Compromised Intestinal Barrier Resilience to Disruption in People With HIV

Area of Science:

• Gastroenterology and Immunology
• HIV Pathogenesis and Comorbidities

Background:

• People with HIV (PWH) often suffer from chronic intestinal barrier dysfunction.
• This dysfunction is linked to persistent inflammation and associated health issues.
• The precise mechanisms driving this gut barrier impairment in PWH are not fully understood.

Purpose of the Study:

• To investigate the hypothesis that HIV compromises intestinal barrier resilience.
• To determine if HIV increases susceptibility to gut leakage when exposed to disruptors.
• To elucidate novel mechanisms of intestinal dysfunction in PWH.

Main Methods:

• Utilized intestinal organoids (colonoids and enteroids) derived from PWH and healthy controls.
• Assessed the impact of alcohol and inflammatory cytokines on the integrity of these organoids.
• Compared the resilience of organoids from PWH versus controls when challenged.

Main Results:

• Organoids derived from PWH demonstrated significantly reduced resilience to disruption compared to control organoids.
• This reduced resilience correlated with observed alterations in critical epithelial integrity pathways.
• Findings suggest a novel mechanism contributing to intestinal dysfunction in PWH.

Conclusions:

• Living with HIV impairs the intestinal barrier's ability to withstand injury.
• This compromised resilience increases the gut's susceptibility to leakage.
• The study reveals a new understanding of intestinal barrier dysfunction in PWH.