Abstract Body

The precise effects of HIV-1 on the human microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV status and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 risk groups.

This was a cross-sectional study where we first tested 129 HIV-1-infected subjects and 27 HIV-negative controls in Barcelona (BCN0). Findings were internally validated in 110 subjects from BCN0 providing a second fecal sample 1 month later (BCN1). External validation was obtained in 77 HIV-1-infected and 7 non-infected subjects from Stockholm (STK). In all study participants, we produced MiSeqTM 16S rRNA sequence data on fecal microbiomes and collected comprehensive metadata. Alpha and beta diversity analyses of the gut microbiota were performed. LASSO regression was used to quantify the strength of the association between sexual practice, HIV-1 status and global fecal microbiota composition.

Men who have sex with men (MSM) consistently had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual practice, HIV-1 infection remained consistently associated with reduced bacterial richness. The lowest microbial richness was observed in HIV-1-infected individuals with immune-virological discordant phenotype. Fecal microbiomes strongly clustered by sexual practice rather than by HIV-1 serostatus, with high concordance between BCN0 and BCN1 (Procrustes m2=0.3475, PROTEST p=0.001). The fecal microbiota composition in BCN and STK significantly differed by sexual practice, with MSM and non-MSM subjects mostly belonging to the Prevotella and Bacteroides enterotypes, respectively. Cross-validation accuracy of the LASSO model was very high for sexual practice (mean AUC=95%), confirming a different fecal microbiota composition in MSM and non-MSM individuals after excluding multiple other potential confounders. In contrast, HIV-1 status was not associated with consistent changes in the global fecal microbiota composition at genus level.

Gay men have a distinct gut microbiota composition, which is a potential confounder of all human fecal microbiome studies. Yet, HIV-1 infection remains independently associated with reduced bacterial richness, which offers new avenues for interventions to improve HIV immune dysfunction.