The Brain, the Bug, and the Binge: the Interplay Between Binge Drinking, Gut Microbiota, and Brain Functioning

Adolescence and youth are periods of significant maturational changes which seems to involve greater susceptibility to disruptive events in the brain such as binge drinking (BD). This prevalent pattern of consumption -characterized by repeated alcohol intoxications- is of special concern, as it has been associated with major neurocognitive impairments in the young brain.

Recent studies indicate that alcohol may disrupt the gut microbiota (GM) and that these disruptions may lead to impairments in brain and behavior. Also, interventions with psychobiotics have been shown to result in reductions in alcohol-induced damage and in improvements on cognitive and brain functioning.

Thus, the present proposal will explore the effects of BD on GM. Additionally, a GM intervention with psychobiotics both in-vivo and in-vitro, will determine whether improvements in GM composition/function may lead to reductions of alcohol-induced brain damage in BD-population, a barely unexplored research field with major clinical applications.

The present study protocol aims to determine the interaction between alcohol consumption, brain function and gut microbiota through several levels of analysis, including techniques to measure brain activity (i.e., magnetic resonance imaging), paradigms to measure cognitive performance, collection of stool and blood samples, and questionnaires. Additionally, this study will investigate the relationship between alcohol, brain activity and gut microbiota and how this can be modified through our diet. The sample will be composed by a cohort of young college students (18-23 years) from the University of Minho (UM; Braga, Portugal) selected according to their drinking patterns. Eighty-two participants will be recruited from UM: 36 non/low-drinkers and 46 binge drinkers (BDs) matched for age and gender. Recruitment will be carried out through an online survey broadcasted using the institutional email. This survey will include a simple sociodemographic section and items regarding the use of alcohol (Alcohol Use Disorder Identification Test - AUDIT, frequency of alcohol consumption, number of drinks consumed on each day of the past week, speed of drinking, etc.). After sample selection, participants will be submitted to the following steps: (1) clinical interview - addresses questions relating to psychological, medical, personal and family history, including questions related to history of alcohol and drug use and some specific questionnaires relating to substance use, as well as those related to physical and psychological symptoms, and personality; (2) neuroimaging assessment - will consist of a structural and functional magnetic resonance imaging (fMRI) at the Hospital de Guimarães (Portugal), while performing different cognitive tasks; (3) evaluation of some microorganisms residing in the gut and certain inflammatory markers - each participant will be asked to collect stool and blood samples; (4) evaluation of the potential of an intervention with psychobiotics.

Thus, this protocol involves the following phases:

1. pre-intervention, consisting of the assessment of the variables of interest to the study by means of a clinical interview, neuropsychological testing, collection of stool and blood samples, and MRI recordings.
2. intervention (only for BDs), consisting of taking a prebiotic for 6 weeks. Depending on the group to which they will be allocated, the participant will take one of two types of fiber: a fiber with benefits for intestinal bacteria (inulin) or a similar fiber with no specific benefits for the intestinal microbiome (maltodextrin). Each participant will not know which group they belong to in order not to bias the results of the study according to scientific standards.
3. post-intervention, which will consist in the re-assessment of the variables previously assessed in the pre-intervention phase.
4. follow-up, consisting of the assessment and monitoring of levels of alcohol consumption and craving during the 3 months following the intervention phase.

Eligibility Criteria:
Inclusion Criteria:

* College students whose native language is Portuguese;
* Age 18-23 years;
* Binge Drinkers: report (i) drinking 4 (for women)/5 (for men) or more drinks on one occasion at least once a month, (ii) drinking at a speed of at least two drinks per hour during these episodes (which brings blood alcohol concentration to 0.08 g/dL or above), and (iii) having an AUDIT score \< 20.
* Non/Low-Drinkers: report (i) never drinking 4/5 or more drinks on one occasion and (ii) having an AUDIT score ≤ 4.

Exclusion Criteria:

* Use of illicit drugs as determined by the Drug Use Disorders Identification Test (DUDIT);
* Alcohol abuse (i.e., AUDIT ≥ 20);
* Personal history of psychopathological disorders (according to DSM-V criteria);
* History of traumatic brain injury or neurological disorder;
* Family history (mother/father) of alcoholism diagnosis of substance abuse;
* Occurrence of one or more episodes of loss of consciousness for more than 30 minutes;
* Non-corrected sensory deficits;
* Diagnosis of any gut disease/problems or other medical conditions: inflammatory bowel disease, irritable bowel syndrome, Crohn's Disease, celiac disease, lactose intolerance, autoimmune disease;
* Consumption of medical drugs with psychoactive effects (e.g., antidepressants, anxiolytics or benzodiazepines) during the 4 weeks prior to the experiment;
* Use of any of the following drugs in the last 4 weeks: laxatives, antibiotics, anticoagulants, non-steroidal anti-inflammatory drugs, analgesics, corticosteroids;
* No type of metal object implanted in the body, especially in the head (orthodontic appliances are not excluded).