Colitis, an
inflammatory bowel disease, is caused by a variety of factors, but
luminal microbiota are thought to play crucial roles in disease development and progression.
Indole is produced by gut microbiota and is believed to protect the colon from inflammatory damage. In the current study, we investigated whether
indole-3-carbinol (I3C), a naturally occurring plant product found in numerous cruciferous vegetables, can prevent
colitis-associated microbial
dysbiosis and attempted to identify the mechanisms. Treatment with I3C led to repressed colonic
inflammation and prevention of microbial
dysbiosis caused by
colitis, increasing a subset of gram-positive bacteria known to produce
butyrate. I3C was shown to increase production of
butyrate, and when mice with
colitis were treated with
butyrate, there was reduced colonic
inflammation accompanied by suppression of Th17 and induction of Tregs, protection of the mucus layer, and upregulation in Pparg expression. Additionally,
IL-22 was increased only after I3C but not
butyrate administration, and neutralization of
IL-22 prevented the beneficial effects of I3C against
colitis, as well as blocked I3C-mediated
dysbiosis and
butyrate induction. This study suggests that I3C attenuates
colitis primarily through induction of
IL-22, which leads to modulation of gut microbiota that promote antiinflammatory
butyrate.