Indole-3-carbinol ameliorates colonic inflammation in DSS-treated, Helicobacter muridarum-infected mice

Abstract

Abstract Enterohepatic Helicobacter species are epidemiologically linked to increased inflammatory bowel disease; however, little research has been done to elucidate potential contributions of individual species. We hypothesized that Helicobacter muridarum (Hm) would alter the course of DSS-induced colitis and the response to indole-3-carbinol (I3C), an anti-inflammatory phytochemical. We treated Hm-infected C57BL/6 mice with1% DSS +/− 40 mg/kg I3C and measured inflammatory biomarkers. We found that H. m exacerbated DSS-induced colitis and increased the percentage of Th17 cells in the mesenteric lymph nodes and spleen and increased IL-17 in colonic tissue compared to the DSS group. Also, we found that Hm bacteria itself produced inflammation and pathology. I3C, on the other hand, ameliorated colitis and shifted the Treg/Th17 balance in DSS+H.m-infected mice. We found that I3C treatment of DSS + H.m-infected mice decreased the expression of pro-inflammatory IL17 and RORC as well as increased anti-inflammatory Foxp3 when compared to the untreated group. The decreased expression of RORC correlated with increased miR-let7a-2 and miR-29a-3p expression and increased FoxP3 correlated with decreased miR-874 expression following I3C treatment. Moreover, I3C reduced the abundance of certain taxa, such as Clostridiales, Actinobacteria, and Erysipelotrichales, and increased the abundance of Ruminococcus. In summary, H. muridarum causes baseline inflammation and exacerbates colitis via microRNA-mediated increases in Th17 cells, while I3C ameliorates colitis via increased Treg populations.