The Role of Dietary Tryptophan on Aryl Hydrocarbon Receptor Activation (Aryl-IMMUNE)

McMaster University

Status: Completed

Conditions: Diet Modification

Treatments: Dietary Supplement: Placebo; Dietary Supplement: L-tryptophan

Study type: Interventional

Funder types: Other

Identifiers

NCT03059862

Aryl-IMMUNE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy volunteer between 18 and 75 years of age.

Exclusion criteria

• Rome IV criteria for any functional gastrointestinal disorder.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups, including a placebo group

Low-tryptophan diet and L-tryptophan.

Experimental group

Description:

Standardized low-tryptophan diet (500-1000 mg of L-tryptophan and 1800 kcal) + L-tryptophan supplements (3 g/day).

Treatment:

Dietary Supplement: L-tryptophan

Low-tryptophan diet and placebo

Placebo Comparator group

Description:

Standardized low-tryptophan diet (500-1000 mg of L-tryptophan and 1800 kcal) + placebo.

Treatment:

Dietary Supplement: Placebo