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

United States Army Research Institute of Environmental Medicine

Status: Enrolling

Conditions: Stress Physiology

Treatments: Dietary Supplement: Probiotic; Dietary Supplement: Prebiotic; Other: Placebo

Study type: Interventional

Funder types: Other U.S. Federal agency; Other

Identifiers

NCT05392556

21-03-HC

M-10901 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 54 estimated patients

Sex: All

Ages: 17 to 39 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• Not willing to refrain from strenuous exercise for 24hr prior to stress exposure days.
• Allergies, intolerances, unwillingness or inability to eat intervention supplements, or provided foods and beverages.
• Following vegetarian/vegan diet or other highly restrictive diet (e.g., ketogenic diet, very high protein diet, Paleo diet).
• Any previous blood donation, within 8 weeks of a study blood draw, of a volume that when combined with the amount of blood to be collected during the study would exceed 550 mL

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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54 participants in 3 patient groups, including a placebo group

Probiotic

Experimental group

Description:

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

Treatment:

Dietary Supplement: Probiotic

Prebiotic

Experimental group

Description:

Bimuno-galactooligosaccharide (Bimuno-GOS; Clasado Biosciences)

Treatment:

Dietary Supplement: Prebiotic

Placebo

Placebo Comparator group

Description:

Maltodextrin placebo

Treatment:

Other: Placebo