Bacterial regulation of GI tract cell proliferation

描述（由申请人提供）：长期以来，人们已经认识到致病性细菌可以引起胃肠道的各种疾病，但非致病性的本地微生物群对出生后胃肠道发育的影响却相对未被探索。研究表明，与传统饲养的兄弟姐妹相比，无菌小鼠和斑马鱼的肠上皮具有更少的增殖细胞。最近，哺乳动物细胞培养模型表明，非致病性细菌可以稳定β - catenin，一种Wnt信号的传感器。哺乳动物胃肠道中增殖和分化细胞之间的平衡受Wnt信号的调控。总的来说，这些数据激发了一个假设，即本地微生物群通过Wnt信号控制肠上皮的增殖速率。这一假设将在整个生物体模型中进行测试，其中Wnt信号和微生物群的存在和组成可以被操纵。这种相互作用的细节与人类健康有关，因为Gl微生物群的活动与几种Gl系的增殖性疾病有关，包括肠易激综合征和结直肠癌。

DESCRIPTION (provided by applicant): 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.