Erica GRANT

Maternal gut microbiome composition and diet modulate early life immune responses
Early life is a critical period for the development of the newborn intestine, which undergoes microbiome colonization concomitant with the maturation of the mucus barrier and the immune system. In order to understanding of the role of the maternal microbiome on immune development in pups, we bred mice colonized with a 13 or 14-member synthetic microbiome community (13SM or 14SM), with or without Akkermansia muciniphila, a mucin-degrading microbe that utilizes milk oligosaccharides in early life. Since dietary fiber also exerts a powerful impact on the microbiome and immune function, we also bred 14SM-colonized mice on a fiber-free (FF) diet. Pups born to dams fed a fiber-rich (FR) diet exhibit an initial expansion of A. muciniphila, which reduces when pups begin to consume solid food (20 postnatal days). Interestingly, A. muciniphila does not proliferate in the colons of mice born to dams fed a fiber-free (FF) diet until the pups switch from maternal milk to a FF diet (20 postnatal days), at which time A. muciniphila and Bacteroides caccae rapidly expand to comprise approximately 70% of the bacterial community abundance at all subsequent time points. Compared to the mice born to FR-fed dams, FF-fed mice also exhibited enrichment of transcripts such as Nos2, Cxcl9, Tgpt1, Gm4841, Gbp2, and Lcn2, corresponding to pathways for response to interferon-gamma and beta and defense response pathways against external antigens. Fluorescence-activated cell sorting at the same time point revealed elevated levels of CD8+ T cells and group 3 innate lymphoid cells among FF-fed mice. Absence (13SM FR) or low-levels (14SM FF) of A. muciniphila was inversely related to the proportions of RORgt+ T effector cells. Our results underscore the powerful influence of maternal dietary fiber intake in the postnatal establishment of mucolytic communities and the maturation of the intestinal mucosal barrier.

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