Mapping the Impact of Gut Microbiota on Brain and Behavior Through the Lens of GABA
ConditionHealthy
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexMale
Age18-50
SponsorUniversity of Reading
About this trial
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:
1. Does the population of gut bacteria capable of producing GABA modulate brain-based measures of GABA? 2. 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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Male
Right-handed
Caucasian/White
Between 18 and 50 years of age
Disqualifiers
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
Trial design
Design model
Crossover
Treatments tested in this trial
Probiotic
Dietary supplementParticipants will be required to take a probiotic supplement of Lactobacillus brevis daily (1 capsule 5B CFU/day)
Placebo
Dietary supplementParticipants will be required to take the placebo maltodextrin daily (1 capsule/day)
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: ProbioticActive comparator 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Changes in GABA concentrations in the brain assessed using Magnetic Resonance Spectroscopy (MRS)
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.
Time frame
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)2
Changes in GABA-ergic activity in the sensorimotor component of the resting state network assessed using resting state functional Magnetic Resonance Imagine (rs-fMRI)
GABA-ergic activity will be measured using rs-fMRI. MRI data will be analysed..
Time frame
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)3
Changes in GABA concentrations in urine assessed by Liquid chromatography-mass spectrometry (LC-MS).
Concentrations of GABA will be measured in urine samples by LC-MS.
Time frame
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)4
Changes in GABA concentrations in serum assessed by Liquid chromatography-mass spectrometry (LC-MS).
Concentrations of GABA will be measured in serum samples by LC-MS.
Time frame
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)Secondary outcomes
1
Changes in faecal bacteria quantity assessed by Fluorescent In Situ Hybridisation Followed by Flow Cytometry (FISH-FCM)
Quantity of faecal bacteria will be assessed by FISH-FCM
Time frame
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)2
Changes in compositional diversity of faecal microbiota attributable to intervention assessed by 16S ribosomal RNA (16S rRNA) gene amplicon sequencing
Compositional diversity of faecal microbiota attributable to intervention will measured by 16S rRNA sequencing methods
Time frame
1. Baseline (Week 0), 2. Following intervention (Week 4 or Week 12, depending on intervention arm assignment)3
Changes in metabolic profile in faecal samples assessed by Nuclear Magnetic Resonance spectroscopy (NMR)
The metabolic profile will be measured in faecal samples using NMR
Time frame
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)4
Changes in metabolic profile in urine samples assessed by Nuclear Magnetic Resonance spectroscopy (NMR)
The metabolic profile will be measured in urine samples using NMR
Time frame
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)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Reading
Lead sponsor
European Research Council
Collaborator
Source ClinicalTrials.gov