Microbiota-mediated mechanisms of mucosal immunity across the lifespan.

TitleMicrobiota-mediated mechanisms of mucosal immunity across the lifespan.
Publication TypeJournal Article
Year of Publication2025
AuthorsIliev ID, J Blander M, Collins N, Guo C-J, Longman RS, Sonnenberg GF, Zeng MY, Artis D
JournalNat Immunol
Volume26
Issue10
Pagination1645-1659
Date Published2025 Oct
ISSN1529-2916
KeywordsAnimals, Gastrointestinal Microbiome, Humans, Immunity, Mucosal, Intestinal Mucosa, Longevity, Microbiota
Abstract

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.

DOI10.1038/s41590-025-02281-w
Custom 1

https://www.ncbi.nlm.nih.gov/pubmed/40957908?dopt=Abstract

Alternate JournalNat Immunol
PubMed ID40957908
PubMed Central IDPMC12700289
Grant ListR01 AR070116 / AR / NIAMS NIH HHS / United States
R01 CA286920 / CA / NCI NIH HHS / United States
R21 AI178327 / AI / NIAID NIH HHS / United States
R01 DK132244 / DK / NIDDK NIH HHS / United States
R00 CA252443 / CA / NCI NIH HHS / United States
R01 AT013241 / AT / NCCIH NIH HHS / United States
R01 AI172027 / AI / NIAID NIH HHS / United States
R01 AI163007 / AI / NIAID NIH HHS / United States
R01 AI143842 / AI / NIAID NIH HHS / United States
U01 AI095608 / AI / NIAID NIH HHS / United States
R37 AI174468 / AI / NIAID NIH HHS / United States
R01 DK113136 / DK / NIDDK NIH HHS / United States
R01 CA274534 / CA / NCI NIH HHS / United States
R01 DK135816 / DK / NIDDK NIH HHS / United States
R01 AI162936 / AI / NIAID NIH HHS / United States
R01 AI170897 / AI / NIAID NIH HHS / United States
R01 AI095466 / AI / NIAID NIH HHS / United States
R01 HL169989 / HL / NHLBI NIH HHS / United States
R01 AI145989 / AI / NIAID NIH HHS / United States
R01 DK121977 / DK / NIDDK NIH HHS / United States
R01 AI123368 / AI / NIAID NIH HHS / United States
R01 DK126871 / DK / NIDDK NIH HHS / United States
R01 AI182043 / AI / NIAID NIH HHS / United States
R01 AI178683 / AI / NIAID NIH HHS / United States
R01 AI151599 / AI / NIAID NIH HHS / United States
R01 HD110118 / HD / NICHD NIH HHS / United States
R01 AI170832 / AI / NIAID NIH HHS / United States

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