Clinical trial NCT03059862: The Role of Dietary Tryptophan on Aryl Hydrocarbon Receptor Activation
Official title: The Role of Tryptophan on Aryl Hydrocarbon Receptor Activation: a Randomized, Double Blind, Placebo-controlled, Crossover Design Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diet Modification
Keywords: immunity
Aryl-hydrocarbon receptor
immune homeostasis
microbiota
tryptophan
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: National Research Agency, France
name: Canadian Institutes of Health Research (CIHR)
First posted: 2017-02-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: All subjects will be following a standardized low-tryptophan diet and randomized to L-tryptophan supplements or placebo, for three weeks. After a 2 weeks washout period, subjects will crossover to the other arm.
Primary purpose: OTHER

Brief summary: This study evaluates the role of dietary L-tryptophan, an essential amino acid, in the activation of a specific cellular component: the aryl hydrocarbon receptor.

Detailed description: The Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor implicated in a range of key cellular events. In the gut, AHR is crucial for maintaining intestinal barrier immune homeostasis. The physiology of the AHR, however, is not completely understood; its precise gut luminal activators and functional consequences are unknown.

Some AHR ligands originate from the diet. Commensals play crucial roles in metabolizing tryptophan and other amino acids such as tyrosine, with the subsequent production of tryptophan metabolites. Previous studies show that inflammatory bowel disease (IBD) patients have impaired production of AHR agonists by the microbiota. Furthermore, dietary supplementation with tryptophan ameliorates clinical parameters of colitis in rodent models. Whether these findings translate into human pathophysiology has not been explored.

In the present study, the investigators will evaluate the effect of high- versus low-tryptophan diet on AHR activation in healthy participants. Briefly, participants will be instructed to follow a standardized low-tryptophan diet and will be randomized to a 3-week L-tryptophan supplement or placebo. Later, after a 2-week washout period, participants will crossover to the other arm. In addition, the effect of tryptophan and microbiota-derived metabolites on AHR activation will be analyzed.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteer between 18 and 75 years of age.

Exclusion Criteria:

* Rome IV criteria for any functional gastrointestinal disorder.

Primary outcomes:
measure: AHR activation levels in stool and duodenal content.
timeFrame: three weeks
Secondary outcomes:
measure: Bacterial and fungal microbiota composition in stool, duodenum and rectum/sigmoid biopsies.
timeFrame: Three weeks
measure: Tryptophan metabolites levels, including host and bacterial catabolites, in blood, urine and stool.
timeFrame: Three weeks
measure: mRNA levels in duodenal and rectum/sigmoid biopsies.
timeFrame: three weeks
measure: Cytokines in serum.
timeFrame: three weeks.
measure: Gastrointestinal symptoms
timeFrame: three weeks.
measure: Mood
timeFrame: three weeks
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster Health Sciences Centre
state: Ontario
Study officials:
affiliation: McMaster University, Department of Medicine, Division of Gastroenterology
name: Premysl Bercik, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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