Gut Microbiota Linked to Sexual Preference and HIV Infection

Abstract

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.

Brief Report: Inflammatory Colonic Innate Lymphoid Cells Are Increased During Untreated HIV-1 Infection and Associated With Markers of Gut Dysbiosis and Mucosal Immune Activation

“…The study was not powered to address alterations in numbers of colonic cytokine-producing ILCs in the setting of HIV-1 infection. The two study groups were not matched for sexual practice, which has recently been reported to impact the intestinal microbiome independent of HIV-1 infection 49,50 and may drive mucosal immune cell activation and inflammation 50 and therefore be a contributing factor to our current observations. Enumeration of the specific ILC subsets was based on criteria used to identify NK22 cells 16 .…”

The gut microbiome and HIV-1 pathogenesis

“…The majority of studies have had small sample sizes of HIV-infected study participants and various uninfected control populations and thus were hypothesis-generating rather than being powered to address microbiome endpoints. Finally, a recent study highlighted the importance of appropriately matching control study participants by sexual preference[45] (discussed in more detail below). Thus clinical as well as technical variables may help to explain the inconsistencies observed among studies investigating the enteric microbiome in the setting of HIV-1 infection.…”

“…Surprisingly, bacterial diversity further decreased in stool samples of HIV-1 infected study participants who were followed after the introduction of ART[46] suggesting antiretroviral drugs themselves may impact the intestinal microbiota. Men who have sex with men (MSM) were found to have greater fecal microbial diversity than non-MSM, but HIV-associated reductions in diversity persisted even when HIV-1 infected subjects were stratified for MSM vs. non-MSM[45]. Mucosal samples exhibited greater differences in diversity than did fecal samples[44].…”

“…are inducers of regulatory T cell function[71]. A recent study suggested that the Prevotella -rich/ Bacteroides -poor community structure was more prevalent among men who have sex with men (MSM), rather than with HIV-1 infection status per se [45]. This finding highlighted the importance of appropriately accounting for the myriad of possible factors that might confound HIV-1 microbiome studies.…”

“…Indeed, a failure to see relatively greater Prevotella abundance in HIV-1 infected individuals in Uganda was suggested to be related, at least in part, to the high abundance of Prevotella typically observed among healthy uninfected study participants in this population[43]. However, given the recent evidence that the Prevotella -rich profile observed in HIV-1 infection may be more closely linked to sexual practice than to diet or HIV-1 infection status[45], future studies will need to include extensive dietary questionnaires that are validated within the target populations with appropriately matched control participants. In this way, the impact of diet on changes in the microbiome during HIV-1 infection can be better addressed.…”