Gut Microbiota-Mediated Inflammatory Interactions Between Alcohol Use Disorders and HIV Infection

Summary

Alcohol use disorder (AUD) has been associated with high prevalence of inflammation-associated co-morbidities in people living with HIV even those receiving effective antiretroviral therapy (ART). Our preliminary data support a model in which the combined insult of AUD and HIV on the gut, specifically on the microbiota and intestinal barrier integrity, exacerbates inflammation. Our preliminary data using intestinal organoids also suggest a potential mechanism for AUD-mediated changes in the gut barrier function during HIV; the intestines of HIV+ individuals have low resilience to alcohol induced intestinal barrier disruption caused by high levels of oxidative stress. Finally, our preliminary data also suggest a potential approach to enhance the integrity of the intestinal barrier and reduce gut derived inflammation in people living with HIV with/without AUD- short chain fatty acid prebiotics. These prebiotics prevent alcohol mediated adverse effects on the intestinal barrier and inflammation by preventing oxidative stress. These prebiotics are safe and decrease gut inflammation in humans. 20 HIV+ ART+ (10 AUD- and 10 AUD +), will be recruited for a prebiotic intervention. This is a proof-of-concept observational study to establish a causal link between microbiota-gut and HIV pathology during ART by asking whether modifying microbiota and gut milieu impacts intestinal barrier function, systemic inflammation, and brain pathology in HIV+ people. Participants will have two study visits, where stool collection and blood draw will be collected, as well as questionnaires. These participants are part of the larger observation study (n=160), which will test the hypothesis that intestines from HIV+ individuals have lower resilience to alcohol mediated gut barrier disruption than intestines from HIV-negative controls. We will recruit the following groups of participants: HIV+ ART+ AUD-; HIV+ ART+ AUD+; HIV- AUD- ; HIV- AUD+. Blood, urine, stool, and intestinal biopsies will be collected from participants to compare intestinal barrier integrity, system and gut inflammation, immune activation, oxidative stress, microbiome/metabolome. and HIV reservois. Second, lleal/colonic organoids from HIV- and HIV ART+ individuals will be generated to examine their resilience to alcohol-induced intestinal barrier disruption.

Eligibility

Age range

45–80 years

Sex

All

Healthy volunteers

Yes

Interventions

• Dietary Supplement
  10 day prebiotic consumption

  20 HIV-infected ART-suppressed individuals will be provided a with commercially available prebiotic (FOS) for 10 days. Participants will be instructed to consume the prebiotic daily during the first three days and then twice daily for an additional seven days. Participants will be instructed to consume the powder in the morning on the first three days, then in the morning and afternoon for the following week. Each participant will have a baseline visit and a follow up visit after 10 days of the FOS intervention. Blood and stool will be collected at both visits.

Location