Clinical trial NCT05392556: Prebiotic and Probiotic Modulation of the Gut Microbiota-gut-brain Axis During Acute Stress
Official title: Prebiotic and Probiotic Modulation of the Gut Microbiota-gut-brain Axis During Acute Stress
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stress Physiology
Keywords: Probiotic
Prebiotic
Microbiome
Stress
Lead sponsor: United States Army Research Institute of Environmental Medicine
Sponsor class: FED
Collaborators: name: United States Army Combat Capabilities Development Command Soldier Center
name: United States Air Force Research Laboratory
First posted: 2022-05-26
Enrollment: 54
Sex: ALL
Minimum age (years): 17
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double blind, placebo controlled
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in intestinal permeability
timeFrame: Days 0 and 29
measure: Difference from baseline in circulating cortisol concentrations
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
Secondary outcomes:
measure: Change from baseline in mean heart rate variability
timeFrame: During stress exposure (up to 4hr) on days 0 and 29.
measure: Change from baseline in performance on decision making under conditions of ambiguity task
timeFrame: Days 0 and 29
measure: Difference from baseline in reaction time.
timeFrame: Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
measure: Difference from baseline in response inhibition
timeFrame: Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
measure: Difference from baseline in working memory
timeFrame: Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
measure: Difference from baseline in distractibility to emotional stimuli
timeFrame: Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
measure: Difference from baseline in emotional states measured by the Depression, Anxiety and Stress Scale (DASS)
timeFrame: Day 0, Week 1, Week 2, Week 3, Day 29
measure: Difference from baseline in mood state measured by the Profile of Mood States 2-A (POMS2A)
timeFrame: Before (-45min) and immediately after exercise, and after cognitive stress exposure on days 0 and 29
measure: Difference from baseline in feelings of pleasantness
timeFrame: Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
measure: Difference from baseline in feelings of arousal
timeFrame: Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
measure: Difference from baseline in gastrointestinal discomfort
timeFrame: Day 0, Week 1, Week 2, Week 3, Day 29
measure: Difference from baseline in gastrointestinal symptoms
timeFrame: Day 0, Week 1, Week 2, Week 3, Day 29
measure: Difference from baseline in circulating cytokines concentrations.
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29
measure: Difference from baseline in circulating dehydroepiandrosterone-sulfate (DHEA-S) concentrations
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29
measure: Difference from baseline in circulating epinephrine concentrations
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
measure: Difference from baseline in circulating norepinephrine concentrations
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
measure: Difference from baseline in circulating neuropeptide Y concentrations
timeFrame: Before (-20min) exercise and immediately before cognitive stress exposure on days 0 and 29
measure: Difference from baseline in circulating brain-derived neurotrophic factor (BDNF) concentrations
timeFrame: Before (-20min) exercise and immediately before cognitive stress exposure on days 0 and 29
measure: Difference from baseline in circulating S100 calcium binding protein B (S100B) concentrations
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
measure: Difference from baseline in circulating lipopolysaccharide concentrations
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
measure: Difference from baseline in circulating zonulin concentrations
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
measure: Difference from baseline in circulating intestinal fatty acid binding protein (I-FABP) concentrations.
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
measure: Difference from baseline in fecal acetate concentrations
timeFrame: Pre-intervention, week 3 and week 4
measure: Difference from baseline in fecal propionate concentrations
timeFrame: Pre-intervention, week 3 and week 4
measure: Difference from baseline in fecal butyrate concentrations
timeFrame: Pre-intervention, week 3 and week 4
measure: Difference from baseline in gut microbiota composition
timeFrame: Pre-intervention, week 3 and week 4
measure: Change from baseline in salivary secretory immunoglobulin A
timeFrame: Day 0 and Day 29
measure: Difference from baseline in salivary cortisol concentrations
timeFrame: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29
Other outcomes:
measure: Change from baseline in mean heart rate
timeFrame: During stress exposure (up to 4hr) on days 0 and 29
measure: Change from baseline in exercise energy expenditure
timeFrame: During exercise (120min) on days 0 and 29
measure: Change from baseline in mean respiratory exchange ratio
timeFrame: During exercise (120min) on days 0 and 29
measure: Difference from baseline in perceived exertion
timeFrame: Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29
measure: Change from baseline in aggression
timeFrame: Days 0 and 29
measure: Subjective pain ratings
timeFrame: Day 29
measure: Difference from baseline in circulating metabolite levels
timeFrame: Before (-20min) exercise and immediately after cognitive stress exposure on days 0 and 29
measure: Difference from baseline in fecal metabolite levels
timeFrame: Pre-intervention, week 3 and week 4
measure: Difference from baseline in circulating glucose concentrations
timeFrame: Before (-20min) and immediately after (120min) exercise on days 0 and 29
measure: Difference from baseline in circulating lactate concentrations
timeFrame: Before (-20min) and immediately after (120min) exercise on days 0 and 29
measure: Difference from baseline in subjective ratings of fatigue
timeFrame: Day 0, Week 1, Week 2, Week 3, Day 29
measure: Difference from baseline in circulating acetate concentrations
timeFrame: Before (-20min) and immediately after (120min) exercise on days 0 and 29
measure: Difference from baseline in circulating propionate concentrations
timeFrame: Before (-20min) and immediately after (120min) exercise on days 0 and 29
measure: Difference from baseline in circulating butyrate concentrations
timeFrame: Before (-20min) and immediately after (120min) exercise on days 0 and 29
measure: Difference from baseline in fecal valerate concentrations
timeFrame: Pre-intervention, week 3 and week 4
measure: Difference from baseline in fecal isobutyrate concentrations
timeFrame: Pre-intervention, week 3 and week 4
measure: Difference from baseline in fecal isovalerate concentrations
timeFrame: Pre-intervention, week 3 and week 4
measure: Difference from baseline in fecal abundance of probiotic bacteria
timeFrame: Pre-intervention, week 3 and week 4
measure: Difference from baseline in gut microbiota gene content
timeFrame: Pre-intervention, week 3 and week 4
Locations:
city: Natick
country: United States
facility: United States Army Research Institute of Environmental Medicine
state: Massachusetts
Study officials:
affiliation: United States Army Research Institute of Environmental Medicine
name: J. Philip Karl, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References: