Oral and anal microbiome from HIV-exposed individuals: role of host-associated factors in taxa composition and metabolic pathways.

Abstract Evidence indicates that the microbiome plays a significant role in HIV immunopathogenesis as well as in HIV-associated complications. In Argentina, men who have sex with men (MSM) and transgender women (TGW) are at the highest risk for infection with HIV and AIDS-related viruses. This study aimed to characterize the oral and anal microbiome of MSM and TGW with and without HIV. One hundred and thirty oral and anal DNA-derived samples were obtained from 78 participants and subjected to shotgun metagenomics sequencing for further microbiome analysis. Results: A significantly lower alpha diversity and higher beta diversity were found in the anal samples compared with oral samples. Significant differences in the microbiome composition were found among subjects associated with HIV infection, gender, sex behavior, CD4+ T cell counts, antiretroviral therapy (ART) and the presence of HPV-associated precancerous anal lesions. For viruses, results confirm the occurrence of oncogenic viromes in this high HIV-risk population. The HIV-associated oral microbiome was characterized by the enrichment of several bacteria related to periodontal disease pathogenesis. Conversely, predominantly anal bacteria showed a significant decrease in HIV-infected subjects (Coprococcus comes, Finegoldia magna, Blautia obeum, Catenibacterium mitsuokai). TGW showed enrichment in species related to sexual transmission, which concurs that most recruited TGW are or have been sex workers. Prevotella bivia and Fusobacterium gonidiaformans were positively associated with the presence of anal precancerous lesions among HIV-infected subjects. The enrichment of Holdemanella biformis and C. comes were associated with detectable viral load and ART untreated patients. Metabolic pathways were distinctively affected according to whether the predominant factors were associated with sexual behavior or HIV pathogenesis. Gene family analysis identified bacterial gene signatures that may potentially be prognostic and/or predictive biomarkers of HIV/AIDS-associated malignancies. Conclusions: We have identified distinctive microbial features at two easily accessible sites related to HIV immunopathogenesis. These could also be implemented as potential biomarkers to predict the risk of precancerous anal lesions or as therapeutic targets.