{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:02:39Z","timestamp":1789783359202,"version":"4.0.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"Background<\/jats:title>Maternal high fat diet (mHFD) exposure expands IL-17 producing group 3 innate lymphoid cells (IL17+ve<\/jats:sup> ILC3) in the small intestine of neonatal murine offspring and increases their susceptibility to intestinal inflammation. How mHFD modulates innate immunity in the fetal offspring remains unclear.<\/jats:p><\/jats:sec>Methods<\/jats:title>Dams were exposed to 60% high fat diet or maintained on regular diet (RD) prior to and during mating. Amniotic fluid (AF) was collected during mid-pregnancy and metabolites examined by global non-targeted mass spectrometry in conventional wild-type (WT) and germ-free pregnant dams. Offspring were delivered by C-section or vaginally and fecal contents examined for major bacterial phyla and small intestinal lamina propria cells (LP) by flow cytometry. Susceptibility to intestinal inflammation was determined using a lipopolysaccharide and platelet-activating factor model (LPS\/PAF) in WT, germ-free and MyD88 deficient offspring. Neonatal germ-free pups were exposed to HFD or RD AF by gavage and LP examined by flow cytometry.<\/jats:p><\/jats:sec>Results<\/jats:title>We identified differentially produced metabolites in mHFD AF when compared to RD AF in conventionally raised mice, with no difference seen in germ-free mice. C-section delivery maintained the mHFD phenotype of expansion of IL17+ve<\/jats:sup> ILC3 and increased susceptibility to inflammation in neonatal offspring. In addition, mHFD offspring had expansion of IL17+ve<\/jats:sup> ILC3 at birth and 2 weeks of life, which was not seen in germ-free and MyD88 KO mice exposed to mHFD. Germ-free and MyD88 KO mice were protected from mHFD induced LPS\/PAF injury and IL17+ve<\/jats:sup> ILC3 expansion, demonstrating that the maternal microbiome and MyD88 are prenatally necessary for the expansion of IL17+ve<\/jats:sup> ILC3 in mHFD offspring. Furthermore, introduction of mHFD AF to neonatal germ-free pups by gavage was sufficient to expand IL17+ve<\/jats:sup> ILC3 in the small intestine.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings indicate that mHFD interacts with the maternal microbiome to modify AF metabolites and signal via MyD88 to expand IL17+ve<\/jats:sup> ILC3 in murine neonatal offspring.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1439804","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T11:13:57Z","timestamp":1731928437000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Maternal high fat diet exposure modifies amniotic fluid metabolites and expands group 3 innate lymphoid cells dependent on the maternal microbiome and 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