A176 RESTORATION OF IMPAIRED MICROBIOTA-MEDIATED ARYL HYDROCARBON RECEPTOR SIGNALING IN PATIENTS WITH CELIAC DISEASE BY ORAL TRYPTOPHAN SUPPLEMENTATION: AN EXPLORATORY STUDY
Bibliographic record
Abstract
Abstract Background Celiac disease (CeD) is an autoimmune condition driven by gluten in individuals expressing celiac-specific genes (HLA-DQ2 and/or DQ8). A strict gluten-free diet (GFD) is currently the only treatment. 30-40% of celiac patients exhibit persistent symptoms despite following a GFD ampersand:003E1 year and are considered non-responsive. Tryptophan is an essential amino acid metabolized by gut microbiota to produce indoles that activate aryl hydrocarbon receptor (AhR), contributing to intestinal barrier homeostasis. Our previous study showed CeD patients have altered tryptophan metabolism and limited AhR activation, only partially improving with a GFD. In healthy volunteers, oral tryptophan supplementation improved AhR activation in the small intestine, thus, indicating its feasibility as adjuvant to the GFD in non-responsive CeD. Aims The study aims were to: 1) determine whether tryptophan supplementation improves celiac specific symptoms in non-responders; and 2) if tryptophan supplementation modifies gut microbiota composition, intestinal indole production and AhR activity. Methods The study is a double-blind, randomized, placebo-controlled trial with the aim to recruit 50 adults from the McMaster University Celiac Clinic. At visit 1, consented participants are randomized 1:1 to L-tryptophan (3g/day) or placebo and receive intervention capsules to be taken for 3 weeks after Visit 2. At Visits 2 and 3, participants complete dietary and symptom questionnaires, provide blood, stool, and urine samples, and undergo endoscopy. The primary outcome, improvement in symptoms, is assessed using the Celiac Symptoms Index (CSI); general GI symptoms by Gastrointestinal Symptoms Rating Scale (GSRS); mood symptoms by Hospital Anxiety and Depression Scale (HADS); quality of life by Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life questionnaire (PAGI-QoL). Results To- date we have recruited 10 participants. We will present blinded results from participants that have completed the study at the time of presentation based on responses to questionnaires pre, and post tryptophan/placebo intervention. At the time of analysis of this abstract, 5 participants had completed the study showing reduced CSI scores post intervention. The GSRS was also significantly reduced post intervention however, no change was observed in HADS and PAGI-QoL. Conclusions As all these results are currently blinded, we cannot attribute the symptom improvement to either tryptophan or the placebo effect. After unblinding the data, we will analyze the data to determine the extent of symptom reduction in relation to tryptophan metabolites (from urine, stool and duodenal aspirates) and AhR activation (from duodenal biopsy samples). Funding Agencies Weston Family Foundation
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".