Researchers found that people living with HIV (PLWH) on antiretroviral therapy (ART) show accelerated biological aging in the intestines and blood compared to people without HIV (PLWoH). This aging is linked to intestinal microbial dysbiosis and increased microbial translocation, which may contribute to inflammation and non-AIDS-related comorbidities. The study used a systems biology approach to analyze colon and ileal biopsies, blood samples, and stool from PLWH and PLWoH. PLWH had lower levels of tight junction proteins and higher microbial translocation, which correlated with faster biological aging and inflammation. They also had higher levels of pro-inflammatory bacteria like Catenibacterium and Prevotella, and lower levels of anti-inflammatory bacteria that produce short-chain fatty acids (SCFAs) like Subdoligranulum and Erysipelotrichaceae. These bacteria were associated with slower biological aging. Correlation networks showed links between specific microbial genera in the colon and ileum, increased aging, and changes in metabolites related to inflammation. The study identified microbial compositions and metabolic pathways linked to intestinal and systemic biological aging, suggesting that factors like HIV infection, ART, and sexual orientation contribute to this process. Understanding these mechanisms could help develop strategies to mitigate accelerated aging and its health complications. The findings highlight the role of the gut microbiome in biological aging and the need for further research into the underlying mechanisms.Researchers found that people living with HIV (PLWH) on antiretroviral therapy (ART) show accelerated biological aging in the intestines and blood compared to people without HIV (PLWoH). This aging is linked to intestinal microbial dysbiosis and increased microbial translocation, which may contribute to inflammation and non-AIDS-related comorbidities. The study used a systems biology approach to analyze colon and ileal biopsies, blood samples, and stool from PLWH and PLWoH. PLWH had lower levels of tight junction proteins and higher microbial translocation, which correlated with faster biological aging and inflammation. They also had higher levels of pro-inflammatory bacteria like Catenibacterium and Prevotella, and lower levels of anti-inflammatory bacteria that produce short-chain fatty acids (SCFAs) like Subdoligranulum and Erysipelotrichaceae. These bacteria were associated with slower biological aging. Correlation networks showed links between specific microbial genera in the colon and ileum, increased aging, and changes in metabolites related to inflammation. The study identified microbial compositions and metabolic pathways linked to intestinal and systemic biological aging, suggesting that factors like HIV infection, ART, and sexual orientation contribute to this process. Understanding these mechanisms could help develop strategies to mitigate accelerated aging and its health complications. The findings highlight the role of the gut microbiome in biological aging and the need for further research into the underlying mechanisms.