Fecal microbiota transplantation in HIV: A pilot placebo-controlled study

Sergio Serrano‐Villar ,María José Gosalbes,Ryan J Elliott,María Jesús Vivancos,Mónica Manzano,Carolina Gutiérrez,Alba Talavera-Rodríguez,Andrés Moya,Javier Martínez-Sanz,Raquel Ron,Nadia Madrid,Val F Lanza,Shrish Budree,Uxua Ansa,José A Pérez‐Molina ,Alejandro Vallejo,Beatriz Navia,Javier Zamora,Fernando Dronda,Majdi Osman,Sabina Herrera,Santiago Moreno

doi:10.1038/s41467-021-21472-1

Abstract

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-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor’s microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

Highlights

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection
The study participants were representative of a population of middle-aged men who have sex with men with wellcontrolled HIV infection
We found that the significant increase of Ruminococcaceae and Lachnospiraceae families in the fecal microbiota transplantation (FMT) arm was driven by engraftment of these taxa in the majority of individuals, rather than being artificially driven by a dramatic increase in a subset of individuals (Supplementary Figure 6)

Summary

Introduction

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In PWH the gut microbiota has shown a high resilience to interventions and remains an elusive therapeutic target It is unknown whether fecal microbiota transplants (FMT) delivered orally can affect the gut microbiota, as a method to attenuate chronic inflammation in PWH. We hypothesized that repeated FMT using capsulized stools will be more efficacious than previous nutritional interventions aimed at shaping the microbiota in PWH and improve systemic markers of inflammation. Because such an intervention has not been explored before, we conducted a controlled, double-blind, placebo-controlled pilot study in which PWH on stable ART received eight courses of oral FMT or a placebo and were subsequently followed for 48 weeks. Because a hallmark of the microbiome abnormalities associated with HIV infection is a depletion of butyrate-producing bacteria (Lachnospiraceae and Ruminococcaceae families)[14], we searched for donors with enrichment for butyrate in their feces

Methods

Results

Conclusion