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Effect of Probiotic Administration on Serum Tryptophan Metabolites in Pediatric Type 1 Diabetes Patients.

ABSTRACT: Type 1 diabetes (T1D) is characterized by anomalous functioning of the immuno regulatory, tryptophan-catabolic enzyme indoleamine 2,3 dioxygenase 1 (IDO1). In T1D, the levels of kynurenine-the first byproduct of tryptophan degradation via IDO1-are significantly lower than in nondiabetic controls, such that defective immune regulation by IDO1 has been recognized as potentially contributing to autoimmunity in T1D. Because tryptophan catabolism-and the production of immune regulatory catabolites-also occurs via the gut microbiota, we measured serum levels of tryptophan, and metabolites thereof, in pediatric, diabetic patients after a 3-month oral course of Lactobacillus rhamnosus GG. Daily administration of the probiotic significantly affected circulating levels of tryptophan as well as the qualitative pattern of metabolite formation in the diabetic patients, while it decreased inflammatory cytokine production by the patients. This study suggests for the first time that a probiotic treatment may affect systemic tryptophan metabolism and restrain proinflammatory profile in pediatric T1D.

SUBMITTER: Mondanelli G

PROVIDER: S-EPMC7534075 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Effect of Probiotic Administration on Serum Tryptophan Metabolites in Pediatric Type 1 Diabetes Patients.

Mondanelli Giada G Orecchini Elena E Volpi Claudia C Panfili Eleonora E Belladonna Maria Laura ML Pallotta Maria Teresa MT Moretti Simone S Galarini Roberta R Esposito Susanna S Orabona Ciriana C

International journal of tryptophan research : IJTR 20200929

Type 1 diabetes (T1D) is characterized by anomalous functioning of the immuno regulatory, tryptophan-catabolic enzyme indoleamine 2,3 dioxygenase 1 (IDO1). In T1D, the levels of kynurenine-the first byproduct of tryptophan degradation via IDO1-are significantly lower than in nondiabetic controls, such that defective immune regulation by IDO1 has been recognized as potentially contributing to autoimmunity in T1D. Because tryptophan catabolism-and the production of immune regulatory catabolites-al ...[more]

PMID: 33061415

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Project description:BackgroundCrohn's disease (CD) exclusion diet combined with partial enteral nutrition (CDED + PEN) or exclusive enteral nutrition (EEN) is effective in inducing remission in mild-to-moderate pediatric CD. Although CDED + PEN is better tolerated and has higher compliance compared to EEN, a subset of patients does not achieve remission. Diet-induced remission is shown to be positively associated with specific changes in tryptophan-metabolites.ObjectivesTo investigate whether the abundance of baseline fecal tryptophan-metabolites predicts dietary therapy outcomes in pediatric CD.DesignDiagnostic accuracy study and secondary analysis of previously conducted Randomized Controlled Trial (RCT).MethodsTwenty-six patients from previously performed RCT of mild-to-moderate pediatric CD were included. The patients were classified as having clinical remission (R) (n = 19 in total; CDED + PEN = 10 and to EEN = 9) or No-Remission (NR) (n = 7 in total; CDED + PEN = 3 and EEN = 4) following 6 weeks of therapy, based on the Pediatric Crohn's Disease Activity Index score (⩽10 = remission). We performed a targeted quantitative analysis of 21 tryptophan-metabolites in baseline (t = 0) fecal samples from both groups, utilizing liquid chromatography coupled with quadrupole mass spectrometry. Receiver operator characteristic curve (ROC) and random forest analysis (RFA) were used to assess the predictive power of fecal tryptophan-metabolites for dietary outcomes at baseline. Ratios of tryptophan-metabolites were compared to investigate different downstream tryptophan pathways.ResultsBaseline fecal kynurenine level was significantly higher in NR compared to R for CDED + PEN (p = 0.02) and EEN (p = 0.04). ROC analysis highlighted the robust predictive power of kynurenine for CDED + PEN (area under the curve (AUC = 0.97)) and EEN (AUC = 0.88)-induced remission. RFA corroborated these observations. The ratio serotonin/kynurenine was the strongest predictor of CDED + PEN-induced remission (AUC = 1). The ratio 5-hydroxytryptophan/kynurenine (AUC = 0.88) predicted EEN-induced remission. By combining data from CDED + PEN and EEN, kynurenine (AUC = 0.91) and ratios of quinolinic acid/kynurenine (AUC = 0.93) and kynurenine/indole-3-acetic acid (AUC = 0.88) demonstrated strong predictive performance for dietary therapy-induced remission.ConclusionBaseline tryptophan metabolites have the potential to serve as a biomarker for dietary remission in pediatric CD. Some tryptophan metabolite ratios showed the most promising predictive capabilities. If confirmed in validation studies, baseline fecal tryptophan markers may be able to provide much-needed guidance to personalize dietary intervention within the management of pediatric CD.Trial registrationNCT01728870.

Dataset Information

Effect of Probiotic Administration on Serum Tryptophan Metabolites in Pediatric Type 1 Diabetes Patients.

Publications

Effect of Probiotic Administration on Serum Tryptophan Metabolites in Pediatric Type 1 Diabetes Patients.

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