Gut Microbiota Linked to Sexual Preference and HIV Infection

• The fecal microbiota of gay men in Europe is systematically richer and has a distinct composition.
• HIV-1 infection is independently associated with reduced gut bacterial richness, more so in immune discordant subjects.
• Interventions to increase gut bacterial richness might offer novel avenues to improve HIV-1-associated immune dysfunction.The human intestinal microbiota is essential for human health and well-being and is driven by genetic, lifestyle and environmental factors. Here, we show in two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Europe that gay men often have a distinct composition of the human fecal microbiota, with increased microbial richness and diversity and enrichment in the Prevotella enterotype. This is independent of HIV-1 status, and with only a limited contribution of diet effects. After accounting for sexual orientation, however, HIV-1 infection remains associated to reduced bacterial richness, more so in subjects with suboptimal CD4 + T-cell count recovery under antiretroviral therapy. Future studies should evaluate if interventions to increase gut bacterial richness could improve HIV-associated immune dysfunction.

The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus 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 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction.