Clinical trial NCT04951674: Dietary Fiber, Microbiota and Cognitive Function in Healthy Adults
Official title: An Observational and Interventional Study on the Association Between Dietary Fibre and Cognitive Function in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Healthy
Keywords: Dietary fiber
Microbiota
Cognition
Diet
Microbiota-Gut-Brain Axis
Lead sponsor: University College Cork
Sponsor class: OTHER
First posted: 2021-07-07
Enrollment: 150
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Dietary fiber is well-known for its many health benefits, including the support of gastrointestinal, metabolic, and mental health. Although studies investigating whole dietary patterns in relation to cognition have demonstrated that diet quality and a healthy dietary pattern are associated with better cognitive performance, the role of dietary fiber in this regard is understudied. In the last decade, the role of the microbiota (trillions of microbes inhabiting the gut) in influencing various aspects of human health, including mental health and behavior, has also become established. Importantly, dietary fiber has been shown to positively affect the microbiota composition.

In this study, the role of dietary fiber in cognition through the lens of the microbiota is investigated. A two-part study including an observational (study 1) and interventional (study 2) arm has been designed. In study 1, the observational arm, 150 healthy individuals (30-60 years of age) will be recruited and grouped into high-fiber (\>25 g/day, n=75) and low-fiber (\<18 grams/day, n=75) consumers based on habitual dietary intake. Cognitive tasks (attention, episodic memory, decision making), psychological dimensions including impulsivity and emotional reactivity, biological samples (feces, blood, saliva, urine) and questionnaires about general health will be collected. In study 2, the interventional arm, a subgroup (n=60) of individuals from the low-fiber group will further be randomized into an 8-week randomized-controlled, parallel, single-blinded intervention to either receive a high fiber (n=30, aim 30 grams/day) or control (n=30) diet education. During the intervention period, individuals will provide repeated fecal samples in order to assess temporal microbial changes. At the end of the intervention period, individuals will undergo the same testing regarding cognitive and psychological variables and the same biological samples will be collected.

The investigators hypothesize that participants with higher dietary fiber intake at baseline will perform better in the cognitive tasks compared to individuals with low fiber intake, and that this difference can, in part, be mediated by the gut microbiota. Further the investigators hypothesize that through the dietary intervention the microbiota composition will positively shift to include more beneficial microbes and that cognitive performance will improve following the intervention.


Eligibility criteria: Inclusion Criteria:

* Be able to give written informed consent.
* Be between 30 and 60 years of age.
* Be in generally good health as determined by the investigator.

Exclusion Criteria:

* Are less than 30 and greater than 60 years of age.
* Have a significant acute or chronic coexisting illness \[cardiovascular, gastrointestinal (GI) \[to include functional GI disorders, inflammatory bowel disease, celiac disease, lactose intolerance, food allergies\], 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). Participants 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 or English is not first language.
* Are color 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.
* Participants 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 the laboratory in the past 4 years.

Primary outcomes:
measure: Cognitive performance - Attention
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
measure: Cognitive performance - Episodic memory
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
measure: Cognitive performance - Risky decision making
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
measure: Cognitive performance - Affective decision making
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
Secondary outcomes:
measure: Microbiota composition and function
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
measure: Blood inflammatory profile
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
measure: Salivary cortisol concentrations
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
measure: Stress assessment
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
measure: Anxiety assessment
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
measure: Emotion sensitivity, intensity, and persistence
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
measure: Impulsivity-related traits
timeFrame: Differences between groups at baseline and changes after 8-week of diet intervention in active group
Other outcomes:
Locations:
city: Cork
country: Ireland
facility: APC Microbiome Ireland, University College Cork
Study officials:
affiliation: APC Microbiome Ireland, University College Cork
name: John F Cryan, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: APC Microbiome Ireland, University College Cork
name: Gerard Clarke, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berding K, Carbia C, Cryan JF. Going with the grain: Fiber, cognition, and the microbiota-gut-brain-axis. Exp Biol Med (Maywood). 2021 Apr;246(7):796-811. doi: 10.1177/1535370221995785. Epub 2021 Feb 28.
citation: Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV, Guzzetta KE, Jaggar M, Long-Smith CM, Lyte JM, Martin JA, Molinero-Perez A, Moloney G, Morelli E, Morillas E, O'Connor R, Cruz-Pereira JS, Peterson VL, Rea K, Ritz NL, Sherwin E, Spichak S, Teichman EM, van de Wouw M, Ventura-Silva AP, Wallace-Fitzsimons SE, Hyland N, Clarke G, Dinan TG. The Microbiota-Gut-Brain Axis. Physiol Rev. 2019 Oct 1;99(4):1877-2013. doi: 10.1152/physrev.00018.2018.