ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Gut microbiome composition influences immunologic alterations in the blood and gut of HIV-positive and negative Men who have Sex with Men
Provisionally accepted
Charles Preston Neff
Janet Siebert
Mallory KarrRicky LippincottRachel Kvaal
Amy T Noe
Elena WallNichole NusbacherSuzanne FiorilloBlair P FennimoreThomas B. CampbellCatherine LozuponeBrent E Palmer*- University of Colorado Anschutz Medical Campus, Aurora, United States
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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 mass cytometry (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.
Keywords: HIV, microbiome, MSM, Colonic, Inflammation, Art, Sexual Behavior, cyTOF
Received: 17 Sep 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 Neff, Siebert, Karr, Lippincott, Kvaal, Noe, Wall, Nusbacher, Fiorillo, Fennimore, Campbell, Lozupone and Palmer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Brent E Palmer, brent.palmer@cuanschutz.edu
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