Integrated analysis of rectal mucosal microbiome and transcriptome reveals a distinct microenvironment among young MSM.

Crosstalk between the microbiome and gut mucosa-resident immune cells plays a pivotal role in modulating immune responses to pathogens, including responses to HIV infection. However, how these interactions may differ between young men who have sex with men (YMSM) disproportionately impacted by HIV, as compared with older adult MSM (AMSM), is not well understood. A broad analysis of associations between the microbiome and rectal transcriptome revealed 10 microbial families/genera correlated with immunologic gene pathways. Specifically, the rectal transcriptome of YMSM was characterized by upregulation of T cell activation/differentiation pathways and signaling from multiple cytokine families compared with AMSM. The microbiome of YMSM was enriched with pathogenic genera, including Peptostreptococcus, shown to be positively correlated with type I IFN pathways important for antiviral immunity. These findings demonstrate that YMSM have a unique immune phenotype and rectal microenvironment and support further evaluation of biological factors that influence rectal HIV transmission.