Indole produced during dysbiosis mediates host–microorganism chemical communication

An imbalance of the gut microbiota, termed dysbiosis, has a substantial impact on host physiology. However, the mechanism by which host deals with gut dysbiosis to maintain fitness remains largely unknown. InC. elegans,E. coli, which is its bacterial diets, proliferates in its intestinal lumen during aging. Here, we demonstrate that progressive intestinal proliferation ofE. coliactivates the transcription factor DAF-16, which is required for maintenance of longevity and organismal fitness in worms with age. DAF-16 up-regulates two lysozymeslys-7andlys-8, thus limiting the bacterial accumulation in the gut of worms during aging. During dysbiosis, the levels of indole produced byE. coliare increased in worms. Indole is involved in the activation of DAF-16 by TRPA-1 in neurons of worms. Our finding demonstrates that indole functions as a microbial signal of gut dysbiosis to promote fitness of the host.