Association Between Gut Microbiota and CD4 Recovery in HIV-1 Infected Patients

Abstract

Composition of the gut microbiota has been linked with human immunedeficiency virus (HIV)-infected patients on antiretroviral therapy (ART). Evidence suggests that ART-treated patients with poor CD4+ T-cell recovery have higher levels of microbial translocation and immune activation. However, the association of the gut microbiota and immune recovery remains unclear. We performed a cross-sectional study on 30 healthy controls (HC) and 61 HIV-infected individuals, including 15 immunological ART responders (IRs), 20 immunological ART non-responders (INRs) and 26 untreated individuals (VU). IR and INR groups were classified by CD4+ T-cell counts of ≥350 cells/mm3 and <350 cells/mm3 after 2 years of ART, respectively. Each subject’s gut microbiota composition was analyzed by metagenomics sequencing. Levels of CD4+ T cells, CD8+HLA-DR+ T cells and CD8+CD38+ T cells were measured by flow cytometry. We identified more Prevotella and fewer Bacteroides in HIV-infected individuals than in HC. Patients in INR group were enriched with Faecalibacterium prausnitzii, unclassified Subdoligranulum sp. and Coprococcus comes when compared with those in IR group. F. prausnitzii and unclassified Subdoligranulum sp. were overrepresented in individuals in VU group with CD4+ T-cell counts <350 cells/mm3. Moreover, we found that the relative abundance of unclassified Subdoligranulum sp. and C. comes were positively correlated with CD8+HLA-DR+ T-cell count and CD8+HLA-DR+/CD8+ percentage. Our study has shown that gut microbiota changes were associated with CD4+ T-cell counts and immune activation in HIV-infected subjects. Interventions to reverse gut dysbiosis and inhibit immune activation could be a new strategy for improving immune reconstitution of HIV-1-infected individuals.

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…This study suggests a pivotal role of microbiota diversity in host immune homeostasis . Several studies have found that HIV‐1‐infected individuals have a significant increase in the relative abundance of the Gram‐negative bacteria Prevotella in conjunction with a decrease in Bacteroides abundance compared to those in healthy controls . A study by Kaur et al.…”

“…Moreover, the relative abundances of unclassified Subdoligranulum sp . and C. comes were positively correlated with CD8 + T‐cell activation and inversely associated with CD4 + T‐cell counts . A study by Pérez‐Santiago et al.…”

“…Bacteroides abundance compared to those in healthy controls. [126][127][128][129][130] A study by Kaur showed that long-term use of proton pump inhibitors was associated with increased microbial translocation, innate immune activation, and poor immune reconstitution in HIV-1-infected individuals on suppressive ART. 135…”

Antiviral Activity of Fecal Water Samples from HIV-1 Infected Subjects Treated with a Specific Probiotic Formulation

“…Gut-associated lymphoid tissue (GALT) is the largest Human Immunodeficiency Virus type-1 (HIV-1) replication site and reservoir [1][2][3][4]. Destruction of Th17 + and Th22 + CD4 + T cells in GALT during early-stages of HIV-1 infection promotes a decline in the immune system and mechanical barrier functions of the gut mucosa [5][6][7][8][9].…”

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

“…However, these studies did not consider the immune response to ART and pay little attention to China [7]. Recently, there are two studies reported that gut microbiota were associated with CD4 recovery in HIV-infected patients [8,9]. The microbiome of chronic HIV infected individuals were studied in China, however, these patients had heterogeneous HIV progression and immune response to ART [10,11].…”