Epithelial cell growth and differentiation III. Promoting diversity in the intestine: Conversations between the micro flora, epithelium, and diffuse GALT

Homeostasis in the self-renewing mouse intestinal epithelium appears to be regulated in large part by cell nonautonomous mechanisms. The society of nonpathogenic bacteria that resides in the intestine is an important source of instructions that modify epithelial differentiation programs. The stability of this society is remarkable given its numerical, compositional, and spatial complexity, the openness of the ecosystem, and the fact that the epithelium is replaced so rapidly. The ability of components of this society to influence epithelial differentiation may represent a critical step in allowing specific groups of organisms to be assembled in specific regions of the gut. Simplified model systems have been created to define and dissect the conversations between microbe and host. These systems use inbred strains of mice that are raised under germ-free conditions and then monocontaminated with a single component of the microflora. The results suggest that a trialogue involving communications between the microflora, the epithelium, and the diffuse gut-associated lymphoid tissue (GALT) may play a key role in establishing and maintaining the spatial diversity of this remarkable ecosystem.