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Glycobiology Advance Access published online on October 13, 2004

Glycobiology, doi:10.1093/glycob/cwi004
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Received June 18, 2004
Revised October 6, 2004
Accepted October 7, 2004

ORIGINAL ARTICLES

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

N. Nanda Nanthakumar 1*, Dingwei Dai 1, Di Meng 1, Niha Chaudry 1, David S. Newburg 1, and W. Allan Walker 1

1 Developmental Gastroenterology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129

* To whom correspondence should be addressed. E-mail: nanthaku{at}helix.mgh.harvard.edu.


   Abstract

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 {beta}1,4-galactosyltransferase ({beta}GT), a marker of glycosyltransferase development, were investigated. In conventional (CONV) mice, {beta}GT and trehalase gene expression rapidly increased to adult levels by the fourth postnatal week. In germ-free (GF) mice, {beta}GT expression remained at initial low levels and was rapidly induced upon 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 {beta}1,4-linked glycoconjugates, products of {beta}GT activity. These results indicate an essential role for microbes in the ontogeny of {beta}GT. In both CONV and GF mice, CA precociously accelerated the ontogeny of {beta}GT and trehalase until maturation of the gut occurred (day 22). In the mature gut of CONV mice, both {beta}GT and trehalase are elevated and insensitive to CA; in GF mature mice, the expression of {beta}GT remains low, while 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, while adult gut {beta}GT 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.

Keywords: microflora; germ-free mice; postnatal development; hormonal regulation.
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