AGA Clinical Practice Guideline on Fecal Microbiota–Based Therapies for Select Gastrointestinal Diseases

Fecal microbiota–based therapies include conventional fecal microbiota transplant and US Food and Drug Administration–approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota–based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome.

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Febbraio 2024

Abstract 108: Gut Microbiota Composition Modifies Behavioral Phenotypes Into Adulthood Following Neonatal Hypoxic-Ischemia in Mice

Stroke, Volume 55, Issue Suppl_1, Page A108-A108, February 1, 2024. Neonatal hypoxic ischemic encephalopathy (HIE) increases the risk for attention deficit disorder and autism spectrum disorders in children. Perturbations in the gut microbiome are associated with behavioral changes in pre-clinical models of neurological injury and development. However, the role of the gut microbiome in behavior after HIE has not been investigated. Also, the therapeutic potential of gut microbiota modification after HIE remains unexplored. We hypothesize that altering the gut microbiome after HIE can improve chronic behavioral deficits in mice. The Rice Vannucci Model (RVM) was used to model HIE on 9-day old C57BL/6 mice. 2 months after injury, fecal samples were collected for 16s rRNA sequencing and behavioral tests were performed. We treated HIE and sham mice with fecal microbiota transfers (FMT) from naïve donors. To determine if the microbiota from HIE mice drives behavioral deficits, we also gave FMT from HIE or sham donors into naïve. Tests were repeated 1 and 3 months after FMT, and mice were sacrificed at 5 months of age. 2 months after injury, baseline open field tests revealed a hyperactive phenotype in HIE mice. There was increased mean velocity, distance moved, and cumulative time in border coupled with decreased cumulative time in center compared to shams (P&lt0.0001, P&lt0.0001, P=0.0168, P=0.025; T test, two cohorts, n=14-18). PCoA on calculated weighted UniFrac distances reveal a significant difference in β-diversity in males (P=0.015) and females (P=0.033) at 2 months. At 5 months, HIE mice with a naïve FMT had normalization of their hyperactive phenotype, measured by a reduction in mean velocity and distance moved (P=0.028 and P=0.0322; Repeated Measures One-way ANOVA, Dunnett’s test), while sham mice had no change. Surprisingly, naïve mice given a FMT from HIE donors became hypoactive with reduced mean velocity and distance moved (P=0.0004 and P=0.0004; Mixed effects Model, Tukey’s test, 2 cohorts n=6-11), while Naive mice with sham FMT had no change. In conclusion, gut microbiota modification through FMT in adult mice with a history of HIE reduced the severity of their hyperactive phenotype. Conversely, FMT from HIE mice into naïve mice induced mild behavioral changes but did not reproduce the hyperactivity seen in HIE mice.

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Febbraio 2024

A CONSORTIA OF CLINICAL E. COLI STRAINS WITH DISTINCT IN-VITRO ADHERENT/INVASIVE PROPERTIES ESTABLISH THEIR OWN CO-COLONIZATION NICHE AND SHAPE THE INTESTINAL MICROBIOTA IN INFLAMMATION-SUSCEPTIBLE MICE

Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation and associated inflammatory bowel disease (IBD). However, it remains unclear if the 24-year-old AIEC in-vitro definition fully predicts mucosal colonization in-vivo. To fill this gap, germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortia of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition.

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Gennaio 2024

A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF PSYLLIUM FIBER AND FECAL MICROBIOTA TRANSPLANTATION FOR MILD TO MODERATE ULCERATIVE COLITIS

Emerging clinical data shows potential for fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), though factors affecting clinical response remain poorly defined. Pre-clinical data suggest the role of dietary fiber in enhancing microbial metabolites to mitigate colitis severity. This study aimed to evaluate the role of the prebiotic psyllium in improving the clinical outcomes of FMT for mild to moderate UC, with the long-term goal of enhancing FMT as a therapeutic strategy for UC.

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Gennaio 2024

A NOVEL MOUSE MODEL OF CROHN’S DISEASE DRIVEN BY THE INTERACTION OF CD4 T CELLS AND GUT MICROBIOTA-RESPONSIVE γδ T CELLS

Inflammatory bowel disease (IBD) is a spectrum of disorders, namely Crohn’s Disease (CD) and Ulcerative Colitis (UC), characterized by distinct patterns of intestinal inflammation, a dysregulated intestinal immune response, and an altered gut microbiota. Given the growing number of new IBD diagnoses (70,000 new cases reported each year) and the inconsistent results of current treatment options, there is a major unmet need to understand IBD pathophysiology to develop more effective treatments. Previous reports indicate that IBD patients have an altered gut microbiota that can influence the development of inflammatory innate and adaptive immune cells that cause intestinal tissue damage and drive IBD pathogenesis.

