Gut microbiome composition influences immunologic alterations in the blood and gut of HIV-positive and HIV-negative men who have sex with men

Background: HIV infection and factors associated with sexual activity among men who have sex with men (MSM) can dysregulate relationships between the gut microbiome and immune system. Methods: To explore these relationships in depth, blood and colonic biopsy samples from HIV+ and HIV- MSM and non-MSM were analyzed using Cytometry by Time of Flight (CyTOF). Immune profiles were then integrated with gut microbiome composition and MSM-related behaviors. Results: HIV infection status influenced immune cell composition in colonic biopsies, marked by a loss of CD4⁺ CD103⁺ and CD8⁺CD103⁺ tissue-resident T cells and group 3 innate lymphoid cells (ILC3s). In the blood, HIV status was linked to reductions in circulating group 2 innate lymphoid cells (ILC2s), and naïve CD8⁺ T cells, while mucosal-associated invariant T (MAIT) cells were reduced in MSM engaging in high-risk sexual behaviors regardless of HIV status. Network analysis revealed distinct, tissue-specific relationships between immune cell populations and gut microbial taxa, further shaped by both HIV infection and MSM-associated factors. Conclusions: These findings provide new insights into host:microbe interactions, with implications for immune regulation, HIV persistence, and transmission among MSM.