The Role of Tryptophan on Aryl Hydrocarbon Receptor Activation: a Randomized, Double Blind, Placebo-controlled, Crossover Design Pilot Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- McMaster University
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- AHR activation levels in stool and duodenal content.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy volunteer between 18 and 75 years of age.
Exclusion Criteria
- •Rome IV criteria for any functional gastrointestinal disorder.
Outcomes
Primary Outcomes
AHR activation levels in stool and duodenal content.
Time Frame: three weeks
Changes in AHR activation levels will be assessed in stool and duodenal samples before and after the intervention (high- and low-tryptophan diets) using an AHR cell-reporter line.
Secondary Outcomes
- Tryptophan metabolites levels, including host and bacterial catabolites, in blood, urine and stool.(Three weeks)
- Bacterial and fungal microbiota composition in stool, duodenum and rectum/sigmoid biopsies.(Three weeks)
- Cytokines in serum.(three weeks.)
- mRNA levels in duodenal and rectum/sigmoid biopsies.(three weeks)
- Gastrointestinal symptoms(three weeks.)
- Mood(three weeks)