It has long been recognized that pathogenic bacteria can cause various maladies of the gastrointestinal (Gl) tract, but the effects of non-pathogenic, indigenous microbiota on post-natal Gl tract development have been relatively unexplored. Studies reveal the intestinal epithelium of germ free (GF) mice and zebrafish have fewer proliferating cells as compared to conventionally reared siblings. Recently, mammalian cell culture models have suggested that non-pathogenic bacteria can stablize Beta-Catenin, a transducer of Wnt signaling. The balance between proliferating and differentiated cells in the mammalian Gl tract is regulated by Wnt signaling. Collectively, these data motivate a hypothesis that the indigenous microbiota controls the rate of proliferation of the intestinal epithelium through Wnt signaling. This hypothesis will be tested in a whole organism model in which Wnt signaling and the presence and composition of the microbiota can be manipulated. The details of this interaction are relevant to human health, as the activities of the Gl microbiota are implicated in several hyperproliferative diseases of the Gl tract, including irritable bowel syndrome and colorectal cancer.
| Cheesman, Sarah E; Neal, James T; Mittge, Erika et al. (2011) Epithelial cell proliferation in the developing zebrafish intestine is regulated by the Wnt pathway and microbial signaling via Myd88. Proc Natl Acad Sci U S A 108 Suppl 1:4570-7 |
| Cheesman, Sarah E; Guillemin, Karen (2007) We know you are in there: conversing with the indigenous gut microbiota. Res Microbiol 158:2-9 |
| Bates, Jennifer M; Mittge, Erika; Kuhlman, Julie et al. (2006) Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol 297:374-86 |
