Modulation of JNK-1/ β-catenin signaling by Lactobacillus casei , inulin and their combination in 1,2-dimethylhydrazine-induced colon cancer in mice.

Colon cancer is a complex disease that involves numerous genetic alterations that change the normal colonic mucosa into invasive adenocarcinoma. In the current study, the protective effects of inulin (prebiotic), Lactobacillus casei ( L. casei , probiotic) and their combination (synbiotic) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male Swiss mice were evaluated. Animals were divided into: Control group, DMH-treated group, DMH plus inulin, DMH plus L. casei and DMH plus inulin plus L. casei -treated groups. Fecal microbiome analysis, biochemical measurements, histopathological examination of the colon tissues, immunostaining and Western blotting analysis of β-catenin, GSK3β and JNK-1 were performed. The prebiotic-, probiotic- and synbiotic-treated groups showed decreased levels of carcinoembryonic antigen and a lower number of aberrant crypt foci compared to the DMH-treated group with the synbiotic group exhibiting a superior effect. Furthermore, all treatments showed a body weight-reducing effect. Administration of inulin, L. casei or their combination increased the expression level of phospho-JNK-1 while they decreased the expression level of β-catenin and phospho-GSK3β. Remarkably, L. casei treatment resulted in enrichment of certain beneficial bacterial genera i.e. Akkermansia and Turicibacter . Therefore, administration of L. casei and inulin as a synbiotic combination protects against colon cancer in mice.