Gut microbiome dysbiosis in men who have sex with men increases HIV infection risk through immunity homeostasis alteration.

Objectives: Recent studies pointed out that gut microbiome dysbiosis in HIV infection was possibly confounded in men who have sex with men (MSM), but there is a lack of evidence. It also remained unclear how MSM-associated gut microbiome dysbiosis affected human health. This study aimed to compare the differences in gut microbiome changes between HIV and MSM and reveal the potential impacts of MSM-associated gut microbiome dysbiosis on the immune system. Methods: We searched available studies based on the PubMed database, and all gut microbiome changes associated with HIV infection and MSM were extracted from the enrolled studies. The gutMgene database was used to identify the target genes and metabolites of the gut microbiome. Bioinformatic technology and single-cell RNA sequencing data analysis were utilized to explore the impacts of these gut microbiome changes on human immunity. Results: The results showed significant overlaps between the gut microbiome associated with HIV and that of MSM. Moreover, bioinformatic analysis revealed that gut microbiome dysbiosis in MSM had an impact on several pathways related to immunity, including the IL-17 signaling pathway and Th17 cell differentiation. Additionally, target genes of MSM-associated gut microbiome were found to be highly expressed in monocytes and lymphocytes, suggesting their potential regulatory role in immune cells. Furthermore, we found that MSM-associated gut microbiome could produce acetate and butyrate which were reported to increase the level of inflammatory factors. Conclusion: In conclusion, this study highlighted that MSM-associated gut microbiome dysbiosis might increase the risk of HIV acquisition by activating the immune system. Further studies are expected to elucidate the mechanism by which gut microbiome dysbiosis in MSM modulates HIV susceptibility.