A248 THE ROLE OF DIETARY TRYPTOPHAN IN INDOLE AND KYNURENINE PRODUCTION AND IMMUNE MODULATION IN HEALTHY INDIVIDUALS
Bibliographic record
Abstract
Abstract Background Natural supplements are widely consumed by the general public, with little evidence of mechanistic support. Tryptophan has gained central attention, being transformed by host and gut microbial enzymes into multiple bioactive metabolites that regulate immunity and mood. Indoles are activators of the aryl hydrocarbon receptor (AhR), crucial for the maintenance of intestinal homeostasis. Tryptophan has been advocated to prevent chronic inflammatory conditions, however the clinical data to support this are missing. Aims To investigate clinical, immune, and metabolic parameters in response to tryptophan supplementation, in healthy subjects on a low tryptophan diet. Methods We performed a randomized, double blind, placebo-controlled crossover study in 20 healthy volunteers (18 - 75 years old). Subjects were instructed to start a low tryptophan diet and then randomly assigned to a 3-week tryptophan supplementation (3g/day) or placebo, in enteric coated capsules. After a 2-week washout period, subjects crossed over to the opposite intervention arm. Questionnaires were used to assess bowel symptoms, anxiety, depression and stress levels (GSRS, HADS and DASS21, respectively). Stool, urine, blood and duodenal aspirates were collected to measure tryptophan metabolites and cytokines. Results Tryptophan supplementation had no changes in gastrointestinal symptoms or behavioral parameters. Compared with placebo, tryptophan increased urinary and plasma levels of indoleamine 2,3-dioxygenase/kynurenine (p= 0.002 and p= 0.02, respectively) and indoles (p= 0.001 and p= 0.01, respectively), suggestive of activation of host and microbial metabolic pathways. Urinary and plasma metabolites were higher than in feces (p=<0.05), suggesting their active absorption in the small intestine. There were no differences in AhR activity in duodenal aspirates or in stool. Although no changes in the cytokine production were detected, serum kynurenine pathway metabolites negatively correlated with IL-8 levels (R=-0.72; p=0.001). Fecal tryptophan metabolites levels positively correlated with anxiety and depression scores, suggesting that the microbial metabolism of dietary tryptophan in the colon impacts host behavior. Conclusions Tryptophan supplementation in healthy individuals was safe and had a measurable influence on microbial and host metabolism, mainly kynurenine and indole pathways, with known immunomodulatory properties. Tryptophan was metabolized and absorbed in the small intestine, reflected by the high metabolite levels in plasma and urine. Fecal metabolites correlating with clinical parameters reflect subjects’ long-term diet. Further studies are warranted to study tryptophan supplementation in disorders with altered AhR pathways. Funding Agencies CIHR
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".