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Gennaio 2024

Efficacy in bowel movement and change of gut microbiota on adult functional constipation patients treated with probiotics-containing products: a systematic review and meta-analysis

Objectives
This study aimed to pool the efficacy in bowel movement and explore the change of gut microbiota on adult functional constipated patients after probiotics-containing products treatment.

Design
Systematic review and meta-analysis.

Data sources
PubMed, Cochrane Library for published studies and ClinicalTrials.gov for ‘grey’ researches were independently investigated for randomised controlled trials up to November 2022.

Eligibility criteria, data extraction and synthesis
The intervention was probiotics-containing product, either probiotics or synbiotics, while the control was placebo. The risk of bias was conducted. The efficacy in bowel movement was indicated by stool frequency, stool consistency and Patient Assessment of Constipation Symptom (PAC-SYM), while the change of gut microbiota was reviewed through α diversity, β diversity, change/difference in relative abundance and so on. The subgroup analysis, sensitivity analysis and random-effect meta-regression were conducted to explore the heterogeneity. The Grading of Recommendations Assessment Development and Evaluation was conducted to grade the quality of evidence.

Results
17 studies, comprising 1256 participants, were included with perfect agreements between two researchers (kappa statistic=0.797). Compared with placebo, probiotics-containing products significantly increased the stool frequency (weighted mean difference, WMD 0.93, 95% CI 0.47 to 1.40, p=0.000, I²=84.5%, ‘low’), improved the stool consistency (WMD 0.38, 95% CI 0.05 to 0.70, p=0.023, I²=81.6%, ‘very low’) and reduced the PAC-SYM (WMD –0.28, 95% CI: –0.45 to –0.11, p=0.001, I²=55.7%, ‘very low’). In subgroup analysis, synbiotics was superior to probiotics to increase stool frequency. Probiotics-containing products might not affect α or β diversity, but would increase the relative abundance of specific strain.

Conclusions
Probiotics-containing products, significantly increased stool frequency, improved stool consistency, and alleviated functional constipation symptoms. They increased the relative abundance of specific strain. More high-quality head-to-head randomised controlled trials are needed.

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Gennaio 2024

Randomised, placebo-controlled, double-blinded trial of fecal microbiota transplantation in severe obesity: a study protocol

Introduction
Obesity is one of the main threats to public health in western countries and increases the risk of several diseases, overall morbidity and mortality. Sustained weight loss will reduce risk factors and improve several obesity comorbidities. Options are conservative treatment such as lifestyle changes, bariatric surgery or medications. Conservative treatment has a low success rate, and bariatric surgery is typically not reversible, with the risk of complications and recurrences. Treatment of obesity with medications has in recent years shown great promise, but the side effects are many, and the long-term effect is unknown. There is also a need for an option for patients where surgery has contraindications and conservative follow-up does not succeed.
The research on obesity and gut microbiota has yielded promising results regarding weight reduction and metabolic health, but more research is needed to better understand the relationship between gut microbiota and severe obesity. This study could show proof of concept that gut microbiota from a lean donor could, in addition to lifestyle intervention, contribute to weight reduction in people suffering from severe obesity.

Method and analysis
This study aims to investigate if a fecal microbiota transplantation (FMT) from a lean donor leads to weight reduction in participants suffering from severe obesity. The study is a single-centre, double-blinded, placebo-controlled, parallel-group study with 60 participants. Participants will be randomised 1:1 for FMT from a lean donor or placebo. FMT or placebo will be delivered once by enema.
We will include participants from the outpatient clinic for severe obesity, at the Medical Department, University Hospital of North Norway, Harstad, by invitation only. The study has a follow-up period of 12 months, with study visits of 3, 6 and 12 months post FMT. The primary endpoint is a weight reduction of ≥10%, 12 months after intervention.
The results of the study will be published in open access journals. At the end of the study, the participants will receive information on which treatment group they belong to.

Ethics and dissemination
The Regional Ethical Committee in North Norway (REK) approved the study protocol (2017/1655/REK Nord). We plan to present the results from the study at (inter)national conferences and publish in open-access general peer-reviewed journals. The enema method for FMT administration used in this study was developed by our study team.

Trial registration number
NCT03273855.

