibly clinical effectiveness, and validate longitudinal strain tracking as a powerful way to monitor the dynamics and impact of microbiota transfer.}, }
@article {pmid35357354, year = {2022}, author = {Kim, SY and Shin, J and Park, JS and Cha, B and Seo, Y and Park, SH and Lee, JH and Kim, JS and Kwon, G}, title = {The first report on effect of fecal microbiota transplantation as a complementary treatment in a patient with steroid-refractory Cronkhite-Canada syndrome: A case report.}, journal = {Medicine}, volume = {101}, number = {12}, pages = {e29135}, doi = {10.1097/MD.0000000000029135}, pmid = {35357354}, issn = {1536-5964}, abstract = {RATIONALE: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease of unknown etiology that is characterized by the appearance of multiple polyps in the entire gastrointestinal (GI) tract, except in the esophagus, with GI and non-GI symptoms. Various factors are associated with the pathogenesis of CCS. Immune dysregulation has been discussed as one of the pathogeneses of CCS, and dysbiosis of the gut microbiota can affect the immune system. Currently, standard treatment has not been established.<br><br>We present the treatment with fecal microbiota transplantation (FMT) in a 67-year-old male patient with steroid-refractory CCS who could not undergo anti-tumor necrosis factor-a treatment due to suspected tuberculosis infection.<br><br>INTERVENTIONS: FMT has recently attracted attention as a method of overcoming drug resistance through immunomodulatory effects through microbiome regulation. We collected the patient's stool samples before FMT and 8weeks after FMT.<br><br>OUTCOMES: We analyzed the microbiome composition of patients by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). After FMT, the number of episodes of diarrhea and hypoalbuminemia were also corrected. The Chao 1 index after FMT, which was significantly higher than that of donors before FMT, changed to a similar level for donors after FMT. Fusobacterium nucleatum, Pyramidobacter piscolens, and Campylobacter concisus disappeared after FMT, suggesting the presence of an association between gut microbiota and CCS.<br><br>LESSONS: Furthermore, we provide the possibility that microbiome modulation by FMT could serve as a complementary treatment in patients with steroid-refractory CCS.}, }
@article {pmid35355860, year = {2022}, author = {Gao, T and Wang, Z and Cao, J and Dong, Y and Chen, Y}, title = {The Role of Aeromonas-Goblet Cell Interactions in Melatonin-Mediated Improvements in Sleep Deprivation-Induced Colitis.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {8133310}, doi = {10.1155/2022/8133310}, pmid = {35355860}, issn = {1942-0994}, abstract = {Background: Our previous studies demonstrated that melatonin could effectively ameliorate sleep deprivation- (SD-) caused oxidative stress-mediated gut microbiota disorder and colitis. The research further clarified the mechanism of melatonin in improving colitis from the perspective of the interaction between Aeromonas and goblet cells.<br><br>Methods: A seventy-two hours SD mouse model with or without melatonin intervention and fecal microbiota transplantation (FMT) to explore the vital position of Aeromonas-goblet cell interactions in melatonin improving SD-induced colitis. Moreover, Aeromonas or LPS-supplied mice were assessed, and the influence of melatonin on Aeromonas-goblet cell interactions-mediated oxidative stress caused colitis. Furthermore, in vitro experiment investigated the regulation mechanism of melatonin.<br><br>Results: Our study showed that SD induced colitis, with upregulation of Aeromonas and LPS levels and reductions in goblet cells number and MUC2 protein. Similarly, FMT from SD mice, Aeromonas veronii colonization, and LPS treatment restored the SD-like goblet cells number and MUC2 protein decrease and colitis. Moreover, LPS treatment downregulated the colonic antioxidant capacity. Yet, melatonin intervention reversed all consequence in SD, A.veronii colonization, and LPS-treated mice. In vitro, melatonin reversed A. veronii- or LPS-induced MUC2 depletion in mucus-secreting human HT-29 cells via increasing the expression level of Villin, Tff3, p-GSK-3β, β-catenin, and melatonin receptor 2 (MT2) and decreasing the level of p-IκB, p-P65, ROS, TLR4, and MyD88 proteins, while the improvement effect was blocked with pretreatment with a MT2 antagonist but were mimicked by TLR4 and GSK-3β antagonists and ROS scavengers.<br><br>Conclusions: Our results demonstrated that melatonin-mediated MT2 inhibits Aeromonas-goblet cell interactions to restore the level of MUC2 production via LPS/TLR4/MyD88/GSK-3β/ROS/NF-κB loop, further improving colitis in SD mice.}, }
@article {pmid35298520, year = {2022}, author = {Groenewegen, B and van Lingen, E and Ooijevaar, RE and Wessels, E and Feltkamp, MCW and Boeije-Koppenol, E and Verspaget, HW and Kuijper, EJ and van Prehn, J and Keller, JJ and Terveer, EM and , }, title = {How to prepare stool banks for an appropriate response to the ongoing COVID-19 pandemic: Experiences in the Netherlands and a retrospective comparative cohort study for faecal microbiota transplantation.}, journal = {PloS one}, volume = {17}, number = {3}, pages = {e0265426}, pmid = {35298520}, issn = {1932-6203}, mesh = {Aged ; COVID-19/epidemiology/*prevention &amp; control/transmission ; Clostridium Infections/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*virology ; Female ; Humans ; Male ; Netherlands/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; *Tissue Banks ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an efficacious treatment for patients with recurrent Clostridioides difficile infections (rCDI). Stool banks facilitate FMT by providing screened faecal suspensions from highly selected healthy donors. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic and the potential risk of SARS coronavirus-2 (SARS-CoV-2) transmission via FMT, many stool banks were forced to temporarily halt and adjust donor activities.<br><br>GOAL: The evaluation of a strategy to effectively continue stool banking activities during the ongoing COVID-19 pandemic.<br><br>STUDY: To restart our stool banking activities after an initial halt, we implemented periodic SARS-CoV-2 screening in donor faeces and serum, and frequent donor assessment for COVID-19 related symptoms. FMT donor and recipient data obtained before (2016-2019) and during the COVID-19 pandemic (March 2020-August 2021) were compared to assess stool banking efficacy.<br><br>RESULTS: Two out of ten donors developed COVID-19. No differences during versus before the COVID-19 pandemic were observed in the number of approved faeces donations (14 vs 22/month, p = 0.06), FMT requests for rCDI (3.9 vs 4.3/month, p = 0.6); rCDI patients eligible for FMT (80.6% vs 73.3%, p = 0.2); rCDI cure rate (90.3% vs 89.2%, p = 0.9); CDI-free survival (p = 0.7); the number of non-rCDI patients treated with FMT (0.5/month vs 0.4/month), and the number of possibly FMT related adverse events (9.5% vs 7.8%, p = 0.7). Two FMTs for rCDI were delayed due to COVID-19.<br><br>CONCLUSIONS: There is a continued need for FMT treatment of rCDI during the COVID-19 pandemic. Appropriate donor screening and SARS-CoV-2 infection prevention measures can be implemented in existing protocols without increasing the burden for donors, and allow safe, effective and efficient FMT during the ongoing COVID-19 pandemic. Stool banks should evaluate their SARS-CoV-2 donor screening protocols for long-term sustainability and efficacy, and share their experiences to help the utilisation, standardisation and improvement of stool banks worldwide.}, }
@article {pmid34370175, year = {2021}, author = {Moustafa, SA and Mohamed, S and Dawood, A and Azar, J and Elmorsy, E and Rizk, NAM and Salama, M}, title = {Gut brain axis: an insight into microbiota role in Parkinson's disease.}, journal = {Metabolic brain disease}, volume = {36}, number = {7}, pages = {1545-1557}, pmid = {34370175}, issn = {1573-7365}, mesh = {Anti-Bacterial Agents/therapeutic use ; Brain-Gut Axis/*physiology ; Dysbiosis/complications ; Fatty Acids, Volatile/physiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Lipids/physiology ; Parkinson Disease/drug therapy/*etiology ; Probiotics/therapeutic use ; alpha-Synuclein/physiology ; }, abstract = {Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. It is characterized neuropathologically by the presence of alpha-synuclein containing Lewy Bodies in the substantia nigra of the brain with loss of dopaminergic neurons in the pars compacta of the substantia nigra. The presence of alpha-synuclein aggregates in the substantia nigra and the enteric nervous system (ENS) drew attention to the possibility of a correlation between the gut microbiota and Parkinson's disease. The gut-brain axis is a two-way communication system, which explains how through the vagus nerve, the gut microbiota can affect the central nervous system (CNS), including brain functions related to the ENS, as well as how CNS can alter various gut secretions and immune responses. As a result, this dysbiosis or alteration in gut microbiota can be an early sign of PD with reported changes in short chain fatty acids, bile acids, and lipids. This gave rise to the use of probiotics and faecal microbiota transplantation as alternative approaches to improve the symptoms of patients with PD. The aim of this review is to discuss investigations that have been done to explore the gastrointestinal involvement in Parkinson's disease, the effect of dysbiosis, and potential therapeutic strategies for PD.}, }
@article {pmid35352640, year = {2022}, author = {Bhatt, S and Kanoujia, J and Mohanalakshmi, S and Patil, CR and Gupta, G and Chellappan, DK and Dua, K}, title = {Role of Brain-Gut-Microbiota Axis in Depression: Emerging Therapeutic Avenues.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/1871527321666220329140804}, pmid = {35352640}, issn = {1996-3181}, abstract = {The human gut microbiota plays a significant role in the pathophysiology of central nervous system related diseases. Recent studies suggest correlations between the altered gut microbiota and major depressive disorder (MDD). It is proposed that normalization of the gut microbiota alleviates MDD. The imbalance of brain-gut-microbiota axis also results in dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. This imbalance has a crucial role in the pathogenesis of depression. Treatment strategies with certain antibiotics lead to the depletion of useful microbes and thereby induce depression like effects in subjects. Microbiota is also involved in the synthesis of various neurotransmitters (NTs) like 5-hydroxy tryptamine (5-HT; serotonin), norepinephrine (NE) and dopamine (DA). In addition to NTs, the gut microbiota also has influence on brain derived neurotrophic factor (BDNF) levels. Recent research findings have exhibited that transfer of stress prone microbiota in mice is also responsible for depression and anxiety-like behaviour in animals. The use of probiotics, prebiotics, synbiotics and proper diet have shown the beneficial effects in the regulation of depression pathogenesis. Moreover, transplantation of fecal microbiota from depressed individuals to the normal subjects also induces depression like symptoms. With the precedence of limited therapeutic benefits from monoamine targeting drugs, the regulation of brain-gut microbiota is emerging as a new treatment modality for MDDs. In this review, we elaborate the significance of brain-gut-microbiota axis in the progression of MDD, particularly focusing on the modulation of the gut microbiota as a mode of treating MDD.}, }
@article {pmid35349076, year = {2022}, author = {Sharma, A and Roy, A and Premkumar, M and Verma, N and Duseja, A and Taneja, S and Grover, S and Chopra, M and Dhiman, RK}, title = {Fecal microbiota transplantation in alcohol-associated acute-on-chronic liver failure: an open-label clinical trial.}, journal = {Hepatology international}, volume = {}, number = {}, pages = {}, pmid = {35349076}, issn = {1936-0541}, abstract = {BACKGROUND: Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF.<br><br>METHODS: Thirty-three patients [13 in the FMT arm; 20 in the standard of care arm (SOC)] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days 7, 28, and 90.<br><br>RESULTS: Survival at 28 and 90 days was significantly better in the FMT arm (100% versus 60%, p = 0.01; 53.84% versus 25%, p = 0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, p = 0.11) patients, while ascites resolved in 100% versus 40% survivors (p = 0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (p = 0.77; p = 0.70). Median IL1beta decreased by 21.39% (IQR - 73.67 to 7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR - 0.88 to 128.11) (p = 0.01). Percentage changes in bilirubin and ALT between baseline and day 7 emerged as predictors of 90-day mortality.<br><br>CONCLUSION: FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF.<br><br>CLINICAL TRIAL NUMBER: NCT03827772 available from http://clinicaltrials.gov/ct2/show/NCT03827772 CTRI Reference number: CTRI/2019/02/017538 dated 7 February 2019.}, }
@article {pmid35347532, year = {2022}, author = {Fang, Z and Chen, M and Qian, J and Wang, C and Zhang, J}, title = {The Bridge Between Ischemic Stroke and Gut Microbes: Short-Chain Fatty Acids.}, journal = {Cellular and molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {35347532}, issn = {1573-6830}, abstract = {Short-chain fatty acids (SCFAs) are monocarboxylates produced by the gut microbiota (GM) and result from the interaction between diet and GM. An increasing number of studies about the microbiota-gut-brain axis (MGBA) indicated that SCFAs may be a crucial mediator in the MGBA, but their roles have not been fully clarified. In addition, there are few studies directly exploring the role of SCFAs as a potential regulator of microbial targeted interventions in ischemic stroke, especially for clinical studies. This review summarizes the recent studies concerning the relationship between ischemic stroke and GM and outlines the role of SCFAs as a bridge between them. The potential mechanisms by which SCFAs affect ischemic stroke are described. Finally, the beneficial effects of SFCAs-mediated therapeutic measures such as diet, dietary supplements (e.g., probiotics and prebiotics), fecal microbiota transplantation, and drugs on ischemic brain injury are also discussed.}, }
@article {pmid35346845, year = {2022}, author = {Chen, J and Wang, M and Zhang, P and Li, H and Qu, K and Xu, R and Guo, N and Zhu, H}, title = {Cordycepin alleviated metabolic inflammation in Western diet-fed mice by targeting intestinal barrier integrity and intestinal flora.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106191}, doi = {10.1016/j.phrs.2022.106191}, pmid = {35346845}, issn = {1096-1186}, abstract = {Metabolic inflammation is a crucial factor in the pathogenesis of obesity and promotes related complications. Accumulating evidence has indicated that regulating intestinal integrity and the gut microbiota may be new treatment strategies for metabolic inflammation and obesity. Cordycepin has been reported to improve obesity, but the mechanism is not yet clear. Here, we showed that cordycepin considerably alleviated systemic inflammation while reducing body weight gain and metabolic disorders in Western diet (WD)-fed mice. Further investigations showed that cordycepin significantly ameliorated WD-induced damage to the intestinal barrier and decreased the leakage of lipopolysaccharide (LPS) into the blood in mice by suppressing intestinal inflammation, oxidative stress damage, and decreasing intestinal epithelial cell apoptosis and pyroptosis. In addition, by using metagenomic sequencing, we found that cordycepin can also regulate the homeostasis of intestinal flora, including selectively increasing the abundance of Akkermansia muciniphila and reducing the production of fecal LPS. Besides, we demonstrated that the intestinal flora partially mediated the beneficial effects of cordycepin on improving intestinal barrier function, and obesity-related symptoms in WD-fed mice by a fecal microbiota transplantation experiment. Hence, our findings provided new insights into the role of cordycepin in improving metabolic inflammation and obesity from the perspective of regulating the intestinal barrier function and intestinal flora, and further provided data support for the utility of cordycepin in the treatment of obesity and its complications.}, }
