title: Glucocorticoids and microbiota regulate ontogeny of intestinal fucosyltransferase 2 requisite for gut homeostasis.
abstract: At weaning, the intestinal mucosa surface glycans change from predominantly sialylated to fucosylated. Intestinal adaptation from milk to solid food is regulated by intrinsic and extrinsic factors. The contribution by glucocorticoid, an intrinsic factor, and colonization by microbiota, an extrinsic factor, was measured as the induction of α1,2/3-fucosyltransferase and sucrase-isomaltase (SI) activity and gene expression in conventionally raised, germ-free, and bacteria-depleted mice. In conventionally raised mice, cortisone acetate (CA) precociously accelerated SI gene expression up to 3 weeks and fut2 to 4 weeks of age. In germ-free mice, CA treatment induces only SI expression but not fucosyltransferase. In post-weaning bacteria-deficient (germ-free and bacteria-depleted) mice, fut2 expression remains at low suckling levels. In microbiota deficient mice, intestinal fut2 (but not fut1, fut4 or fut7) was induced only by adult microbiota, but not immature microbiota or CA. Fut2 induction could also be restored by colonization by Bacteroides fragilis, but not by a B. fragilis mutant unable to utilize fucose. Restoration of fut2 expression (by either microbiota or B. fragilis) in bacteria-depleted mice is necessary for recovery from dextran sulfate sodium-induced mucosal injury. Thus, glucocorticoids and microbes regulate distinct aspects of gut ontogeny: CA precociously accelerates SI expression and, only in colonized mice, fut2 early expression. The adult microbiota is required for the fut2 induction responsible for the highly fucosylated adult gut phenotype and is necessary for recovery from intestinal injury. Fut2-dependent recovery from inflammation may explain the high incidence of inflammatory disease (Crohn's and necrotizing enterocolitis) in populations with mutant FUT2 polymorphic alleles.
authors.affiliation: Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: N Nanda
authors.initials: NN
authors.lastname: Nanthakumar
authors.forename: Di
authors.initials: D
authors.lastname: Meng
authors.forename: David S
authors.initials: DS
authors.lastname: Newburg
mesh_terms: D000818:Animals; D001441:Bacteroides fragilis; D003348:Cortisone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005643:Fucose / Q000378:metabolism; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D007422:Intestines / Q000187:drug effects / Q000201:enzymology* / Q000382:microbiology; D051379:Mice; D064307:Microbiota; D013394:Sucrase-Isomaltase Complex / Q000235:genetics / Q000378:metabolism; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D003348:Cortisone; D005643:Fucose; D005647:Fucosyltransferases; D013394:Sucrase-Isomaltase Complex; D000097631:Galactoside 2-alpha-L-fucosyltransferase
keywords: germ-free mice; hormonal regulation; microflora; post-natal development