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<p>The microbiota has a fundamental role in regulating homeostasis and inflammation across the barrier surfaces of the body. The gut is a unique bioreactor where the high concentration of microorganisms, microbial and dietary metabolites, microbial-derived molecular structures, immune cells, stroma and neurons form a complex, highly interactive and precisely regulated system. The mucosal immune system in the gut has profound local and systemic effects, influencing both health and disease. A critical period of immune imprinting occurs early in life, shaped by the neonatal microbiota and nutrition, to influence immune development and long-term disease susceptibility. Microbiota-derived metabolites have crucial roles in immune modulation, influencing epithelial integrity, oral tolerance and inflammatory responses. This Review explores the interactions between the microbiota and the mucosal immune system from infancy to adulthood, highlighting the impact on health and disease. We also discuss therapeutic interventions, including microbiota-derived molecules, dietary metabolites and emerging microbiome-based co-therapies.</p>

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Microbiota-mediated mechanisms of mucosal immunity across the lifespan

  • 期刊论文

  • 发表日期：

    2025年9月16日

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  • Iliyan D. Iliev,
  • J. Magarian Blander,
  • Nicholas Collins,
  • Chun-Jun Guo,
  • Randy S. Longman,
  • Gregory F. Sonnenberg,
  • Melody Y. Zeng,
  • David Artis

摘要

The microbiota has a fundamental role in regulating homeostasis and inflammation across the barrier surfaces of the body. The gut is a unique bioreactor where the high concentration of microorganisms, microbial and dietary metabolites, microbial-derived molecular structures, immune cells, stroma and neurons form a complex, highly interactive and precisely regulated system. The mucosal immune system in the gut has profound local and systemic effects, influencing both health and disease. A critical period of immune imprinting occurs early in life, shaped by the neonatal microbiota and nutrition, to influence immune development and long-term disease susceptibility. Microbiota-derived metabolites have crucial roles in immune modulation, influencing epithelial integrity, oral tolerance and inflammatory responses. This Review explores the interactions between the microbiota and the mucosal immune system from infancy to adulthood, highlighting the impact on health and disease. We also discuss therapeutic interventions, including microbiota-derived molecules, dietary metabolites and emerging microbiome-based co-therapies.