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Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV
Netanya S Utay1,2, Ana N Monczor3, Anoma Somasunderam1
1Division of General Medicine, Department of Internal Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas.
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.
Insights
Fecal microbiota transplants (FMT) were safe for people with HIV (PWH), increasing gut microbial diversity during treatment. Future studies should focus on PWH with significant inflammation or gut damage for better FMT response.
Area of Science:
- Microbiome research
- Immunology
- Gastroenterology
Background:
- Reduced gut microbiota diversity (dysbiosis) in people with HIV (PWH) is linked to inflammation, increasing morbidity and mortality.
- Fecal microbiota transplantation (FMT) is being explored as a therapeutic strategy to restore gut microbial balance.
Purpose of the Study:
- To evaluate the safety and tolerability of weekly oral FMT in people with HIV (PWH).
- To assess the impact of FMT on gut microbiota diversity and inflammatory markers in PWH.
Main Methods:
- Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly oral doses of lyophilized fecal microbiota from healthy donors.
- Stool samples were analyzed using shotgun sequencing before, during, and after FMT.
- Biomarkers for inflammation and gut permeability were measured.
Main Results:
- FMT was found to be safe and well-tolerated in all participants.
- Four participants showed increased gut microbial alpha diversity during the 6-week treatment period, particularly those with lower baseline diversity.
- While overall metagenomic analysis showed no consistent changes, one participant with high gut permeability and inflammation markers experienced improvement.
Conclusions:
- Weekly oral FMT is a safe and tolerable intervention for PWH.
- FMT can increase gut microbial alpha diversity, especially in individuals with significant dysbiosis.
- Future randomized controlled trials should target PWH with pronounced inflammation, gut damage, or dysbiosis for potentially greater therapeutic benefits.
