The Role of Dietary Tryptophan on Aryl Hydrocarbon Receptor Activation
NCT ID: NCT03059862
Last Updated: 2023-04-13
Study Results
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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COMPLETED
NA
20 participants
INTERVENTIONAL
2017-11-01
2018-06-30
Brief Summary
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Detailed Description
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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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Study Design
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RANDOMIZED
CROSSOVER
OTHER
QUADRUPLE
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).
L-tryptophan
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.
Placebo
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.
Placebo
A placebo will be added to the standardized low-tryptophan diet. Duration: 3 weeks.
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
18 Years
75 Years
ALL
Yes
Sponsors
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National Research Agency, France
OTHER
Canadian Institutes of Health Research (CIHR)
OTHER_GOV
McMaster University
OTHER
Responsible Party
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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
Countries
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
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Aryl-IMMUNE
Identifier Type: -
Identifier Source: org_study_id
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