Journal
VIRUSES-BASEL
Volume 13, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/v13081567
Keywords
SIV; ART; macaques; microbiome; IFABP; sCD14; LBP
Categories
Funding
- NIGMS, NIH grant [P20GM103629]
- NIH [P51OD011104]
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Chronic HIV infection and ART treatment can lead to gut dysbiosis, characterized by changes in the composition of the gut microbiome and an increase in inflammatory markers. The loss of specific beneficial bacteria such as Faecalibacterium prausnitzii and Treponema succinifaciens may contribute to gut inflammation and metabolic alterations despite effective viral suppression. Understanding the correlation between anti-inflammatory bacteria and healthy gut barrier functions during long-term ART may impact the management of inflammatory comorbidities in HIV-infected individuals.
Gut dysbiosis is a common feature associated with the chronic inflammation of HIV infection. Toward understanding the interplay of chronic treated HIV infection, dysbiosis, and systemic inflammation, we investigated longitudinal fecal microbiome changes and plasma inflammatory markers in the nonhuman primate model. Following simian immunodeficiency virus (SIV) infection in rhesus macaques, significant changes were observed in several members of the phylum Firmicutes along with an 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, however, the specific loss of Faecalibacterium prausnitzii and Treponema succinifaciens significantly correlated with an increase in plasma inflammatory cytokines including IL-6, G-CSF, I-TAC, and MIG. Further, the loss of T. succinifaciens correlated with an increase in circulating biomarkers of gut epithelial 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. A better understanding of the correlations between the anti-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.
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