Association between CD4+ T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders

BackgroundCD4(+) T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4(+) T cell counts in HIV-infected individuals. However, the association between CD4(+) T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4(+) T cell counts<500 cells/mu L) from Yunnan Province, China, has not been previously investigated. MethodsTo address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count>200 cells/mu L group and CD4 count<200 cells/mu L group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8(+) T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups.ResultsCompared to INRs with CD4 count>200 cells/mu L, those with CD4 count<200 cells/mu L had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-alpha, interferon-gamma-inducible protein (IP)-10 and interleukin (IL)-1 alpha. Ruminococcaceae was less abundant in the CD4 count<200 cells/mu L group than in the CD4 count>200 cells/mu L group, and difference in alpha diversity was observed between the two groups. Moreover, CD4(+) T cell counts were negatively associated with TNF-alpha and IL-1 alpha levels and positively associated with the relative abundance of Ruminococcaceae.ConclusionsOur study demonstrated that lower CD4(+) T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4(+) T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.

Automated summary

Our study revealed that lower CD4(+) T cell counts in immunological non-responders (INRs) with HIV infection are associated with reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. This suggests that interventions targeting the gut microbiota to increase CD4(+) T cell counts could be a potential strategy for promoting immune reconstitution in HIV-infected INRs.