Curr Opin Immunol. 2025 Dec 16;98:102710. doi: 10.1016/j.coi.2025.102710. Online ahead of print.

ABSTRACT

Indole is an abundant metabolite in the mammalian gut. Both mammals and microorganisms sense it. Indole is a signal used to communicate and gauge the gut environment. Indole is produced by bacteria that encode the tryptophanase enzyme. However, indole sensing is not limited to the organisms that produce it; mammals, as well as microbes incapable of producing this molecule, have receptors for it. Indole signaling has varying activities, from contributing to intestinal barrier integrity, modifying brain signaling, and preventing aging. In microorganisms, it represses biofilm formation and modulates the virulence of enteric pathogens, among other phenotypes. Although there is a renaissance in indole research, comprehensive knowledge of its signaling pathways is limited. Here, we review indole signaling across species and kingdoms. By understanding the integration of the activity of indole at the host, microbiota, and pathogen interface, one may be able to develop novel dietary and therapeutic approaches.

PMID:41406557 | DOI:10.1016/j.coi.2025.102710