Abstract

Abstract Although under highly effective antiretroviral therapy, people with HIV (PWH) still experience an increased risk of developing cancer compared to people without HIV (PWOH). Dysbiosis of the oral microbiota in PWH can contribute to persistent inflammation and cancer risk. We previously showed higher levels of inflammation in saliva of PWH measured by TGF-β1 and IL-2. In addition, microbial products such as short-chain fatty acids (SCFA) can regulate the transcription of immune-related genes, particularly those necessary for the innate immune response to pathogens. In this study, we characterized the composition of the oral bacteriome and mycobiome in saliva of Puerto Rican PWH and PWOH, and analyzed these data in relation to markers of inflammation and cancer risk in saliva. Saliva, sociodemographic, and clinical data from 100 adults were collected (50 PWH and 50 PWOH). PWH were virally suppressed (<50 copies/mL) and had a median CD4 count of 699.8 cells/µL. We sequenced the 16S rDNA and the ITS in extracted DNA from saliva to characterize and quantify the bacterial and fungal communities, respectively. Furthermore, measurement of inflammatory markers (TGF-β1, IL-2, and IL-8) in saliva was performed using quantitative immunoassays. Microbiome data was processed using Qiime2, and statistical analysis was carried out using R-statistical software. Biological pathways associated to changes in the microbiome were inferred using PiCRUST2. PWH showed lower alpha diversity in the oral bacteriome (Observed OTUs: p=0.02, Faith: p=0.03) and oral mycobiome (Shannon: p=0.02) when compared to PWOH. In a multivariate analysis, lower alpha diversity in the bacteriome was associated with biological sex and HIV status. Lower alpha diversity in the oral bacteriome was associated with higher levels of acetate (r=-0.38, p<0.001) and lower levels of IL-8 (r= 0.21, p= 0.056) in saliva independent of HIV status. Taxonomic analyses showed PWH had a significantly lower abundance of Porphyromonas, Peptostreptococcus, Oribacterium, Parvimonas, Leptotrichia, Fusobacterium, Eubacterium, Dialister, and Alkalibacter genera of bacteria but there not significant changes in taxonomy in the oral mycobiome. Biological processes significantly affected by dysbiosis of the oral mycobiome include cytosolic and mitochondrial NADPH production, amino acid and sugar degradation, and phospholipid remodeling. Dysbiosis of both the oral bacteriome and mycobiome occur in HIV infection, which can contribute to chronic inflammation. However, the bacteriome and mycobiome may have different biological mechanisms, which suggest different roles in increasing cancer risk in Puerto Rican PWH. These findings provide more information regarding the oral health in people with HIV and may contribute to innovative cancer prevention strategies and screening guidelines for this high-risk population. Citation Format: Veronica Sofia Sanchez Gonzalez, Yakshi N. Ortiz-Maldonado, Gabriel Borges-Vélez, Tanner L. Shull, Jeannette L. Salgado-Montilla, Josué Pérez-Santiago1. The contribution of the oral bacteriome and mycobiome in cancer risk in people with HIV in Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7475.

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