Dietary and microbial influences on intestinal immune activation in treated people living with HIV and a Th17-deficient mouse model.

Abstract

The objectives of this work were to analyze intestinal microbiota, barrier integrity, and inflammatory/immune markers in long-term virally suppressed people living with human immunodeficiency virus (HIV) (PLWH) with high CD4+ T-cell counts, and to evaluate the influence of a Mediterranean diet. Additionally, these parameters will be analyzed in Batf-/- mice, which lack a gene crucial for Th17 lymphocytes differentiation, to explore the effect of pre- and probiotic on gut microbiota and immune function. Forty PLWH with undetectable HIV load for a median of 121 months and 20 healthy controls (HC) were included. Diversity and composition of intestinal microbiota, markers of barrier integrity, bacterial translocation and inflammatory/immune activation, and adherence to Mediterranean diet were analyzed. These parameters were also analyzed in Batf-/- and wild-type (WT) mice before and after diet supplementation with prebiotic (digestion-resistant maltodextrin) or commercial multi-strain probiotic. PLWH and HC exhibited comparable alpha and beta diversities in their intestinal microbiota, with significantly lower abundances of Akkermansia and Paraprevotella in PLWH. High adherence to a Mediterranean diet was associated with an increase in the alpha diversity of the intestinal microbiota. Measures of barrier integrity, bacterial translocation, and inflammatory/immune activation were similar regardless of diet adherence. Batf-/- mice had lower Th17 lymphocyte counts and higher inflammatory/immune activation than WT mice. Probiotic supplementation, but not prebiotic, induced an enrichment of Candidatus Arthromitus, a segmented filamentous bacteria, together with a significant increase in the Th17 lymphocyte count and a decrease in inflammatory/immune activation. In conclusion, treated PLWH with controlled HIV replication shows a lower abundance in the gut of bacteria that have been previously suggested to be involved in promoting intestinal barrier integrity (Akkermansia or Paraprevotella). High adherence to Mediterranean diet favors an enrichment of intestinal microbiota. In Batf-/- mice, probiotic supplementation is associated with changes in specific genera implicated in the differentiation of Th17 lymphocytes.