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

Abstract

Background CD4+ 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/μL) from Yunnan Province, China, has not been previously investigated. Methods To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/μL group and CD4 count < 200 cells/μL 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. Results Compared to INRs with CD4 count > 200 cells/μL, those with CD4 count < 200 cells/μL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/μL group than in the CD4 count > 200 cells/μL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4+ T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae. Conclusions Our 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.

Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus

“…In this respect, we found a weak negative correlation between plasma Pseudomonas spp. and CD4 þ T-cell counts in HEI, whereas, in disagreement with others [38][39][40][41], the fecal microbiome did not associate with immune reconstitution.…”

Alterations in circulating markers in HIV/AIDS patients with poor immune reconstitution: Novel insights from microbial translocation and innate immunity

“…Danfeng Lu et al. reported lower levels of luminococci in INRs than in IRs and observed differences in alpha diversity between the two groups ( 27 ). Judit Villar-García et al.…”

“…Further, lower CD4 + T cell counts in INRs were linked to decreased intestinal flora abundance and higher serum pro-inflammatory cytokines. TNF-α and IL-1α levels were also adversely correlated with CD4 + T cell counts ( 27 ).…”

Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study

“…We also evaluated whether a skewed distribution of HIVrelated variables or metabolic comorbidities between the study groups might have affected our results. Among HIV-specific factors, for example, low CD4 þ count has been associated with reduced microbial diversity [22,23]. However, the study groups were comparable regarding all HIV-specific variables (CD4 þ count, time since diagnosis of HIV, duration of ART, distribution of different PIs).…”