Dataset Information

Amelioration of AOM/DSS-Induced Murine Colitis-Associated Cancer by Evodiamine Intervention is Primarily Associated with Gut Microbiota-Metabolism-Inflammatory Signaling Axis.

ABSTRACT: Evodiamine (EVO), an indole alkaloid derived from Rutaceae plants Evodia rutaecarpa (Juss.) Benth.、Evodia rutaecarpa (Juss.) Benth. Var. bodinieri (Dode) Huang or Evodia rutaecarpa (Juss.) Benth. Var. officinalis (Dode) Huang, has anti-inflammatory and anti-tumor activities. Our previous study found that EVO attenuates colitis by regulating gut microbiota and metabolites. However, little is known about its effect on colitis-associated cancer (CAC). In this study, the protective effects of EVO on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis and tumor mice were observed, and the underlying potential mechanism was clarified. The results suggested that EVO ameliorated AOM/DSS-induced colitis by inhibiting the intestinal inflammation and improving mucosal barrier function. And EVO significantly reduced the number and size of AOM/DSS-induced colorectal tumors along with promoted apoptosis and inhibited proliferation of epithelial cell. Moreover, EVO promoted the enrichment of SCFAs-producing bacteria and reduced the levels of the pro-inflammatory bacteria, which contributes to the changes of microbiota metabolism, especially tryptophan metabolism. Furthermore, inflammatory response (like Wnt signaling pathway、Hippo signaling pathway and IL-17 signaling pathway) were effectively alleviated by EVO. Our study demonstrated that the protective therapeutic action of EVO on CAC is to inhibit the development of intestinal inflammation-cancer by regulating gut microbiota metabolites and signaling pathways of colon intestinal epithelial, which may represent a novel agent for colon cancer prevention via manipulation of gut microbiota.

SUBMITTER: Wang M

PROVIDER: S-EPMC8740177 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Inflammatory bowel diseases encompass gastrointestinal illnesseses typified by chronic inflammation, loss of epithelial integrity and gastrointestinal microbiota dysbiosis. In an effort to counteract these characteristic perturbations, we used stem cells and/or a probiotic preparation in a murine model of Dextran Sodium Sulfate induced colitis to examine both their efficacy in ameliorating disease and impact on niche-specific microbial communities of the lower GI tract. Colitis was induced in C57BL/6 mice by administering 3% DSS in drinking water for 10 days prior to administering one of three treatment plans: daily probiotic (VSL#3) supplementation for 3 days, a single tail vein injection of 1x106 murine mesenchymal stem cells, or both. Controls included DSS-untreated mice and DSS-treated mice that received no therapy. Ileal, cecal and colonic sections were collected for microbiota and histological analyses. Microbiota profiling revealed distinct bacterial community compositions in the ileum, cecum and colon of control untreated animals, all of which were predicted in silico to be enriched for a number of discrete KEGG pathways, indicating compositional and functional niche specificity in healthy animals. DSS- treatment perturbed community composition in all three niches with ileal communities exhibiting the greatest change relative to control animals. Stem cell, VSL#3 and the combination treated animals exhibited treatment-specific microbiota composition in the lower GI tract, though disease scores were only improved in VSL#3 treated animals. This VSL#3-associated shift in the ileal microbiota was characterized by significant Enterobacteriaceae enrichment compared to colitic animals (p<0.05), Mice (n=40) were randomly divided into five experimental groups, four of which received Dextran Sodium Sulfate (DSS; 3% solution in drinking water) for 10 days to induce colitis. Three of the DSS-treated groups received the following treatment modalities: VSL#3 (VSL#3, n=5), mesenchymal stem cells (MSC, n=5), or VSL#3 + mesenchymal stem cells (DUAL, n=5). The fourth DSS-treated group received no intervention (DSS; n=10). The additional fifth group of animals received neither DSS nor any therapeutic intervention and acted as untreated controls (CNTL, n=15). Following colitis induction (Day 10), DSS administration was halted and mice in the VSL#3, MSC and DUAL groups received the following interventions respectively: daily oral supplementation with 5x106 CFUs per supplement of VSL#3 in 100ul PBS (VSL#3); a single tail vein injection of 1x106 murine mesenchymal stem cells in 100_l PBS on Day 10 (MSC) or a combination of both treatments To provide control data for comparison, CNTL mice (n=5 per time point) were euthanized and sampled on days 1, 10, and 14, while DSS mice (n=5 per time point) were euthanized on days 10 and 14. All MSC, VSL#3, and DUAL mice were euthanized on Day 14. Samples collected from each animal included terminal ileum (1cm proximal to the cecum), cecum (divided transversely and stored as two separate samples), and proximal colon. All samples were added to RNAlater, prior to storage at -80C for analysis. Additional colonic samples were obtained, proximal to the initial sample site for microbiome analyses, and were preserved in paraformaldehyde for histological analyses.

Dataset Information

Amelioration of AOM/DSS-Induced Murine Colitis-Associated Cancer by Evodiamine Intervention is Primarily Associated with Gut Microbiota-Metabolism-Inflammatory Signaling Axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure