Molecular Analysis of Microbiota-Host Cross-Talk in the Intestine

Abstract

The resident microbiota of the mammalian intestine influences diverse homeostatic functions of the gut, including regulation of cellular growth, restitution after injury, maintenance of barrier function, and modulation of immune responses. However, it is unknown how commensal prokaryotic organisms mechanistically influence eukaryotic signaling networks. We have shown that epithelia contacted by enteric commensal bacteria in vitro and in vivo rapidly generate reactive oxygen species (ROS), and distinct microbial taxa have markedly different potencies in stimulating this response. This physiologically generated ROS is known to participate in a variety of cellular signal pathways via the rapid and transient oxidative inactivation of a number of regulatory enzymes. We show that these oxidant sensitive enzymes include key control points in the proinflammatory NF-κB pathway and in the regulation of cytoskeletal dynamics. Accordingly, we show various commensal bacterial have the ability to suppress inflammatory signaling and stimulate cell motility both in cell culture and in animal models. These events are consistent with known effects of the microbiota and selected probiotics. Collectively, our studies outline a molecular mechanism that may account for aspects of microbial-host cross-talk in the intestine in normal physiology and during therapeutic intervention with probiotics.