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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 03 Jul 2022 at 01:41 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2022-07-01

Li X, Wu P, Zeng X, et al (2022)

Protocol for correlation analysis of the murine gut microbiome and meta-metabolome using 16S rDNA sequencing and UPLC-MS.

STAR protocols, 3(3):101494 pii:S2666-1667(22)00374-4 [Epub ahead of print].

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).

RevDate: 2022-07-01

Yang J, Yang H, Y Li (2022)

The triple interactions between gut microbiota, mycobiota and host immunity.

Critical reviews in food science and nutrition [Epub ahead of print].

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.

RevDate: 2022-07-01

Lee SH, Park HK, Kang CD, et al (2022)

High Dose Intramuscular Vitamin D3 Supplementation Impacts the Gut Microbiota of Patients With Clostridioides Difficile Infection.

Frontiers in cellular and infection microbiology, 12:904987.

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.

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.

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.

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.

RevDate: 2022-06-29

El Hage Chehade N, Ghoneim S, Shah S, et al (2022)

Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

Inflammatory bowel diseases pii:6619552 [Epub ahead of print].

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.

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.

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.

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.

RevDate: 2022-06-29

Wang H, Yao J, Chen Y, et al (2022)

Gut dysbacteriosis attenuates resistance to Mycobacterium bovis infection by decreasing Cyclooxygenase 2 to inhibit endoplasmic reticulum stress.

Emerging microbes & infections [Epub ahead of print].

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.

RevDate: 2022-06-29

Hu LP, Huang W, Wang X, et al (2022)

Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression.

Molecular therapy : the journal of the American Society of Gene Therapy pii:S1525-0016(22)00375-6 [Epub ahead of print].

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.

RevDate: 2022-06-28

Ma P, Mo R, Liao H, et al (2022)

Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice.

Journal of neuroinflammation, 19(1):169.

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.

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.

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.

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.

RevDate: 2022-06-29
CmpDate: 2022-06-29

Hurych J, Vejmelka J, Hlinakova L, et al (2022)

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.

BMJ open, 12(6):e056594 pii:bmjopen-2021-056594.

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.

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.

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.

TRIAL REGISTRATION NUMBER: NCT04899869.

RevDate: 2022-06-29
CmpDate: 2022-06-29

Davis BT, Chen Z, Islam MBAR, et al (2022)

Fecal Microbiota Transfer Attenuates Gut Dysbiosis and Functional Deficits After Traumatic Brain Injury.

Shock (Augusta, Ga.), 57(6):251-259.

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.

HYPOTHESIS: We hypothesized that fecal microbiota transfer would attenuate neurocognitive, anatomic, and pathologic deficits after TBI.

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.

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).

CONCLUSION: These data suggest that restoring a pre-injury gut microbial community structure may be a promising therapeutic intervention after TBI.

RevDate: 2022-06-29

Borody TJ, Dolai S, Gunaratne AW, et al (2022)

Targeting the microbiome in Crohn's disease.

RevDate: 2022-06-28

Rakotonirina A, Galperine T, E Allémann (2022)

Fecal microbiota transplantation: a review on current formulations in Clostridioides difficile infection and future outlooks.

Expert opinion on biological therapy [Epub ahead of print].

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.

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.

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.

RevDate: 2022-06-28

Ma L, Shen Q, Lyu W, et al (2022)

Clostridium butyricum and Its Derived Extracellular Vesicles Modulate Gut Homeostasis and Ameliorate Acute Experimental Colitis.

Microbiology spectrum [Epub ahead of print].

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.

RevDate: 2022-06-28
CmpDate: 2022-06-28

Gulliver EL, Young RB, Chonwerawong M, et al (2022)

Review article: the future of microbiome-based therapeutics.

Alimentary pharmacology & therapeutics, 56(2):192-208.

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.

AIM: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development.

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'.

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.

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.

RevDate: 2022-06-27

Li Z, Ke H, Lin Q, et al (2022)

Global trends in gut microbiota and clostridioides difficile infection research: A visualized study.

