The Brain, the Bugs, and the Binge: A Protocol Intervention Examining the Interplay Between Binge drinking, Gut Microbiota, and Brain Functioning
Authors: Prata-Martins Diogo , Nobre Clarisse , Almeida-Antunes Natália , Azevedo Pedro , Sousa Sónia S. , Crego Alberto , Cryan John F. , Sampaio Adriana , Carbia Carina , López-Caneda Eduardo 
Published: December 2024

AbstractBackgroundAdolescence and youth are periods of significant maturational changes which seem to involve greater susceptibility to disruptive events in the brain such as binge drinking (BD). This pattern -characterized by repeated alcohol intoxications- is of special concern, as it has been associated with significant alterations in the young brain. Recent research indicates that alcohol may also induce changes in gut microbiota composition and that these disturbances can lead to impairments in the brain and behaviour. Additionally, there is evidence suggesting that microbiota-targeted interventions (psychobiotics) may have a beneficial impact on mitigating alcohol-induced damage in chronic alcoholics, while also potentially influencing cognitive/brain functioning. However, this triadic relationship between BD, gut microbiota, and brain structure/functioning as well as the therapeutic potential of gut microbiota-targeted interventions in youths with a BD pattern remains largely unexplored.MethodThis double-blind, parallel, randomized controlled study (registered in the clinical trials database;NCT05946083) aims to evaluate whether a BD pattern may disrupt gut microbiota balance in young college students. Furthermore, it seeks to determine whether alcohol-induced alterations in the microbial composition and functions are associated with immune, cognitive, neurostructural, and neurofunctional impairments. For this purpose, 82 college students (36 non/low drinkers and 46 binge drinkers [BDs]), matched for age and gender, will be recruited. During the pre-intervention phase, all participants will undergo comprehensive assessments, including microbiota and inflammatory profiling, neuropsychological testing, and evaluations of brain structure and function using magnetic resonance imaging. Subsequently, only BDs will proceed to the intervention phase, which involves a 6-week regimen of either a prebiotic (inulin) or placebo (maltodextrin). Following the intervention, the baseline variables will be re-evaluated and, over the subsequent 3 months, levels of craving and alcohol consumption will be monitored.DiscussionThis will, to our knowledge, be the first study to assess the potential relationship between gut microbiota and neurocognitive functioning in young BDs. The administration of psychobiotics is expected to promote the restoration of gut microbiota, thereby decreasing pro-inflammatory responses and mitigating alcohol-induced brain disruptions. This reduction in the detrimental effects of alcohol is anticipated to lead to cognitive enhancements and neurofunctional changes. Collectively, these findings might have major implications for understanding and treating alcohol misuse, potentially leading to new therapeutic strategies targeting the gut-brain axis to alleviate some of the detrimental effects associated with excessive alcohol use.Clinical Trial registrationClinicalTrials.gov, ID:NCT05946083.Strengths and LimitationsThe present protocol has several notable strengths such as:Novel insights into the influence of alcohol on the microbiota-gut-brain axis. This study is the first to date to examine the interaction between binge drinking, gut microbiota, and brain function.Breakthrough therapeutic impact. This is a double-blind, parallel, randomized controlled trial focuses on a relevant population group -young college students- who are particularly vulnerable to harmful alcohol consumption patterns. By exploring prebiotic interventions, the study introduces innovative strategies to mitigate the neurotoxic effects of alcohol, opening new ways for therapeutic approaches in mental health and preventive medicine.Multidisciplinary approach. By integrating analyses of gut microbiota, inflammatory profile, and neuropsychological and neurostructural assessments, this study offers a comprehensive investigation of the impact of binge drinking on the microbiota-gut-brain axis.However, there are limitations to consider, including:Potential for low adherence: Young binge drinkers may have low adherence to a six-week intervention, which could compromise data validity.Uncontrolled external factors: Factors such as diet, exercise, sleep, and stress, which can affect both microbiota and brain function, are not fully controlled. This could hinder the interpretation of the results and mask the effects of the intervention.