Effect of Obesity on the Gut Microbiome and Inflammatory Biomarkers 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 uncontrolled 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 bacteria and 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, suggest that microbiome changes and systemic inflammation may not directly correlate during SIV infection and ART.