@article {pmid35346337, year = {2022}, author = {Newsome, RC and Gharaibeh, RZ and Pierce, CM and da Silva, WV and Paul, S and Hogue, SR and Yu, Q and Antonia, S and Conejo-Garcia, JR and Robinson, LA and Jobin, C}, title = {Interaction of bacterial genera associated with therapeutic response to immune checkpoint PD-1 blockade in a United States cohort.}, journal = {Genome medicine}, volume = {14}, number = {1}, pages = {35}, pmid = {35346337}, issn = {1756-994X}, abstract = {BACKGROUND: Recent studies show that human gut microbial composition can determine whether a patient is a responder or non-responder to immunotherapy but have not identified a common microbial signal shared by responding patients. The functional relationship between immunity, intestinal microbiota, and NSCLC response to immune checkpoint inhibitor/inhibition (ICI) in an American cohort remains unexplored.<br><br>METHODS: RNAlater-preserved fecal samples were collected from 65 pre-treatment (baseline) and post-treatment stage III/IV NSCLC patients undergoing ICI therapy, categorized as responders or non-responders according to RECIST criteria. Pooled and individual responder and non-responder microbiota were transplanted into a gnotobiotic mouse model of lung cancer and treated with ICIs. 16S rDNA and RNA sequencing was performed on patient fecal samples, 16S rDNA sequencing on mouse fecal samples, and flow cytometric analysis on mouse tumor tissue.<br><br>RESULTS: Responder patients have both a different microbial community structure than non-responders (P = 0.004) and a different bacterial transcriptome (PC2 = 0.03) at baseline. Taxa significantly enriched in responders include amplicon sequence variants (ASVs) belonging to the genera Ruminococcus, Akkermansia, and Faecalibacterium. Pooled and individual responder microbiota transplantation into gnotobiotic mice decreased tumor growth compared to non-responder colonized mice following ICI (P = 0.023, P = 0.019, P = 0.008, respectively). Responder tumors showed an increased anti-tumor cellular phenotype following ICI treatment. Responder mice are enriched with ASVs belonging to the genera Bacteroides, Blautia, Akkermansia, and Faecalibacterium. Overlapping taxa mapping between human and mouse cohorts correlated with tumor size and weight revealed a network highlighting responder-associated ASVs belonging to the genera Colidextribacter, Frisingicoccus, Marvinbryantia, and Blautia which have not yet been reported.<br><br>CONCLUSIONS: The role of isolate-specific function and bacterial gene expression in gut microbial-driven responsiveness to ICI has been underappreciated. This work supports further investigation using isolate-driven models to characterize the mechanisms underlying this phenomenon.}, }
@article {pmid35345829, year = {2022}, author = {Zhang, F and Zhou, Y and Chen, H and Jiang, H and Zhou, F and Lv, B and Xu, M}, title = {Curcumin Alleviates DSS-Induced Anxiety-Like Behaviors via the Microbial-Brain-Gut Axis.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {6244757}, doi = {10.1155/2022/6244757}, pmid = {35345829}, issn = {1942-0994}, abstract = {The anxiety and depression caused by inflammatory bowel diseases (IBD) are known to greatly affect the mental health of patients. The mechanism of psychiatric disorders caused by IBD is not fully understood. Previous research has suggested that the gut microbiome plays a key role in IBD. Curcumin is a yellow polyphenol extracted from the rhizome of the ginger plant, which has been shown to have effects against both depression and anxiety. Research has indicated that curcumin affects the gut microbiome and exerts antianxiety and neuroprotective effects through the microbiota-gut-brain axis (MGB). However, whether curcumin can alleviate the psychiatric disorders caused by IBD and how curcumin affects the MGB axis through the gut microbiota have not been fully understood. Therefore, this study was aimed at determining the metabolic parameters and microbiological environment in the peripheral and central nervous system to determine the effects of curcumin against anxiety induced by dextran sulfate sodium salt (DSS) in mice. To elaborate on the link between the gut microbiota and how curcumin alleviates anxiety-like behaviors, we performed a fecal microbiota transplantation (FMT) experiment. The results suggested that curcumin can effectively relieve anxiety-like behaviors caused by DSS in mice. Further, curcumin treatment can alleviate disturbances in the gut microbiota and systemic disorders of lipid metabolism caused by DSS. Finally, through FMT, we verified that curcumin increased phosphatidylcholine in the prefrontal cortex of the mice and alleviated DSS-induced anxiety-like behaviors by modulating specific gut microbiota. We also revealed that Muribaculaceae may be a key part of the gut microbiota for curcumin to alleviate DSS-induced anxiety-like behaviors through the MGB axis.}, }
@article {pmid35345443, year = {2022}, author = {Fan, Y and Su, Q and Chen, J and Wang, Y and He, S}, title = {Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {836953}, doi = {10.3389/fonc.2022.836953}, pmid = {35345443}, issn = {2234-943X}, abstract = {Glioma is the most common malignant tumor of the central nervous system (CNS), with high degree of malignancy and poor prognosis. The gut microbiome (GM) is composed of microorganisms with different properties and functions, which play an important role in human physiology and biological activities. It has been proved that GM can affect the development of glioma through natural immunity, but whether GM can affect glioma through adaptive immunity and whether there are some microorganisms in the GM that may affect glioma growth still remain unclear. In our study, we evaluated the relationship between GM and glioma. We proved that (I) glioma growth can induce structural changes of mouse GM, including the decreased abundance of Bacteroidia and increased abundance of Firmicutes. (II) GM dysbiosis can downregulate Foxp3 expression in the brain and promote glioma growth. A balanced environment of GM can upregulate the expression of Foxp3 in the brain and delay the development of glioma. (III) The increased abundance of Bacteroidia is associated with accelerated glioma progression, while its decreased abundance is associated with delayed glioma progression, which may be one of the key microorganisms affecting glioma growth. This study is helpful to reveal the relationship between GM and glioma development and provide new ideas for adjuvant therapy of glioma.}, }
@article {pmid35344215, year = {2022}, author = {Noye Tuplin, EW and Alukic, E and Lowry, DE and Chleilat, F and Wang, W and Cho, NA and Sampsell, K and Sales, KM and Mayengbam, S and McCoy, KD and Reimer, RA}, title = {Dietary fiber combinations to mitigate the metabolic, microbial, and cognitive imbalances resulting from diet-induced obesity in rats.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {36}, number = {5}, pages = {e22269}, doi = {10.1096/fj.202101750R}, pmid = {35344215}, issn = {1530-6860}, support = {//Snyder Institute for Chronic Diseases/ ; //Alberta Innovates | Alberta Innovates - Health Solutions (AIHS)/ ; //U of C | Alberta Children's Hospital Research Institute (ACHRI)/ ; //Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; //Faculty of Kinesiology Dean's Doctoral Scholarship/ ; //University of Calgary Eyes High Postdoctoral Fellowship/ ; }, abstract = {Dietary fiber promotes a healthy gut microbiome and shows promise in attenuating the unfavorable microbial changes resulting from a high-fat/sucrose (HFS) diet. High-fiber diets consisting of oligofructose alone (HFS/O) or in combination with β-glucan (HFS/OB), resistant starch (HFS/OR), or β-glucan and resistant starch (HFS/OBR) were fed to diet-induced obese rats for 8 weeks to determine if these fibers could attenuate the obese phenotype. Only the HFS/O group displayed a decrease in body weight and body fat, but all fiber interventions improved insulin sensitivity and cognitive function. The HFS/O diet was the least effective at improving cognitive function and only the HFS/OB group showed improvements in glucose tolerance, thus highlighting the differential effects of fiber types. Hippocampal cytokines (IL-6, IL-10) were more pronounced in the HFS/OB group which coincided with the most time spend in the open arms of the elevated plus maze. All fiber groups showed an increase in beneficial Bifidobacterium and Lactobacillus abundance while the HFS group showed higher abundance of Clostridium. Fecal microbiota transplant from fiber-treated rats into germ-free mice did not alter body composition in the mice but did result in a higher abundance of Bacteroides in the HFS/O and HFS/OB groups compared to HFS. The HFS/OB recipient mice also had higher insulin sensitivity compared to the other groups. This study highlights the influence of dietary fiber type on metabolic and cognitive outcomes suggesting that the type of supplementation (single or combined fibers) could be tailored to specific targeted outcomes.}, }
@article {pmid35340247, year = {2022}, author = {Feng, H and He, L and Wang, Z and Pi, B and Liu, Z}, title = {Phillygenin Protects the Intestinal Barrier from Dysfunction via let-7b Signaling Pathway and Regulation of Intestinal Microbiota.}, journal = {Journal of healthcare engineering}, volume = {2022}, number = {}, pages = {4769709}, doi = {10.1155/2022/4769709}, pmid = {35340247}, issn = {2040-2309}, abstract = {The study investigates the positive effects of phillygenin on intestinal tight junction via the let-7b signaling pathway and the regulation of intestinal microbiota. The expression levels of tight junction proteins are determined through PCR and Western blot. DSS-induced mice colitis is used to verify the protective effects of phillygenin on intestinal barrier and tight junction. Fecal microbiota transplantation is used to verify the role intestinal microbiota. let-7b is detected in the colon tissues of patients with acute stercoral obstruction. Phillygenin could promote the expression of occludin, which might be inhibited by let-7b inhibitor. DSS-induced mice colitis showed that phillygenin could lower the colonic permeability and maintain the tight junction-associated proteins. The effects of phillygenin could be deprived by anti-let-7b and rescued by FMT of normal intestinal microbiota. Clinical samples verified a lower level of let-7b in stercoral obstruction patients. Phillygenin could protect the intestinal barrier from dysfunction via the signaling pathway of let-7b by regulating intestinal microbiota.}, }
@article {pmid35339829, year = {2022}, author = {Yang, J and Zhang, Z and Xie, Z and Bai, L and Xiong, P and Chen, F and Zhu, T and Peng, Q and Wu, H and Zhou, Y and Ma, Y and Zhang, Y and Chen, M and Gao, J and Tian, W and Shi, K and Du, Y and Duan, Y and Wang, H and Xu, Y and Kuang, YQ and Zhu, M and Yu, J and Wang, K}, title = {Metformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {149}, number = {}, pages = {112837}, doi = {10.1016/j.biopha.2022.112837}, pmid = {35339829}, issn = {1950-6007}, abstract = {BACKGROUND: Metformin exhibits therapeutic potential in behavioural deficits induced by methamphetamine (METH) in rats. Emerging studies suggest gut microbiota may impact psychiatric symptoms, but there is no direct evidence supporting metformin's participation in the pathophysiology of withdrawal symptoms via modulation of gut microbiota.<br><br>METHODS: In order to define the functional impacts of gut microbiota and metformin to the behavioural deficits during METH withdrawal, we utilized a combination of fecal microbiota transplantation (FMT), high-throughput sequencing, and untargeted metabolomics technologies.<br><br>RESULTS: First, METH addicts exhibited higher α diversity and distinct microbial structures compared to healthy controls. In particular, the relative abundance of Rikenellaceae was positively correlated with the severity of anxiety and depression. Second, both human-to-mouse and mouse-to-mouse FMTs confirmed that METH-altered-microbiota transplantation is sufficient to promote anxiety and depression-like behaviours in recipient germ-free mice, and these behavioural disturbances could be ameliorated by metformin. In-depth analysis revealed that METH significantly altered the bacterial composition and structure as well as relative abundance of several bacterial taxa and metabolites, including Rikenellaceae and inosine, respectively, whereas add-on metformin could remodel these alterations. Finally, the inosine complementation successfully restored METH-induced anxiety and depression-like behaviours in mice.<br><br>CONCLUSION: This study demonstrates that METH withdrawal-induced anxiety and depression-like behaviours are reversible and transmissible via gut microbiota in a mouse model. The therapeutic effects of metformin on psychiatric manifestations are associated with microbiota-derived metabolites, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.}, }
@article {pmid35339730, year = {2022}, author = {Kattner, AA}, title = {About gladiators and a sacred disease.}, journal = {Biomedical journal}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bj.2022.03.006}, pmid = {35339730}, issn = {2320-2890}, abstract = {In this special edition of the Biomedical Journal the reader gains an insight into drug-resistant epilepsy and according treatment approaches involving deep brain stimulation, the ketogenic diet and fecal microbiota transplant. Another emphasis is put on personalized medicine strategies, and covered in articles about the use of natriuretic peptides against cancer, along with an article about companion diagnostics involving extracellular vesicles. Recurrent infection with C. difficile, associated risk factors and therapeutic options are discussed. We learn about a mechanism that helps Leishmania evade a host control mechanism, receive an update about human adenovirus and are presented with characteristic magnetic resonance neuroimaging in COVID-19 pediatric patients. An advanced assessment in pediatric septic shock and an improved model for a pediatric early warning system are proposed. Some of the genetic causes of renal hypomagnesemia are explored, the impact of air pollution on children is examined, and an antisiphon device is described for surgical treatment of hydrocephalus. The relation between energy metabolism, circadian rhythm and its influence on the ATPase in the SCN are investigated, and among others some of the genetics influencing smoking duration and lung cancer. Finally it is discussed how embryo quality can be improved in in vitro fertilization, and what impact high estradiol has on blastocyst implantation. The outcome of surgery to correct mandibular deficiency is assessed, and in two letters the inclusion of observational studies in the evaluation of clinical trials related to COVID-19 is elaborated.}, }
