Gut microbiome changes associated with epithelial barrier damage and systemic inflammation during antiretroviral ther-apy of chronic SIV infection

Gut dysbiosis is a common feature associated with chronic inflammation of HIV infection. To-ward understanding the interplay of chronic treated HIV infection, dysbiosis and systemic in-flammation, we investigated longitudinal fecal microbiome changes and plasma inflammatory markers in the nonhuman primate model. Following simian immunodeficiency virus (SIV) infec-tion in rhesus macaques, significant changes were observed in several members of the phylum Firmicutes along with increase in Bacteroidetes. Viral suppression with antiretroviral therapy (ART) resulted in an early but partial recovery of compositional changes and butyrate producing genes in the gut microbiome. Over the course of chronic SIV infection and long-term ART, howev-er, specific loss of Faecalibacterium prausnitzii and Treponema succinifaciens significantly corre-lated with increase in plasma inflammatory cytokines including IL-6, G-CSF, I-TAC, and MIG. Further, the loss of T. succinifaciens correlated with increase in circulating biomarkers of gut epi-thelial barrier damage (IFABP) and microbial translocation (LBP and sCD14). As F. prausnitzii and T. succinifaciens are major short-chain fatty acid producing bacteria, their sustained loss during chronic SV-ART may contribute to gut inflammation and metabolic alterations despite effective long-term control of viremia. Better understanding of correlations between the an-ti-inflammatory bacterial community and healthy gut barrier functions in the setting of long-term ART may have a major impact on the clinical management of inflammatory comorbidities in HIV infected individuals.