PT - JOURNAL ARTICLE AU - Erica T. Grant AU - Marie Boudaud AU - Arnaud Muller AU - Andrew J. Macpherson AU - Mahesh S. Desai TI - Maternal diet and gut microbiome composition modulate early life immune responses AID - 10.1101/2023.03.06.531289 DP - 2023 Jan 01 TA - bioRxiv PG - 2023.03.06.531289 4099 - http://biorxiv.org/content/early/2023/03/06/2023.03.06.531289.short 4100 - http://biorxiv.org/content/early/2023/03/06/2023.03.06.531289.full AB - In early life, the intestinal mucosa and immune system undergo a critical developmental process to contain the expanding gut microbiome while promoting tolerance towards commensals, yet the influence of maternal diet and gut microbial composition on offspring immune maturation remains poorly understood. We colonized gnotobiotic mice with a defined consortium of 14 strains, fed them a fiber-free diet, and then longitudinally assessed offspring development during the weaning period. Unlike pups born to dams fed a standard, fiber-rich chow, pups of fiber-deprived dams demonstrated delayed colonization with Akkermansia muciniphila, a mucin-foraging bacterium that can also utilize milk oligosaccharides. The pups of fiber-deprived dams exhibited an enrichment of colonic tissue transcripts corresponding to defense response pathways and a peak in Il22 expression at weaning. Removal of A. muciniphila from the community, but maintenance on the fiber-rich diet, was associated with reduced proportions of RORĪ³t-positive innate and adaptive immune cell subsets. Our results highlight the potent influence of maternal dietary fiber intake and discrete changes in microbial composition on the postnatal microbiome assemblage and early immune priming.Competing Interest StatementMahesh S. Desai works as a consultant and an advisory board member at Theralution GmbH, Germany.