@article {pmid35337386, year = {2022}, author = {Podlesny, D and Arze, C and Dörner, E and Verma, S and Dutta, S and Walter, J and Fricke, WF}, title = {Metagenomic strain detection with SameStr: identification of a persisting core gut microbiota transferable by fecal transplantation.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {53}, pmid = {35337386}, issn = {2049-2618}, support = {316130265//Deutsche Forschungsgemeinschaft/ ; 316130265//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: The understanding of how microbiomes assemble, function, and evolve requires metagenomic tools that can resolve microbiota compositions at the strain level. However, the identification and tracking of microbial strains in fecal metagenomes is challenging and available tools variably classify subspecies lineages, which affects their applicability to infer microbial persistence and transfer.<br><br>RESULTS: We introduce SameStr, a bioinformatic tool that identifies shared strains in metagenomes by determining single-nucleotide variants (SNV) in species-specific marker genes, which are compared based on a maximum variant profile similarity. We validated SameStr on mock strain populations, available human fecal metagenomes from healthy individuals and newly generated data from recurrent Clostridioides difficile infection (rCDI) patients treated with fecal microbiota transplantation (FMT). SameStr demonstrated enhanced sensitivity to detect shared dominant and subdominant strains in related samples (where strain persistence or transfer would be expected) when compared to other tools, while being robust against false-positive shared strain calls between unrelated samples (where neither strain persistence nor transfer would be expected). We applied SameStr to identify strains that are stably maintained in fecal microbiomes of healthy adults over time (strain persistence) and that successfully engraft in rCDI patients after FMT (strain engraftment). Taxonomy-dependent strain persistence and engraftment frequencies were positively correlated, indicating that a specific core microbiota of intestinal species is adapted to be competitive both in healthy microbiomes and during post-FMT microbiome assembly. We explored other use cases for strain-level microbiota profiling, as a metagenomics quality control measure and to identify individuals based on the persisting core gut microbiota.<br><br>CONCLUSION: SameStr provides for a robust identification of shared strains in metagenomic sequence data with sufficient specificity and sensitivity to examine strain persistence, transfer, and engraftment in human fecal microbiomes. Our findings identify a persisting healthy adult core gut microbiota, which should be further studied to shed light on microbiota contributions to chronic diseases. Video abstract.}, }
@article {pmid35333590, year = {2022}, author = {Puntillo, M and Segli, F and Champagne, CP and Raymond, Y and Vinderola, G}, title = {Functional Microbes and Their Incorporation into Foods and Food Supplements: Probiotics and Postbiotics.}, journal = {Annual review of food science and technology}, volume = {13}, number = {}, pages = {385-407}, doi = {10.1146/annurev-food-052720-011545}, pmid = {35333590}, issn = {1941-1421}, abstract = {Life expectancy has dramatically increased over the past 200 years, but modern life factors such as environmental exposure, antibiotic overuse, C-section deliveries, limited breast-feeding, and diets poor in fibers and microbes could be associated with the rise of noncommunicable diseases such as overweight, obesity, diabetes, food allergies, and colorectal cancer as well as other conditions such as mental disorders. Microbial interventions that range from transplanting a whole undefined microbial community from a healthy gut to an ill one, e.g., so-called fecal microbiota transplantation or vaginal seeding, to the administration of selected well-characterized microbes, either live (probiotics) or not (postbiotics), with efficacy demonstrated in clinical trials, may be effective tools to treat or prevent acute and chronic diseases that humans still face, enhancing the quality of life.}, }
@article {pmid35325852, year = {2022}, author = {Du, L and Li, Q and Yi, H and Kuang, T and Tang, Y and Fan, G}, title = {Gut microbiota-derived metabolites as key actors in type 2 diabetes mellitus.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {149}, number = {}, pages = {112839}, doi = {10.1016/j.biopha.2022.112839}, pmid = {35325852}, issn = {1950-6007}, abstract = {Type 2 diabetes mellitus (T2DM) is one of the most risk factors threatening human health. Although genetic and environmental factors contribute to the development of T2DM, gut microbiota has also been found to be involved. Gut microbiota-derived metabolites are a key factor in host-microbe crosstalk, and have been revealed to play a central role in the physiology and physiopathology of T2DM. In this review, we provide a timely and comprehensive summary of the microbial metabolites that are protective or causative for T2DM, including some amino acids-derived metabolites, short-chain fatty acids, trimethylamine N-oxide, and bile acids. The mechanisms by which metabolites affect T2DM have been elaborated. Knowing more about these processes will increase our understanding of the causal relationship between gut microbiota and T2DM. Moreover, some frontier therapies that target gut microbes and their metabolites to improve T2DM, including dietary intervention, fecal microbiota transplantation, probiotics, prebiotics or synbiotics intervention, and drugging microbial metabolism, have been critically discussed. This review may provide novel insights for the development of targeted and personalized treatments for T2DM based on gut microbial metabolites. More high-quality clinical trials are needed to accelerate the clinical translation of gut-targeted therapies for T2DM.}, }
@article {pmid35316318, year = {2022}, author = {Liu, Z and Yan, C and Lin, X and Ai, C and Dong, X and Shao, L and Wang, S and Song, S and Zhu, B}, title = {Responses of the gut microbiota and metabolite profiles to sulfated polysaccharides from sea cucumber in humanized microbiota mice.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d1fo04443e}, pmid = {35316318}, issn = {2042-650X}, abstract = {Sea cucumber Stichopus japonicus has been consumed as functional food traditionally in Asia, and its sulfated polysaccharide (SCSPsj) demonstrates health-promoting effects in rodents which are related to the regulation of the gut microbiota. However, little is known about the response of the human gut microbiota to SCSPsj. Therefore, the present study aimed to study the response of the donor microbiota to SCSPsj in vivo through a humanized microbiota mice model, which was constructed by antibiotic treatment combined with fecal microbiota transplant. The results revealed that the SCSPsj supplement could positively interact with the specific donor microbiota. It could significantly regulate the gut microbiota community, especially the abundance of Lactobacillus. In addition, SCSPsj could modulate the metabolites in serum and cecal contents of mice, including short-chain fatty acids (SCFAs) and lactic acid, and the changes of some bioactive metabolites were associated with the gut microbiota enriched by SCSPsj. Furthermore, in vitro experiments demonstrated that the Lactobacillus strains isolated could not be proliferated directly by SCSPsj, but SCSPsj significantly promoted biofilm formation and mucus binding of Lactobacillus spp., which contributed to the enrichment of Lactobacillus in vivo. The present study could provide insight into the application of SCSPsj as microbiota-directed food.}, }
@article {pmid35312296, year = {2022}, author = {Ju, Z and Shen, L and Zhou, M and Luo, J and Yu, Z and Qu, C and Lei, R and Lei, M and Huang, R}, title = {Helicobacter pylori and Alzheimer's Disease-Related Metabolic Dysfunction: Activation of TLR4/Myd88 Inflammation Pathway from p53 Perspective and a Case Study of Low-Dose Radiation Intervention.}, journal = {ACS chemical neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1021/acschemneuro.2c00082}, pmid = {35312296}, issn = {1948-7193}, abstract = {Gut dysbiosis is observed in Alzheimer's disease (AD) and is frequently associated with AD-induced metabolic dysfunction. However, the extent and specific underlying molecular mechanisms triggered by alterations of gut microbiota composition and function mediating AD-induced metabolic dysfunction in AD remain incompletely uncovered. Here, we indicate that Helicobacter pylori (H. pylori) is abundant in AD patients with relative metabolic dysfunction. Fecal microbiota transplantation from the AD patients promoted metabolic dysfunction in mice and increased gut permeability. H. pylori increased gut permeability through activation of the TLR4/Myd88 inflammation pathway in a p53-dependent manner, leading to metabolic dysfunction. Moreover, p53 deficiency reduced bile acid concentration, leading to an increased abundance of H. pylori colonization. Overall, these data identify H. pylori as a key promoter of AD-induced metabolic dysfunction.}, }
@article {pmid35312112, year = {2022}, author = {Wang, Y and Xu, Y and Xu, X and Wang, H and Wang, D and Yan, W and Zhu, J and Hao, H and Wang, G and Cao, L and Zhang, J}, title = {Ginkgo biloba extract ameliorates atherosclerosis via rebalancing gut flora and microbial metabolism.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.7439}, pmid = {35312112}, issn = {1099-1573}, support = {81720108032//National Natural Science Foundation of China/ ; 81773986//National Natural Science Foundation of China/ ; 81930109//National Natural Science Foundation of China/ ; 81973559//National Natural Science Foundation of China/ ; G20582017001//Overseas Expertise Introduction Project for Discipline Innovation/ ; SZSM201801060//Sanming Project of Medicine in Shenzhen/ ; SKLNMZZ202020//the Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University/ ; }, abstract = {The Ginkgo biloba leave extract (GbE) is widely applied in the prevention and treatment of atherosclerotic cardiovascular diseases in clinical practice. However, its mechanism of actions has not been totally elucidated. In this study, we confirmed the beneficial effects of GbE in alleviating hypercholesterolemia, inflammation and atherosclerosis in Ldlr-/- mice, which were fed 12 weeks of Western diet (WD). Moreover, 16S rRNA sequencing revealed that GbE treatment reshaped the WD-perturbed intestinal microbiota, particularly decreased the Firmicutes/Bacteroidetes ratio and elevated the abundance of Akkermansia, Alloprevotella, Alistipes, and Parabacteroides. Furthermore, GbE treatment downregulated the intestinal transcriptional levels of proinflammatory cytokines and enhanced the expression of tight junction proteins, exerting the roles of attenuating the intestinal inflammation as well as repairing the gut barrier. Meanwhile, the targeted metabolomic analysis displayed that GbE treatment significantly reversed the dysfunction of the microbial metabolic phenotypes, including promoting the production of short chain fatty acids, indole-3-acetate and secondary bile acids, which were correlated with the atherosclerotic plaque areas. Finally, we confirmed GbE-altered gut microbiota was sufficient to alleviate atherosclerosis by fecal microbiota transplantation. In summary, our findings provide important insights into the pharmacological mechanism underlying the antiatherogenic efficacy of GbE.}, }
@article {pmid35310733, year = {2022}, author = {Tominaga, K and Tsuchiya, A and Mizusawa, T and Matsumoto, A and Minemura, A and Oka, K and Takahashi, M and Yoshida, T and Kojima, Y and Ogawa, K and Kawata, Y and Nakajima, N and Kimura, N and Abe, H and Setsu, T and Takahashi, K and Sato, H and Ikarashi, S and Hayashi, K and Mizuno, KI and Yokoyama, J and Tajima, Y and Nakano, M and Shimada, Y and Kameyama, H and Wakai, T and Terai, S}, title = {Utility of autologous fecal microbiota transplantation and elucidation of microbiota in diversion colitis.}, journal = {DEN open}, volume = {2}, number = {1}, pages = {e63}, pmid = {35310733}, issn = {2692-4609}, abstract = {Objectives: Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota.<br><br>Methods: Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double-ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method.<br><br>Results: All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2-3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α-diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT.<br><br>Conclusions: This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.}, }
@article {pmid35309933, year = {2022}, author = {Liu, J and Gao, Z and Liu, C and Liu, T and Gao, J and Cai, Y and Fan, X}, title = {Alteration of Gut Microbiota: New Strategy for Treating Autism Spectrum Disorder.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {792490}, pmid = {35309933}, issn = {2296-634X}, abstract = {Autism spectrum disorder (ASD) is defined as a complex heterogeneous disorder and characterized by stereotyped behavior and deficits in communication and social interactions. The emerging microbial knowledge has pointed to a potential link between gut microbiota dysbiosis and ASD. Evidence from animal and human studies showed that shifts in composition and activity of the gut microbiota may causally contribute to the etiopathogenesis of core symptoms in the ASD individuals with gastrointestinal tract disturbances and act on microbiota-gut-brain. In this review, we summarized the characterized gut bacterial composition of ASD and the involvement of gut microbiota and their metabolites in the onset and progression of ASD; the possible underlying mechanisms are also highlighted. Given this correlation, we also provide an overview of the microbial-based therapeutic interventions such as probiotics, antibiotics, fecal microbiota transplantation therapy, and dietary interventions and address their potential benefits on behavioral symptoms of ASD. The precise contribution of altering gut microbiome to treating core symptoms in the ASD needs to be further clarified. It seemed to open up promising avenues to develop microbial-based therapies in ASD.}, }
@article {pmid35308555, year = {2022}, author = {Cao, C and Zhu, H and Yao, Y and Zeng, R}, title = {Gut Dysbiosis and Kidney Diseases.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {829349}, pmid = {35308555}, issn = {2296-858X}, abstract = {Gut dysbiosis is defined as disorders of gut microbiota and loss of barrier integrity, which are ubiquitous on pathological conditions and associated with the development of various diseases. Kidney diseases are accompanied with gut dysbiosis and metabolic disorders, which in turn contribute to the pathogenesis and progression of kidney diseases. Microbial alterations trigger production of harmful metabolites such as uremic toxins and a decrease in the number of beneficial ones such as SCFAs, which is the major mechanism of gut dysbiosis on kidney diseases according to current studies. In addition, the activation of immune responses and mitochondrial dysfunction by gut dysbiosis, also lead to the development of kidney diseases. Based on the molecular mechanisms, modification of gut dysbiosis via probiotics, prebiotics and synbiotics is a potential approach to slow kidney disease progression. Fecal microbiota transplantation (FMT) and genetic manipulation of the gut microbiota are also promising choices. However, the clinical use of probiotics in kidney disease is not supported by the current clinical evidence. Further studies are necessary to explore the causal relationships of gut dysbiosis and kidney diseases, the efficiency and safety of therapeutic strategies targeting gut-kidney axis.}, }
