Altered gut microbiota correlate with different immune response to HAART in HIV-infected individuals

Abstract

Background: Although gut microbiota dysbiosis has recently been reported in HIV infected individuals, the relationship between the gut microbiota and immune activation in patients with a different immune response to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (Health Control) and 58 HIV-infected individuals which included 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and <200 CD4+ T-cell counts/µl after 2 years of HIV-1 viral suppression respectively) without comorbidities. Results: Metagenome sequencing revealed that the gut microbiota dysbiosis could not be recovered completely in HIV-infected immunological responders and immunological non-responders although with long-term suppressive antiretroviral treatment. At the 97% similarity level, Fusobacterium, Ruminococcus_gnavus and Megamonas were more abundant, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacteriumrectale and Roseburia were more depleted in the IR and INR groups than that in the health control. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8+CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundance of genus Ruminococcus and Fusobacterium, but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than that in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8+CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8+CD57+ T-cell counts. Conclusions: Gut microbiota dysbiosis may be one of the factors contributing to different immune response to HAART. Fusobacterium, Alistipes, Ruminococcaceae, Faecalibacterium, Escherichia-Shigella, Roseburia and Blautia maybe the major genus contributed to different immune response in immunodiscordant and immunoconcordant patients on long-term suppressive ART. Blautia and Roseburia might be associated with treatment outcome.