Journal of infection and public health, 15(7):806-815 pii:S1876-0341(22)00155-1 [Epub ahead of print].

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.

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.

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.

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.

RevDate: 2022-06-27

Jiang L, Hong Y, Xiao P, et al (2022)

The Role of Fecal Microbiota in Liver Toxicity Induced by Perfluorooctane Sulfonate in Male and Female Mice.

Environmental health perspectives, 130(6):67009.

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.

OBJECTIVES: We aimed to investigate the role of liver-fecal microbiota axis in modulating PFOS-induced liver injury in mice.

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.

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.

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.

RevDate: 2022-06-27

Soto Chervin C, TF Gajewski (2020)

Microbiome-based interventions: therapeutic strategies in cancer immunotherapy.

Immuno-oncology technology, 8:12-20 pii:S2590-0188(20)30036-8.

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.

RevDate: 2022-06-27

Chen M, Liu M, Li C, et al (2022)

Fecal Microbiota Transplantation Effectively Cures a Patient With Severe Bleeding Immune Checkpoint Inhibitor-Associated Colitis and a Short Review.

Frontiers in oncology, 12:913217.

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.

RevDate: 2022-06-27

Aira A, Rubio E, Ruiz A, et al (2022)

New Procedure to Maintain Fecal Microbiota in a Dry Matrix Ready to Encapsulate.

Frontiers in cellular and infection microbiology, 12:899257.

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.

RevDate: 2022-06-26

Li X, Xiao F, Li Y, et al (2022)

Characteristics and management of children with Clostridiodes difficile infection at a tertiary pediatric hospital in China.

The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases pii:S1413-8670(22)00067-8 [Epub ahead of print].

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.

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.

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.

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.

RevDate: 2022-06-27
CmpDate: 2022-06-27

Bian J, Liebert A, Bicknell B, et al (2022)

Faecal Microbiota Transplantation and Chronic Kidney Disease.

Nutrients, 14(12): pii:nu14122528.

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.

RevDate: 2022-06-23

Carneiro PV, Montenegro NA, Lana A, et al (2022)

Lipids from gut microbiota: pursuing a personalized treatment.

Trends in molecular medicine pii:S1471-4914(22)00156-3 [Epub ahead of print].

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.

RevDate: 2022-06-25

Liu T, Li YL, Zhou LJ, et al (2022)

Mineralocorticoid Receptor Deficiency in Treg Cells Ameliorates DSS-Induced Colitis in a Gut Microbiota-Dependent Manner.

Immunology [Epub ahead of print].

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.

RevDate: 2022-06-24

Catalán-Serra I, Ricanek P, T Grimstad (2022)

"Out of the box" new therapeutic strategies for Crohn´s disease: moving beyond biologics.

Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva [Epub ahead of print].

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.

RevDate: 2022-06-24

Yang C, Sung J, Long D, et al (2022)

Prevention of Ulcerative Colitis by Autologous Metabolite Transfer from Colitogenic Microbiota Treated with Lipid Nanoparticles Encapsulating an Anti-Inflammatory Drug Candidate.

Pharmaceutics, 14(6): pii:pharmaceutics14061233.

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.

RevDate: 2022-06-24

Alam MJ, Xie L, Yap YA, et al (2022)

Manipulating Microbiota to Treat Atopic Dermatitis: Functions and Therapies.

Pathogens (Basel, Switzerland), 11(6): pii:pathogens11060642.

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.

RevDate: 2022-06-23

Qiao L, Zhang X, Pi S, et al (2022)

Dietary supplementation with biogenic selenium nanoparticles alleviate oxidative stress-induced intestinal barrier dysfunction.

NPJ science of food, 6(1):30.

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.

RevDate: 2022-06-23

Rei D, Saha S, Haddad M, et al (2022)

Age-associated gut microbiota impairs hippocampus-dependent memory in a vagus-dependent manner.

