The Brain, the Bug, and the Binge: a Double-blind, Randomized Controlled Trial Investigating the Interplay Between Binge Drinking, Gut Microbiota and Brain Functioning
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Fecal Microbiota - Quantification of SCFAs levels
研究概览
简要总结
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.
详细描述
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:
- 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.
- 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.
- post-intervention, which will consist in the re-assessment of the variables previously assessed in the pre-intervention phase.
- follow-up, consisting of the assessment and monitoring of levels of alcohol consumption and craving during the 3 months following the intervention phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 23 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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 <
- •Non/Low-Drinkers: report (i) never drinking 4/5 or more drinks on one occasion and (ii) having an AUDIT score ≤ 4.
排除标准
- •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).
研究组 & 干预措施
Binge Drinkers with Inulin Intervention
23 binge drinkers (~50 % male and ~50 % female) will be given a daily dose of inulin.
干预措施: Inulin Intervention (Dietary Supplement)
Binge Drinkers with Maltodextrin Intervention
23 binge drinkers (~50 % male and ~50 % female) will be given a daily dose of maltodextrin.
干预措施: Maltodextrin Intervention (Dietary Supplement)
Non/Low-Drinkers
36 non/low-drinkers will not be given any dietary fiber.
结局指标
主要结局
Fecal Microbiota - Quantification of SCFAs levels
时间窗: Immediately post-intervention.
The concentration of SCFAs present in each collected faecal sample shall be quantified by HPLC.
Fecal Microbiota - Species Richness
时间窗: Immediately post-intervention.
Faecal samples will be collected only from binge drinkers subjected to the intervention for microbiota α-diversity analysis by 16S rRNA metagenomics (Illumina sequencing). The Chao1 Index will be used as an estimator of nonparametric microbial species richness in each sample.
Fecal Microbiota - Species Diversity
时间窗: Immediately post-intervention
Faecal samples will be collected only from binge drinkers subjected to the intervention for microbiota α-diversity analysis by 16S rRNA metagenomics (Illumina sequencing). The Shannon Diversity Index (metric combining richness and evenness, with equal weighting given to abundant and rare species) and the Simpson Diversity Index (metric of richness and evenness, in which more weighting is given to abundant species) will be used.
Fecal Microbiota - Species Richness
时间窗: At baseline (pre-intervention)
Faecal samples will be collected from all participants for microbiota α-diversity analysis by 16S rRNA metagenomics (Illumina sequencing). The Chao1 Index will be used as an estimator of nonparametric microbial species richness in each sample.
Fecal Microbiota - Species Diversity
时间窗: At baseline (pre-intervention)
Faecal samples will be collected from all participants for microbiota α-diversity analysis by 16S rRNA metagenomics (Illumina sequencing). The Shannon Diversity Index (metric combining richness and evenness, with equal weighting given to abundant and rare species) and the Simpson Diversity Index (metric of richness and evenness, in which more weighting is given to abundant species) will be used.
Fecal Microbiota - Quantification of SCFAs levels
时间窗: At baseline (pre-intervention)
The concentration of short-chain fatty acids (SCFAs) present in each collected faecal sample shall be quantified by High Performance Liquid Chromatography (HPLC).
次要结局
- Neurofunctional level - Emotional Face Matching (EFM) Task(Immediately post-intervention)
- Neurofunctional level - Alcohol Cue Reactivity (ACR) Task(Immediately post-intervention)
- Alcohol Consumption - Drinking pattern(3 months post-intervention)
- Alcohol Craving - Short-term acute craving(3 months post-intervention)
- Neuropsychological Evaluation - Memory(Immediately post-intervention)
- Neuropsychological Evaluation - Emotion and Social Cognition(Immediately post-intervention)
- Neuropsychological Evaluation - Executive Function(Immediately post-intervention)
- Alcohol Cue Reactivity - Emotional measures(Immediately post-intervention.)
- Memory Inhibition Performance(Immediately post-intervention.)
- Ability of Emotional Recognition(Immediately post-intervention.)
- Blood samples - Presence of Inflammatory Markers(Immediately post-intervention.)
- Neurofunctional level - Think/No-Think Alcohol (TNTA) Task(Immediately post-intervention)
- Neurofunctional level - Emotional Face Matching (EFM) Task(Immediately post-intervention)
- Neurofunctional level - Alcohol Cue Reactivity (ACR) Task(Immediately post-intervention)
- Alcohol Consumption - Drinking pattern(Immediately post-intervention)
- Alcohol Craving - Short-term acute craving(Immediately post-intervention)
- Neuropsychological Evaluation - Memory(At baseline (pre-intervention))
- Neuropsychological Evaluation - Emotion and Social Cognition(At baseline (pre-intervention))
- Neuropsychological Evaluation - Executive Function(At baseline (pre-intervention))
- Alcohol Cue Reactivity - Emotional measures(At baseline (pre-intervention))
- Memory Inhibition Performance(At baseline (pre-intervention))
- Ability of Emotional Recognition(At baseline (pre-intervention))
- Blood samples - Presence of Inflammatory Markers(At baseline (pre-intervention))
- Neurofunctional level - Think/No-Think Alcohol (TNTA) Task(At baseline (pre-intervention))
- Neurofunctional level - Emotional Face Matching (EFM) Task(At baseline (pre-intervention))
- Neurofunctional level - Alcohol Cue Reactivity (ACR) Task(At baseline (pre-intervention))
研究者
Eduardo López-Caneda
Assistant Reseacher
University of Minho