PROJECT SUMMARY
One in four people with HIV (PWH) report hazardous drinking [i.e., >7 (14) drinks per week or >3 (4) drinks per
occasion for women (men)]. Of this population, 65% report depressive symptoms or smoking, and 21% report
all three- constituting an alcohol-associated syndemic (i.e., interaction of 2+ conditions to increase risk for poor
outcomes). This syndemic is associated with increased risk of incident cardiovascular disease (CVD). The
gastrointestinal (GI) microbiome is a strong candidate mechanistic pathway for the syndemic-related excess
CVD risk, through GI dysbiosis, microbial translocation (MT), and systemic inflammation. Dysbiosis is
characterized as a decrease in beneficial bacteria and increase in pro-inflammatory bacteria. GI dysbiosis
leads to MT, in which tight junctions of the GI lumen are compromised, driving systemic inflammation- a
leading cause of CVD. HIV, hazardous drinking, smoking and depression are independently associated with GI
dysbiosis, MT and inflammation. Beneficial butyrate producing bacteria, which downregulate pro-inflammatory
mediators, are depleted in hazardous drinking PWH. In humans with alcohol use disorder, probiotic use
attenuates MT and inflammation. Among PWH, probiotic (e.g., butyrate producing bacteria) with prebiotic use
(nutrients for bacterial growth), a combination known as “synbiotic”, favorably alters the GI microbiome within
4-16 weeks. We hypothesize that the alcohol-associated syndemic is associated with GI dysbiosis and
subsequent CVD related biomarkers and that targeted supplementation may restore GI microbiome
homeostasis and reduce inflammation. With a transdisciplinary mentoring panel at Vanderbilt University
Medical Center (VUMC), my career development plan will advance skills in clinical investigation of alcohol
syndemic phenotypes; microbiome structure, function, diversity and immunology; clinical & translational
research; and primary data collection, responsible conduct of research, and leadership. Aim 1 will identify
changes in the GI microbiome among PWH with the alcohol-associated syndemic over 12 months, Aim 2 will
determine changes in biomarker profiles related to GI permeability, MT, and inflammation among PWH with the
alcohol-associated syndemic over 12 months, and Aim 3 will evaluate the a) feasibility of administering a
butyrate supplement pill followed by a multi-strain synbiotic (prebiotic + probiotic) pill and b) treatment effects
on GI microbiome structures and CVD-related biomarkers among PWH with the alcohol-associated syndemic
(n=40). Aims 1 & 2 leverage secondary data from an NIAAA-funded microbiome study of 200 PWH with
existing GI microbiome data, sero-biomarker data, and validated self-reports of alcohol use, smoking, and
depressive symptoms. Aim 3 utilizes the infrastructure of the Tennessee Center for AIDS Research at VUMC,
which has a strong record of supporting Early Career Faculty. This award will facilitate my transition to an
independent investigator with expertise in alcohol/CVD epidemiology, microbiome structure and function, and
clinical trial development among PWH, and will also provide informative data for an R01 application.