A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability

Not Applicable

Recruiting

Interventions: Dietary Supplement: L-Tryptophan
Dietary Supplement: Prebiotic
Dietary Supplement: Placebo

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Executive functions during a prolonged stress task (the Leuven Prolonged Stress Test)	Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.	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.

Secondary Outcome Measures

Name	Time	Method
Intestinal permeability after a prolonged stress task (the Leuven Prolonged Stress Test)	Measured at the pre-intervention and immediately after the 4 week intervention.	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.
Stress response to a prolonged stress test (the Leuven Prolonged Stress Test)	During the stress task (at multiple time points during 120 min), measured at the pre-intervention and immediately after the 4 week intervention.	Cortisol, blood pressure, and subjective stress. Cortisol will be measured in saliva. Subjective stress will be measured using a Visual Analogue Scale (VAS)