Background: Significant sex differences exist in regard to alcohol use disorder (AUD) and
alcoholic liver disease (ALD). To date, no studies have examined the brain-gut-microbiome
(BGM) axis (which is the relationship between the gut, brain, and the bacteria within the
gut) and sex-differences in AUD and ALD.
Aims: 1) Demonstrate baseline sex differences in the microbiome and metatranscriptome of AUD
and ALD and correlate those differences to severity, 2) determine if these baseline sex
differences predicts abstinence or ALD related outcomes, and 3) show how altering the
microbiome can decrease the severity of AUD and ALD in a sexdependent manner. Hypothesis: Our
project is aimed to explore the hypothesis that sex-related differences of the BGM axis in
AUD and ALD explains the variation in patient severity and outcome by sex, and that
alterations of the BGM axis can decrease the severity of AUD and ALD in a sex-dependent
manner.
Methods: A pilot randomized placebo (VSL#3 vs placebo) control trial will be performed in
patients with AUD and ALD for 6 months. Questionnaire data, clinical labs, serum, and feces
for shotgun metagenomics will be collected at baseline, 3-months, and 6-months.
Anticipated Results: Patients with severe AUD/ALD will have more microbes and microbial genes
associated with inflammation. These differences will predict outcomes at 6-months and that
changes of this baseline microbiome with VSL#3 will lead to more positive outcomes than
placebo, with men having greater benefit from VSL#3 than women.
Implications and Future Studies: The discovery of the mechanisms underlying sex-related
differences in AUD/ALD is needed for the development of personalized recommendations for
prevention and treatment in men and women