JCI insight pii:147700 [Epub ahead of print].

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.

RevDate: 2022-06-22
CmpDate: 2022-06-22

Thakur S, JD Sheppard (2022)

Gut Microbiome and Its Influence On Ocular Surface and Ocular Surface Diseases.

Eye & contact lens, 48(7):278-282.

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.

RevDate: 2022-06-20

Zhang J, Guo Y, L Duan (2022)

Features of Gut Microbiome Associated With Responses to Fecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review.

Frontiers in medicine, 9:773105.

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.

RevDate: 2022-06-20

Zhang Y, Zhang J, Pan Z, et al (2022)

Effects of Washed Fecal Bacteria Transplantation in Sleep Quality, Stool Features and Autism Symptomatology: A Chinese Preliminary Observational Study.

Neuropsychiatric disease and treatment, 18:1165-1173 pii:355233.

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.

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.

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.

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.

RevDate: 2022-06-20

Tan J, Gong J, Liu F, et al (2022)

Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse.

Frontiers in nutrition, 9:918098.

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.

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.

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.

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.

RevDate: 2022-06-20

Zhao HJ, Zhang XJ, Zhang NN, et al (2022)

Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials.

Frontiers in nutrition, 9:890357.

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.

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.

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).

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).

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.

RevDate: 2022-06-18

Qu Z, Tian P, Yang B, et al (2022)

Fecal microbiota transplantation for diseases: Therapeutic potential, methodology, risk management in clinical practice.

Life sciences pii:S0024-3205(22)00419-2 [Epub ahead of print].

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.

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.

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.

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.

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.

RevDate: 2022-06-20
CmpDate: 2022-06-20

Liu Y, M Chen (2022)

Clostridioides difficile Infection in Liver Cirrhosis: A Concise Review.

Canadian journal of gastroenterology & hepatology, 2022:4209442.

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.

RevDate: 2022-06-20
CmpDate: 2022-06-20

Zhong W, Wu K, Long Z, et al (2022)

Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis.

Microbiome, 10(1):94.

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.

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).

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.

RevDate: 2022-06-21

Wen S, Zhao Y, Liu S, et al (2022)

Polystyrene microplastics exacerbated liver injury from cyclophosphamide in mice: Insight into gut microbiota.

The Science of the total environment, 840:156668 pii:S0048-9697(22)03765-2 [Epub ahead of print].

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.

RevDate: 2022-06-16

El-Salhy M, Winkel R, Casen C, et al (2022)

Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome at three years after transplantation.

Gastroenterology pii:S0016-5085(22)00625-4 [Epub ahead of print].

BACKGROUND & 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.

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.

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.

CONCLUSIONS: FMT performed according to our protocol resulted in high response rates and long-standing effects with only few mild self-limited adverse events.

RevDate: 2022-06-20
CmpDate: 2022-06-20

Mullish BH, McDonald JAK, JR Marchesi (2022)

Intestinal microbiota transplantation: do not forget the metabolites.

The lancet. Gastroenterology & hepatology, 7(7):594.

RevDate: 2022-06-14

Zhou W, Yang T, Xu W, et al (2022)

The polysaccharides from the fruits of Lycium barbarum L. confer anti-diabetic effect by regulating gut microbiota and intestinal barrier.

Carbohydrate polymers, 291:119626.

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.

RevDate: 2022-06-13

Kattner AA (2022)

A finger in every pie - the versatility of chemokines.

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.

RevDate: 2022-06-13

Liu T, Su D, Lei C, et al (2022)

Treatment of Radiation Enteritis With Fecal Transplantation.

The American surgeon [Epub ahead of print].

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.

RevDate: 2022-06-13

Cai M, Xiao Y, Lin Z, et al (2022)

Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai.

Frontiers in pharmacology, 13:889181 pii:889181.

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.

RevDate: 2022-06-13

Gupta K, Tappiti M, Nazir AM, et al (2022)

Fecal Microbiota Transplant in Recurrent Clostridium Difficile Infections: A Systematic Review.

