Maternal gut microbiome composition and diet modulate early life immune development
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. As dietary fiber exerts a powerful impact on both the microbiome and immune function in adult mice, we sought to understand its role in early life by breeding mice colonized with a 14-member synthetic microbiome community (14SM), fed a fiber-rich (FR) and fiber-free (FF) diet. We then performed longitudinal sampling of distal colon contents and tissue among pups between 10–30 days old. Pups born to dams fed a fiber-rich diet exhibited an initial colonisation of Akkermansia muciniphila, a mucin-degrading microbe that utilizes milk oligosaccharides in early life, which was followed by expansion of fiber-degrading bacteria when began to consume solid food (20 postnatal days). Interestingly, A. muciniphila did not proliferate in the colons of mice born to dams fed a FF diet until the pups switched from maternal milk to a FF diet (20 postnatal days), at which time mucolytic A. muciniphila and Bacteroides caccae, rapidly expanded to comprise approximately 70% of the bacterial community at all subsequent time points. Compared to the mice born to FR-fed dams, FF-fed mice also exhibited enrichment of transcripts corresponding to defense response pathways against external antigens at 15 days of age. Flow cytometry at the same time point revealed elevated levels of CD8+ T cells and group 3 innate lymphoid cells among FF-fed mice. Removal of Akkermansia from the community but maintaining a fiber-rich diet (13SM FR) was inversely related to the proportions of RORgt+ T effector cells, at the expense of Th1 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.