Impact of intestinal bacteria on the anatomy and physiology of the intestinal tract in the PRM/Alf mouse model

肠道细菌在一定程度上与饮食成分一起对宿主生理产生深远影响，但其潜在机制在很大程度上尚不清楚。PRM/ALF鼠标提供了获得对这些机制的新见解的独特机会。PRM/Alf小鼠的肠道发育时间比对照品系长三分之一。对无菌和常规PRM/Alf小鼠的比较表明，肠道微生物区系在这种延长中起到了作用。为了确定所涉及的细菌因素，我们的法国项目合作伙伴将用复杂的小鼠微生物群和我们小组提供的七种已知细菌组成的联合体来定植无菌的PRM/Alf小鼠。将分析这些小鼠肠道上皮细胞的基因和蛋白表达，以探索宿主对肠道细菌的反应。我们将分析PRM/Alf的盲肠内容物，并控制与不同细菌群落相关的小鼠的细菌产生的营养因子，如多胺和短链脂肪酸，这些可能有助于肠道延长。此外，盲肠内容物和细菌细胞的胞浆部分将被寻找在肠道延长中起作用的差异表达的细菌蛋白。预期的结果将为肠道细菌影响宿主的解剖和生理的方式提供新的见解。

Partly in conjunction with dietary components, intestinal bacteria have a profound impact on host physiology but the underlying mechanisms are largely unknown. The PRM/Alf mouse offers the unique opportunity to gain new insights into these mechanisms. PRM/Alf mice develop a gut that is one third longer than of control strains. A comparison of germfree and conventional PRM/Alf mice indicated a role of the intestinal microbiota in this elongation. To identify the bacterial factors involved, our French project partners will colonize germfree PRM/Alf mice with a complex mouse microbiota and with a consortium of seven known bacterial species provided by our group. Gene and protein expression in the intestinal epithelium of these mice will be analyzed to explore the host response to gut bacteria. We will analyze caecal contents of PRM/Alf and control mice associated with different bacterial communities for bacterially produced trophic factors such as polyamines and short chain fatty acids that possibly contribute to gut elongation. In addition, caecal contents and cytosolic fractions of bacterial cells will be searched for differentially expressed bacterial proteins that play a role in gut lengthening. The expected results will provide new insights in the way intestinal bacteria influence the anatomy and physiology of the host.