Anti-inflammatory effect of indoleacrylic acid (IA)

Host factors in the intestine, such as mucus secretion, play an important role in selecting for the colonization of bacteria that contribute to intestinal health. Here we characterized the capability of commensal species to cleave and transport mucin-associated monosaccharides and found that several members of the Clostridiales order can utilize intestinal mucins as an energy source. One such mucin utilizer, Peptostreptococcus russellii, reduces susceptibility to epithelial injury in mice. Several Peptostreptococcus species contain a gene cluster that enables the production of the tryptophan metabolite indoleacrylic acid (IA), which we show has a beneficial effect on intestinal epithelial barrier function and mitigates inflammatory responses. Furthermore, metagenomic analysis of human stool samples revealed that the genetic capability of microbes to utilize mucins and metabolize tryptophan was diminished in patients with inflammatory bowel disease. Our data suggest that stimulating the production of IA to promote anti-inflammatory responses could have therapeutic benefit. Overall design: Isolated hPBMCs treated with IA or 0.1% DMSO followed by LPS stimulation. Comparisons of interest: 490_DMSO_vs_490_IA 1685_DMSO_vs_1685_IA 406_DMSO_vs_406_IA ALL_DMSO_vs_ALL_IA