Cureus, 14(5):e24754.

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.

RevDate: 2022-06-12

Li T, Tian D, Lu M, et al (2022)

Gut microbiota dysbiosis induced by polychlorinated biphenyl 126 contributes to increased brain proinflammatory cytokines: Landscapes from the gut-brain axis and fecal microbiota transplantation.

Ecotoxicology and environmental safety, 241:113726 pii:S0147-6513(22)00566-8 [Epub ahead of print].

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.

RevDate: 2022-06-11

Huang C, Yi P, Zhu M, et al (2022)

Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial.

Journal of autoimmunity pii:S0896-8411(22)00052-X [Epub ahead of print].

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.

RevDate: 2022-06-11

Gu Y, Wang C, Qin X, et al (2022)

Saccharomyces boulardii, a yeast probiotic, inhibits gut motility through upregulating intestinal serotonin transporter and modulating gut microbiota.

Pharmacological research pii:S1043-6618(22)00236-5 [Epub ahead of print].

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.

RevDate: 2022-06-10

Zhang KK, Liu JL, Chen LJ, et al (2022)

Gut microbiota mediates methamphetamine-induced hepatic inflammation via the impairment of bile acid homeostasis.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association pii:S0278-6915(22)00406-9 [Epub ahead of print].

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.

RevDate: 2022-06-10

Sampsell K, Wang W, Ohland C, et al (2022)

Exercise and Prebiotic Fiber Provide Gut Microbiota-Driven Benefit in a Survivor to Germ-Free Mouse Translational Model of Breast Cancer.

Cancers, 14(11): pii:cancers14112722.

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.

RevDate: 2022-06-10

Huang C, Mei Q, Lou L, et al (2022)

Ulcerative Colitis in Response to Fecal Microbiota Transplantation via Modulation of Gut Microbiota and Th17/Treg Cell Balance.

Cells, 11(11): pii:cells11111851.

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.

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.

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).

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.

RevDate: 2022-06-10

Hui Y, Vestergaard G, Deng L, et al (2022)

Donor-dependent fecal microbiota transplantation efficacy against necrotizing enterocolitis in preterm pigs.

NPJ biofilms and microbiomes, 8(1):48.

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.

RevDate: 2022-06-09

Tang XW, DP Wu (2022)

[How I treat gastrointestinal tract acute graft versus host disease with fecal microbiota transplantation].

Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi, 43(5):365-369.

RevDate: 2022-06-09
CmpDate: 2022-06-09

Joachim A, Schwerd T, Hölz H, et al (2022)

[Fecal Microbiota Transfer (FMT) in Children and Adolescents - Review and statement by the GPGE microbiome working group].

Zeitschrift fur Gastroenterologie, 60(6):963-969.

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.

RevDate: 2022-06-09
CmpDate: 2022-06-09

Ting NL, Lau HC, J Yu (2022)

Cancer pharmacomicrobiomics: targeting microbiota to optimise cancer therapy outcomes.

Gut, 71(7):1412-1425.

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.

RevDate: 2022-06-07

Bose D, Chatterjee S, Older E, et al (2022)

Host gut resistome in Gulf War chronic multisymptom illness correlates with persistent inflammation.

Communications biology, 5(1):552.

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.

RevDate: 2022-06-06

Chen Y, Zhiliang L, Jiaqu C, et al (2022)

Fecal Microbiota and Human Intestinal Fluid Transplantation: Methodologies and Outlook.

Frontiers in medicine, 9:830004.

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.

RevDate: 2022-06-06

Li M, Yang L, Mu C, et al (2022)

Gut microbial metabolome in inflammatory bowel disease: From association to therapeutic perspectives.

Computational and structural biotechnology journal, 20:2402-2414 pii:S2001-0370(22)00113-1.

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.

RevDate: 2022-06-06

Liu P, Zhou X, Zhang H, et al (2022)

Danggui-Shaoyao-San Attenuates Cognitive Impairment via the Microbiota-Gut-Brain Axis With Regulation of Lipid Metabolism in Scopolamine-Induced Amnesia.

