Diet Modification
Conditions
Keywords
immunity, Aryl-hydrocarbon receptor, immune homeostasis, microbiota, tryptophan
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.
Interventions
DIETARY_SUPPLEMENTL-tryptophan
3 g/day of L-tryptophan added to the standardized low-tryptophan diet. Duration: 3 weeks.
DIETARY_SUPPLEMENTPlacebo
A placebo will be added to the standardized low-tryptophan diet. Duration: 3 weeks.
Sponsors
National Research Agency, France
Canadian Institutes of Health Research (CIHR)
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteer between 18 and 75 years of age.
Exclusion criteria
* Rome IV criteria for any functional gastrointestinal disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AHR activation levels in stool and duodenal content. | 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
| Measure | Time frame | Description |
|---|---|---|
| Tryptophan metabolites levels, including host and bacterial catabolites, in blood, urine and stool. | Three weeks | Changes in tryptophan metabolites leves will be compared before and after the intervention, in blood, urine and stool samples. |
| mRNA levels in duodenal and rectum/sigmoid biopsies. | three weeks | Changes in mRNA levels in duodenal and rectum/sigmoid biopsies will be assessed before and after the intervention. |
| Bacterial and fungal microbiota composition in stool, duodenum and rectum/sigmoid biopsies. | Three weeks | Changes in bacterial and fungal microbiota composition will be assessed before and after the intervention in stool samples, duodenum and rectum biopsies. |
| Gastrointestinal symptoms | three weeks. | Changes in gastrointestinal symptoms before and after the intervention will be assessed using a validated questionnaire (The Gastrointestinal Symptoms Rating Scale) |
| Mood | three weeks | Changes in mood before and after the intervention will be assessed using a validated questionnaire (Hospital anxiety and depression scale) |
| Cytokines in serum. | three weeks. | Changes in cytokines in the serum (IL-22, IL-6, IL-2, IL-10, IL-12p70, IL-23p19, IFNγ, TNFα and CRP will be measured by ELISA in cell culture supernatants after stimulation with LPS, curdlan and ConA ) will be measured before and after the intervention and patients will be grouped into two categories for each measurement: high vs. low, according to the cutoff reference test value for each of the cytokines. |
Countries
Canada
Outcome results
None listed