Preimmune Recognition and Response to Microbial Metabolites

It is now well understood that the eukaryotic host has evolved multiple mechanisms to monitor and respond to the diverse and biochemically active microbiota that thrives in a symbiotic fashion in the gut and other tissues. Generally, these mechanisms are based on traditional notions of innate and adaptive immune processes, which are mediated by recognition of, and response to, microbially derived macromolecules. Microbes themselves are metabolically active and contribute a vast array of small molecules, not present in germ-free model systems, with diverse putative and unknown biological function, and intensive work is ongoing to unravel their roles in physiological systems. Metazoans have evolved and maintain distinct gene regulatory networks to detect and respond to environmental, non-self-molecules (xenobiotics), and interestingly, recent investigation has shown that these pathways are operational in the detection and response to microbiota-derived small metabolites. These processes likely represent a general mechanism of host-microbe crosstalk, and they have clinical implications in drug and xenobiotic metabolism.