A taxon-specific measurement of disruption in a multi-modal study of microbiomes and metabolomes reveals system-wide dysbiosis preceding HIV-1 infection.

The microbiome plays an important role in immune responses and inflammation in HIV-1 infection. Hence, a deeper understanding of the changes in the microbiome, its function and metabolites, and their interactions prior to HIV-1 infection is potentially important for HIV-1 prevention strategies. Using stool, oral washes, and plasma biospecimens obtained from men who have sex with men (MSM) and who were without HIV-1, we found several differences in microbial ecologies, gene functions, and metabolites between MSM who became HIV-1 infected (Pre-HIV) within six months and those who remained HIV-1 uninfected (Non-HIV). The Pre-HIV group had an enrichment of enzymes involved in purine metabolism, lower amino acid metabolism, and higher oxidative stress before the infection compared to the Non-HIV group. We also introduced a novel and broadly applicable taxon-specific measure of DISruption in COrrelations (DISCO) with other features, such as microbial taxa and metabolites in a given group (e.g., Pre-HIV group) relative to a reference group (e.g., Non-HIV group). Using DISCO, we identified several gut and oral species with disrupted correlations prior to HIV-1 infection. Application of DISCO to external datasets revealed that Prevotella spp. are consistently disrupted in their correlations across multiple cohorts prior to or following HIV-1 infection.