Bacterial-modulated signaling pathways in gut homeostasis.

Abstract

Symbiotic mutualism with gut microbes occurs in all metazoans, and it is well established that commensal bacteria influence multiple aspects of host gut physiology such as innate immunity and development. However, our understanding of these coevolved interactions between prokaryotes and eukaryotes remains unclear. One mechanism by which commensal bacteria modulate host intracellular signaling pathways in order to avoid excess inflammation has now been determined. In this process, bacterial-induced reactive oxygen species in gut epithelial cells act as key messengers that inhibit the cullin-1-dependent protein degradation machinery, which in turn results in the stabilization of a master negative regulator of inflammation, inhibitor of nuclear factor-kappaB (IkappaB). Furthermore, this bacterial-mediated system also appears to be involved in the stabilization of a key developmental regulator, beta-catenin. These findings provide new insights into the molecular mechanisms by which commensal microbes shape host cellular physiology.