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<p>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.</p>

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Functional gut variability drives metabolic and transcriptional features in neonatal piglets

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月16日

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  • Xuan He,
  • Shannon Shoff,
  • Hanna Lee,
  • Merete Lindberg Hartvigsen,
  • Anne Staudt Kvistgaard,
  • Carolyn M. Slupsky

摘要

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.