Gut Microbiota-Mediated Inflammatory Interactions Between Alcohol Use Disorders and HIV Infection
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.
• HIV+ Group :
• Age 45 to 80 years
• Infection with HIV-1, as documented by a licensed ELISA and confirmed by a Western blot or HIV-1 RNA
• On ART for at least 12 months
• No change in ART for at least three months
• CD4+ T cell count of 350 cells/µl
• Plasma HIV-1 RNA level consistently below the limit of detection of commercial ultrasensitive assays for at least six months before study entry.
• Ability and willingness to provide informed consent
• HIV Negative Group:
• Age 45 to 80 years
• Matched to the HIV+ ART-treated group (age (+/- 5 years), gender, ethnicity, sexual orientation, smoking, and body mass index (+/-3)).
• Ability and willingness to provide informed consent