Clinical trial NCT05931562: The Impact of Diet on the Gut-Microbiota-Brain Axis
Official title: An Interventional Study on the Association Between Diet, Cognitive Function, Stress and the Gut Microbiota in Healthy Volunteers.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Healthy
Keywords: Microbiota-gut-brain axis
Diet
Cognition
Stress
Dietary Fibre
Fermented foods
Lead sponsor: University College Cork
Sponsor class: OTHER
First posted: 2023-07-05
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Randomized-controlled, parallel, single-blinded design
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Trait stress/mood: self-report
timeFrame: Change from baseline at 8 weeks
measure: Trait stress/mood: hypothalamic-pituitary-adrenal axis activity
timeFrame: Change from baseline at 8 weeks
measure: Responses to acute stress: self-report
timeFrame: Change from baseline at 8 weeks
measure: Responses to acute stress: sympathetic-adrenal-medullary pathway activity
timeFrame: Change from baseline at 8 weeks
measure: Responses to acute stress: hypothalamic-pituitary-adrenal axis activity
timeFrame: Change from baseline at 8 weeks
Secondary outcomes:
measure: Cognitive performance: working memory
timeFrame: Change from baseline at 8 weeks
measure: Cognitive performance: episodic memory
timeFrame: Change from baseline at 8 weeks
measure: Cognitive performance: decision making
timeFrame: Change from baseline at 8 weeks
measure: Cognitive performance: emotional inhibition
timeFrame: Change from baseline at 8 weeks
measure: Cognitive performance: sustained attention
timeFrame: Change from baseline at 8 weeks
measure: Cognitive performance: visual pattern recognition memory
timeFrame: Change from baseline at 8 weeks
measure: Cognitive performance: cognitive flexibility
timeFrame: Change from baseline at 8 weeks
measure: Cognitive performance: social cognition
timeFrame: Change from baseline at 8 weeks
measure: Cognitive performance: affective perceptual bias
timeFrame: Change from baseline at 8 weeks
measure: Microbiota composition and function
timeFrame: Change from baseline at 8 weeks
measure: Microbial and host metabolomics
timeFrame: Change from baseline at 8 weeks
measure: Inflammation
timeFrame: Change from baseline at 8 weeks
Other outcomes:
Locations:
city: Cork
country: Ireland
facility: APC Microbiome Ireland
Study officials:
affiliation: APC Microbiome Ireland
name: John Cryan, PhD
role: PRINCIPAL_INVESTIGATOR
References: