Bacterial fecal microbiome composition associated with HIV stage among rural and peri-urban adults living with HIV in Uganda

Background: Gut microbiome composition in HIV-infection provides insight into HIV pathogenesis and potentially offers avenues to adjunctive HIV therapies. Although two-thirds of people living with HIV (PLHIV) are in Africa, studies of the gut microbiome PLHIV have focused on non-African populations. Additionally, social, cultural, and environmental factors influence the gut microbiome and differ substantially between African and Western and urban and rural communities. Here, we quantify the relationships between immune status and fecal microbiome composition in 175 rural Ugandan PLHIV. Methods: In 2013, 175 Ugandan PLHIV contributed a single fecal sample as part of a cohort study of 202 participants. We measured CD4 + T cells at baseline and followed the individuals longitudinally via chart review for 12 months. Fecal samples were assessed for parasitic infection, and standard 16S bacterial rRNA sequencing determined microbiome composition. We assessed alpha and beta diversity by clinical factors, e.g., ART duration, CD4 + T cells/µL, parasitic infection, and differential relative abundances via non-parametric tests and adjusted regression. We assessed the relationship between taxa and longitudinal change in CD4 + cells/µL via linear mixed models. Results: This analysis of microbiome data among 175 participants found that alpha diversity was lower in participants with < 100 CD4 + T cells/µL versus their peers with higher CD4 + counts. Only the presence of Anaerococcus was inversely associated with CD4 + T cells/µL (Spearman correlation − 0.3207; p-value = 0.0000152). We observed no trends in beta diversity across clinical or demographic groups. Presence of Sutterella and Alcaligenaceae at baseline were associated with increasing CD4 + T cells/µL over time. Conclusions: We identified three taxa associated with clinical parameters, and, importantly, that the fecal microbiome is less diverse at lower CD4 + T cells counts, which is concerning for relatively increased dysbiosis and worse outcomes. Given the large prevalence of HIV in Sub-Saharan Africa, key differences in factors that influence microbiome, and the apparent importance of the microbiome in health status, future microbiome research focused on diverse and rural African populations is warranted. Clinical trial: Not applicable. This was not a clinical trial as no intervention was applied to the participant.