Frontiers in immunology, 13:796542.

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.

RevDate: 2022-06-07

You H, Tan Y, Yu D, et al (2022)

The Therapeutic Effect of SCFA-Mediated Regulation of the Intestinal Environment on Obesity.

Frontiers in nutrition, 9:886902.

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.

RevDate: 2022-06-07

Yan S, Chang J, Hao X, et al (2022)

Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 102:154217 pii:S0944-7113(22)00296-3 [Epub ahead of print].

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.

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.

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.

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.

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.

RevDate: 2022-06-06

Fang H, Fang M, Wang Y, et al (2022)

Indole-3-Propionic Acid as a Potential Therapeutic Agent for Sepsis-Induced Gut Microbiota Disturbance.

Microbiology spectrum [Epub ahead of print].

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.

RevDate: 2022-06-02

Xu L, Zhang Q, Dou X, et al (2022)

Fecal microbiota transplantation from young donor mice improves ovarian function in aged mice.

Journal of genetics and genomics = Yi chuan xue bao pii:S1673-8527(22)00157-6 [Epub ahead of print].

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.

RevDate: 2022-06-02

Duan S, Li X, Fan G, et al (2022)

Targeting bile acid signaling for the treatment of liver diseases: From bench to bed.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 152:113154 pii:S0753-3322(22)00543-1 [Epub ahead of print].

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.

RevDate: 2022-06-01

Pu Y, Zhang Q, Tang Z, et al (2022)

Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation.

Translational psychiatry, 12(1):223.

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.

RevDate: 2022-06-01

Zhi W, Song W, Abdi Saed Y, et al (2022)

Fecal Capsule as a Therapeutic Strategy in IgA Nephropathy: A Brief Report.

Frontiers in medicine, 9:914250.

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.

RevDate: 2022-06-01

Said I, Ahad H, A Said (2022)

Gut microbiome in non-alcoholic fatty liver disease associated hepatocellular carcinoma: Current knowledge and potential for therapeutics.

World journal of gastrointestinal oncology, 14(5):947-958.

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.

RevDate: 2022-06-01

Hoilat GJ, Suhail FK, Adhami T, et al (2022)

Evidence-based approach to management of hepatic encephalopathy in adults.

World journal of hepatology, 14(4):670-681.

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.

RevDate: 2022-06-01

He Z, Ma Y, Yang S, et al (2022)

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.

Microbiome, 10(1):79.

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.

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.

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.

RevDate: 2022-06-01

Liu Q, Zuo T, Lu W, et al (2022)

Longitudinal Evaluation of Gut Bacteriomes and Viromes after Fecal Microbiota Transplantation for Eradication of Carbapenem-Resistant Enterobacteriaceae.

mSystems [Epub ahead of print].

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.

RevDate: 2022-06-01

Fang H, Wang Y, Deng J, et al (2022)

Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice.

mSystems [Epub ahead of print].

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.

RevDate: 2022-05-31

Li WJ, Zhang L, Wu HX, et al (2022)

Intestinal Microbiota Mediates Gossypol-Induced Intestinal Inflammation, Oxidative Stress, and Apoptosis in Fish.

Journal of agricultural and food chemistry [Epub ahead of print].

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.

RevDate: 2022-05-31

González-Dávila P, Schwalbe M, Danewalia A, et al (2022)

Gut microbiota transplantation drives the adoptive transfer of colonic genotype-phenotype characteristics between mice lacking catestatin and their wild type counterparts.

Gut microbes, 14(1):2081476.

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.

RevDate: 2022-05-31

Xia Y, Shi H, Qian C, et al (2022)

Modulation of Gut Microbiota by Magnesium Isoglycyrrhizinate Mediates Enhancement of Intestinal Barrier Function and Amelioration of Methotrexate-Induced Liver Injury.

Frontiers in immunology, 13:874878.

