In concordance with data from animal

In concordance with data from animal models (Handley et al., 2012) and studies matching for HIV risk factors (Yu et al., 2013), we were unable to identify a consistent HIV-specific fecal dysbiosis pattern after stratifying for HIV transmission group. Yet, HIV-1 infection remained associated with reduced bacterial richness independently of sexual orientation, indicating that the most evident hallmark of HIV infection on the gut microbiome is, like in other intestinal inflammatory diseases (Manichanh et al., 2012), a reduction in bacterial richness. In line with previous observations linking bacterial richness with immune dysfunction (Nowak et al., 2015), the lowest bacterial richness was found in immune discordant subjects, followed by immune concordant individuals with adequate immune recovery on ART. Conversely, bacterial richness was conserved in subjects initiating ART during the first 6months of HIV infection, as well as in ART-naïve individuals with >500CD4+counts/mm3, suggesting that early ART RVX-208 Supplier might help to preserve gut microbial richness. The strong epidemiological association of fecal microbiota composition with sexual orientation in two independent cities is yet to be translated into specific mechanisms. We ruled out multiple confounders and only found a limited effect of diet in our setting. We did not collect information on exercise, but exercise has been linked to fecal microbiota composition in athletes (Clarke et al., 2014) and even in them diet plays an important role. A formal assessment of the socioeconomic status of our patients was out of the scope of this work, although based on our findings, rigorous studies assessing the role of socioeconomic status in the fecal microbiota composition are needed. Non-MSM subjects in our study were older and more likely to be co-infected with HBV and HCV than MSM, reflecting current trends of the HIV epidemic in Europe, i.e.: most new HIV-1 infections occur in young MSM who rarely use intravenous drugs. Fecal consistency was also softer in MSM than in non-MSM subjects, which, indirectly, might reflect better overall health habits, including a healthier diet, higher water consumption and physical activity. However, none of these factors, nor ethnicity, achieved a significant weight in LASSO models. Further studies are needed to evaluate the existence of ecological adaptations of commensal bacteria to changes in gut mucosa induced by sexual practices. Populations of commensal bacteria are controlled by substrate competition and glycan availability (Koropatkin et al., 2012) and several factors might affect distal colorectal mucosa, including hyperosmolar substances like semen or certain lubricants (Fuchs et al., 2007; McGowan, 2012), colorectal cleansing or use of sexual toys. Longitudinal studies should also clarify if the observed association is stable over time, and if it varies according to the number of sexual partners (i.e., long-term single relationships versus frequent partner exchange) or by insertive versus receptive anal sex. It is also important to clarify if the observed association remains in heterosexual women who engage in receptive anal sex and if increased microbiota richness can be related to person-to-person transmission of commensal bacteria. Future studies should also investigate if the observed association has implications for transmission of infectious agents, including HIV-1. We did not find an association between fecal microbiome and HBV, HCV, syphillis or rectal HPV, C. trachomatis or N. gonorrhoeae infections, but did not evaluate HSV-2 infection. In our study, the observed association between sexual orientation and microbiota composition did not translate into gross differences in terms of systemic inflammation or microbial translocation. Shotgun metagenomic analyses of bacterial species and richness, as well as the virome and perhaps the mycobiome, in clinical trials balanced by HIV risk factors might provide novel clues as to the impact of HIV infection on the gut microbiome.