The Impact of Diet on the Gut-Microbiota-Brain Axis

Not Applicable

Recruiting

• Conditions: Healthy
• Interventions: Other: Combined Diet; Other: Control; Other: Fermented Foods; Other: High Fibre

• Registration Number: NCT05931562
• Lead Sponsor: University College Cork

Brief Summary

This study aims to investigate the effects of an 8-week dietary intervention on cognitive function, stress, and the gut microbiota in healthy adults with low fibre intake.

Detailed Description

The gut microbiota communicates bidirectionally with the brain via the microbiota-gut-brain axis to influence various aspects of human physiology, including host metabolism, immune function, behaviour, and cognition. Diet is a key modulator of the microbial composition, suggesting that the microbiota could explain the association between poor nutrition and decreasing health of the population. Dietary fibre is the main energy source for the gut microbiota and fundamentally impacts its composition and function. The microbiota-gut-brain axis has been proposed to mediate some of the effects of dietary fibre on the brain, for example through microbial metabolites (e.g., short-chain fatty acids (SCFA)), regulation of the immune system, and the microbial impact on gut hormones and neurotransmitters. Similarly, intake of fermented foods is positively associated with cognitive health and has been shown to alter the microbiota composition and function and exert an anti-inflammatory effect. However, no studies to date have examined the singular and combined effects of fermented and fibrous foods on the gut microbiota, cognition, and emotion. The present study aims to determine the role of diet on the microbiota-gut-brain axis and mental health.

Using a randomized-controlled, parallel, single-blinded design, participants consuming a habitually low fibre diet (N=200) will undergo an 8-week dietary intervention. Participants will receive one of four diets (n=50 in each group): high fibre (aim 24-35 grams/day), fermented foods (aim 4-6 portions/day), combined diet of fermented foods and high fibre (aim 25-30g/day of fibre and 3-4 servings/day of fermented foods) or control (dietary education according to national Irish guidelines). Cognitive, psychological, and biological measures will be compared at baseline and endpoint. During the intervention period, individuals will provide repeated faecal samples to assess temporal microbial changes.

Study Timeline

• Study Start: 2022-07-14
• Study First Submitted: 2023-06-12
• Study First Submitted QC: 2023-06-27
• Study First Posted: 2023-07-05
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-15
• Last Update Posted: 2024-07-16
• Primary Completion: 2026-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Be able to give written informed consent.
• Be between 18 and 50 years of age.
• Have a body mass index (BMI) between 18.5-29.9 Kg/m2.
• Be in generally good health as determined by the investigator.

Exclusion Criteria

• Are less than 18 and greater than 50 years of age.
• Have a BMI below 18.5 or above 29.9 Kg/m2.
• Have a significant acute or chronic coexisting illness [cardiovascular, gastrointestinal (GI) [to include functional GI disorders, inflammatory bowel disease, coeliac disease, lactose intolerance, food allergies], immunological, psychiatric [to include formal or as determined by MINI Psychiatric interview, diagnosis of current major depression, anxiety disorder, bipolar spectrum disorder, schizophrenia, other DSM-IV Axis I disorder], neurodevelopmental disorders, immunological, metabolic disorders [to include type I or II diabetes], or any condition which contraindicates, in the investigators judgement, entry to the study,
• Have a condition or taking a medication that the investigator believes would interfere with the objectives of the study, pose a safety risk, or confound the interpretation of the study results; all psychoactive medications [to include anxiolytics, antipsychotics, antidepressants, anticonvulsants, centrally acting corticosteroids, and opioid pain relievers), laxatives, enemas, antibiotics, anti-coagulants, over-the counter non-steroidal anti-inflammatories (NSAIDS). Subjects should have a wash-out period of 4 weeks.
• Current prebiotic or probiotic supplement use (a wash-out period of 4 weeks after cessation will allow entry to the study).
• Females who are peri-menopausal, menopausal or post-menopausal.
• Females who are pregnant or planning a pregnancy, or lactating.
• Participants who are not fluent in English.
• Are colour blind.
• Have dyslexia or dyscalculia.
• Are a current habitual daily smoker.
• Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the trial.
• Subjects receiving treatment involving experimental drugs. If the subject has been in a recent experimental trial, these must have been completed not less than 30 days prior to this study.
• Have a malignant disease or any concomitant end-stage organ disease.
• Have completed a study in our laboratory in the past 4 years.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Combined Diet	Combined Diet	Combined diet high in fibre and fermented foods (fibre aim 24-35 grams/day, fermented foods aim 4-6 portions/day)
Control	Control	Participants will recieve dietary education based on the healthy eating guidleines provided by the Health Service Executive (HSE).
Fermented Foods	Fermented Foods	Fermented foods diet (4-6 portions/day)
High Fibre	High Fibre	High fibre diet (24-35 grams/day)

Primary Outcome Measures

Name	Time	Method
Responses to acute stress: self-report	Change from baseline at 8 weeks	Self-report questionnaires
Responses to acute stress: hypothalamic-pituitary-adrenal axis activity	Change from baseline at 8 weeks	Cortisol from saliva samples
Trait stress/mood: self-report	Change from baseline at 8 weeks	self-report questionnaires
Responses to acute stress: sympathetic-adrenal-medullary pathway activity	Change from baseline at 8 weeks	Galvanic skin response taken from the skin on the hand
Trait stress/mood: hypothalamic-pituitary-adrenal axis activity	Change from baseline at 8 weeks	Cortisol from saliva samples

Secondary Outcome Measures

Name	Time	Method
Cognitive performance: social cognition	Change from baseline at 8 weeks	Emotion Recognition Task
Cognitive performance: working memory	Change from baseline at 8 weeks	Spatial Working Memory
Cognitive performance: decision making	Change from baseline at 8 weeks	Iowa Gambling Task
Inflammation	Change from baseline at 8 weeks	Inflammatory markers in lipopolysaccharide stimulated and unstimulated bloods
Microbial and host metabolomics	Change from baseline at 8 weeks	Untargeted metabolomics analysis
Cognitive performance: emotional inhibition	Change from baseline at 8 weeks	Emotional Stroop
Cognitive performance: sustained attention	Change from baseline at 8 weeks	Rapid Visual Information Processing
Cognitive performance: affective perceptual bias	Change from baseline at 8 weeks	Emotional Bias Task
Cognitive performance: episodic memory	Change from baseline at 8 weeks	Modified Rey Auditory Verbal Learning Test (ModRey)
Cognitive performance: visual pattern recognition memory	Change from baseline at 8 weeks	Pattern Recognition Memory
Cognitive performance: cognitive flexibility	Change from baseline at 8 weeks	Intra-Extra Dimensional Set Shifting
Microbiota composition and function	Change from baseline at 8 weeks	Shotgun metagenomics of fecal samples

Trial Locations

Locations (1)

APC Microbiome Ireland; 🇮🇪 Cork, Ireland