Antivirulence Activity of the Human Gut Metabolome

ABSTRACT Themammalian gut contains a complex assembly of commensal microbes termedmicrobiota. Althoughmuch has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined.We have re-cently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. There-fore, we hypothesized that these molecules function as chemical cues used by hosts andmicrobes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor of Salmonella virulence, obliterating expres-sion of the Salmonella pathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota pro-tects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Fur-ther investigations should reveal the exact biological role of this molecule as well as its therapeutic potential. IMPORTANCE Microbes can communicate through the production and sensing of small molecules. Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells. Deciphering such a molecular dialect wil