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Dicembre 2023

Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs

The gastrointestinal ecosystem has received the most attention when examining the contributions of the human microbiome to health and disease. This concentration of effort is logical due to the overwhelming abundance of microbes in the gut coupled with the relative ease of sampling compared with other organs. However, the intestines are intimately connected to multiple extraintestinal organs, providing an opportunity for homeostatic microbial colonisation and pathogenesis in organs traditionally thought to be sterile or only transiently harbouring microbiota. These habitats are challenging to sample, and their low microbial biomass among large amounts of host tissue can make study challenging. Nevertheless, recent findings have shown that many extraintestinal organs that are intimately linked to the gut harbour stable microbiomes, which are colonised from the gut in selective manners and have highlighted not just the influence of the bacteriome but that of the mycobiome and virome on oncogenesis and health.

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Dicembre 2023

Solutions to Enhance Health with Alternative Treatments (SEHAT) protocol: a double-blinded randomised controlled trial for gut microbiota-targeted treatment of severe acute malnutrition using rice bran in ready-to-use therapeutic foods in Indonesia

Introduction
Current formulations of ready-to-use therapeutic foods (RUTFs) to treat severe acute malnutrition (SAM) in children focus on nutrient density and quantity. Less attention is given to foods targeting gut microbiota metabolism and mucosal barrier functions. Heat-stabilised rice bran contains essential nutrients, prebiotics, vitamins and unique phytochemicals that have demonstrated favourable bioactivity to modulate gut microbiota composition and mucosal immunity. This study seeks to examine the impact of RUTF with rice bran on the microbiota during SAM treatment, recovery and post-treatment growth outcomes in Jember, Indonesia. Findings are expected to provide insights into rice bran as a novel food ingredient to improve SAM treatment outcomes.

Methods and analysis
A total of 200 children aged 6–59 months with uncomplicated SAM (weight-for-height z-scores (WHZ)

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Novembre 2023

Correction: Mucus barrier, mucins and gut microbiota: the expected slimy partners?

Paone P, Cani PD. Mucus barrier, mucins and gut microbiota: the expected slimy partners? Gut 2020;69:2232-43.
There is a misspelling of the Cftr gene in this article. The article has Ctfr instead of Cftr in the following sentence, which should read as:
For example, during high-fat diet feeding, there is an impairment in mucus production and secretion, an enrichment in barrier-disrupting species, and a decrease in the expression of the Cftr gene in mouse ileal enterocytes, causing a reduction in viscosity and density of the mucus and an increase in intestinal permeability.
doi:10.1136/gutjnl-2020-322260corr1

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Novembre 2023

Abstract 13116: Profiling the Role of Gut Microbiota-Derived Trimethylamine-N-Oxide in Cardiac Fibrosis — Evidence From a Primary Human in vitro Model

Circulation, Volume 148, Issue Suppl_1, Page A13116-A13116, November 6, 2023. Introduction:The gut derived trimethylamine-N-oxide (TMAO) is correlated with increased atrial inflammation and fibrosis and associated with atrial fibrillation, heart failure, and stroke. However, the mechanisms mediating these links remain unresolved.Hypothesis:TMAO and its precursor metabolite L-carnitine (LCART) induce the transformation of atrial fibroblasts into pro-fibrotic phenotypes.Aim:To characterise the association between TMAO and cardiac fibrosis.Methods:Primary human cardiac (atrial) fibroblasts (hCFs) were sourced from healthy donors. hCFs were starved for 24 h and treated with PBS (control), 20 ng/mL transforming growth factor beta 1 (TGFβ1), 10 mM TMAO, or 1.0 mM LCART for 72 h (n=6 in each), then analysed by flow cytometry for α-smooth muscle actin (αSMA) expression. Unbiased proteomics was performed using LC-MS/MS to determine protein expression profile.Results:Analysis of αSMA expression revealed 3 hCF states: quiescent (Fbs), quiescent-to-myofibroblast (intermediate [Fbs-myoFbs]), and fully activated myofibroblast (myoFbs), (Fig-A). Compared to controls, there was no difference in the intermediate state after TGFβ1, TMAO, or LCART treatment (p=0.30). TMAO and LCART resulted in a significant induction of myofibroblast states compared to controls and TGFβ1 group. Unbiased proteomics identified 92, 65, and 43 proteins to be overexpressed and 84, 46, and 78 proteins downregulated following TGFβ1, TMAO, and LCART treatments (Fig-B). Both TGFβ1 and TMAO demonstrated shared enrichment for oxidative stress-regulated ferroptosis pathway (fold enrichment [FE] 31.8 and 22.2, p

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Novembre 2023