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

HIV infection was associated with loss of CD4+ CD103+ and CD8+ CD103+ tissue-resident T cells in colonic biopsies.

• Colonic biopsy samples were analyzed using Cytometry by Time of Flight (CyTOF)
• Participants included HIV+ and HIV- MSM and non-MSM
• CD103 is an integrin associated with tissue-resident memory T cell identity in the gut mucosa
• These losses were identified as part of HIV infection status-influenced immune cell composition in colonic biopsies

HIV infection was associated with loss of group 3 innate lymphoid cells (ILC3s) in colonic biopsies.

• ILC3s were identified in colonic biopsy samples via CyTOF
• Loss of ILC3s was among the HIV status-linked immune alterations in gut tissue
• ILC3s have known roles in gut mucosal immunity and barrier maintenance
• This finding was identified alongside losses of tissue-resident T cells in the colon

HIV infection was linked to reductions in circulating group 2 innate lymphoid cells (ILC2s) in the blood.

• Blood samples were analyzed using CyTOF alongside colonic biopsy samples
• ILC2 reductions were specific to the blood compartment, representing a tissue-specific finding
• Both blood and colonic biopsy samples were included in the analysis to allow compartment-specific comparisons
• ILC2 reductions were identified as part of a broader set of blood immune alterations linked to HIV status

HIV infection was associated with reductions in naive CD8+ T cells in the blood.

• Naive CD8+ T cell reductions were observed in blood samples from HIV+ individuals
• This finding was identified as a blood-compartment-specific alteration associated with HIV status
• Analysis was performed using CyTOF on blood samples from HIV+ and HIV- MSM and non-MSM

Mucosal-associated invariant T (MAIT) cells were reduced in MSM engaging in high-risk sexual behaviors regardless of HIV status.

• MAIT cell reductions were associated with MSM-related high-risk sexual behaviors rather than HIV status per se
• This finding held regardless of HIV infection status, suggesting an independent behavioral association
• MAIT cells are innate-like T cells known to interact with the gut microbiome and mucosal immunity
• Participants were stratified by both HIV status and MSM-associated behaviors including high-risk sexual behaviors

Network analysis revealed distinct, tissue-specific relationships between immune cell populations and gut microbial taxa that were further shaped by HIV infection and MSM-associated factors.

• Network analysis was used to integrate immune profiles with gut microbiome composition
• Relationships between immune cells and microbial taxa differed between blood and colonic tissue compartments
• Both HIV infection status and MSM-associated factors further modified these host-microbe interaction networks
• Gut microbiome composition and MSM-related behaviors were both incorporated into the integrated analysis

The study used Cytometry by Time of Flight (CyTOF) to analyze immune profiles from both blood and colonic biopsy samples across HIV+ MSM, HIV- MSM, and non-MSM participants.

• CyTOF was applied to both blood and colonic biopsy samples allowing high-dimensional immune profiling
• Participant groups included HIV+ MSM, HIV- MSM, and non-MSM individuals
• Immune profiles were integrated with gut microbiome composition data and MSM-related behavioral data
• The study design allowed for tissue-specific and group-specific comparisons of immune-microbiome relationships