Effects of viremia and CD4 recovery on gut “microbiome-immunity” axis in treatment-naïve HIV-1-infected patients undergoing antiretroviral therapy
Edda Russo, Giulia Nannini, Gaetana Sterrantino, Seble Tekle Kiros, Vincenzo Di Pilato, Marco Coppi, Simone Baldi, Elena Niccolai, Federica Ricci, Matteo Ramazzotti, Marco Pallecchi, Filippo Lagi, Gian María Rossolini, Alessandro Bartoloni, Gianluca Bartolucci, Amedeo Amedei
Abstract
BACKGROUND: naïve patients before starting ART and after reaching virological suppression, after 24 wk of ART therapy. In addition, we compared the microbiota composition, microbial metabolites, and cytokine profile of patients with CD4/CD8 ratio < 1 (immunological non-responders [INRs]) and CD4/CD8 > 1 (immunological responders [IRs]), after 24 wk of ART therapy. AIM: naïve patients before starting ART and after reaching virological suppression (HIV RNA < 50 copies/mL) after 24 wk of ART. METHODS: naïve HIV-infected patients receiving ART (mainly based on integrase inhibitors). Fecal microbiota composition was assessed through next generation sequencing. In addition, a comprehensive analysis of a blood broad-spectrum cytokine panel was performed through a multiplex approach. At the same time, serum free fatty acid (FFA) and fecal short chain fatty acid levels were obtained through gas chromatography-mass spectrometry. RESULTS: in INRs. Simultaneously, fecal isobutyric, isovaleric, and 2-methylbutyric acids were also increased in INRs. CONCLUSION: Our results provided an additional perspective about the impact of HIV infection, ART, and immune recovery on the "microbiome-immunity axis" at the metabolism level. These factors can act as indicators of the active processes occurring in the gastrointestinal tract. Individuals with HIV-1 infection, before ART and after reaching virological suppression with 24 wk of ART, displayed a microbiota with unchanged overall bacterial diversity; moreover, their systemic inflammatory status seems not to be completely restored. In addition, we confirmed the role of the GM metabolites in immune reconstitution.