Mapping the Impact of Gut Microbiota on Brain and Behavior Through the Lens of GABA

NCT05698862 | Recruiting

• 1 other identifier: GBGABAWP2
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Does the population of gut bacteria capable of producing GABA modulate brain-based measures of GABA?
2. 2.Does the population of gut bacteria capable of producing GABA influence performance in behavioural tasks known to depend on GABA-ergic function?

Conditions

Healthy

Keywords

Gamma Amino Butyric Acid (GABA); Brain function; Gut microbiota; Behaviour; Probiotics

Outcome Measures

Primary Outcomes (4)

• 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.

  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 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..

  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 GABA concentrations in urine assessed by Liquid chromatography-mass spectrometry (LC-MS).

  Concentrations of GABA will be measured in urine samples by LC-MS.

  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 GABA concentrations in serum assessed by Liquid chromatography-mass spectrometry (LC-MS).

  Concentrations of GABA will be measured in serum samples by LC-MS.

  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 (11)

• 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 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 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)

Study Arms (2)

Probiotic

ACTIVE COMPARATOR

Probiotic supplement (Lactobacillus brevis)

Dietary Supplement: Probiotic

Placebo

PLACEBO COMPARATOR

Placebo (maltodextrin)

Dietary Supplement: Placebo

Interventions

Probiotic DIETARY_SUPPLEMENT

Participants will be required to take a probiotic supplement of Lactobacillus brevis daily (1 capsule 5B CFU/day)

Probiotic

Placebo DIETARY_SUPPLEMENT

Participants will be required to take the placebo maltodextrin daily (1 capsule/day)

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Reading: lead
• European Research Council: collaborator

Study Sites (1)

University of Reading

Reading, RG6 6AH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Behavior

Interventions

Probiotics

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Bhismadev Chakrabarti, PhD

  University of Reading

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bhismadev chakrabarti, PhD

CONTACT

+44 118 378 5551; b.chakrabarti@reading.ac.uk

Glenn Gibson

CONTACT

+44 118 378 8715; g.r.gibson@reading.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neuroscience and Mental Health

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: January 26, 2023
• Study Start: May 21, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 26, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)