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

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.

Colitis-Mediated Dysbiosis of the Intestinal Flora and Impaired Vitamin A Absorption Reduce Ovarian Function in Mice

“…Erysipelatoclostridium was found to be positively correlated with the DAI scores, pathological score, TNF-α, and IL-1β [40]. Bacteroides have been shown to be associated with the deterioration of inflammatory bowel disease [41][42][43][44][45]. In contrast, Muribaculaceae and Lactobacillus can produce succinate, acetate, propionate [46], and butyrate [47], which alleviate inflammatory bowel disease by reducing the level of intestinal inflammatory factors and restoring the balance of the intestinal microbiota [48,49].…”

Gut Microbiota-Derived 5-Hydroxyindoleacetic Acid Alleviates Diarrhea in Piglets via the Aryl Hydrocarbon Receptor Pathway

“…Intestinal microbiota can metabolize tryptophan into indole and its derivatives that contribute to the maintenance of intestinal homeostasis. , For instance, certain indole derivatives, like indole-3-carbinol, indole-3-lactic acid, and 5-HIAA, act as ligands binding to AHR . AHR is a ligand-dependent transcription factor that regulates the development and function of immune cells in the intestine. − Transcriptional activation of CYP1A1 and CYP1B1 was determined to be directly related to activation of the AHR signaling pathway . Notably, Bifidobacterium metabolizes dietary tryptophan into 5-HIAA in the host intestine .…”