@article {pmid35308525, year = {2022}, author = {Chen, L and Zhu, Y and Hou, X and Yang, L and Chu, H}, title = {The Role of Gut Bacteria and Fungi in Alcohol-Associated Liver Disease.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {840752}, pmid = {35308525}, issn = {2296-858X}, abstract = {Cirrhosis and liver cancer caused by alcohol-associated liver disease (ALD) are serious threats to people's health. In addition to hepatic cell apoptosis and liver inflammation caused by oxidative stress during alcohol metabolism, intestinal microbiota disorders are also involved in the onset and development of ALD. Ethanol and its' oxidative and non-oxidative metabolites, together with dysbiosis-caused-inflammation, destroys the intestinal barrier. Changes of several microbial metabolites, such as bile acids, short-chain fatty acids, and amino acid, are closely associated with gut dysbiosis in ALD. The alcohol-caused dysbiosis can further influence intestinal barrier-related proteins, such as mucin2, bile acid-related receptors, and aryl hydrocarbon receptor (AhR), and these abnormal changes also participate in the injury of the intestinal barrier and hepatic steatosis. Gut-derived bacteria, fungi, and their toxins, such as lipopolysaccharide (LPS) and β-glucan translocate into the liver through the damaged intestinal barrier and promote the progression of inflammation and fibrosis of ALD. Thus, the prevention of alcohol-induced disruption of intestinal permeability has a beneficial effect on ALD. Currently, multiple therapeutic treatments have been applied to restore the gut microbiota of patients with ALD. Fecal microbial transplantation, probiotics, antibiotics, and many other elements has already shown their ability of restoring the gut microbiota. Targeted approaches, such as using bacteriophages to remove cytolytic Enterococcus faecalis, and supplement with Lactobacillus, Bifidobacterium, or boulardii are also powerful therapeutic options for ALD.}, }
@article {pmid35307002, year = {2022}, author = {Singhal, S and Rani, V}, title = {Therapeutic Effects of Gut Microbiota on Metabolic Syndrome: A Patent Review.}, journal = {Recent patents on food, nutrition &amp; agriculture}, volume = {}, number = {}, pages = {}, doi = {10.2174/2212798412666220318162322}, pmid = {35307002}, issn = {1876-1429}, abstract = {BACKGROUND: The balanced composition of the gut microbiota is essential for human health. The dysbiotic condition may develop various complex diseases. A metabolic syndrome is a group of biochemical and physiological abnormalities that can increase the risk of cardiovascular diseases, diabetes, and inflammatory diseases. It has become a serious concern worldwide because there is no acceptable medication to overcome this problem.<br><br>OBJECTIVE: This review aims to evaluate the relationship between gut microbiota and metabolic syndrome. Balance of gut microbiota relates to human health as well as diseases. Patents-related to significant findings on probiotics, prebiotics, synbiotics, and fecal microbiota transplantation signify the importance of the proposed theme and provide promising therapeutic strategies to modulate the dysbiotic condition and reoccurrence of beneficial microbial species during metabolic syndromes. Screening of patents-related databases can be worth full to track new technology. Therefore, some selected recent patents related to gut microbiota and associated therapies have been discussed in the present manuscript.<br><br>CONCLUSION: Under the existing situation, the role of gastrointestinal microbiota as a therapeutic agent is becoming more utilized for treating human health issues and various metabolic syndromes including obesity, diabetes, and cardiovascular diseases. Understanding gut dysbiosis and associated complex interactions between microbes and hosts would be effective for designing future therapeutic interventions for metabolic syndrome. Our detailed patent analysis reflects that gut dysbiosis has a prominent role in metabolic syndromes and dietary therapeutic strategies can improve health by modulating the human microbiota, their metabolites ad stability.}, }
@article {pmid35305720, year = {2022}, author = {Giles, J and Roberts, A}, title = {Clostridioides difficile: Current overview and future perspectives.}, journal = {Advances in protein chemistry and structural biology}, volume = {129}, number = {}, pages = {215-245}, doi = {10.1016/bs.apcsb.2021.11.003}, pmid = {35305720}, issn = {1876-1631}, abstract = {The most common world-wide cause of antibiotic-associated infectious diarrhea and colitis is the toxin producing bacterium, Clostridioides difficile (C. difficile). Here we review the background and characteristics of the bacterium and the toxins produced together with the epidemiology and the complex pathogenesis that leads to a broad clinical spectrum of disease. The review describes the difficulties faced in obtaining a quick and accurate diagnosis despite the range of sensitive and specific diagnostic tools available. We also discuss the problem of disease recurrence and the importance of disease prevention. The high rates of infection recurrence mean that treatment strategies are constantly under review and we outline the diverse treatment options that are currently in use and explore the emerging treatment options of pulsed antibiotic use, microbial replacement therapies and the use of monoclonal antibodies. We summarize the future direction of treatment strategies which include the development of novel antibiotics, the administration of oral polyclonal antibody formulations, the use of vaccines, the administration of competitive non-toxigenic spores and the neutralization of antibiotics at the microbiota level. Future successful treatments will likely involve a combination of therapies to provide the most effective and robust approach to C. difficile management.}, }
@article {pmid34902790, year = {2021}, author = {Yao, D and Dai, W and Dong, M and Dai, C and Wu, S}, title = {MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis.}, journal = {EBioMedicine}, volume = {74}, number = {}, pages = {103751}, doi = {10.1016/j.ebiom.2021.103751}, pmid = {34902790}, issn = {2352-3964}, mesh = {Anti-Bacterial Agents/therapeutic use ; Colitis, Ulcerative/*metabolism/microbiology/pathology/therapy ; Combined Modality Therapy ; Dietary Supplements ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/pathology ; Mucin-2/*metabolism ; }, abstract = {The mucin2 (MUC2) mucus barrier acts as the first barrier that prevents direct contact between intestinal bacteria and colonic epithelial cells. Bacterial factors related to the MUC2 mucus barrier play important roles in the response to changes in dietary patterns, MUC2 mucus barrier dysfunction, contact stimulation with colonic epithelial cells, and mucosal and submucosal inflammation during the occurrence and development of ulcerative colitis (UC). In this review, these underlying mechanisms are summarized and updated, and related interventions for treating UC, such as dietary adjustment, exogenous repair of the mucus barrier, microbiota transplantation and targeted elimination of pathogenic bacteria, are suggested. Such interventions are likely to induce and maintain a long and stable remission period and reduce or even avoid the recurrence of UC. A better mechanistic understanding of the MUC2 mucus barrier and its related bacterial factors may help researchers and clinicians to develop novel approaches for treating UC.}, }
@article {pmid34801681, year = {2022}, author = {Huang, S and Hu, S and Liu, S and Tang, B and Liu, Y and Tang, L and Lei, Y and Zhong, L and Yang, S and He, S}, title = {Lithium carbonate alleviates colon inflammation through modulating gut microbiota and Treg cells in a GPR43-dependent manner.}, journal = {Pharmacological research}, volume = {175}, number = {}, pages = {105992}, doi = {10.1016/j.phrs.2021.105992}, pmid = {34801681}, issn = {1096-1186}, mesh = {Adult ; Aged ; Animals ; Anti-Inflammatory Agents/pharmacology/*therapeutic use ; Colitis/chemically induced/*drug therapy/immunology/microbiology ; Dextran Sulfate ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Humans ; Lithium Carbonate/pharmacology/*therapeutic use ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Receptors, G-Protein-Coupled/*genetics ; T-Lymphocytes, Regulatory/*drug effects/immunology ; }, abstract = {BACKGROUND: Recent evidence suggests that neuropsychiatric stabilizers have a place in resolving gastrointestinal disorders. Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we estimate the therapeutic function of LC against colitis and investigate the mechanism of intestinal flora and metabolism modulation.<br><br>METHODS: A colitis model was constructed by continuously administering 2.5% dextran sodium sulfate (DSS) solution daily for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene high-throughput sequencing. Spectrum antibiotic cocktail (ABX) and faecal microbiota transplantation (FMT) were employed to evaluate the protective effect of intestinal flora. Colonic Treg cells and related immune responses were detected by flow cytometry.<br><br>RESULTS: LC treatment significantly alleviated colon inflammation by regulating gut microbial diversity and altering flora composition. Notably, LC treatment upregulated short-chain fatty acid (SCFA)-producing bacteria, especially Akkermansia muciniphila (A. muciniphila), and transformed metabolite SCFA profiles. LC activated anti-inflammatory Treg cell responses in colonic lamina propria (LP) in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm the above mechanism.<br><br>CONCLUSIONS: As an intestinal microbiome and metabolite modulator, LC alleviates colon inflammation in a GPR43-dependent manner through activating Treg cell responses. Therefore, the therapeutic strategy of the microbiome-metabolite-immune axis, as observed in the A. muciniphila-SCFA-Treg cell axis in our study, might provide a new direction for the treatment of IBD.}, }
@article {pmid34555295, year = {2022}, author = {Shan, Y and Lee, M and Chang, EB}, title = {The Gut Microbiome and Inflammatory Bowel Diseases.}, journal = {Annual review of medicine}, volume = {73}, number = {}, pages = {455-468}, doi = {10.1146/annurev-med-042320-021020}, pmid = {34555295}, issn = {1545-326X}, support = {RC2 DK122394/DK/NIDDK NIH HHS/United States ; R01 DK113788/DK/NIDDK NIH HHS/United States ; }, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; *Microbiota ; }, abstract = {Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host-microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions.}, }
@article {pmid34189475, year = {2021}, author = {Choo, JM and Rogers, GB}, title = {Gut microbiota transplantation for colonization of germ-free mice.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100610}, pmid = {34189475}, issn = {2666-1667}, mesh = {Anaerobiosis ; Animals ; Bioreactors ; *Fecal Microbiota Transplantation ; Germ-Free Life ; Mice ; }, abstract = {The use of germ-free mice is integral to the understanding of host-gut microbiome relationships. Such models rely on faithful replication of the donor microbiome to establish causal effects of the gut microbiota on host pathophysiology. This protocol describes the preparation and transfer of donor microbiota, focusing on strict anaerobic processing methods and multiple instillations by gavage for optimal gut microbiota recovery. For complete details on the generation and use of this protocol, please refer to Choo and Rogers (2021).}, }
@article {pmid35303781, year = {2022}, author = {Wei, Y and Peng, S and Lian, C and Kang, Q and Chen, J}, title = {Anorexia nervosa and gut microbiome: implications for weight change and novel treatments.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17474124.2022.2056017}, pmid = {35303781}, issn = {1747-4132}, abstract = {INTRODUCTION: Host-microbiota interactions may be involved in many physical and psychological functions ranging from the digestion of food, maintenance of immune homeostasis, to the regulation of mood and cognition. Microbiome dysbiosis has been consistently described in many diseases. The pathogenesis and weight regulation mechanism in anorexia nervosa (AN) also seem to be implicated in the dynamic bidirectional adjustment of the microbiota-gut-brain axis. This review aims at elucidating this relationship.<br><br>AREA COVERED: This review starts with a description of pathogenic gut-brain pathways. Next we focus on the latest research on the associations between gut microbiota and weight change in the condition of AN. The strategies to alter the intestinal microbiome for the treatment of this disorder are discussed, including dietary, probiotics, prebiotics, synbiotics and fecal microbiota transplantation.<br><br>EXPERT OPINION: Gut microbiome is inextricably linked to AN. It may regulate weight gain in the process of refeeding via the microbiota-gut-brain axis, while the specific mechanism has yet to be clearly established. In the future, a better understanding of gut microbiome could have implications for developing microbiome-based prevention, diagnostics and therapies.}, }
@article {pmid35234303, year = {2022}, author = {Majewska-Szczepanik, M and Kowalczyk, P and Marcińska, K and Strzępa, A and Lis, GJ and Wong, FS and Szczepanik, M and Wen, L}, title = {Obesity aggravates contact hypersensitivity reaction in mice.}, journal = {Contact dermatitis}, volume = {}, number = {}, pages = {}, doi = {10.1111/cod.14088}, pmid = {35234303}, issn = {1600-0536}, support = {DK045735//Foundation for the National Institutes of Health/ ; IP2012 0443 72//Ministry of Science and Higher Education/ ; K/ZDS/007123//Ministry of Science and Higher Education/ ; }, abstract = {BACKGROUND: Obesity is associated with chronic, low-grade inflammation in tissues and predisposes to various complications, including inflammatory skin diseases. However, the link between obesity and contact hypersensitivity (CHS) is not fully understood.<br><br>OBJECTIVES: We sought to determine the influence of obesity on T helper 1 (Th1)-mediated CHS.<br><br>METHODS: The activity/phenotype/cytokine profile of the immune cells was tested in vivo and in vitro. Using quantitative polymerase chain reaction (qPCR) and fecal microbiota transplantation (FMT), we tested the role of a high-fat diet (HFD)-induced gut microbiota (GM) dysbiosis in increasing the effects of CHS.<br><br>RESULTS: Exacerbated CHS correlates with an increased inflammation-inducing GM in obese mice. We showed a proinflammatory milieu in the subcutaneous adipose tissue of obese mice, accompanied by proinflammatory CD4+ T cells and dendritic cells in skin draining lymph nodes and spleen. Obese interleukin (IL)-17A-/-B6 mice are protected from CHS aggravation, suggesting the importance of IL-17A in CHS aggravation in obesity.<br><br>CONCLUSIONS: Obesity creates a milieu that induces more potent CHS-effector cells but does not have effects on already activated CHS-effector cells. IL-17A is essential for the pathogenesis of enhanced CHS during obesity. Our study provides novel knowledge about antigen-specific responses in obesity, which may help with the improvement of existing treatment and/or in designing novel treatment for obesity-associated skin disorders.}, }
@article {pmid35302268, year = {2022}, author = {El-Salhy, M and Mazzawi, T and Hausken, T and Hatlebakk, JG}, title = {Irritable bowel syndrome patients who are not likely to respond to fecal microbiota transplantation.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14353}, doi = {10.1111/nmo.14353}, pmid = {35302268}, issn = {1365-2982}, support = {40145//Helse Fonna/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) interventions have recently been advocated to not succeed in every irritable bowel syndrome (IBS) patient, since the outcome of FMT varies with the IBS subset. This study investigated the factors potentially affecting FMT response using the same patient cohort used in our previous study.<br><br>METHODS: This study included 109 patients who received allogenic FMT. Patients completed five questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT. Patients also provided fecal samples at baseline and 1 month after FMT. The fecal bacterial profile and dysbiosis index (DI) were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9. Response to FMT was defined as a decrease of ≥50 points in the total IBS-SSS score after FMT.<br><br>RESULTS: An IBS patient's response or nonresponse to FMT was not determined by age, IBS duration, IBS subtype, IBS symptoms, fatigue, quality of life, or DI. There were more male nonresponders than responders, and the fluorescence signals of Alistipes were lower in nonresponders than in responders.<br><br>CONCLUSIONS: We concluded that IBS patients who are male and/or have low fecal Alistipes levels are most likely to not respond to FMT treatment. Whether low fecal Alistipes levels could be used as a marker for predicting the outcome of FMT remains to be determined. www.<br><br>CLINICALTRIALS: gov (NCT03822299).}, }
