Regulation of intestinal ontogeny: effect of glucocorticoids and luminal microbes on galactosyltransferase and trehalase induction in mice

Intestinal maturation can be influenced by intrinsic factors (glucocorticoid hormones) and by extrinsic factors (resident microflora); their relative roles in ontogeny of mouse intestinal trehalase expression, a marker of general gut development, and of beta1,4-galactosyltransferase (betaGT), a marker of glycosyltransferase development, were investigated. In conventional (CONV) mice, betaGT and trehalase gene expression rapidly increased to adult levels by the fourth postnatal week.,In germ-free (GF) mice, betaGT expression remained at initial low levels and was rapidly induced on reintroduction of luminal microbes of the adult gut but not of microbes characteristic of the suckling gut. Similar developmental patterns were observed for colonic galactosyl beta1,4-linked glycoconjugates, products of betaGT. activity. These results indicate an essential role for microbes in the ontogeny of betaGT. In both CONV and GF mice, cartisone acetate (CA) precociously accelerated the ontogeny of betaGT and trehalase until maturation of the gut occurred (day 22). In the mature gut of CONV mice, both betaGT and trehalase are elevated and insensitive to CA; in GF mature mice, the expression of betaGT remains low, whereas the expression of trehalase was at mature levels, regardless of CA treatment. These changes in enzyme activity were accompanied by parallel changes in mRNA, implying transcriptional regulation. Thus both microbes and cortisone regulate gut ontogeny, but only suckling gut responds to CA, an intrinsic factor, whereas adult gut betaGT expression remains sensitive to microflora, an extrinsic factor. However, induction of the adult pattern of glycosyltransferase expression in mature gut requires colonization by microflora typical of adult gut, suggesting an essential role for intestinal colonization in the ontogeny of normal intestinal mucosal cell surface glycoconjugate receptors.