Exploring Gut-Brain and Brain-Gut Interactions in Alcohol Use Disorder Via Microbiota Investigations: A Pilot Study

Objective:

An increasing body of preclinical literature suggests a role of the gut microbiota in a wide
range of medical disorders, including neuropsychiatric diseases like autism, anxiety, and
depression. Preliminary studies have reported alterations in microbiota composition,
inflammation, and intestinal permeability in alcohol-dependent patients. However, there is
little research on the association between these alterations and behavioral outcomes
associated with alcohol use disorder (AUD), such as alcohol craving and drinking. The main
goal is to investigate gut microbiota differences in current drinking versus abstinent
individuals with AUD, and whether microbial profiles are correlated with alcohol cue-induced
craving. Finally, another goal of this project will be to conduct preliminary translational
bed-to-bench work using rodent models of excessive alcohol use via collaborations with basic
science laboratories.

Study population:

Alcohol use disorder participants (current drinkers and abstinent) and healthy controls.

Study Design:

Between subject, observational study

Outcome measures:

We will compare the gut microbiota of AUD participants who have been abstinent to that of
current drinkers. In addition, we will further compare the gut microbiota of these two groups
to a third group of healthy controls with no prior or current diagnosis of AUD. The secondary
aim of this study is to examine whether the overall microbial community composition, function
and individual taxa correlate with alcohol cue-induced craving.

- INCLUSION CRITERIA:

- Male or female individuals 21-70 years old (inclusive)

Specific For Abstinent Group; AB

- Current Alcohol Use Disorder (AUD) by DSM-5 criteria

- Being alcohol abstinent for at least 4 weeks, with a minimum of 2 weeks in a
non-protective environment at the time of study screening.

Specific For Current Drinking Group; CD

- Current Alcohol Use Disorder (AUD) by DSM-5 criteria

- Participants not seeking treatment for their alcohol use will be included.

- Satisfying heavy drinking criteria during the 4-weeks prior to screening (i.e., for
men, >14 standard drinks in any one week or greater than or equal to 4 drinks per
occasion at least once per month over the past 30 days; for women, >7 drinks per week
or greater than or equal to 3 drinks per occasion at least at least once per month
over the past 30 days) and any drinking during the 2-day prior to signing the
study-specific consent.

Specific For Healthy Control Group; HC

- No current or past diagnostic of AUD by DSM-5 criteria

- Moderate alcohol consumers: i.e., up to 1 drink per day on average and not meeting
NIAAA criteria for:

- -heavy (i.e., for men, >14 standard drinks in any one week or greater than or equal to
4 drinks per occasion at least once per month over the past 30 days; for women, >7
drinks per week or greater than or equal to 3 drinks per occasion at least at least
once per month over the past 30 days)

- -or binge drinking (i.e., drinking 5 or more standard drinks on the same occasion on
at least 1 day in the past 30 days for both male and female)

If any answer is No , subject may not be enrolled.

EXCLUSION CRITERIA:

Exclusion - All Participants (at the time subject are evaluated for this protocol)

- Current pregnancy or lactation

- Positive Urine Drug Test for illegal drugs

- Body Mass Index (BMI) less than or equal to 18.5 kg/m(2) or BMI greater than or equal
to 40 kg/m(2)

- Presence of active implantable electronic devices (e.g., defribillators, pumps,
pacemakers)

- Current medical history of the following medical conditions:

--diabetes; chronic gut inflammatory diseases; GI or any other type of cancer; short
bowel syndrome; conditions requiring parenteral nutrition;

- Diarrhea or other symptoms of possible enteritis in the past 7 days (self-reported)

- Recent history of sigmoidoscopy or colonoscopy (past 30 days)

- Current use (past 90 days) of the following medications:

--oral antimicrobials (specifcally: antiviral, antifungal, or antibiotics);
prebiotics; probiotics; laxatives; antispasmodic drugs; oral, IM or IV steroids

- Any other reason or clinical condition that the PI, or Medical Advisory Investigator
(MAI) considers unsafe or not in the best interest of the study research integrity

If any answer is Yes , subject may not be enrolled.