@article {pmid35301705, year = {2022}, author = {Pan, Z and Hu, Y and Huang, Z and Han, N and Li, Y and Zhuang, X and Yin, J and Peng, H and Gao, Q and Zhang, W and Huang, Y and Cui, Y and Bi, Y and Xu, ZZ and Yang, R}, title = {Alterations in gut microbiota and metabolites associated with altitude-induced cardiac hypertrophy in rats during hypobaric hypoxia challenge.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {35301705}, issn = {1869-1889}, abstract = {The gut microbiota is involved in host responses to high altitude. However, the dynamics of intestinal microecology and their association with altitude-related illness are poorly understood. Here, we used a rat model of hypobaric hypoxia challenge to mimic plateau exposure and monitored the gut microbiome, short-chain fatty acids (SCFAs), and bile acids (BAs) over 28 d. We identified weight loss, polycythemia, and pathological cardiac hypertrophy in hypoxic rats, accompanied by a large compositional shift in the gut microbiota, which is mainly driven by the bacterial families of Prevotellaceae, Porphyromonadaceae, and Streptococcaceae. The aberrant gut microbiota was characterized by increased abundance of the Parabacteroides, Alistipes, and Lactococcus genera and a larger Bacteroides to Prevotella ratio. Trans-omics analyses showed that the gut microbiome was significantly correlated with the metabolic abnormalities of SCFAs and BAs in feces, suggesting an interaction network remodeling of the microbiome-metabolome after the hypobaric hypoxia challenge. Interestingly, the transplantation of fecal microbiota significantly increased the diversity of the gut microbiota, partially inhibited the increased abundance of the Bacteroides and Alistipes genera, restored the decrease of plasma propionate, and moderately ameliorated cardiac hypertrophy in hypoxic rats. Our results provide an insight into the longitudinal changes in intestinal microecology during the hypobaric hypoxia challenge. Abnormalities in the gut microbiota and microbial metabolites contribute to the development of high-altitude heart disease in rats.}, }
@article {pmid35300220, year = {2022}, author = {Hu, C and Patil, Y and Gong, D and Yu, T and Li, J and Wu, L and Liu, X and Yu, Z and Ma, X and Yong, Y and Chen, J and Gooneratne, R and Ju, X}, title = {Heat Stress-Induced Dysbiosis of Porcine Colon Microbiota Plays a Role in Intestinal Damage: A Fecal Microbiota Profile.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {686902}, doi = {10.3389/fvets.2022.686902}, pmid = {35300220}, issn = {2297-1769}, abstract = {The pathological mechanisms of gastrointestinal disorders, including inflammatory bowel disease (IBD), in pigs are poorly understood. We report the induction of intestinal inflammation in heat-stressed (HS) pigs, fecal microbiota transplantation from pigs to mice, and explain the role of microorganisms in IBD. 24 adult pigs were subjected to HS (34 ± 1 °C; 75-85% relative humidity for 24h) while 24 control pigs (CP) were kept at 25 ± 3°C and the same humidity. Pigs were sacrificed on days 1, 7, 14, 21. Colonic content microbiome analyses were conducted. Pseudo-germ-free mice were fed by gavage with fecal microbiota from HS-pigs and CP to induce pig-like responses in mice. From 7 d, HS-pigs exhibited fever and diarrhea, and significantly lower colonic mucosal thickness, crypt depth/width, and goblet cell number. Compared with each control group, the concentration of cortisol in the peripheral blood of HS pigs gradually increased, significantly so on days 7, 14, and 21 (P < 0.01). While the concentration of LPS in HS pigs' peripheral blood was significantly higher on days 7, 14 (P < 0.01), and 21 (P < 0.05) compared with that of the control group. The colonic microbiome composition of HS-pigs was different to that of CP. By day 14, opportunistic pathogens (e.g., Campylobacterales) had increased in HS-pigs. The composition of the colonic microbiome in mice administered feces from HS-pigs was different from those receiving CP feces. Bacteroides were significantly diminished, Akkermansia were significantly increased, and intestinal damage and goblet cell numbers were higher in mice that received HS-pig feces. Moreover, we verified the relevance of differences in the microbiota of the colon among treatments. Heat stress promotes changes in gut microbiome composition, which can affect the colonic microbial structure of mice through fecal microbiota transplantation; the molecular mechanisms require further investigation. This study enhanced our understanding of stress-induced inflammation in the colon and the increase in diarrhea in mammals subjected to prolonged HS. Our results provide useful information for preventing or ameliorating deficits in pig production caused by prolonged exposure to high temperatures.}, }
@article {pmid35299780, year = {2022}, author = {Liu, CK and Seo, J and Pravodelov, V and Frazier, S and Guy, M and Concilio, K and Lau-Ng, R and Brandeis, G and Watson, J and van der Velde, J and Olesen, SW and Budree, S and Njenga, M and Kassam, Z and Osman, M}, title = {Pilot study of autologous fecal microbiota transplants in nursing home residents: Feasibility and safety.}, journal = {Contemporary clinical trials communications}, volume = {27}, number = {}, pages = {100906}, doi = {10.1016/j.conctc.2022.100906}, pmid = {35299780}, issn = {2451-8654}, abstract = {Introduction: Antibiotic resistant bacterial infections (ARBIs) are extremely common in nursing home residents. These infections typically occur after a course of antibiotics, which eradicate both pathological and beneficial organisms. The eradication of beneficial organisms likely facilitates subsequent ARBIs. Autologous fecal microbiota transplant (aFMT) has been proposed as a potential treatment to reduce ARBIs in nursing home residents. Our objective was to determine the feasibility and safety of aFMT in a nursing home population.<br><br>Methods: Pilot clinical trial. We evaluated feasibility as total number of stool samples collected for aFMT production and safety as the number and relatedness of serious (SAE) and non-serious adverse events (AE).<br><br>Results: We screened 468 nursing home residents aged ≥18 years for eligibility; 67 enrolled, distributed among three nursing homes. Participants were 62.7% female and 35.8% Black. Mean age was 82.2 ± 8.5 years. Thirty-three participants underwent successful stool collection. Seven participants received antibiotics; four participants underwent aFMT. There were 40 SAEs (17 deaths) and 11 AEs. In the aFMT group, there were 3 SAEs (2 deaths) and 10 AEs. All SAEs and AEs were judged unrelated to the study intervention.<br><br>Conclusions: In this pilot study of aFMT in nursing home residents, less than half were able to provide adequate stool samples for aFMT. There were no related SAEs or AEs during the study. In sum, we conclude aFMT has limited feasibility in a nursing home population due to logistic and technical challenges but is likely safe.<br><br>Trial registration: ClinicalTrials.gov Identifier: NCT03061097.}, }
@article {pmid35297473, year = {2022}, author = {Nivet, C and Duhalde, V and Beaurain, M and Delobel, P and Quelven, I and Alric, L}, title = {Fecal Microbiota Transplantation for Refractory Clostridioides Difficile Infection Is Effective and Well Tolerated Even in Very Old Subjects: A Real-Life Study.}, journal = {The journal of nutrition, health &amp; aging}, volume = {26}, number = {3}, pages = {290-296}, doi = {10.1007/s12603-022-1756-1}, pmid = {35297473}, issn = {1760-4788}, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is an innovative therapy indicated for the treatment of recurrent Clostridioides difficile infections. Although CDI and its complications are more common in very old patients (≥80 years) due to their comorbidities, frailty and senescence of the immune system, limited data are available for this older patient population.<br><br>DESIGN: This was a single-center, real-life cohort study with retrospective outcome data registration, conducted at Toulouse, France.<br><br>SETTING AND PARTICIPANTS: Older people group was compared to the control group aged 18-79 years.<br><br>MEASUREMENTS: The primary outcome was overall survival at 52 weeks for ≥80 years patients compared to the control group after FMT. Recurrence-free survival at 52 weeks and, the occurrence of adverse events in the short and long term were the secondary endpoints.<br><br>RESULTS: A total of 58 patients were included, 19 were aged ≥80 years and 39 were aged 18-79 years. Overall survival at 52 weeks after FMT of the very old patients was not different from the control group (78.9% versus 89.7%, p= 0.29). Recurrence-free survival of CDI was not different between groups, with 94.3% in the 18-79-group versus 86.9% in the ≥80 group (p=0.44). The occurrence of short- or long-term adverse events was not statistically different between the two groups (36.8% vs 41%, p=0.45).<br><br>CONCLUSIONS: FMT is effective and well-tolerated in very old frail patients. This treatment brings a rapid benefit and limits the loss of functions. It also favors their maintenance at home or in a non-medical institution dedicated to dependent subjects and improves their quality of life.}, }
@article {pmid35297188, year = {2022}, author = {Ishibashi, R and Furusawa, Y and Honda, H and Watanabe, Y and Fujisaka, S and Nishikawa, M and Ikushiro, S and Kurihara, S and Tabuchi, Y and Tobe, K and Takatsu, K and Nagai, Y}, title = {Isoliquiritigenin attenuates adipose tissue inflammation and metabolic syndrome by modifying gut bacteria composition in mice.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e2101119}, doi = {10.1002/mnfr.202101119}, pmid = {35297188}, issn = {1613-4133}, abstract = {SCOPE: Isoliquiritigenin (ILG) has been reported to attenuate adipose tissue inflammation and metabolic disorder; however, the underlying mechanisms remain to be elucidated. The aim of this study is to elucidate whether ILG shows the anti-inflammatory and antimetabolic syndrome effects through gut microbiota modification.<br><br>METHODS &amp; RESULTS: Mice were fed a high-fat diet (HFD) with or without ILG for up to 12 weeks. The effect of ILG on body weight, blood glucose level, adipose tissue inflammation, gut barrier function, and gut microbiota composition were investigated. ILG supplementation alleviated HFD-induced obesity, glucose tolerance, and insulin resistance and suppressed inflammatory gene expression in epididymal white adipose tissue (eWAT). Moreover, ILG supplementation modified gut bacterial composition by increasing the abundance of antimetabolic disease-associated species (e.g., Parabacteroides goldsteinii and Akkemansia muciniphila) and up-regulated genes associated with gut barrier function. Fecal microbiome transplantation (FMT) from ILG-fed donors counteracted HFD-induced body and eWAT weight changes, inflammation-related gene expression, glucose tolerance, and insulin resistance, thereby suggesting that ILG-responsive gut bacteria exert anti-inflammatory and antimetabolic syndrome effects.<br><br>CONCLUSION: Alterations in gut bacteria underly the beneficial effects of ILG against adipose tissue inflammation and metabolic disorders. ILG may be a promising prebiotic for the prevention and treatment of metabolic syndrome . This article is protected by copyright. All rights reserved.}, }
@article {pmid35295757, year = {2022}, author = {Wu, J and Lv, L and Wang, C}, title = {Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {827395}, doi = {10.3389/fcimb.2022.827395}, pmid = {35295757}, issn = {2235-2988}, abstract = {Background: Randomized controlled trials (RCTs) have examined the efficacy of fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) with inconsistent results. We performed a meta-analysis to assess both the short- and long-term efficacy of FMT in IBS.<br><br>Methods: MEDLINE, EMBASE, and the Cochrane Central Register were searched through September 2021. RCTs recruiting adult patients with IBS that compared FMT with placebo with dichotomous data of response to therapy were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of symptom not improving after therapy. RR was also pooled for adverse events (AEs). Continuous data were calculated using a mean difference for IBS-Quality of Life (IBS-QoL). GRADE methodology was used to assess quality of evidence.<br><br>Results: The search strategy generated 658 citations. Seven RCTs comprising 472 patients with IBS were included. FMT was not associated with a significant improvement in global symptom in IBS at 12 weeks in comparison with placebo (RR 0.75, 95% CI 0.43-1.31) with high heterogeneity between studies (I2 87%). Subgroup analyses showed that FMT was superior to placebo when administered via colonoscopy or gastroscope (RR 0.70, 95% CI 0.51-0.96; RR 0.37, 95% CI 0.14-0.99, respectively, while FMT was inferior to placebo when administered via oral capsules (RR 1.88, 95% CI 1.06-3.35). FMT induced a significant improvement in IBS-QoL compared to placebo (mean difference 9.39, 95% CI 3.86-14.91) at 12 weeks. No significant difference in the total number of AEs was observed between FMT and placebo (RR 1.20, 95% CI 0.59-2.47). FMT did not significantly improve global symptom in IBS at 1-year follow-up compared with placebo (RR 0.90, 95% CI 0.72-1.12). The GRADE quality evidence to support recommending FMT in IBS was very low.<br><br>Conclusion: IBS patients may benefit from FMT when administered via colonoscopy or gastroscope. FMT may improve the quality of life of IBS. The long-term use of FMT in IBS warrants further investigation. There is very-low-quality evidence to support recommending FMT in IBS.}, }
@article {pmid35292746, year = {2022}, author = {Hosokawa, M and Endoh, T and Kamata, K and Arikawa, K and Nishikawa, Y and Kogawa, M and Saeki, T and Yoda, T and Takeyama, H}, title = {Strain-level profiling of viable microbial community by selective single-cell genome sequencing.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {4443}, pmid = {35292746}, issn = {2045-2322}, support = {21H01733//Japan Society for the Promotion of Science/ ; 17H06158//Japan Society for the Promotion of Science/ ; }, abstract = {Culture-independent analysis with high-throughput sequencing has been widely used to characterize bacterial communities. However, signals derived from non-viable bacteria and non-cell DNA may inhibit its characterization. Here, we present a method for viable bacteria-targeted single-cell genome sequencing, called PMA-SAG-gel, to obtain comprehensive whole-genome sequences of surviving uncultured bacteria from microbial communities. PMA-SAG-gel uses gel matrixes that enable sequential enzymatic reactions for cell lysis and genome amplification of viable single cells from the microbial communities. PMA-SAG-gel removed the single-amplified genomes (SAGs) derived from dead bacteria and enabled selective sequencing of viable bacteria in the model samples of Escherichia coli and Bacillus subtilis. Next, we demonstrated the recovery of near-complete SAGs of eight oxygen-tolerant bacteria, including Bacteroides spp. and Phocaeicola spp., from 1331 human feces SAGs. We found the presence of two different strains in each species and identified their specific genes to investigate the metabolic functions. The survival profile of an entire population at the strain level will provide the information for understanding the characteristics of the surviving bacteria under the specific environments or sample processing and insights for quality assessment of live bacterial products or fecal microbiota transplantation and for understanding the effect of antimicrobial treatments.}, }
