Abstract
Background:Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.Methods:Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured.Results:Median age at week 0 was 39 years, CD4+ T cell count 496 cells/mm3, HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. α diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest α diversity at week 0. At week 26, α diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low α diversity that improved between weeks 0 and 6 with a shift in distribution.Conclusions:Weekly FMT was safe and well-tolerated. α diversity increased in participants with the lowest baseline α diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560
Highlights
People with HIV (PWH) taking suppressive antiretroviral therapy (ART) remain at increased risk of cardiovascular events, malignancies, and other comorbidities, likely due to persistent inflammation [1]
Levels of biomarkers of increased gut permeability, microbial translocation, and systemic inflammation remain increased despite the long-term treatment of HIV infection, and these biomarkers predict morbidity and mortality [3,4,5]
Many studies have demonstrated that people with HIV (PWH) have an abnormal gut microbiome, characterized by decreased a diversity and a shift toward more pro-inflammatory Proteobacteria and fewer anti-inflammatory bacteria that produce short chain fatty acids (SCFAs) [6]
Summary
People with HIV (PWH) taking suppressive antiretroviral therapy (ART) remain at increased risk of cardiovascular events, malignancies, and other comorbidities, likely due to persistent inflammation [1]. Erysipelotrichaceae, Enterobacteriaceae, Desulfovibrionaceae, and Fusobacteria are increased, whereas Lachnospiraceae, Ruminococceae, Bacteroides, and Rikenellaceae are decreased in the microbiomes of PWH. This abnormal microbiome may perpetuate gut damage and chronic systemic inflammation [7]. Proteobacteria, Desulfovibrio, Enterobacteriaceae, Fusobacteria, Ruminococcaceae, and Lachnowww.PaiJournal.com spiraceae do not seem to differ between MSM and non-MSM participants [6]. These findings suggest that sexual activity needs to be considered when conducting microbiome studies. Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis
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