Impact of obesity on the gut microbiome and inflammatory markers during SIV infection and antiretroviral therapy.

Dysbiosis and impaired gut barrier integrity contribute to chronic immune activation associated with both obesity and HIV infection. Given the increased incidence of obesity in people living with HIV, we explored the impact of obesity on the gut microbiome and microbial translocation (MT) biomarkers during HIV infection and antiretroviral therapy (ART). Lean and obese rhesus macaques were infected with simian immunodeficiency virus (SIV) and subsequently treated with ART. Obese animals exhibited higher initial MT and inflammation biomarkers that remained constant throughout the study, while lean animals exhibited significant increases in these biomarkers that approached levels observed in obese animals. Lean and obese animals exhibited similar observed amplicon sequence variants (ASVs) at baseline, with obese animals exhibiting reduced ASVs during acute SIV infection that rebounded after 39 weeks of ART treatment. Beta diversity differed between groups and was longitudinally altered in obese animals. Obese animals exhibited significant changes in differential abundance in four times as many bacterial genera compared to lean animals. Our finding that MT and inflammation biomarkers significantly changed in lean animals, while obese animals exhibited significant alterations in microbial diversity, suggests that microbiome changes and systemic inflammation may not directly correlate during SIV infection and ART.IMPORTANCEIn response to the obesity epidemic, the incidence of obesity at the time of HIV diagnosis has increased, but the impacts of pre-existing obesity throughout antiretroviral therapy (ART)-treated HIV infection remain underexplored. Both obesity and HIV infection have been associated with inflammatory and microbiome perturbations. Here, we utilized 16S rRNA amplicon sequencing and quantification of systemic inflammation markers to longitudinally characterize the fecal microbiome and systemic inflammation in lean and obese rhesus macaques throughout simian immunodeficiency virus (SIV) infection and ART. Lean animals exhibited marked increases in inflammatory markers corresponding with minimal gut microbiome perturbations throughout SIV infection and ART. In contrast, obese animals exhibited minimal inflammatory alterations corresponding with distinct differentially abundant fecal bacterial taxa throughout SIV infection and ART. Our results provide crucial insights into the interactions between pre-existing obesity, inflammation, and the gut microbiome that may aid in developing therapeutic strategies for obese individuals diagnosed with HIV.