Role for the Bacterial Signal Indole in Promoting Epithelial Cell Barrier Function

ABSTRACT

Interkingdom (IK) signaling, in which pathogenic bacteria recognize human hormones in the gastrointestinal tract to initiate infection, has recently emerged as an important contributor to gastrointestinal tract infections. While a majority of studies have primarily focused on the effect of host molecules on pathogens, recent work from our lab has demonstrated that human intestinal epithelial cells can also recognize bacterial signaling molecules. We demonstrated that indole, secreted to ~ 500 μM by commensal Escherichia coli, increased expression of tight junction proteins and genes involved in mucin production in HCT-8 intestinal epithelial cells, thus enhancing their barrier properties. These results were consistent with an observed increased in trans-epithelial resistance on exposure to indole over 24 h. Since indole is structurally similar to melatonin, and melatonin is a hormone that regulates the dark-cycle in the eye, we also investigated role of indole on human retinal pigment epithelium (RPE) cells. Our data show that indole increases trans-epithelial resistance of RPE cells, and attenuated their proliferation and migration. Our results suggest a beneficial role for indole in the treatment of eye diseases, and are discussed in detail in this article.