Prebiotic and Probiotic Modulation of the Gut Microbiota-gut-brain Axis During Acute Stress

NCT05392556 | Completed

• 2 other identifiers: 21-03-HCM-10901
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

Emerging evidence supports the existence of a microbiota-gut-brain axis through which gut microbes influence cognition, mood and behavior. Targeting this axis with probiotics and/or prebiotics may provide novel strategies for mitigating stress-induced decrements in gastrointestinal and cognitive function. This double-blind, placebo-controlled, randomized, parallel-arm trial will determine the effects of a prebiotic and a probiotic dietary intervention on gastrointestinal, cognitive and physiologic responses to acute military-relevant physical and cognitive stress. Healthy men and women will be recruited and randomized to receive a placebo, probiotic or prebiotic for 4wk. Volunteers will be fed a controlled diet during the 4th week of supplementation. Fecal, blood, urine and saliva samples will be collected. Physical stress will be induced by a weighted walk on a treadmill, and will be followed by a cognitively challenging testing scenario that uses intermittent electric shocks to the abdomen to induce a stress response.

Conditions

Stress Physiology

Keywords

Probiotic; Prebiotic; Microbiome; Stress

Outcome Measures

Primary Outcomes (2)

• Change from baseline in intestinal permeability

  A differential sugar absorption test will be used to assess intestinal permeability. Participants will consume 2g sucralose and 4g mannitol dissolved in 180 mL water prior to starting exercise. Participants will then collect all urine produced over the subsequent 4hr. Urine sucralose and mannitol concentrations will be analyzed.

  Days 0 and 29

• Difference from baseline in circulating cortisol concentrations

  Serum cortisol concentrations will be measured in serial blood samples collected via an indwelling venous catheter.

  Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.

Secondary Outcomes (28)

• Change from baseline in mean heart rate variability

  During stress exposure (up to 4hr) on days 0 and 29.

• Change from baseline in performance on decision making under conditions of ambiguity task

  Days 0 and 29

• Difference from baseline in reaction time.

  Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.

• Difference from baseline in response inhibition

  Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.

• Difference from baseline in working memory

  Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.

Other Outcomes (19)

• Change from baseline in mean heart rate

  During stress exposure (up to 4hr) on days 0 and 29

• Change from baseline in exercise energy expenditure

  During exercise (120min) on days 0 and 29

• Change from baseline in mean respiratory exchange ratio

  During exercise (120min) on days 0 and 29

Study Arms (3)

Probiotic

EXPERIMENTAL

Bifidobacterium longum R0175; Lactobacillus helveticus R0052 (Cerebiome; Lallemand Health Solutions)

Dietary Supplement: Probiotic

Prebiotic

EXPERIMENTAL

Bimuno-galactooligosaccharide (Bimuno-GOS; Clasado Biosciences)

Dietary Supplement: Prebiotic

Placebo

PLACEBO COMPARATOR

Maltodextrin placebo

Other: Placebo

Interventions

Probiotic DIETARY_SUPPLEMENT

Cerebiome (Lallemand Health Solutions): probiotic supplement containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052, and maltodextrin. Dosing: Oral, 3.6 g/d containing 3x10\^9 CFU/d (powder form)

Probiotic

Prebiotic DIETARY_SUPPLEMENT

Bimuno-GOS (Clasado Biosciences): Dosing: Oral; 3.6 g/d containing 2.75 g active GOS/d (powder form)

Prebiotic

Placebo OTHER

Maltodextrin 3.6 g/d (powder form)

Placebo

Eligibility Criteria

• Age: 17 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Men and women aged 18 - 39 years (active duty personnel who are 17 yr of age will also be allowed to participate).
• In good health as determined by Medical Clearance.
• Physically active:
• If military, passed most recent record Combat or Physical Fitness Test, and ≥4 d/wk aerobic and/or resistance exercise.
• If civilian, ≥4 d/wk aerobic and/or resistance exercise.
• Meet Army weight for height and body composition standards as defined in Army Regulation 600-9:
• Self-reports ≥4 bowel movements/week.
• Self-reports normal hearing.
• Willing to maintain usual diet until provided diet phase of study.

You may not qualify if:

• Pregnant, expecting to become pregnant during study, or breastfeeding.
• Abnormal menstrual cycles \[i.e., not between 26-32 days in duration; or not 5-6 menstrual cycles within the past 6 months\], or those that have had an IUD placed within the last month or removed within the past 3 months.
• Less than 20/20 acuity on the Snellen eye chart of normal or corrected-to-normal acuity.
• Any of the following medical conditions:
• Neurological or psychological disorder (such as depression, anxiety disorders, migraines, cluster headaches, seizures, post-traumatic stress disorder or panic attacks).
• Cardiac disease (including arrhythmia or fast or skipped heart beats) Hypertension Has a pacemaker Insomnia Musculoskeletal injuries that compromise exercise capability Metabolic or cardiovascular abnormalities (e.g., kidney disease, diabetes, etc.) Disease of the GI tract including, but not limited to diverticulitis, inflammatory bowel disease, irritable bowel syndrome, peptic ulcer disease, Crohn's disease, and ulcerative colitis Excessive alcohol use or other substance abuse issues Immunodeficiency disorder Allergy to skin adhesive
• Colonoscopy within 3 months of study participation.
• Any use of antibiotics or antimycotics, except topical antibiotics/antimycotics, within 3 months of study participation.
• Regular use of over-the-counter medications (including antacids, laxatives, stool softeners, and anti-diarrheals) unless approved by medical office and study PI.
• Taking prescription medications other than a contraceptive (unless approved by medical office and study PI)
• Not willing or able to refrain from using over the counter medications for 72hr before stress exposure days.
• Not willing or able to stop consumption of dietary supplements at least 2 weeks before and throughout study participation.
• Not willing or able to stop consumption of probiotic-containing foods (e.g., yogurt, etc.) or foods containing added prebiotics (e.g., inulin) at least 2 weeks before and throughout study participation.
• Not willing to abstain from non-provided foods and beverages, including alcohol, during the controlled-diet period.
• Not willing to abstain from caffeine and any nicotine containing products (smoking, chewing, vaping, etc.) during the week prior to stress exposure days.

Sponsors & Collaborators

• United States Army Research Institute of Environmental Medicine: lead
• United States Army Combat Capabilities Development Command Soldier Center: collaborator
• United States Air Force Research Laboratory: collaborator

Study Sites (1)

United States Army Research Institute of Environmental Medicine

Natick, Massachusetts, 01760, United States

Location

MeSH Terms

Interventions

Probiotics; Prebiotics

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides

Study Officials

• J. Philip Karl, PhD, RD

  United States Army Research Institute of Environmental Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, study investigators, and study staff will be blinded to the intervention. A staff member not involved in the study will randomize the participants and inform the Principal Investigator of the randomization order upon enrollment of each participant.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Randomized, double blind, placebo controlled

Study Record Dates

• First Submitted: May 9, 2022
• First Posted: May 26, 2022
• Study Start: July 6, 2022
• Primary Completion: October 28, 2025
• Study Completion: October 28, 2025
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)