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

## TL;DR

The gut microbiome affects immune responses in HIV-positive and HIV-negative men who have sex with men, with distinct immune changes linked to HIV status and sexual behaviors.

## Contribution

The study reveals how gut microbiome-immune interactions differ in HIV+ and HIV- men who have sex with men, influenced by both infection and sexual risk behaviors.

## Key findings

- HIV+ individuals showed reduced CD4⁺ CD103⁺ and CD8⁺CD103⁺ T cells in colonic biopsies.
- High-risk sexual behaviors in MSM correlated with reduced MAIT cells in the blood.
- Network analysis identified tissue-specific immune-microbiome relationships shaped by HIV and MSM factors.

## Abstract

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.

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.

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.

These findings provide new insights into host:microbe interactions, with implications for immune regulation, HIV persistence, and transmission among MSM.