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

People living with HIV (PLWH) with long-term viral suppression showed comparable alpha and beta diversities in intestinal microbiota compared to healthy controls, but had significantly lower abundances of Akkermansia and Paraprevotella.

• 40 PLWH with undetectable HIV load for a median of 121 months and 20 healthy controls (HC) were included.
• Alpha and beta diversities were comparable between PLWH and HC.
• Akkermansia and Paraprevotella were significantly lower in abundance in PLWH compared to HC.
• Both Akkermansia and Paraprevotella have been previously suggested to be involved in promoting intestinal barrier integrity.

High adherence to a Mediterranean diet was associated with increased alpha diversity of the intestinal microbiota in PLWH.

• Adherence to Mediterranean diet was assessed in the 40 PLWH participants.
• High adherence to Mediterranean diet was associated with an increase in alpha diversity of intestinal microbiota.
• Measures of barrier integrity, bacterial translocation, and inflammatory/immune activation were similar regardless of diet adherence.
• Mediterranean diet adherence did not significantly affect markers of barrier integrity or immune activation despite microbiota diversity changes.

Batf-/- mice, which lack a gene crucial for Th17 lymphocyte differentiation, had lower Th17 lymphocyte counts and higher inflammatory/immune activation than wild-type mice.

• Batf-/- mice were used as a model of Th17 deficiency to explore the effect of pre- and probiotic supplementation on gut microbiota and immune function.
• Batf-/- mice showed lower Th17 lymphocyte counts compared to wild-type (WT) mice.
• Batf-/- mice exhibited higher inflammatory/immune activation than WT mice.
• This mouse model was used to explore the relationship between Th17 cells, gut microbiota, and intestinal immune activation relevant to HIV pathophysiology.

Probiotic supplementation, but not prebiotic supplementation, induced enrichment of Candidatus Arthromitus (a segmented filamentous bacteria) in Batf-/- mice, along with a significant increase in Th17 lymphocyte count and decrease in inflammatory/immune activation.

• The prebiotic used was digestion-resistant maltodextrin; the probiotic was a commercial multi-strain formulation.
• Probiotic supplementation led to enrichment of Candidatus Arthromitus, a segmented filamentous bacteria.
• Probiotic supplementation was associated with a significant increase in Th17 lymphocyte count in Batf-/- mice.
• Probiotic supplementation was associated with a decrease in inflammatory/immune activation in Batf-/- mice.
• Prebiotic supplementation did not produce these effects on Th17 counts or inflammatory activation.

Markers of intestinal barrier integrity and bacterial translocation were assessed in PLWH and were comparable to healthy controls after long-term viral suppression.

• Markers of barrier integrity, bacterial translocation, and inflammatory/immune activation were analyzed in PLWH and HC.
• These parameters were found to be similar between groups in the context of long-term virally suppressed PLWH with high CD4+ T-cell counts.
• The study population had undetectable HIV load for a median of 121 months, suggesting that long-term viral control may normalize some gut integrity parameters.