Commensal Bacteria-Dependent Indole Production Enhances Epithelial Barrier Function in the Colon

Abstract

Microbiota have been shown to have a great influence on functions of intestinal epithelial cells (ECs). The role of indole as a quorum-sensing (QS) molecule mediating intercellular signals in bacteria has been well appreciated. However, it remains unknown whether indole has beneficial effects on maintaining intestinal barriers in vivo. In this study, we analyzed the effect of indole on ECs using a germ free (GF) mouse model. GF mice showed decreased expression of junctional complex molecules in colonic ECs. The feces of specific pathogen-free (SPF) mice contained a high amount of indole; however the amount was significantly decreased in the feces of GF mice by 27-fold. Oral administration of indole-containing capsules resulted in increased expression of both tight junction (TJ)- and adherens junction (AJ)-associated molecules in colonic ECs in GF mice. In accordance with the increased expression of these junctional complex molecules, GF mice given indole-containing capsules showed higher resistance to dextran sodium sulfate (DSS)-induced colitis. A similar protective effect of indole on DSS-induced epithelial damage was also observed in mice bred in SPF conditions. These findings highlight the beneficial role of indole in establishing an epithelial barrier in vivo.

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

“…This may have been evident, at least in part, in the positive effects seen previously in some studies testing probiotics (5,6,8,11). Another possibility is that indole acts on host tissues to enhance the innate response by increasing epithelial integrity (23) and/or stimulating anti-inflammatory pathways (24).…”

“…Indole's effects in-clude regulation of bacterial motility, epithelial barrier integrity, and biofilm formation (reviewed in references 14 and 18), as well as changes in the virulence and drug resistance of enteric pathogens (19)(20)(21)(22). Further, oral administration of indole to germfree mice enhanced intestinal integrity (23) and indole added to cell cultures was anti-inflammatory (24). Lastly, cells exposed to indole showed differential regulation of Ͼ4,000 genes involved in a variety of functions, including barrier enhancement (25,26).…”

Isomaltodextrin Prevents DSS-induced Colitis by Strengthening Tight Junctions in Mice

“…When colitis was induced by DSS in GF mice with a lower expression of TJs, all SPF mice survived on day 7 after initiating DSS administration while most GF mice died. Feeding a capsule containing indole to GF mice for 2 wk resulted in significantly increased colonic expression of occludin and claudin-7 and decreased DSS-induced mortality from 90% to 15% in GF mice, indicating that TJ preservation reduces DSS-induced colitis (Shimada et al, 2013). Furthermore, it was described that DSS-induced colitis significantly inhibited the decreased expression of occludin and claudin-3 in the proximal and distal colon.…”

The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy

“…16 A mechanism by which the microbiota might influence NSAID-induced intestinal mucosal damage is by producing metabolites that protect intestinal epithelial cells. 17,18 Previously, we identified tryptophan metabolites, including indole, as an important class of GI microbiota-derived compounds. 19 Indole is a quorum-sensing molecule produced by bacterial metabolism of L-tryptophan that mediates communication among bacterial population and inter-kingdom signaling between the host and microbe.…”