Enterohepatic Helicobacter species modulate severity of DSS-induced colitis but do not prevent amelioration by indole-3-carbinol

Abstract

Abstract Enterohepatic Helicobacter (EHH) species are bacteria that colonize the colons and biliary ducts of humans and other mammals. Virtually nothing is known about the mechanisms of EHH-induced colitis in wild-type mice or humans. Indole-3-carbinol (I3C), a chemical extracted from cruciferous vegetables, ameliorates Dextran sulfate sodium (DSS)-induced colitis. We hypothesized that specific EHH species would alter the course of DSS-induced colitis and possibly the responses to I3C treatment. We infected C57BL/6 mice with human- and rodent-associated EHH species and measured the effects on DSS-induced colitis and response to I3C treatment. We found that H. muridarum(H.m) and H. cinaedi exacerbate DSS-induced colitis and delay recovery. Furthermore, I3C ameliorated colitis and shifted the Treg/Th17 balance in H.m-infected mice. Moreover, the microRNAs expression pattern was altered in H.m-infected mice when compared to that of uninfected mice. Interestingly, enhanced colitis, as well as increased Th17 cells in spleens and mesenteric lymph nodes, were observed in H.m-infected DSS-treated mice(DHM). I3C treatment of DSS + H.m-infected mice (DMI) decreased the expression of pro-inflammatory IL17 and RORC as well as increased anti-inflammatory Foxp3 when compared to DHM group. These immunological changes correlated with the microRNAs expression. This demonstrates that the presence of EHH species alters susceptibility to DSS-induced colitis. Importantly, mice with exacerbated colitis respond to I3C. In the future, we plan to study the mechanisms underlying the effects of EHH on colon cancer development and the efficacy of I3C in both the colitis and colon cancer models.