A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability

KU Leuven48 enrolled

Overview

The interaction between the gut microbiome, the intestinal barrier, and the host plays an important role in human health. The integrity of the intestinal barrier is essential to protect against translocation of food antigens and immunostimulatory microbial metabolites from the gut lumen. Accumulating studies show that stress may negatively affect the intestinal barrier function. In a previous study, the investigators developed the Leuven Prolonged Acute Stress Test (L-PAST), which combines physical (cold water), mental (arithmetic), and social (negative feedback) aspects of stress for a prolonged (2h) time. In the current study the investigators would like, as a first aim, to investigate whether the L-PAST 1) increases intestinal permeability compared to baseline intestinal permeability, and 2) whether a nutritional intervention can improve baseline intestinal permeability as well as intestinal permeability after exposure to the L-PAST in both healthy females and men. As a second aim of the present study, the investigators would like to investigate whether prebiotics and/or L-tryptophan can attenuate the cortisol response to stress. Lastly, as acute psychosocial stress impairs cognitive functions, the investigators would like as a third aim to investigate whether prebiotics and/or L-tryptophan supplementation may prevent these impairments.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Stress, Psychological

Interventions

PrebioticDIETARY_SUPPLEMENT

Group 1 (prebiotic and placebo L-tryptophan): prebiotic (oligofructose, Orafti®P95, 20g/day) and placebo L-tryptophan (microcrystalline cellulose, 3g/day)

L-TryptophanDIETARY_SUPPLEMENT

Group 2 (placebo prebiotic and L-tryptophan): L-tryptophan (3g/day) and placebo prebiotic (microcrystalline cellulose, 20g/day)

PlaceboDIETARY_SUPPLEMENT

Group 3 (placebo prebiotic and placebo L-tryptophan): placebo prebiotic (microcrystalline cellulose, 20g/day) and placebo L-tryptophan (microcrystalline cellulose, 3g/day).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18 till 40 years (both included) * BMI range: 18.5 - 25 kg/m² * Females: Use of contraceptives, and have to use the current contraceptive method for at least 4 months. A regular menstrual cycle (between 25 and 35 days; if not using oral contraceptives) * Subject is willing to not consume caffeine, or alcohol, to refrain from smoking, and not to engage in heavy physical exercise three days before the test days, as well as to not consume dairy products and chewing gum the day before and the day of the test days * Subject is willing to not take any non-steroidal anti-inflammatory drugs (NSAIDs) two weeks before the test days (see Appendix G for an overview of NSAIDs) * Subject, upon briefing of the content of the present study, fully understands and agrees to its objective and has given written (dated and signed) informed consent form to take part in the study * Subject is able to communicate well with the investigator and follow instructions given by the investigator Exclusion Criteria: * Subject has a previous or current neurological, psychiatric, gastrointestinal, or endocrine disorder, or other relevant medical history * Subject has one or more diagnoses based on the MINI international neuropsychiatric interview * Subject has one or more diagnoses based on the ROME-IV for GI disorders * Subject uses regular medication (i.e., anti-allergy medication, PPI's, and medication that can affect gut motility), currently or recently (in the last 2 weeks) (except for oral contraceptives) * Subject has used recreational drugs in the past 6 months * Subject consumes regularly (\>1/week) more than 3 units of alcohol per day * Subjects smokes \>7 cigarettes per week * Subject has to work in night-shifts * Subject is pregnant or lactating * Subject has previous experience with the stress test used in the study * Subject has taken prebiotics or probiotics in the last month * Subject has taken antibiotics in the last 3 months * Subjects consumes \>25g of fiber per day in their habitual diet

Outcomes

Primary Outcomes

Executive functions during a prolonged stress task (the Leuven Prolonged Stress Test)

Working memory, cognitive flexibility, and response inhibition. Working memory will be assessed using the forward digit span. Cognitive flexibility will be assessed using the Wisconsin Card Sorting Test. Response inhibition will be assessed using the Stop Signal Task.

Time frame: Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.

Secondary Outcomes

Intestinal permeability after a prolonged stress task (the Leuven Prolonged Stress Test)

Intestinal permeability will be measured using the lactulose-mannitol test. The lactulose-mannitol ratio will be calculated and used as a measure for small intestinal permeability. Fractional excretion of lactulose and mannitol will also be assessed.

Time frame: Measured at the pre-intervention and immediately after the 4 week intervention.

Stress response to a prolonged stress test (the Leuven Prolonged Stress Test)

Cortisol, blood pressure, and subjective stress. Cortisol will be measured in saliva. Subjective stress will be measured using a Visual Analogue Scale (VAS)

Time frame: During the stress task (at multiple time points during 120 min), measured at the pre-intervention and immediately after the 4 week intervention.