Coffee Consumption, the Gut Microbiome, and the Microbiota-Gut-Brain Axis

The aim of this study is to investigate the potential of coffee to act as a prebiotic to alter gut microbiota and improve mood, memory and cognitive performance.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Caffeinated coffee; Other: Decaffeinated coffee

Detailed Description

The aim of this study is to investigate the potential of coffee to act as a prebiotic to alter gut microbiota and improve mood, memory and cognitive performance. Additional gut-brain axis pathways-related parameters such as inflammation, short chain fatty acids and other metabolites production and physiological stress levels will be explored. Moreover, differences between caffeinated and decaffeinated coffee consumption will be investigated to determine whether observed effects are attributed to caffeine or other coffee components.

To determine the mechanism of action underlying the beneficial effects of coffee, coffee drinkers abstained from coffee and caffeine for a 2-week washout period following the baseline visit. Coffee drinkers further underwent an intervention in which they consumed either 4 sachets (1.8 grams each) of instant caffeinated or decaffeinated coffee per day for 3 weeks of using a double-blind, randomised, parallel design. Reaction time, socioemotional processing, visual and episodic memory, learning, and an attentional task were administered to measure cognitive performance. Self-report questionnaires on mood, behavior and lifestyle were administered and response to an acute stressor was assessed. Biological samples of saliva, urine, blood, and stool were collected to investigate microbiome-gut-brain-axis signaling.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ireland
  • Cork, Ireland
    • University College Cork

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Be able to give written informed consent.
2. Be between 30 and 50 years of age.
3. Be in generally good health as determined by the investigator.
4. Drink moderate amounts of coffee daily (3-5 cups/day)

Exclusion Criteria:

1. Are less than 30 and greater than 50 years of age.
2. 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,
3. 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.
4. Be hypertensive.
5. Current prebiotic or probiotic supplement use (a wash-out period of 4 weeks after cessation will allow entry to the study), or habitual consumption of foods deemed by the investigator to be particularly rich in prebiotic fibres or probiotic strains or are vegan.
6. Females who are pregnant or planning a pregnancy, or lactating.
7. Participants who are not fluent in English.
8. Participants who have dyslexia or dyscalculia.
9. Are a current habitual daily smoker.
10. 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.
11. 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.
12. Have a malignant disease or any concomitant end-stage organ disease.
13. Have already done a study in the lab in the past 4 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Caffeinated coffee; 4 sachets (1.8 grams each) of instant, caffeinated coffee	Other: Caffeinated coffee; After 2 weeks of coffee abstinence (washout), participants who were coffee drinkers were randomly allocated to receive either 4 sachets (1.8g each) of caffeinated instant coffee per day for 3 weeks. Participants were blinded to coffee contents.
Experimental: Decaffeinated coffee; 4 sachets (1.8 grams each) of instant, decaffeinated coffee	Other: Decaffeinated coffee; After 2 weeks of coffee abstinence (washout), participants who were coffee drinkers were randomly allocated to receive either 4 sachets (1.8g each) of decaffeinated instant coffee per day for 3 weeks. Participants were blinded to coffee contents.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota composition and function	Shotgun metagenomics of fecal samples	Differences between groups at baseline, at 2-week coffee abstinence and at 3-week coffee intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbial metabolites (including Short-Chain fatty acids)	Untargeted metabolomics of fecal samples	Differences between groups at baseline, at 2-week coffee abstinence and at 3-week coffee intervention
Coffee-related metabolites	Targeted metabolomics of coffee-related metabolomics in fecal and urine samples	Differences between groups at baseline, at 2-week coffee abstinence and at 3-week coffee intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive performance: attention	Assessment of attention using the Paced Auditory Serial Addition Test (PASAT)	Differences between groups at baseline, at 2-week coffee abstinence and at 3-week coffee intervention
Cognitive performance - Episodic memory	Assessment of episodic memory using the Modified Rey Auditory Verbal Learning Test (ModRey)	Differences between groups at baseline and at 3-week coffee intervention
Cognitive performance - Learning and visual memory	Assessment of learning and visual memory using the Paired Associates Learning task	Differences between groups at baseline and at 3-week coffee intervention
Cognitive performance - Processing speed	Assessment of processing speed using the Motor Screening Test	Differences between groups at baseline and at 3-week coffee intervention
Cognitive performance - socioemotional processing	Assessment of socioemotional processing using the Emotion Recognition Task	Differences between groups at baseline and at 3-week coffee intervention
Responses to acute stressor	Self-report mood and cortisol responses to the Socially Evaluated Cold Pressor Test	Differences between groups at baseline and at 3-week coffee intervention
Inflammatory profile	Inflammatory markers analysis in LPS-stimulated blood and in the plasma using MSD multiplex technology. The inflammatory markers analyzed were: C-reactive protein, IL6,IL10,IL8, INFgamma, TNFalpha, IL1beta.	Differences between groups at baseline, at 2-week coffee abstinence and at 3-week coffee intervention
Cortisol awakening response	Cortisol awakening response measurement using ELISAs	Differences between groups at baseline, at 2-week coffee abstinence and at 3-week coffee intervention
Self-reported questionnaires	Completion of self-reported questionnaires on mood, depression, anxiety, impulsivity, emotional reactivity, stress, and sleep quality. Low scores represents better outcomes.	Differences between groups at baseline, at 2-week coffee abstinence and at 3-week coffee intervention
Genotyping adenosine receptor A2A	Genotyping of 2 SNPs of the A2A receptor using blood (caffeine is an antagonist of the A2A receptor.	At the baseline

Collaborators and Investigators

• Sponsor: University College Cork
• Investigators: Principal Investigator: John F Cryan, PhD, UCC

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2021
• Primary Completion (Actual): January 18, 2023
• Study Completion (Actual): January 18, 2023

Study Registration Dates

• First Submitted: May 29, 2023
• First Submitted That Met QC Criteria: June 21, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Stress; Prebiotic; Behavior; Cognition; Polyphenol; Mood; Gut Microbiota; Caffeine; Coffee; Microbiome-gut-brain-axis
• Other Study ID Numbers: APC115

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No