Dietary Salt Administration Decreases Enterotoxigenic Bacteroides fragilis (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation

• Published in: International journal of molecular sciences 2020-10, Vol.21 (21), p.8034
• Main Authors: Hwang, Soonjae, Yi, Hye Chin, Hwang, Samnoh, Jo, Minjeong, Rhee, Ki-Jong
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune diseases; Azoxymethane; Bacteroides fragilis; Bacteroides fragilis - pathogenicity; Bacteroides Infections - complications; Bacteroides Infections - microbiology; Body weight loss; Cancer; Carcinogenesis; Carcinogenesis - immunology; Carcinogenesis - pathology; Carcinogens; Colitis; Colon; Colonic Neoplasms - etiology; Colonic Neoplasms - pathology; Colonic Neoplasms - prevention & control; Colonization; Colorectal carcinoma; Cytokines; Dextran; Dextran sulfate; Dextrans; Diet; E-cadherin; enterotoxigenic Bacteroides fragilis; Epithelial cells; Epithelium; Female; high salt diet; Hyperplasia; Infections; Inflammation; Inflammation - etiology; Inflammation - pathology; Inflammation - prevention & control; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 8; Mice; Mice, Inbred C57BL; Microbiota; Nitric oxide; Nitric-oxide synthase; Risk analysis; Risk factors; Rounding; Salt; Serum levels; Sodium chloride; Sodium Chloride, Dietary - administration & dosage; Spleen; Splenomegaly; Survival analysis; Tumorigenesis; Weight loss
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21218034

Consumption of a Western-type diet has been linked to gut-microbiota-mediated colon inflammation that constitutes a risk factor for colorectal cancer. A high salt diet (HSD) exacerbates IL-17A-induced inflammation in inflammatory bowel disease and other autoimmune diseases. Enterotoxigenic (ETBF) is a gut commensal bacterium and reported to be a potent initiator of colitis via secretion of the toxin (BFT). BFT induces ectodomain cleavage of E-cadherin in colonic epithelial cells, consequently leading to cell rounding, epithelial barrier disruption, and the secretion of IL-8, which promotes tumorigenesis in mice via IL-17A-mediated inflammation. A HSD is characteristic of the Western-type diet and can exhibit inflammatory effects. However, a HSD induces effects in ETBF-induced colitis and tumorigenesis remain unknown. In this study, we investigated HSD effects in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis as well as ETBF colitis mice. Unexpectedly, ETBF-infected mice fed a HSD exhibited decreased weight loss and splenomegaly and reduction of colon inflammation. The HSD significantly decreased the expression of IL-17A and inducible nitric oxide synthase (iNOS) in the colonic tissues of ETBF-infected mice. In addition, serum levels of IL-17A and nitric oxide (NO) were also diminished. However, HT29/C1 colonic epithelial cells treated with sodium chloride showed no changes in BFT-induced cellular rounding and IL-8 expression. Furthermore, HSD did not affect ETBF colonization in mice. In conclusion, HSD decreased ETBF-induced tumorigenesis through suppression of IL-17A and iNOS expression in the colon. HSD also inhibited colonic polyp numbers in the ETBF-infected AOM/DSS mice. Taken together, these findings suggest that a HSD consumption inhibited ETBF-promoted colon carcinogenesis in mice, indicating that a HSD could have beneficial effects under certain conditions.