Dietary Salt Exacerbates Experimental Colitis

• Published in: The Journal of immunology (1950) 2017-08, Vol.199 (3), p.1051-1059
• Main Authors: Tubbs, Alan L, Liu, Bo, Rogers, Troy D, Sartor, R Balfour, Miao, Edward A
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Colitis; Colitis - chemically induced; Colitis - etiology; Colitis - immunology; Colitis - physiopathology; Colon; Colon - chemistry; Colon - immunology; Colon - pathology; Culture Media - chemistry; Cytokines - biosynthesis; Cytokines - immunology; Dendritic cells; Dendritic Cells - drug effects; Dextran; Dextran Sulfate - administration & dosage; Dextran Sulfate - adverse effects; Disease Models, Animal; Disease Progression; Environmental factors; Food processing; Immediate-Early Proteins - immunology; Immune response; Immunity, Innate; Infections; Inflammation - etiology; Inflammation - immunology; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - etiology; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - pathology; Innate immunity; Interleukin 10; Interleukin-10 - deficiency; Interleukin-10 - genetics; Interleukin-10 - immunology; Intestinal Mucosa - immunology; Intestine; MAP kinase; Mice; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases - immunology; Processed foods; Protein-Serine-Threonine Kinases - immunology; Rodents; Salmonella; Salmonella Infections, Animal - immunology; Salmonella typhimurium - immunology; Salt; Salts; Sodium; Sodium chloride; Sodium Chloride, Dietary - administration & dosage; Sodium Chloride, Dietary - adverse effects; Sodium Chloride, Dietary - immunology; Sodium sulfate; Sugar; Sulfates; TLR4 protein; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 3 - immunology; Toll-like receptors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1700356

The Western diet is characterized by high protein, sugar, fat, and low fiber intake, and is widely believed to contribute to the incidence and pathogenesis of inflammatory bowel disease (IBD). However, high sodium chloride salt content, a defining feature of processed foods, has not been considered as a possible environmental factor that might drive IBD. We set out to bridge this gap. We examined murine models of colitis on either a high salt diet (HSD) or a low salt diet. We demonstrate that an HSD exacerbates inflammatory pathology in the IL-10-deficient murine model of colitis relative to mice fed a low salt diet. This was correlated with enhanced expression of numerous proinflammatory cytokines. Surprisingly, sodium accumulated in the colons of mice on an HSD, suggesting a direct effect of salt within the colon. Similar to the IL-10-deficient model, an HSD also enhanced cytokine expression during infection by This occurred in the first 3 d of infection, suggesting that an HSD potentiates an innate immune response. Indeed, in cultured dendritic cells we found that high salt media potentiates cytokine expression downstream of TLR4 activation via p38 MAPK and SGK1. A third common colitis model, administration of dextran sodium sulfate, was hopelessly confounded by the high sodium content of the dextran sodium sulfate. Our results raise the possibility that high dietary salt is an environmental factor that drives increased inflammation in IBD.