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.

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.

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.

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.

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.

RevDate: 2022-05-28

Yoo JW, Shin YJ, Ma X, et al (2022)

The Alleviation of Gut Microbiota-Induced Depression and Colitis in Mice by Anti-Inflammatory Probiotics NK151, NK173, and NK175.

Nutrients, 14(10): pii:nu14102080.

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.

RevDate: 2022-05-28

Wang P, Ma Y, Wang D, et al (2022)

Protective Effects of Dietary Resveratrol against Chronic Low-Grade Inflammation Mediated through the Gut Microbiota in High-Fat Diet Mice.

Nutrients, 14(10): pii:nu14101994.

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.

RevDate: 2022-05-28

Gan L, Bo T, Liu W, et al (2022)

The Gut Microbiota May Affect Personality in Mongolian Gerbils.

Microorganisms, 10(5): pii:microorganisms10051054.

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.

RevDate: 2022-05-28

Shang L, Tu J, Dai Z, et al (2022)

Microbiota Transplantation in an Antibiotic-Induced Bacterial Depletion Mouse Model: Reproducible Establishment, Analysis, and Application.

Microorganisms, 10(5): pii:microorganisms10050902.

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.

RevDate: 2022-05-28

Ugrayová S, Švec P, Hric I, et al (2022)

Gut Microbiome Suffers from Hematopoietic Stem Cell Transplantation in Childhood and Its Characteristics Are Positively Associated with Intra-Hospital Physical Exercise.

Biology, 11(5): pii:biology11050785.

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.

RevDate: 2022-05-28

Dey P, S Ray Chaudhuri (2022)

Cancer-Associated Microbiota: From Mechanisms of Disease Causation to Microbiota-Centric Anti-Cancer Approaches.

Biology, 11(5): pii:biology11050757.

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.

RevDate: 2022-05-27

Jee JJ, Lim J, Park S, et al (2022)

The gut microbial community differentially characterizes patients with nonalcoholic fatty liver disease.

Journal of gastroenterology and hepatology [Epub ahead of print].

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.

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.

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.

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.

RevDate: 2022-05-27

Pane K, Boccella S, Guida F, et al (2022)

Role of gut microbiota in neuropathy and neuropathic pain states: A systematic preclinical review.

Neurobiology of disease pii:S0969-9961(22)00165-6 [Epub ahead of print].

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).

RevDate: 2022-05-27

Hu Y, Ye Z, Wu M, et al (2022)

Corrigendum: The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.

Frontiers in medicine, 9:886105.

[This corrects the article DOI: 10.3389/fmed.2021.766126.].

RevDate: 2022-05-27

Zhang B, Chen T, Cao M, et al (2022)

Gut Microbiota Dysbiosis Induced by Decreasing Endogenous Melatonin Mediates the Pathogenesis of Alzheimer's Disease and Obesity.

Frontiers in immunology, 13:900132.

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.

RevDate: 2022-05-26

Yan X, Zhai Y, Zhou W, et al (2022)

Intestinal Flora Mediates Antiobesity Effect of Rutin in High-Fat-Diet Mice.

Molecular nutrition & food research [Epub ahead of print].

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.

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.

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.

RevDate: 2022-05-25

Fu Y, Hu J, Erasmus MA, et al (2022)

Effects of early-life cecal microbiota transplantation from divergently selected inbred chicken lines on growth, gut serotonin, and immune parameters in recipient chickens.

Poultry science, 101(7):101925 pii:S0032-5791(22)00217-6 [Epub ahead of print].

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.

RevDate: 2022-05-24

Zeyue YU, Liyu H, Zongyuan LI, et al (2022)

Correlation between slow transit constipation and spleen deficiency, and gut microbiota: a pilot study.

Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan, 42(3):353-363.

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.

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.

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.

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.

RevDate: 2022-05-24

Li M, Guo W, Dong Y, et al (2022)

Beneficial effects of celastrol on immune balance by modulating gut microbiota in experimental ulcerative colitis.

