Compromised Intestinal Barrier Resilience to Disruption in People With HIV

Abstract People with HIV (PWH) experience chronic intestinal barrier dysfunction, which contributes to chronic inflammation and its comorbidities. The mechanisms underlying this phenomenon remain unclear. We hypothesize that living with HIV compromises the intestinal barrier's resilience to injurious agents, increasing susceptibility to leakage upon exposure to disruptors. Using intestinal organoids (colonoids and enteroids) derived from PWH and controls, we assessed the impact of alcohol and inflammatory cytokines on barrier integrity. Organoids from PWH exhibited reduced resilience to disruption compared to controls, correlating with alterations in pathways critical to epithelial integrity. These findings reveal a novel mechanism underlying intestinal dysfunction in PWH.