The Role of Dietary Tryptophan on Aryl Hydrocarbon Receptor Activation

NCT ID: NCT03059862

Last Updated: 2023-04-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-01

Study Completion Date

2018-06-30

Brief Summary

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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

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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.

Conditions

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Diet Modification

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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 Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Low-tryptophan diet and L-tryptophan.

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

Group Type EXPERIMENTAL

L-tryptophan

Intervention Type DIETARY_SUPPLEMENT

3 g/day of L-tryptophan added to the standardized low-tryptophan diet. Duration: 3 weeks.

Low-tryptophan diet and placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DIETARY_SUPPLEMENT

A placebo will be added to the standardized low-tryptophan diet. Duration: 3 weeks.

Interventions

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L-tryptophan

3 g/day of L-tryptophan added to the standardized low-tryptophan diet. Duration: 3 weeks.

Intervention Type DIETARY_SUPPLEMENT

Placebo

A placebo will be added to the standardized low-tryptophan diet. Duration: 3 weeks.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Healthy volunteer between 18 and 75 years of age.

Exclusion Criteria

* Rome IV criteria for any functional gastrointestinal disorder.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Research Agency, France

OTHER

Sponsor Role collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

McMaster University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Premysl Bercik, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University, Department of Medicine, Division of Gastroenterology

Locations

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McMaster Health Sciences Centre

Hamilton, Ontario, Canada

Site Status

Countries

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Canada

References

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Barouki R, Coumoul X, Fernandez-Salguero PM. The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein. FEBS Lett. 2007 Jul 31;581(19):3608-15. doi: 10.1016/j.febslet.2007.03.046. Epub 2007 Mar 30.

Reference Type BACKGROUND
PMID: 17412325 (View on PubMed)

Behnsen J, Raffatellu M. Keeping the peace: aryl hydrocarbon receptor signaling modulates the mucosal microbiota. Immunity. 2013 Aug 22;39(2):206-7. doi: 10.1016/j.immuni.2013.08.012.

Reference Type BACKGROUND
PMID: 23973218 (View on PubMed)

Bender DA. Biochemistry of tryptophan in health and disease. Mol Aspects Med. 1983;6(2):101-97. doi: 10.1016/0098-2997(83)90005-5. No abstract available.

Reference Type BACKGROUND
PMID: 6371429 (View on PubMed)

Cynober L, Bier DM, Kadowaki M, Morris SM Jr, Elango R, Smriga M. Proposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly. J Nutr. 2016 Dec;146(12):2652S-2654S. doi: 10.3945/jn.115.228478. Epub 2016 Nov 9.

Reference Type BACKGROUND
PMID: 27934658 (View on PubMed)

Hubbard TD, Murray IA, Bisson WH, Lahoti TS, Gowda K, Amin SG, Patterson AD, Perdew GH. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Sci Rep. 2015 Aug 3;5:12689. doi: 10.1038/srep12689.

Reference Type BACKGROUND
PMID: 26235394 (View on PubMed)

Kiss EA, Vonarbourg C, Kopfmann S, Hobeika E, Finke D, Esser C, Diefenbach A. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science. 2011 Dec 16;334(6062):1561-5. doi: 10.1126/science.1214914. Epub 2011 Oct 27.

Reference Type BACKGROUND
PMID: 22033518 (View on PubMed)

Kiss EA, Vonarbourg C. Aryl hydrocarbon receptor: a molecular link between postnatal lymphoid follicle formation and diet. Gut Microbes. 2012 Nov-Dec;3(6):577-82. doi: 10.4161/gmic.21865. Epub 2012 Aug 22.

Reference Type BACKGROUND
PMID: 22909905 (View on PubMed)

Li Y, Innocentin S, Withers DR, Roberts NA, Gallagher AR, Grigorieva EF, Wilhelm C, Veldhoen M. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell. 2011 Oct 28;147(3):629-40. doi: 10.1016/j.cell.2011.09.025. Epub 2011 Oct 13.

Reference Type BACKGROUND
PMID: 21999944 (View on PubMed)

Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, Zecchi R, D'Angelo C, Massi-Benedetti C, Fallarino F, Carvalho A, Puccetti P, Romani L. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013 Aug 22;39(2):372-85. doi: 10.1016/j.immuni.2013.08.003.

Reference Type BACKGROUND
PMID: 23973224 (View on PubMed)

Qiu J, Heller JJ, Guo X, Chen ZM, Fish K, Fu YX, Zhou L. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity. 2012 Jan 27;36(1):92-104. doi: 10.1016/j.immuni.2011.11.011. Epub 2011 Dec 15.

Reference Type BACKGROUND
PMID: 22177117 (View on PubMed)

Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, Brot L, Taleb S, Couturier-Maillard A, Nion-Larmurier I, Merabtene F, Seksik P, Bourrier A, Cosnes J, Ryffel B, Beaugerie L, Launay JM, Langella P, Xavier RJ, Sokol H. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016 Jun;22(6):598-605. doi: 10.1038/nm.4102. Epub 2016 May 9.

Reference Type RESULT
PMID: 27158904 (View on PubMed)

Other Identifiers

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Aryl-IMMUNE

Identifier Type: -

Identifier Source: org_study_id

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