Mapping the Impact of Gut Bacteria on Brain and Behaviour Through the Lens of GABA (GutBrainGABA)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Changes in GABA concentrations in the brain assessed using Magnetic Resonance Spectroscopy (MRS)
研究概览
简要总结
Gut microbiota produce different metabolites within the human body, which include neurotransmitters. Animal studies have demonstrated a critical role for the gut microbiota in various aspects of brain and behavioural function, and a smaller number of studies in humans have shown differences of gut microbiota composition in psychiatric conditions. However, almost nothing is known about the impact of neurotransmitters produced by the gut microbiota on human brain and behaviour.
The way in which differences in brain, behaviour and personality traits are associated with the gut microbiota, and how they are influenced by a probiotic will be explored, with a special focus on GABA (Gamma Amino Butyric Acid).
Abnormalities of microbiota composition have been identified in metabolic disorders, such as inflammatory bowel disease and obesity, and psychiatric conditions, such as depression and anxiety.
The aim of this intervention trial will be to answer the following fundamental questions:
- Does the population of gut bacteria capable of producing GABA modulate brain-based measures of GABA?
- Does the population of gut bacteria capable of producing GABA influence performance in behavioural tasks known to depend on GABA-ergic function?
The impact of a GABA producing probiotic on the measures of GABA in the brain and serum, relevant metabolites in blood, faecal and urine samples and performance in GABA dependent behavioural tasks will be investigated in this trial.
详细描述
This interventional trial will involve a double-blind placebo-controlled crossover trial structured in 4 appointments: week 0 (W0), week 4 (W4), week 8 (W8) and week 12 (W12). The study will therefore last 12 weeks, and will include a screening visit and 4 study visits.
The interventional study has a cross-over design, and participants will therefore be invited to consume both the active probiotic supplement and the placebo at different times. The probiotic supplement (Lactobacillus brevis) was chosen based on the ability to produce GABA in vitro (Monteagudo et al., 2022). The placebo will be maltodextrin The products will be provided as capsules and are identical in texture and appearance.
For participants to be considered compliant and therefore included in the study they will be require:
- to take the probiotic supplement or placebo at least 6 out of every 7 days of the trial for the week period;
- to provide faecal, blood and urine samples and to be tested with a battery involving behaviour and brain measures relating to GABA levels/activity and
- to complete a food diary using an online app once every 4 weeks.
As age and BMI are factors associated with significant variation in gut microbiota composition/brain and behaviour functioning, both study arms will be matched on these criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Right-handed
- •Caucasian/White
- •Between 18 and 50 years of age
- •Grew up in the UK or other European country
- •Body Mass Index 18.5 to 30.
排除标准
- •Use of antibiotics within the last 3 months
- •Use of protonic pump inhibitors (PPIs) within the last 3 months
- •Current or history of regular smoking within the last 6 months
- •Regular consumption of >14 units of alcohol per week
- •Current use of psychotropic drugs for medicinal or recreational purposes
- •Current use of probiotic/prebiotic supplements
- •Current diagnosis of neurological, developmental or psychiatric condition
- •Current diagnosis of gut microbiota related conditions such as inflammatory bowel disease or irritable bowel syndrome
结局指标
主要结局
Changes in GABA concentrations in the brain assessed using Magnetic Resonance Spectroscopy (MRS)
时间窗: 1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment)
Concentrations of GABA will be quantified using MRS. MRS data will be analysed separately in the time domain using an open-source magnetic resonance spectroscopy analysis tool, such as Osprey.
Changes in GABA concentrations in urine assessed by Liquid chromatography-mass spectrometry (LC-MS).
时间窗: 1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment)
Concentrations of GABA will be measured in urine samples by LC-MS.
Changes in GABA concentrations in serum assessed by Liquid chromatography-mass spectrometry (LC-MS).
时间窗: 1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment)
Concentrations of GABA will be measured in serum samples by LC-MS.
Changes in GABA-ergic activity in the sensorimotor component of the resting state network assessed using resting state functional Magnetic Resonance Imagine (rs-fMRI)
时间窗: 1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment)
GABA-ergic activity will be measured using rs-fMRI. MRI data will be analysed..
次要结局
- Changes in compositional diversity of faecal microbiota attributable to intervention assessed by 16S ribosomal RNA (16S rRNA) gene amplicon sequencing(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in metabolic profile in faecal samples assessed by Nuclear Magnetic Resonance spectroscopy (NMR)(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in faecal bacteria quantity assessed by Fluorescent In Situ Hybridisation Followed by Flow Cytometry (FISH-FCM)(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in metabolic profile in urine samples assessed by Nuclear Magnetic Resonance spectroscopy (NMR)(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in metabolic profile in serum samples assessed by Nuclear Magnetic Resonance spectroscopy (NMR)(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in emotion recognition performance assessed by reaction time and accuracy(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in blood pressure assessed by measures of systolic and diastolic blood pressure(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in motor function performance assessed by reaction time(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in levels of trait and state anxiety assessed by the State-Trait Anxiety Inventory (STAI)(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in levels of depression assessed by the Centre for Epidemiological Studies Depression questionnaire (CES-D)(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
- Changes in tactile discrimination performance assessed by reaction time, static threshold and dynamic threshold(1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment), 3. Following washout (Week 8), 4. Following placebo (Week 4 or Week 12, depending on intervention arm assignment))
研究者
Bhismadev Chakrabarti
Professor of Neuroscience and Mental Health
University of Reading