@article {pmid35292630, year = {2022}, author = {Daniel, N and Nachbar, RT and Tran, TTT and Ouellette, A and Varin, TV and Cotillard, A and Quinquis, L and Gagné, A and St-Pierre, P and Trottier, J and Marcotte, B and Poirel, M and Saccareau, M and Dubois, MJ and Joubert, P and Barbier, O and Koutnikova, H and Marette, A}, title = {Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {1343}, pmid = {35292630}, issn = {2041-1723}, abstract = {Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt's health effects.}, }
@article {pmid35291651, year = {2022}, author = {Bae, J and Park, K and Kim, YM}, title = {Commensal Microbiota and Cancer Immunotherapy: Harnessing Commensal Bacteria for Cancer Therapy.}, journal = {Immune network}, volume = {22}, number = {1}, pages = {e3}, doi = {10.4110/in.2022.22.e3}, pmid = {35291651}, issn = {1598-2629}, abstract = {Cancer is one of the leading causes of death worldwide and the number of cancer patients is expected to continuously increase in the future. Traditional cancer therapies focus on inhibiting cancer growth while largely ignoring the contribution of the immune system in eliminating cancer cells. Recently, better understanding of immunological mechanisms pertaining to cancer progress has led to development of several immunotherapies, which revolutionized cancer treatment. Nonetheless, only a small proportion of cancer patients respond to immunotherapy and maintain a durable response. Among multiple factors contributing to the variability of immunotherapy response rates, commensal microbiota inhabiting patients have been identified as one of the most critical factors determining the success of immunotherapy. The functional diversity of microbiota differentially affects the host immune system and controls the efficacy of immunotherapy in individual cancer patients. Moreover, clinical studies have demonstrated that changing the gut microbiota composition by fecal microbiota transplantation in patients who failed a previous immunotherapy converts them to responders of the same therapy. Consequently, both academic and industrial researchers are putting extensive efforts to identify and develop specific bacteria or bacteria mixtures for cancer immunotherapy. In this review, we will summarize the immunological roles of commensal microbiota in cancer treatment and give specific examples of bacteria that show anticancer effect when administered as a monotherapy or as an adjuvant agent for immunotherapy. We will also list ongoing clinical trials testing the anticancer effect of commensal bacteria.}, }
@article {pmid34514495, year = {2022}, author = {Sarbagili Shabat, C and Scaldaferri, F and Zittan, E and Hirsch, A and Mentella, MC and Musca, T and Cohen, NA and Ron, Y and Fliss Isakov, N and Pfeffer, J and Yaakov, M and Fanali, C and Turchini, L and Masucci, L and Quaranta, G and Kolonimos, N and Godneva, A and Weinberger, A and Kopylov, U and Levine, A and Maharshak, N}, title = {Use of Faecal Transplantation with a Novel Diet for Mild to Moderate Active Ulcerative Colitis: The CRAFT UC Randomised Controlled Trial.}, journal = {Journal of Crohn's &amp; colitis}, volume = {16}, number = {3}, pages = {369-378}, pmid = {34514495}, issn = {1876-4479}, support = {//Azrieli Foundation/ ; }, mesh = {Adult ; *Colitis, Ulcerative/drug therapy/surgery ; Colonoscopy ; Diet ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Remission Induction ; }, abstract = {BACKGROUND: We evaluated whether integration of novel diets for donors and patients, in addition to faecal transplantation [FT], could increase FT remission rate in refractory ulcerative colitis [UC].<br><br>METHODS: This was a blinded, randomised, controlled trial in adults with active UC, defined by a simple clinical colitis activity index [SCCAI] of ≥5 and ≤11 and endoscopic Mayo score 2-3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on Day 1and rectal enemas on Days 2 and 14 without dietary conditioning of the donor. Group 2 received FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet [UCED] for the patients. Group 3 received the UCED alone. The primary endpoint was Week 8 clinical steroid-free remission, defined as SCCAI <3.<br><br>RESULTS: Of 96 planned patients, 62 were enrolled. Remission Week 8 Group 1 was 2/17 [11.8%], Group 2 was 4/19 [21.1%], Group 3 was 6/15 [40%] [non-significant]. Endoscopic remission Group 1 was 2/17 [12%], Group 2 was 3/19 [16%], Group 3 was 4/15 [27%] [Group 1 vs 3 p = 0.38]. Mucosal healing [Mayo 0] was achieved only in Group 3 [3/15, 20%] vs 0/36 FT patients [p = 0.022]. Exacerbation of disease occurred in 3/17 [17.6%] of Group 1, 4/19 [21.1%] of Group 2, and 1/15 [6.7%] of Group 3 [Group 2 vs 3, p = 0.35].<br><br>CONCLUSIONS: UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board.}, }
@article {pmid35288507, year = {2022}, author = {Li, H and Wang, Y and Zhao, C and Liu, J and Zhang, L and Li, A}, title = {Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, doi = {10.1097/CM9.0000000000001885}, pmid = {35288507}, issn = {2542-5641}, abstract = {BACKGROUND: Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.<br><br>METHODS: TS mice model (TSMO) (n = 80) were established with 3,3'-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.<br><br>RESULTS: A total of 18 discriminative microbial signatures (linear discriminant analysis score >3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W = 336.5, P = 0.046) compared with TSMO without transplantation.<br><br>CONCLUSIONS: This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.}, }
@article {pmid35279084, year = {2022}, author = {Orenstein, R and Dubberke, ER and Khanna, S and Lee, CH and Yoho, D and Johnson, S and Hecht, G and DuPont, HL and Gerding, DN and Blount, KF and Mische, S and Harvey, A}, title = {Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial.}, journal = {BMC infectious diseases}, volume = {22}, number = {1}, pages = {245}, pmid = {35279084}, issn = {1471-2334}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; *Microbiota ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; }, abstract = {BACKGROUND: Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660-a standardized microbiota-based investigational live biotherapeutic-and a closely-matched historical control cohort.<br><br>METHODS: This prospective, multicenter, open-label Phase 2 study enrolled patients who had experienced either ≥ 2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or ≥ 2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered with doses 7 days apart. Treatment success was defined as the absence of CDI diarrhea without the need for retreatment for 8 weeks after completing study treatment. A historical control group with matched inclusion and exclusion criteria was identified from a retrospective chart review of participants treated with standard-of-care antibiotics for recurrent CDI who matched key criteria for the study. The primary objective was to compare treatment success of RBX2660 to the historical control group. A key secondary outcome was the safety profile of RBX2660, including adverse events and CDI occurrence through 24 months after treatment. In addition, fecal samples from RBX2660-treated participants were sequenced to evaluate microbiome composition and functional changes from before to after treatment.<br><br>RESULTS: In this Phase 2 open-label clinical trial, RBX2660 demonstrated a 78.9% (112/142) treatment success rate compared to a 30.7% (23/75) for the historical control group (p < 0.0001; Chi-square test). Post-hoc analysis indicated that 91% (88/97) of evaluable RBX2660 responders remained CDI occurrence-free to 24 months after treatment demonstrating durability. RBX2660 was well-tolerated with mostly mild to moderate adverse events. The composition and diversity of RBX2660 responders' fecal microbiome significantly changed from before to after treatment to become more similar to RBX2660, and these changes were durable to 24 months after treatment.<br><br>CONCLUSIONS: In this Phase 2 trial, RBX2660 was safe and effective for reducing rCDI recurrence as compared to a historical control group. Microbiome changes are consistent with restorative changes implicated in resisting C. difficile recurrence. Clinical Trials Registration NCT02589847 (10/28/2015).}, }
@article {pmid35105621, year = {2022}, author = {Chen, Y and Xueying, Z and Jiaqu, C and Qiyi, C and Huanlong, Q and Ning, L and Yasong, D and Xiaoxin, Z and Rong, Y and Jubao, L and Xiaoqiong, L and Chunlian, M and Yu, W and Shidong, C and Guifang, K and Dongmei, Z and Shuanfeng, F and Xujing, Z and Binrang, Y and Yanxia, W and Ling, L and Song, Y and Xiang, Z and Beihua, Z and Lin, J and Hong, J and , }, title = {FTACMT study protocol: a multicentre, double-blind, randomised, placebo-controlled trial of faecal microbiota transplantation for autism spectrum disorder.}, journal = {BMJ open}, volume = {12}, number = {1}, pages = {e051613}, pmid = {35105621}, issn = {2044-6055}, mesh = {*Autism Spectrum Disorder/etiology/therapy ; Child ; Child, Preschool ; Double-Blind Method ; Fecal Microbiota Transplantation/methods ; Feces ; *Gastrointestinal Microbiome ; Humans ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: Autism spectrum disorder (ASD) is a complicated diffuse developmental disorder that commonly involves gastrointestinal distress and dysbacteriosis. Emerging lines of evidence have shown faecal microbiota transplantation (FMT) to be a potential therapeutic strategy for improving the clinical outcomes of patients with ASD by re-establishing their intestinal microflora. We are undertaking the first-ever multicentre, double-blind, randomised controlled trial of FMT for the treatment of children with both ASD and gastrointestinal symptoms and will assess the feasibility and efficacy outcomes of this strategy.<br><br>METHODS: In total, 318 children with both ASD and gastrointestinal symptoms will be enrolled (from 15 hospitals in China) to receive either FMT intervention (n=212) or a placebo (control, n=106). Children aged 3-6 years will take two capsules two times a day, and those older than 6 years will take three capsules two times a day. Each patient will receive four treatment courses, with each 12-day course being repeated every month. Outcomes will be evaluated at baseline, throughout the period of intervention, and at subsequent follow-ups for 2 months. The primary trial objective is to investigate the remodelling effect of FMT on the intestinal microflora in patients with ASD. The secondary objective focuses on the clinical efficacy and safety of FMT, including its improvement of the clinical response and metabonomics.<br><br>ETHICS AND DISSEMINATION: Ethical approval was obtained from the hospital Ethics Committee of each Faecal Transfer for ASD China Multicenter Trial Working Group. The ongoing FMT clinical trial is intended to support the approval of the new technology and its administration. The results of this trial will provide high-quality evidence to inform the future clinical application of this new therapy.<br><br>TRIAL REGISTRATION NUMBER: ChiCTR2100043906; Pre-results.}, }
@article {pmid35286970, year = {2022}, author = {Vellingiri, B and Aishwarya, SY and Benita Jancy, S and Sriram Abhishek, G and Winster Suresh Babu, H and Vijayakumar, P and Narayanasamy, A and Mariappan, S and Sangeetha, R and Valsala Gopalakrishnan, A and Parthasarathi, R and Iyer, M}, title = {An anxious relationship between Autism Spectrum Disorder and Gut Microbiota: A tangled chemistry?.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {99}, number = {}, pages = {169-189}, doi = {10.1016/j.jocn.2022.03.003}, pmid = {35286970}, issn = {1532-2653}, abstract = {Autism spectrum disorder (ASD) is a serious multifactorial neurodevelopmental disorder often accompanied by strained social communication, repetitive behaviour, immune dysregulation, and gastrointestinal (GI) issues. Recent studies have recorded a link between dysbiosis in the gut microbiota (gm) and the primary stages of ASD. A bidirectional connection (also called microbiota-gut-brain-axis) exchanges information between the gut bacteria and central nervous system. When the homeostasis of the microenvironment of the gut is dysregulated, it causes oxidative stress, affecting neuronal cells and neurotransmitters, thereby causing neurodevelopmental disorders. Studies have confirmed a difference in the constitution of gut bacteria among ASD cases and their controls. Numerous studies on animal models of ASD have shown altered gm and its association with abnormal metabolite profile and altered behaviour phenotype. This process happens due to an abnormal metabolite production in gm, leading to changes in the immune system, especially in ASD. Hence, this review aims to question the current knowledge on gm dysbiosis and its related GI discomforts and ASD behavioural symptoms and shed light on the possible therapeutic approaches available to deal with this situation. Thereby, though it is understood that more research might be needed to prove an association or causal relationship between gm and ASD, therapy with the microbiome may also be considered as an effective strategy to combat this issue.}, }
@article {pmid35279514, year = {2022}, author = {Xu, J and Liu, C and Shi, K and Sun, X and Song, C and Xu, K and Liu, Y}, title = {Atractyloside-A ameliorates spleen deficiency diarrhea by interfering with TLR4/MyD88/NF-κB signaling activation and regulating intestinal flora homeostasis.}, journal = {International immunopharmacology}, volume = {107}, number = {}, pages = {108679}, doi = {10.1016/j.intimp.2022.108679}, pmid = {35279514}, issn = {1878-1705}, abstract = {PURPOSE: Spleen deficiency diarrhea (SDD) is one of the most common types of diarrhea and is linked to intestinal barrier dysfunction and intestinal flora disorders. Atractyloside-A (AA) is one of the main components of Atractylodes Lancea(Thunb.) DC., which acts on the gastrointestinal tract and has therapeutic effects on diarrhea. Folium sennae is a medicinal plant inducing diarrhea; thus, it is one of the effective methods to obtain a diarrhea model. However, the mechanism of action of AA in the treatment of SDD induced by Folium sennae is unclear.<br><br>METHODS: The intestinal thrapeutic effect of AA on SDD in mice was evaluated by colon pathology. RNA sequencing (RNA-seq) was used to analyze the colonic transcriptome profiles. In addition, 16S rDNA sequencing and fecal microbiota transplantation (FMT) were carried out to verify the role of AA in the regulation of the intestinal flora.<br><br>RESULTS: The findings revealed that AA alleviated SDD by ameliorating the pathological symptoms while suppressing intestinal inflammatory responses through the TLR4/MyD88/NF-kB signaling and reversing the impairment of mucin synthesis. Furthermore, AA improved the integrity of the intestinal barrier. RNA-seq identified 436 common DEGs out of 1033 DEGs between SDD and AA, and 1933 DEGs between SDD and Ctrl, which are highly enriched in the NF-κB and TNF pathways. Moreover, AA altered the composition of the intestinal flora and FMT reduced SDD.<br><br>CONCLUSION: AA exerted a therapeutic effect on SDD through the regulation of the intestinal flora and the inflammation by interfering with the TLR4/MyD88/NF-κB signaling pathway.}, }
