Glycobiology Advance Access originally published online on October 13, 2004
Glycobiology 2005 15(3):221-232; doi:10.1093/glycob/cwi004
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Glycobiology vol. 15 no. 3 © Oxford University Press 2005; all rights reserved.
Regulation of intestinal ontogeny: effect of glucocorticoids and luminal microbes on galactosyltransferase and trehalase induction in mice
Developmental Gastroenterology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, 114 16th Street (114-3650), Charlestown, MA 02129 and Harvard Medical School, Boston, MA
1 To whom correspondence should be addressed; e-mail: nanthaku{at}helix.mgh.harvard.edu
Received on June 18, 2004; revised on October 6, 2004; accepted on October 7, 2004
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 ß1,4-galactosyltransferase (ßGT), a marker of glycosyltransferase development, were investigated. In conventional (CONV) mice, ßGT and trehalase gene expression rapidly increased to adult levels by the fourth postnatal week. In germ-free (GF) mice, ßGT 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 ß1,4-linked glycoconjugates, products of ßGT activity. These results indicate an essential role for microbes in the ontogeny of ßGT. In both CONV and GF mice, cartisone acetate (CA) precociously accelerated the ontogeny of ßGT and trehalase until maturation of the gut occurred (day 22). In the mature gut of CONV mice, both ßGT and trehalase are elevated and insensitive to CA; in GF mature mice, the expression of ßGT 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 ßGT 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.
Key words: germ-free mice / hormonal regulation / microflora / postnatal development