# Functional gut variability drives metabolic and transcriptional features in neonatal piglets

## TL;DR

This study explores how gut variability in neonatal piglets affects metabolic and gene activity responses to a specific protein in formula.

## Contribution

The study reveals individualized responses to α-lactalbumin linked to host tryptophan use or microbial indole-3-lactate production.

## Key findings

- Transcriptional and metabolomics analysis showed divergent responses to α-lactalbumin in neonatal piglets.
- Variability in responses was linked to either host tryptophan utilization or microbial indole-3-lactate production.
- Differences in metabolic and immunological effects were observed in a tissue-specific manner.

## Abstract

The inherent inter-individual variability and associated complexity of dietary response constitute a major research challenge, but also present an opportunity to trace personalized patterns that may serve as targets for improving health. Here, we investigated the function of α-lactalbumin, a rich source of tryptophan, in a formula feeding study. We leveraged neonatal piglets as a preclinical model for human infants and took a systems-level approach that integrates evidence from serum, urine, liver, brain, and the gastrointestinal tract. 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.