Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV

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.

Keywords: HIV; fecal microbiota transplant; inflammation; microbiome.

Figure 1.

Changes in HIV parameters during treatment period (weeks 0 to 6) and after 20 weeks of follow-up without FMT.

Figure 2.

A) α diversity by observed species in each recipient before fecal microbiota transplant (FMT; week 0), after 6 weekly oral FMTs (week 6), and 20 weeks after last FMT (week 26), as well as in donors. B) Microbiome distribution by Bray-Curtis principal component analysis in each recipient at weeks 0, 6, and 26 and in the donors. Circles on the graph reflect the donors (light and dark gray). Triangles indicate week 0, squares indicate week 6, and diamonds indicate week 26; each is color-coded for participant according to the color in the circle in the key.

Figure 3.

Microbial composition of the participants and donors at the family level. Families with abundance <5% were grouped into “others” category.

Figure 4.

Changes in the microbiota at the strain level in PID3, the participant who had the highest zonulin, intestinal fatty acid binding protein (I-FABP), soluble TNF receptors I and II, soluble TNF receptor superfamily 8 (sCD30), and osteopontin levels and had a dramatic shift in distribution. A) Increases in strain abundance by at least 1%. B) Decreases in strain abundance by at least 1%.

Figure 5.

Changes in biomarkers of gut damage (zonulin, intestinal fatty acid binding protein [I-FABP]), microbial translocation (soluble CD14 [sCD14], flagellin, and (1,3)-β-D-glucan), and inflammation (soluble tumor necrosis factor [TNF] receptor II [sTNFRII], and soluble TNF receptor superfamily 8 [sTNFRSF8]).