@article {pmid35277036, year = {2022}, author = {Upreti, D and Ishiguro, S and Robben, N and Nakashima, A and Suzuki, K and Comer, J and Tamura, M}, title = {Oral Administration of Water Extract from Euglena gracilis Alters the Intestinal Microbiota and Prevents Lung Carcinoma Growth in Mice.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/nu14030678}, pmid = {35277036}, issn = {2072-6643}, support = {2018 CVM-SMILE//Kansas State University/ ; N/A//Euglena Research Fund/ ; 2020 JCRC-CRA//Kansas State University/ ; P20 GM103418/GM/NIGMS NIH HHS/United States ; DMR-1945589//National Science Foundation/ ; }, abstract = {The antitumor effects of a partially purified water extract from Euglena gracilis (EWE) and EWE treated by boiling (bEWE) were evaluated using orthotopic lung cancer syngeneic mouse models with Lewis lung carcinoma (LLC) cells. Daily oral administration of either EWE or bEWE started three weeks prior to the inoculation of LLC cells significantly attenuated tumor growth as compared to the phosphate buffered saline (PBS) control, and the attenuation was further enhanced by bEWE. The intestinal microbiota compositions in both extract-treated groups were more diverse than that in the PBS group. Particularly, a decrease in the ratio of Firmicutes to Bacteroidetes and significant increases in Akkermansia and Muribaculum were observed in two types of EWE-treated groups. Fecal microbiota transplantation (FMT) using bEWE-treated mouse feces attenuated tumor growth to an extent equivalent to bEWE treatment, while tumor growth attenuation by bEWE was abolished by treatment with an antibiotic cocktail. These studies strongly suggest that daily oral administration of partially purified water extracts from Euglena gracilis attenuates lung carcinoma growth via the alteration of the intestinal microbiota.}, }
@article {pmid35277027, year = {2022}, author = {Varesi, A and Pierella, E and Romeo, M and Piccini, GB and Alfano, C and Bjørklund, G and Oppong, A and Ricevuti, G and Esposito, C and Chirumbolo, S and Pascale, A}, title = {The Potential Role of Gut Microbiota in Alzheimer's Disease: From Diagnosis to Treatment.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/nu14030668}, pmid = {35277027}, issn = {2072-6643}, abstract = {Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer's Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease.}, }
@article {pmid35276971, year = {2022}, author = {Abujamel, TS and Al-Otaibi, NM and Abuaish, S and AlHarbi, RH and Assas, MB and Alzahrani, SA and Alotaibi, SM and El-Ansary, A and Aabed, K}, title = {Different Alterations in Gut Microbiota between Bifidobacterium longum and Fecal Microbiota Transplantation Treatments in Propionic Acid Rat Model of Autism.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/nu14030608}, pmid = {35276971}, issn = {2072-6643}, support = {RGP-1441-0027//Deanship of Scientific Research, Princess Nora Bint Abdulrahman University/ ; }, abstract = {Autism spectrum disorders (ASD) consist of a range of neurodevelopmental conditions accompanied by dysbiosis of gut microbiota. Therefore, a number of microbiota manipulation strategies were developed to restore their balance. However, a comprehensive comparison of the various methods on gut microbiota is still lacking. Here, we evaluated the effect of Bifidobacterium (BF) treatment and fecal microbiota transplantation (FT) on gut microbiota in a propionic acid (PPA) rat model of autism using 16S rRNA sequencing. Following PPA treatment, gut microbiota showed depletion of Bacteroidia and Akkermansia accompanied by a concomitant increase of Streptococcus, Lachnospiraceae, and Paraeggerthella. The dysbiosis was predicted to cause increased levels of porphyrin metabolism and impairments of acyl-CoA thioesterase and ubiquinone biosynthesis. On the contrary, BF and FT treatments resulted in a distinct increase of Clostridium, Bifidobacterium, Marvinbryantia, Butyricicoccus, and Dorea. The taxa in BF group positively correlated with vitamin B12 and flagella biosynthesis, while FT mainly enriched flagella biosynthesis. In contrast, BF and FT treatments negatively correlated with succinate biosynthesis, pyruvate metabolism, nitrogen metabolism, beta-Lactam resistance, and peptidoglycan biosynthesis. Therefore, the present study demonstrated that BF and FT treatments restored the PPA-induced dysbiosis in a treatment-specific manner.}, }
@article {pmid35276821, year = {2022}, author = {Prosperi, M and Santocchi, E and Guiducci, L and Frinzi, J and Morales, MA and Tancredi, R and Muratori, F and Calderoni, S}, title = {Interventions on Microbiota: Where Do We Stand on a Gut-Brain Link in Autism? A Systematic Review.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/nu14030462}, pmid = {35276821}, issn = {2072-6643}, support = {2757130//Ricerca Corrente, and the "5 × 1000" voluntary contributions, Italian Ministry of Health/ ; }, abstract = {The alteration of the microbiota-gut-brain axis has been recently recognized as a critical modulator of neuropsychiatric health and a possible factor in the etiopathogenesis of autism spectrum disorders (ASD). This systematic review offers practitioners an overview of the potential therapeutic options to modify dysbiosis, GI symptoms, and ASD severity by modulating the microbiota-gut-brain axis in ASD, taking into consideration limits and benefits from current findings. Comprehensive searches of PubMed, Scopus, the Web of Science Core Collection, and EMBASE were performed from 2000 to 2021, crossing terms referred to ASD and treatments acting on the microbiota-gut-brain axis. A total of 1769 publications were identified, of which 19 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Despite the encouraging findings, considering the variability of the treatments, the samples size, the duration of treatment, and the tools used to evaluate the outcome of the examined trials, these results are still partial. They do not allow to establish a conclusive beneficial effect of probiotics and other interventions on the symptoms of ASD. In particular, the optimal species, subspecies, and dosages have yet to be identified. Considering the heterogeneity of ASD, double-blind, randomized, controlled trials and treatment tailored to ASD characteristics and host-microbiota are recommended.}, }
@article {pmid33914709, year = {2021}, author = {Chaves, LD and Abyad, S and Honan, AM and Bryniarski, MA and McSkimming, DI and Stahura, CM and Wells, SC and Ruszaj, DM and Morris, ME and Quigg, RJ and Yacoub, R}, title = {Unconjugated p-cresol activates macrophage macropinocytosis leading to increased LDL uptake.}, journal = {JCI insight}, volume = {6}, number = {11}, pages = {}, pmid = {33914709}, issn = {2379-3708}, support = {UL1 TR001412/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Aorta/drug effects/*metabolism/pathology ; Cholesterol/metabolism ; Cholesterol, LDL/drug effects/*metabolism ; Coronary Artery Disease/*metabolism/pathology ; Coronary Vessels/drug effects/metabolism/pathology ; Cresols/*metabolism/pharmacology ; Diet, High-Fat ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Kidney Failure, Chronic/metabolism/microbiology ; Liver/drug effects/*metabolism/pathology ; Macrophages/drug effects/*metabolism ; Mice ; Pinocytosis/drug effects/*physiology ; Renal Insufficiency, Chronic/*metabolism/microbiology ; Triglycerides/metabolism ; }, abstract = {Patients with chronic kidney disease (CKD) and end-stage renal disease suffer from increased cardiovascular events and cardiac mortality. Prior studies have demonstrated that a portion of this enhanced risk can be attributed to the accumulation of microbiota-derived toxic metabolites, with most studies focusing on the sulfonated form of p-cresol (PCS). However, unconjugated p-cresol (uPC) itself was never assessed due to rapid and extensive first-pass metabolism that results in negligible serum concentrations of uPC. These reports thus failed to consider the host exposure to uPC prior to hepatic metabolism. In the current study, not only did we measure the effect of altering the intestinal microbiota on lipid accumulation in coronary arteries, but we also examined macrophage lipid uptake and handling pathways in response to uPC. We found that atherosclerosis-prone mice fed a high-fat diet exhibited significantly higher coronary artery lipid deposits upon receiving fecal material from CKD mice. Furthermore, treatment with uPC increased total cholesterol, triglycerides, and hepatic and aortic fatty deposits in non-CKD mice. Studies employing an in vitro macrophage model demonstrated that uPC exposure increased apoptosis whereas PCS did not. Additionally, uPC exhibited higher potency than PCS to stimulate LDL uptake and only uPC induced endocytosis- and pinocytosis-related genes. Pharmacological inhibition of varying cholesterol influx and efflux systems indicated that uPC increased macrophage LDL uptake by activating macropinocytosis. Overall, these findings indicate that uPC itself had a distinct effect on macrophage biology that might have contributed to increased cardiovascular risk in patients with CKD.}, }
@article {pmid35275989, year = {2022}, author = {Aby, ES and Vaughn, BP and Enns, EA and Rajasingham, R}, title = {Cost-effectiveness of fecal microbiota transplantation for first recurrent Clostridioides difficile infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciac207}, pmid = {35275989}, issn = {1537-6591}, abstract = {BACKGROUND: Both the American College of Gastroenterology and the Infectious Disease Society of America (IDSA) / Society of Healthcare Epidemiology of American 2021 Clostridioides difficile infection (CDI) guidelines recommend fecal microbiota transplantation (FMT) for persons with multiple recurrent CDI. Emerging data suggest that FMT may have high cure rates when used for first recurrent CDI. The aim of this study was to assess the cost-effectiveness of FMT for first recurrent CDI.<br><br>METHODS: We developed a Markov model to simulate a cohort of patients presenting with initial CDI infection. The model estimated the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the 2021 IDSA guidelines, with the additional option of FMT for first recurrent CDI. The model includes stratification by the severity of initial infection, estimates of cure, recurrence, and mortality. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).<br><br>RESULTS: When FMT is available for first recurrent CDI, the optimal cost-effective treatment strategy is fidaxomicin for initial non-severe CDI, Vancomycin for initial severe CDI, and FMT for first and subsequent recurrent CDI, with an ICER of $27,135/QALY. In probabilistic sensitivity analysis at a $100,000 cost-effectiveness threshold, FMT for first and subsequent CDI recurrence was cost-effective 90% of the time given parameter uncertainty.<br><br>CONCLUSIONS: FMT is a cost-effective strategy for first recurrent CDI. Prospective evaluation of FMT for first recurrent CDI is warranted to determine the efficacy and risk of recurrence.}, }
@article {pmid35273972, year = {2022}, author = {Ishikawa, D and Zhang, X and Nomura, K and Seki, N and Haraikawa, M and Haga, K and Shibuya, T and Kim, YG and Nagahara, A}, title = {A Randomized Placebo-Controlled Trial of Combination Therapy With Post-triple-antibiotic-therapy Fecal Microbiota Transplantation and Alginate for Ulcerative Colitis: Protocol.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {779205}, doi = {10.3389/fmed.2022.779205}, pmid = {35273972}, issn = {2296-858X}, abstract = {Background: Fecal microbiota transplantation (FMT) has been widely performed for ulcerative colitis (UC) treatment at the clinical trial stage. Previous reports have used multiple FMT methods to enhance the colonization of healthy donor microbiota in the recipient's intestines. FMT following triple antibiotic therapy with amoxicillin, fosfomycin, and metronidazole (A-FMT) is not only effective but also requires only one FMT, which improves dysbiosis caused by reduced Bacteroidetes diversity in patients with UC. Alginate and its derivatives have the potential to induce the growth of intestinal bacteria including Bacteroides members and produce short-chain fatty acids (SCFAs), which are beneficial in regulating overactive autoimmunity. Our trial aims to investigate whether post-intervention with alginate, which can improve the intestinal environment, will enhance the therapeutic effect of A-FMT in UC and increase the long-term remission rate.<br><br>Methods and Analysis: This trial is a double-blinded, randomized, placebo-controlled, parallel assignment trial. Patients with UC and fecal donation candidates will undergo strict screening before being involved in the trial. Eligible patients are randomly divided into two groups: one group will drink one bottle of alginate twice a day for 8 consecutive weeks after A-FMT, while the other group will take a placebo instead of the alginate drink. The primary endpoints are the changes in the Total Mayo Score at 8 weeks after study initiation and A-FMT from baseline. The secondary endpoint is the comparison of clinical features, microbiota, and metabolomic analysis before and after 8 weeks of study food intake. Changes at 6, 12, 18, and 24 months after A-FMT will be assessed. Finally, a subpopulation analysis of the relationship between patients and donors is an exploratory endpoint.<br><br>Discussion: The FMT post-treatment used in this study is an oral alginate drink that is easily accepted by patients. If the regimen achieves the desired results, it can further improve the A-FMT regimen and provide evidence for clinical practice guidelines for UC.<br><br>Clinical Trial Registration: https://jrct.niph.go.jp/latest-detail/jRCTs031200103, identifier: jRCTs031200103.}, }
@article {pmid35273587, year = {2022}, author = {Chen, Y and Song, S and Shu, A and Liu, L and Jiang, J and Jiang, M and Wu, Q and Xu, H and Sun, J}, title = {The Herb Pair Radix Rehmanniae and Cornus Officinalis Attenuated Testicular Damage in Mice With Diabetes Mellitus Through Butyric Acid/Glucagon-Like Peptide-1/Glucagon-Like Peptide-1 Receptor Pathway Mediated by Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {831881}, doi = {10.3389/fmicb.2022.831881}, pmid = {35273587}, issn = {1664-302X}, abstract = {Growing body of research indicates that Traditional Chinese Medicine (TCM) interact with gut microbiota (GM) after oral administration. Radix Rehmanniae and Cornus Officinalis (RR-CO), a well-known TCM pair, is often used to treat diabetes mellitus (DM) and its complications. The current study aimed to explore the protective effects of RR-CO on DM induced testicular damage by modulating GM. The RR-CO treatments significantly reduced hyperglycemia, ameliorated testicular ultrastructural damage and inflammation in DM model to varying degrees. Additionally, 16S-ribosomal DNA (rDNA) sequencing results showed that RR-CO treatment increased the amount of butyric acid-producing GM, such as Clostridiaceae_1 family, and decreased the abundance of Catabacter, Marvinbryantia, and Helicobacter genera. RR-CO fecal bacteria transplantation (RC-FMT) increased the abundance of Clostridiaceae_1 in the Model FMT (M-FMT) group and ameliorated testicular damage. Furthermore, treatment with RR-CO increased the fecal butyric acid level, serum Glucagon-like peptide-1 (GLP-1) level, and testicular GLP-1 receptor (GLP-1R) expression compared to those in DM mice. Finally, intraperitoneal administration of sodium butyrate (SB) significantly improved the pathological damage to the testis and reduced inflammation in the DM group. These data demonstrated a protective effect of RR-CO on DM-induced testicular damage by modulation of GM, which may be mediated by the butyric acid/GLP/GLP-1R pathway.}, }
