Fecal microbiota transplantation in HIV: A pilot placebo-controlled study.
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ABSTRACT:
SUBMITTER: Serrano-Villar S
PROVIDER: S-EPMC7892558 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Fecal microbiota transplantation in HIV: A pilot placebo-controlled study.
Serrano-Villar Sergio S Talavera-Rodríguez Alba A Gosalbes María José MJ Madrid Nadia N Pérez-Molina José A JA Elliott Ryan J RJ Navia Beatriz B Lanza Val F VF Vallejo Alejandro A Osman Majdi M Dronda Fernando F Budree Shrish S Zamora Javier J Gutiérrez Carolina C Manzano Mónica M Vivancos María Jesús MJ Ron Raquel R Martínez-Sanz Javier J Herrera Sabina S Ansa Uxua U Moya Andrés A Moreno Santiago S
Nature communications 20210218 1
Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-a ...[more]
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Project description:ObjectivesSystemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc.MethodsTen patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing.ResultsACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo.ConclusionsFMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.
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Project description:BackgroundHypertension is currently the leading modifiable cause of global morbidity and mortality, leading to substantial health and financial burdens. Although multiple studies of management models and innovative therapeutic strategies for hypertension have been conducted, there are still gaps in the field, with a poor control rate reflecting a lack of novel, effective, clinically translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between the microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between the gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention for treating hypertension is thus postulated, and fecal microbiota transplantation (FMT) from healthy donors was performed.MethodsA multicenter, randomized, placebo-controlled, blinded clinical trial will be performed in 120 grade 1 hypertensive patients for 3 months. All recruited patients will be randomly assigned in a 1:1 ratio to take oral FMT capsules or placebo capsules on day 1, day 7, and day 14 and will be followed up on day 30, day 60, and day 90. The primary outcome is the change in office systolic blood pressure from baseline to day 30. The main secondary outcomes are BP indicators, including changes in systolic and diastolic blood pressure from office and 24-h ambulatory blood pressure monitoring; assessments of ankle-branchial index and pulse wave velocity; profiling of fecal microbial composition and function; profiling of fecal and serum metabolome; changes in levels of blood glucose, blood lipids, and body mass index; and assessment of adverse events as a measure of safety.DiscussionExpanding upon our previous research on the role of the gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and explores the potential of fecal microbiota transplantation for treating hypertension. The underlying mechanisms, particularly the roles of specific microorganisms or their postbiotics in blood pressure amelioration, will also be investigated via multiple approaches, such as metagenomic sequencing and metabolomic profiling.Trial registrationClinicalTrials.gov NCT04406129 . Registered on May 28, 2020.
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Project description:BackgroundBipolar disorder (BD) is a chronic, debilitating illness with significant medical morbidity, often secondary to current treatments, and a high recurrence rate. This burden of disease reflects limitations in the tolerability and efficacy of current treatments. There is a compelling body of evidence linking the gut microbiota to mental illness, and while microbial manipulation via probiotic use has been studied as a therapeutic in BD, targeted trials of fecal microbiota transplantation (FMT) have not been conducted in this population.Methods and designWe describe a pilot randomized controlled trial of FMT in participants with BD depression to assess the feasibility, efficacy, safety, and tolerability of this intervention. Individuals between 18 and 65 years of age will be enrolled in the study if they meet diagnostic criteria for a major depressive episode of at least moderate severity in the context of a BD diagnosis and have not responded to treatment for BD. Participants will be randomized 1:1 to receive either screened and processed donor stool (allogenic FMT) or their own stool (autologous FMT) via colonoscopy and monitored for 24 weeks post intervention. Depressive and manic symptoms, treatment acceptability, and gastrointestinal and other side effects are assessed at baseline (prior to randomization) and weekly. Stool samples to assess microbiome composition are obtained at baseline and 3 and 6 months.DiscussionCurrently, FMT represents a novel therapeutic option for treating BD depression. This protocol allows for the assessment of the feasibility, efficacy, acceptability, and safety of an intervention aimed at changing the microbiome in those with BD. Results from this pilot study will guide the development of larger trials of FMT for BD depression and may give more insight into how the gut microbiome are altered in those with BD depression.Trial registrationClinical Trials Gov NCT03279224.
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