Microbiota and glucocorticoids regulate postnatal developmental of intestinal Fut2 gene expression

Abstract

Intestinal maturation is regulated by intrinsic (glucocorticoid) and extrinsic (resident microflora) factors and the goal of this study is to determine the relative contribution of these two regulators in the postnatal development of α1,2‐fucosyltransferase II (Fut2) and sucrase‐isomaltase (SI) gene expression. In conventional raised (CONV) mice, ontogeny of Fut2 and SI gene expression was completed by fourth week. In the absence of colonization in germ‐free (GF) and bacteria‐depleted (BD) mice, intestinal Fut2 expression returned to low suckling levels. Ten days after colonization with adult, but not with suckling, gut microbiome, expression of Fut2 mRNA, α1,2‐fucosyltransferase activity and fucose α1,2‐linked glycoconjugates expression is fully recovered. In the GF mice, the rate of Fut2 and SI ontogeny was significantly delayed. Cortisone acetate (CA) precociously accelerated both Fut2 and SI gene expression in conventionally raised suckling pups. In the GF suckling mice, CA treatment precociously induced development of SI but not Fut2 gene expression. Thus, both microbes and glucocorticoids regulate gut ontogeny, but only suckling gut responds to CA and Fut2 expression remains primarily sensitive to adult microbiome. Complete recovery from mucosal injury caused by DSS‐treatment was observed in the CONV, but not in BD mice. Lack of recovery in BD mice correlated with the level of Fut2 expression in the gut. Thus, colonization by adult microbiota stimulated mature Fut2 gene expression and fucosylated gut phenotype; this colonization‐dependent Fut2 induction is necessary for full recovery from intestinal injury. This may explain the significant association observed between individuals expressing low Fut2 gene expression because of specific Fut2 polymorphic alleles and Crohn's disease and necrotizing enterocolitis.Supported by D059126, HD013021, AI075563, and DK070260.