@article {pmid35271405, year = {2022}, author = {Rotz, SJ and Sangwan, N and Nagy, M and Tzeng, A and Jia, M and Moncaliano, M and Majhail, NS and Eng, C}, title = {Fecal microbiota of adolescent and young adult cancer survivors and metabolic syndrome: an exploratory study.}, journal = {Pediatric hematology and oncology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/08880018.2022.2049937}, pmid = {35271405}, issn = {1521-0669}, abstract = {Metabolic syndrome and obesity occur commonly in long-term pediatric cancer survivors. The intestinal microbiome is associated with metabolic syndrome and obesity in the general population, and is perturbed during cancer therapy. We aimed to determine if long-term survivors of pediatric cancer would have reduced bacterial microbiome diversity, and if these findings would be associated with components of the metabolic syndrome, obesity, and chronic inflammation. We performed a cross-sectional exploratory study examining the intestinal microbiome via 16S amplicon sequencing, treatment history, clinical measurements (blood pressure, body mass index) and biomarkers (hemoglobin A1c, lipoproteins, adiponectin: leptin ratio, C-reactive protein, TNFα, Interleukin-6, and Interleukin-10) between 35 long-term survivors and 32 age, sex, and race matched controls. All subjects were aged 10-40 years, and survivors were at least five years from therapy completion. Survivors had lower alpha diversity compared to controls (Shannon index p = .001, Simpson index p = .032) and differently abundant bacterial taxa. Further, among survivors, those who received radiation (18/35) to the central nervous system or abdomen/pelvis had decreased alpha diversity compared to those who did not receive radiation (Shannon and Simpson p < .05 for both). Although, no specific component of metabolic syndrome or cytokine was associated with measures of alpha diversity, survivors with low adiponectin-lectin ratio, elevated body mass index, and elevated C-reactive protein had differently abundant taxa compared to those with normal measures. The microbiome of cancer survivors remains less diverse than controls even many years after diagnosis, and exposure to radiation may lead to further loss of diversity in survivors.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049937.}, }
@article {pmid35269538, year = {2022}, author = {Li, Z and Li, Y and Sun, Q and Wei, J and Li, B and Qiu, Y and Liu, K and Shao, D and Ma, Z}, title = {Targeting the Pulmonary Microbiota to Fight against Respiratory Diseases.}, journal = {Cells}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/cells11050916}, pmid = {35269538}, issn = {2073-4409}, abstract = {The mucosal immune system of the respiratory tract possesses an effective "defense barrier" against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation sequencing technology has accelerated the studies about the microbial communities and immune regulating functions of lung microbiota during the past two decades. The acquisition and maturation of respiratory microbiota during childhood are mainly determined by the birth mode, diet structure, environmental exposure and antibiotic usage. However, the formation and development of lung microbiota in early life might affect the occurrence of respiratory diseases throughout the whole life cycle. The interplay and crosstalk between the gut and lung can be realized by the direct exchange of microbial species through the lymph circulation, moreover, the bioactive metabolites produced by the gut microbiota and lung microbiota can be changed via blood circulation. Complicated interactions among the lung microbiota, the respiratory viruses, and the host immune system can regulate the immune homeostasis and affect the inflammatory response in the lung. Probiotics, prebiotics, functional foods and fecal microbiota transplantation can all be used to maintain the microbial homeostasis of intestinal microbiota and lung microbiota. Therefore, various kinds of interventions on manipulating the symbiotic microbiota might be explored as novel effective strategies to prevent and control respiratory diseases.}, }
@article {pmid35268045, year = {2022}, author = {Li, W and Zhang, L and Xu, Q and Yang, W and Zhao, J and Ren, Y and Yu, Z and Ma, L}, title = {Taxifolin Alleviates DSS-Induced Ulcerative Colitis by Acting on Gut Microbiome to Produce Butyric Acid.}, journal = {Nutrients}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/nu14051069}, pmid = {35268045}, issn = {2072-6643}, abstract = {Taxifolin is a bioflavonoid which has been used to treat Inflammatory Bowel Disease. However, taxifolin on DSS-induced colitis and gut health is still unclear. Here, we studied the effect of taxifolin on DSS-induced intestinal mucositis in mice. We measured the degree of intestinal mucosal injury and inflammatory response in DSS treated mice with or without taxifolin administration and studied the changes of fecal metabolites and intestinal microflora using 16S rRNA. The mechanism was further explored by fecal microbiota transplantation. The results showed that the weight loss and diarrhea score of the mice treated with taxifolin decreased in DSS-induced mice and longer colon length was displayed after taxifolin supplementation. Meanwhile, the expression of GPR41 and GPR43 in the colon was significantly increased by taxifolin treatment. Moreover, the expression of TNF-α, IL-1β, and IL-6 in colon tissue was inhibited by taxifolin treatment. The fecal metabolism pattern changed significantly after DSS treatment, which was reversed by taxifolin treatment. Importantly, taxifolin significantly increased the levels of butyric acid and isobutyric acid in the feces of DSS-treated mice. In terms of gut flora, taxifolin reversed the changes of Akkermansia, and further decreased uncultured_bacterium_f_Muribaculaceae. Fecal transplantation from taxifolin-treated mice showed a lower diarrhea score, reduced inflammatory response in the colon, and reduced intestinal mucosal damage, which may be related to the increased level of butyric acid in fecal metabolites. In conclusion, this study provides evidence that taxifolin can ameliorate DSS-induced colitis by altering gut microbiota to increase the production of SCFAs.}, }
@article {pmid35266816, year = {2022}, author = {He, S and Cui, S and Song, W and Jiang, Y and Chen, H and Liao, D and Lu, X and Li, J and Chen, X and Peng, L}, title = {Interleukin-17 Weakens the NAFLD/NASH Process by Facilitating Intestinal Barrier Restoration Depending on the Gut Microbiota.}, journal = {mBio}, volume = {}, number = {}, pages = {e0368821}, doi = {10.1128/mbio.03688-21}, pmid = {35266816}, issn = {2150-7511}, abstract = {Interleukin-17 (IL-17) is associated with nonalcoholic fatty liver disease (NAFLD) and gut microbiota, and how IL-17 mediates the NAFLD/nonalcoholic steatohepatitis (NASH) process depending on the gut microbiota is unclear. We found that T helper 17 (TH17) cells were decreased in the small intestine in a methionine choline-deficient (MCD) diet-induced NASH model. IL-17-deficient (Il17-/-) mice showed alterations in intestinal microbiota, including the inhibition of probiotic growth and the overgrowth of certain pathogenic bacteria, and were prone to higher endotoxemia levels and more severe gastrointestinal barrier defects than wild-type (WT) mice. Furthermore, TH17 cells were responsible for restoring the intestinal barrier after administration of recombinant IL-17 to Il17-/- mice or injection of CD4+ T cells into a Rag1-/- mouse model. Additionally, transplantation of the microbiota from WT mice to Il17-/- mice restored the intestinal barrier. Notably, microbiota-depleted Il17-/- mice were resistant to MCD diet-induced intestinal barrier impairment. Fecal microbiota transplantation from Il17-/- mice to microbiota-depleted mice aggravated intestinal barrier impairment and then promoted the development of NASH. Collectively, this study showed that host IL-17 could strengthen intestinal mucosal barrier integrity and reduce dysbiosis-induced intestinal injury and secondary extraintestinal organ injury induced by a special diet. IMPORTANCE The morbidity of NASH has increased, with limited effective treatment options. IL-17 plays a protective role in the gut mucosa in high-fat-diet (HFD)-related metabolic disorders, and HFD-related microbiota dysbiosis is responsible for a decreased number of T helper 17 (TH17) cells in the lamina propria. The mechanism by which IL-17 mediates the NAFLD/NASH process depending on the gut microbiota is unclear. In our study, IL-17 originating from TH17 cells maintained intestinal barrier integrity and determined the outcomes of diet-related disease, which may be a target strategy for NAFLD/NASH.}, }
@article {pmid35262957, year = {2022}, author = {Hu, C and Xu, B and Wang, X and Wan, WH and Lu, J and Kong, D and Jin, Y and You, W and Sun, H and Mu, X and Feng, D and Chen, Y}, title = {Gut microbiota-derived short-chain fatty acids regulates group 3 innate lymphoid cells in hepatocellular carcinoma.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.32449}, pmid = {35262957}, issn = {1527-3350}, abstract = {BACKGROUND AND AIMS: Type 3 innate lymphoid cells (ILC3s) are essential for host defense against infection and tissue homeostasis. However, its role in the development of hepatocellular carcinoma (HCC) has not been adequately confirmed. In this study, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) derived from intestinal microbiota in ILC3 regulation.<br><br>APPROACH AND RESULTS: Here, we reported that the Lactobacillus reuteri was markedly reduced in the gut microbiota of mice with hepatocellular carcinoma (HCC), accompanied by decreased short chain fatty acids (SCFAs) levels, especially acetate. Additionally, transplantation of fecal bacteria from wild type mice or Lactobacillus reuteri could promote an anticancer effect, elevate acetate level and reduce IL17A secretion in mice with HCC. Mechanistically, acetate reduced the production of IL17A in hepatic ILC3s through inhibiting histone deacetylase (HDAC) activity, increasing the acetylation of Sox13 in the site of K30 and decreasing expression of Sox13. Moreover, the combination of acetate with PD-1/PD-L1 blockade significantly enhanced anti-tumor immunity. Consistently, Tumor-infiltrating ILC3s correlated with negative prognosis in patients with HCC, which could be functionally mediated via acetate.<br><br>CONCLUSIONS: These findings suggested that modifying bacteria, changing SCFAs, reducing IL17A-producing ILC3s infiltration and combining with immune checkpoint inhibitors will contribute to the clinical treatment of HCC.}, }
@article {pmid35245613, year = {2022}, author = {Dong, S and Sun, M and He, C and Cheng, H}, title = {Brain-gut-microbiota axis in Parkinson's disease: A historical review and future perspective.}, journal = {Brain research bulletin}, volume = {183}, number = {}, pages = {84-93}, doi = {10.1016/j.brainresbull.2022.02.015}, pmid = {35245613}, issn = {1873-2747}, abstract = {Parkinson's disease (PD) is the second most common degenerative disease of the central nervous system (CNS) after Alzheimer's disease. In addition to the typical motor symptoms, the clinical manifestations of patients with PD include gastrointestinal symptoms, which even precede the motor symptoms. Recent research has found that the gut microbiota regulates the brain-gut axial interaction through immune, endocrine, and direct neural mechanisms, supporting the hypothesis that the pathological process of PD spreads from the gut to the brain. In this review article, we highlight the landmark findings in the field of PD, with particular attention to the brain-gut-microbiota axis. We summarize the changes and their clinical effects on the gut microbiota and metabolites observed in PD. The intestinal microbiota may contain appropriate targets for the prevention and treatment of PD. Clinical cohort studies suggest that certain intestinal microbes have protective or pathogenic effects on the progression of PD. A better understanding of the interaction between the gut-brain axis, the gut microbiota, and PD has the potential to lead to new diagnostic and therapeutic approaches. Animal experiments suggest that fecal microbiota transplantation (FMT) is helpful for treating PD, and FMT is expected to be an effective treatment for PD in the future.}, }
@article {pmid35259427, year = {2022}, author = {Vicentini, FA and Szamosi, JC and Rossi, L and Griffin, L and Nieves, K and Bihan, D and Lewis, IA and Pittman, QJ and Swain, MG and Surette, MG and Hirota, SA and Sharkey, KA}, title = {Colitis-associated microbiota drives changes in behaviour in male mice in the absence of inflammation.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2022.03.001}, pmid = {35259427}, issn = {1090-2139}, abstract = {Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. IBD are associated with a high prevalence of cognitive, behavioural and emotional comorbidities, including anxiety and depression. The link between IBD and the development of behavioural comorbidities is poorly understood. As the intestinal microbiota profoundly influences host behaviour, we sought to determine whether the altered gut microbiota associated with intestinal inflammation contributes to the development of behavioural abnormalities. Using the dextran sulphate sodium (DSS) model of colitis, we characterized intestinal inflammation, behaviour (elevated plus maze and tail suspension test) and the composition of the microbiota in male mice. Cecal contents from colitic mice were transferred into germ-free (GF) or antibiotic (Abx)-treated mice, and behaviour was characterized in recipient mice. Gene expression was measured using qPCR. DSS colitis was characterized by a significant reduction in body weight and an increase in colonic inflammatory markers. These changes were accompanied by increased anxiety-like behaviour, an altered gut microbiota composition, and increased central Tnf expression. Transfer of the cecal matter from colitic mice induced similar behavioural changes in both GF and Abx-treated recipient mice, with no signs of colonic or neuroinflammation. Upon characterization of the microbiota in donor and recipient mice, specific taxa were found to be associated with behavioural changes, notably members of the Lachnospiraceae family. Behavioural abnormalities associated with intestinal inflammation are transmissible via transfer of cecal matter, suggesting that alterations in the composition of the gut microbiota play a key role in driving behavioural changes in colitis.}, }
@article {pmid35258452, year = {2022}, author = {Zhang, X and Zhang, X and Tong, F and Cai, Y and Zhang, Y and Song, H and Tian, X and Yan, C and Han, Y}, title = {Gut microbiota induces high platelet response in patients with ST segment elevation myocardial infarction after ticagrelor treatment.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, doi = {10.7554/eLife.70240}, pmid = {35258452}, issn = {2050-084X}, support = {82170297//National Natural Science Foundation of China/ ; 82070300//National Natural Science Foundation of China/ ; }, abstract = {Background: Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear.<br><br>Methods: To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokinetic assessment result showed that the plasma concentrations of ticagrelor and its metabolism production, AR-C124910XX, were lower in HPR patients than controls. Further single nucloetide polymorphism (SNP) analysis identified that there is no difference in ATP binding cassette subfamily B member 1 (ABCB1) gene expression between the NPR group and the HPR group. Metagenomic and metabolomic analyses of fecal samples showed that HPR patients had higher microbial richness and diversity. Transplantation of the gut microbiota from HPR donors to microbiota-depleted mice obviously decreased plasma concentration of ticagrelor.<br><br>Results: Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with STEMI and support that modify gut microbiota is a potential therapeutic option for STEMI.<br><br>Conclusions: Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with ST elevation myocardial infarction (STEMI) and support that modify gut microbiota is a potential therapeutic option for STEMI.<br><br>Funding: NSFC 82170297 and 82070300 from the National Natural Science Foundation of China.}, }
@article {pmid35255932, year = {2022}, author = {Gebrayel, P and Nicco, C and Al Khodor, S and Bilinski, J and Caselli, E and Comelli, EM and Egert, M and Giaroni, C and Karpinski, TM and Loniewski, I and Mulak, A and Reygner, J and Samczuk, P and Serino, M and Sikora, M and Terranegra, A and Ufnal, M and Villeger, R and Pichon, C and Konturek, P and Edeas, M}, title = {Microbiota medicine: towards clinical revolution.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {111}, pmid = {35255932}, issn = {1479-5876}, abstract = {The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrat