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

Официальное название

The Brain, the Bug, and the Binge: a Double-blind, Randomized Controlled Trial Investigating the Interplay Between Binge Drinking, Gut Microbiota and Brain Functioning

Обзор

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.

Подробное описание

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.

Вмешательства

• Пищевая добавка Inulin Intervention
  For 6 weeks, 23 binge drinkers will be given a daily dose (divided into three times a day) of 15g of a dietary fiber with benefits for intestinal bacteria (inulin).
• Пищевая добавка Maltodextrin Intervention
  For 6 weeks, 23 binge drinkers will be given a daily dose (divided into three times a day) of 15g of dietary fiber with no specific benefits for the intestinal microbiome (maltodextrin).

Первичные конечные точки

• Fecal Microbiota - Species Richness [Срок оценки: At baseline (pre-intervention)]
• Fecal Microbiota - Species Richness [Срок оценки: Immediately post-intervention.]
• Fecal Microbiota - Species Diversity [Срок оценки: At baseline (pre-intervention)]
• Fecal Microbiota - Species Diversity [Срок оценки: Immediately post-intervention]
• Fecal Microbiota - Quantification of SCFAs levels [Срок оценки: At baseline (pre-intervention)]
• Fecal Microbiota - Quantification of SCFAs levels [Срок оценки: Immediately post-intervention.]

Вторичные конечные точки (12)

• Alcohol Consumption - Drinking pattern [Срок оценки: Immediately post-intervention]
• Alcohol Consumption - Drinking pattern [Срок оценки: 3 months post-intervention]
• Alcohol Craving - Short-term acute craving [Срок оценки: Immediately post-intervention]
• Alcohol Craving - Short-term acute craving [Срок оценки: 3 months post-intervention]
• Neuropsychological Evaluation - Memory [Срок оценки: At baseline (pre-intervention)]
• Neuropsychological Evaluation - Memory [Срок оценки: Immediately post-intervention]
• Neuropsychological Evaluation - Emotion and Social Cognition [Срок оценки: At baseline (pre-intervention)]
• Neuropsychological Evaluation - Emotion and Social Cognition [Срок оценки: Immediately post-intervention]
• Neuropsychological Evaluation - Executive Function [Срок оценки: At baseline (pre-intervention)]
• Neuropsychological Evaluation - Executive Function [Срок оценки: Immediately post-intervention]
• Alcohol Cue Reactivity - Emotional measures [Срок оценки: At baseline (pre-intervention)]
• Alcohol Cue Reactivity - Emotional measures [Срок оценки: Immediately post-intervention.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

Португалия · 1 центр

• Psychological Neuroscience Laboratory, Psychology Research Center, University of Minho — Braga

Публикации

• Carbia C, Bastiaanssen TFS, Iannone LF, Garcia-Cabrerizo R, Boscaini S, Berding K, Strain CR, Clarke G, Stanton C, Dinan TG, Cryan JF. The Microbiome-Gut-Brain axis regulates social cognition & craving in young binge drinkers. EBioMedicine. 2023 Mar;89:104442. doi: 10.1016/j.ebiom.2023.104442. Epub 2023 Feb 2. PMID 36739238
• Sousa SS, Sampaio A, Marques P, Lopez-Caneda E, Goncalves OF, Crego A. Functional and structural connectivity of the executive control network in college binge drinkers. Addict Behav. 2019 Dec;99:106009. doi: 10.1016/j.addbeh.2019.05.033. Epub 2019 Jun 3. PMID 31487578
• Almeida-Antunes N, Crego A, Carbia C, Sousa SS, Rodrigues R, Sampaio A, Lopez-Caneda E. Electroencephalographic signatures of the binge drinking pattern during adolescence and young adulthood: A PRISMA-driven systematic review. Neuroimage Clin. 2021;29:102537. doi: 10.1016/j.nicl.2020.102537. Epub 2020 Dec 17. PMID 33418172
• White A, Hingson R. The burden of alcohol use: excessive alcohol consumption and related consequences among college students. Alcohol Res. 2013;35(2):201-18. doi: 10.35946/arcr.v35.2.11. PMID 24881329
• Carbia C, Lannoy S, Maurage P, Lopez-Caneda E, O'Riordan KJ, Dinan TG, Cryan JF. A biological framework for emotional dysregulation in alcohol misuse: from gut to brain. Mol Psychiatry. 2021 Apr;26(4):1098-1118. doi: 10.1038/s41380-020-00970-6. Epub 2020 Dec 7. PMID 33288871
• Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012 Oct;13(10):701-12. doi: 10.1038/nrn3346. Epub 2012 Sep 12. PMID 22968153
• Cryan JF, O'Riordan KJ, Sandhu K, Peterson V, Dinan TG. The gut microbiome in neurological disorders. Lancet Neurol. 2020 Feb;19(2):179-194. doi: 10.1016/S1474-4422(19)30356-4. Epub 2019 Nov 18. PMID 31753762
• Leclercq S, Matamoros S, Cani PD, Neyrinck AM, Jamar F, Starkel P, Windey K, Tremaroli V, Backhed F, Verbeke K, de Timary P, Delzenne NM. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4485-93. doi: 10.1073/pnas.1415174111. Epub 2014 Oct 6. PMID 25288760

Идентификаторы

NCT: NCT05946083 · CEICSH 078/2022 · PTDC/PSI-ESP/1243/2021

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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