EPITHELIAL-CELL GROWTH AND DIFFERENTIATION .3. PROMOTING DIVERSITY INTHE INTESTINE - CONVERSATIONS BETWEEN THE MICROFLORA, EPITHELIUM, ANDDIFFUSE GALT

Homeostasis in the self-renewing mouse intestinal epithelium appears t o be regulated in large part by cell nonautonomous mechanisms. The soc iety of nonpathogenic bacteria that resides in the intestine is an imp ortant source of instructions that modify epithelial differentiation p rograms. The stability of this society is remarkable given its numeric al, compositional, and spatial complexity, the openness of the ecosyst em, and the fact that the epithelium is replaced so rapidly. The abili ty of components of this society to influence epithelial differentiati on may represent a critical step in allowing specific groups of organi sms to be assembled in specific regions of the gut. Simplified model s ystems have been created to define and dissect the conversations betwe en microbe and host. These systems use inbred strains of mice that are raised under germ-free conditions and then monocontaminated with a si ngle 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 remarkab le ecosystem.