Effect of Early Diet on Gene Expression in Gastrointestinal Tract, Liver and Brain Regions of Neonatal Piglets
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 a-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 a-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. Overall design: 30 Piglets stayed with their sows for the first 5 days post-birth to consume colostrum. We conducted a feeding trial from postnatal day 6 to 16. On postnatal day 6, they were stratified by weight, sex, and litter and then randomly assigned to either continue with sow's milk (SF reference group) or to start one of two piglet formulas: an a-lactalbumin enriched formula (ALAC group) or an formula cotaining a-lactalbumin reduced, whey protein isolate WPI formula (WPI group). We evaluated the gene expression profile of jejunum, ileum, colon, prefrontal cortex, striatum, hippocampus, hypothalamus and liver on postnatal day 16.