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Effect of Early Diet on Gene Expression in Gastrointestinal Tract, Liver and Brain Regions of Neonatal Piglets

ABSTRACT: We leveraged neonatal piglets as a preclinical model for human infants, with a system-level approach that integrates evidence from serum, urine, liver, brain and the gastrointestinal tract (GIT), with the bioactive function of α-lactalbumin, a rich source of tryptophan, in a formula feeding study. Complementing metabolomics data generated throughout the GIT during the early feeding period, we further integrated quantitative serum, liver, brain and urine metabolome data, as well as liver and brain transcriptome data to investigate the metabolic consequences behind the differential responses to diet. Transcriptional and metabolomics analysis revealed an individualized, divergent response to α-lactalbumin linked to either efficient utilization of tryptophan by the host, or production of indole-3-lactate by intestinal microbiota. This variability was further highlighted by differences in metabolic and immunological effects in a tissue-specific manner. Our work highlights the importance of considering the nutrition-microbiota-host metabolism axis to optimize the phenotypic response of a diet.

ORGANISM(S): Sus scrofa

PROVIDER: GSE281726 | GEO | 2025/09/11

REPOSITORIES: GEO

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Project description:Stavrum2013 - Tryptophan Metabolism in Liver This model is described in the article: Model of tryptophan metabolism, readily scalable using tissue-specific gene expression data. Stavrum AK, Heiland I, Schuster S, Puntervoll P, Ziegler M. J. Biol. Chem. 2013 Nov; 288(48): 34555-34566 Abstract: Tryptophan is utilized in various metabolic routes including protein synthesis, serotonin, and melatonin synthesis and the kynurenine pathway. Perturbations in these pathways have been associated with neurodegenerative diseases and cancer. Here we present a comprehensive kinetic model of the complex network of human tryptophan metabolism based upon existing kinetic data for all enzymatic conversions and transporters. By integrating tissue-specific expression data, modeling tryptophan metabolism in liver and brain returned intermediate metabolite concentrations in the physiological range. Sensitivity and metabolic control analyses identified expected key enzymes to govern fluxes in the branches of the network. Combining tissue-specific models revealed a considerable impact of the kynurenine pathway in liver on the concentrations of neuroactive derivatives in the brain. Moreover, using expression data from a cancer study predicted metabolite changes that resembled the experimental observations. We conclude that the combination of the kinetic model with expression data represents a powerful diagnostic tool to predict alterations in tryptophan metabolism. The model is readily scalable to include more tissues, thereby enabling assessment of organismal tryptophan metabolism in health and disease. This model is hosted on BioModels Database and identified by: BIOMD0000000602. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Effect of Early Diet on Gene Expression in Gastrointestinal Tract, Liver and Brain Regions of Neonatal Piglets

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