Submitted on January 5, 2007
Accepted on July 29, 2007
BACTERIAL SYMBIONTS INDUCE A FUT2-DEPENDENT FUCOSYLATED NICHE ON COLONIC EPITHELIUM VIA ERK AND JNK SIGNALING
Di Meng1, David S. Newburg2, Cheryl Young1, Amy Baker1, Susan L. Tonkonogy3, R. Balfour Sartor4, W. Allan Walker5, and N. Nanda Nanthakumar6*
1 Developmental Gastroenterology Laboratory, Pediatric Gastroenterology and Nutrition Unit, Massachusetts General Hospital, Charlestown, Massachusetts, United States
2 Developmental Gastroenterology Laboratory, Pediatric Gastroenterology and Nutrition Unit, Massachusetts General Hospital, Charlestown, Massachusetts, United States; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States
3 Department of Microbiology, Pathology and Parasitology, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, United States
4 Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
5 Developmental Gastroenterology Laboratory, Pediatric Gastroenterology and Nutrition Unit, Massachesetts General Hospital, Charlestown, Massachusetts, United States; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States
6 Pediatric GI & Nutrition, Massachesetts General Hospital, Charlestown, Massachusetts, United States; Developmental Gastroenterology Laboratory, Pediatric Gastroenterology and Nutrition Unit, Massachesetts General Hospital, Charlestown, Massachusetts, United States; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: nanthaku{at}helix.mgh.harvard.edu.
The intestinal epithelium of the adult gut supports a complex dynamic microbial ecosystem and expresses highly fucosylated glycans on its surface. Uncolonized gut contains little fucosylated glycan. The transition toward adult colonization, such as during recovery from germ-free status or from antibiotic treatment, increased expression of fucosylated epitopes occurs in the colonic epithelium. This increase in fucosylation is accompanied by induction of fut2-mRNA expression and 
1,2/3-fucosyltransferase activity. Colonization stimulates ERK and JNK signal transduction pathways resulting in activation of transcription factors ATF2 and c-jun, respectively. This results in increased transcription of FUT 2 mRNA and expression of 1,2/3-fucosyltransferase activity, resulting in a highly fucosylated intestinal mucosa characteristic of the adult mammalian gut. Blocking the ERK and JNK signaling cascade inhibits the ability of colonization to induce elevated fut2 mRNA and fucosyltransferase activity in the mature colon. Thus, pioneer mutualist symbiotic bacteria may utilize the ERK and JNK signaling cascade to induce the mammalian colon to express the highly degree of fucosylation characteristic of adult, and we speculate that this fucosylation facilitates colonization by a stable adult microbiota.
