Indole produced during dysbiosis mediates host-microorganism chemical communication.

Abstract

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. In <i>Caenorhabditis elegans</i>, <i>Escherichia coli</i>, which is its bacterial diet, proliferates in its intestinal lumen during aging. Here, we demonstrate that progressive intestinal proliferation of <i>E. coli</i> activates the transcription factor DAF-16, which is required for maintenance of longevity and organismal fitness in worms with age. DAF-16 up-regulates two lysozymes <i>lys-7</i> and <i>lys-8</i>, thus limiting the bacterial accumulation in the gut of worms during aging. During dysbiosis, the levels of indole produced by <i>E. coli</i> are 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.