Genomics, proteomics & bioinformatics pii:S1672-0229(22)00066-3 [Epub ahead of print].

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.

RevDate: 2022-05-23

Sun Y, Sun P, Hu Y, et al (2022)

Elevated testicular apoptosis is associated with elevated sphingosine driven by gut microbiota in prediabetic sheep.

BMC biology, 20(1):121.

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.

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.

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.

RevDate: 2022-05-23

Benítez-Páez A, Hartstra AV, Nieuwdorp M, et al (2022)

Species- and strain-level assessment using rrn long-amplicons suggests donor's influence on gut microbial transference via fecal transplants in metabolic syndrome subjects.

Gut microbes, 14(1):2078621.

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).

RevDate: 2022-05-23

Wang J, Zhou X, Li X, et al (2022)

Fecal Microbiota Transplantation Alters the Outcome of Hepatitis B Virus Infection in Mice.

Frontiers in cellular and infection microbiology, 12:844132.

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.

RevDate: 2022-05-23

Singh R, Stogios N, Smith E, et al (2022)

Gut microbiome in schizophrenia and antipsychotic-induced metabolic alterations: a scoping review.

Therapeutic advances in psychopharmacology, 12:20451253221096525 pii:10.1177_20451253221096525.

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.

RevDate: 2022-05-22

Batra M, Bhatnager R, Kumar A, et al (2022)

Interplay between PCOS and Microbiome: The road less travelled.

American journal of reproductive immunology (New York, N.Y. : 1989) [Epub ahead of print].

: 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.

RevDate: 2022-05-20

Chen H, Ye C, Cai B, et al (2022)

Berberine inhibits intestinal carcinogenesis by suppressing intestinal pro-inflammatory genes and oncogenic factors through modulating gut microbiota.

BMC cancer, 22(1):566.

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.

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.

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.

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.

RevDate: 2022-05-20

Quaranta G, Mandrioli J, Bibbò S, et al (2022)

Rummeliibacillus suwonensis: First Time Isolation from Human Feces by Culturomics.

Current microbiology, 79(7):197.

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.

RevDate: 2022-05-20

Bashir R, Wani IA, MA Ganie (2022)

Insights into new therapeutic approaches for the treatment and management of polycystic ovary syndrome: An updated review.

Current pharmaceutical design pii:CPD-EPUB-123741 [Epub ahead of print].

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.

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.

METHODS: Manual search on PubMed, Cochrane, Scopus databases was performed for relevant articles, preclinical and clinical trials based on related keywords.

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.

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.

RevDate: 2022-05-19
CmpDate: 2022-05-19

Sorbara MT, EG Pamer (2022)

Microbiome-based therapeutics.

Nature reviews. Microbiology, 20(6):365-380.

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.

RevDate: 2022-05-19

Bajaj JS, Ng SC, B Schnabl (2022)

Promises of microbiome-based therapies.

Journal of hepatology, 76(6):1379-1391.

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.

RevDate: 2022-05-19

Yan S, Chen J, Zhu L, et al (2022)

Oryzanol Attenuates High Fat and Cholesterol Diet-Induced Hyperlipidemia by Regulating the Gut Microbiome and Amino Acid Metabolism.

Journal of agricultural and food chemistry [Epub ahead of print].

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.

RevDate: 2022-05-18

Yan J, Liao C, Taylor BP, et al (2022)

A compilation of fecal microbiome shotgun metagenomics from hematopoietic cell transplantation patients.

Scientific data, 9(1):219.

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.

RevDate: 2022-05-19

Benech N, Galperine T, Sokol H, et al (2022)

SER-109 for Recurrent Clostridioides difficile Infection.

The New England journal of medicine, 386(20):1956-1957.

RevDate: 2022-05-17

Renu S, Deblais L, Patil V, et al (2022)

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.

Microbiology spectrum [Epub ahead of print].

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.

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ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

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In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

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Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

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In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

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Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

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When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

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