High salt diet stimulates gut Th17 response and exacerbates TNBS-induced colitis in mice

Abstract

This study focuses on characterizing the effect of a high salt diet (HSD) on intestinal immunity and the risk of inflammatory bowel diseases (IBD). We found that mice on a HSD had an increased frequency of IL-17A producing cells in the intestinal lamina propria (LP) compared to mice on a normal diet (ND). Furthermore, most intestinal IL-17A producing cells were CD4+TCRβ+ cells. A HSD increased the LP T helper 17 (Th17) responses in both the small and large intestines but did not increase the Th17 response of other gut-associated lymphoid organ. Although, HSD did not change the percentage of regulatory T (Treg) cells, HSD significantly inhibit secretion of IL-10 and the suppressive function of Treg cells. Moreover, we found that HSD exacerbates trinitrobenzenesulfonic acid (TNBS) induced colitis, and Th17 response was significantly increased in the colonic LP of HSD TNBS-treated mice compared with the ND TNBS-treated mice. This study demonstrates that HSD stimulates the intestinal Th17 response but inhibits the function of Treg cells. Moreover, HSD exacerbates TNBS induced mice colitis, suggesting that HSD disrupts the intestinal immunity and increases the risk of IBD.

High-Salt Diet Gets Involved in Gastrointestinal Diseases through the Reshaping of Gastroenterological Milieu

“…IBD has long been recognized as a multi-factor-induced inflammatory disease. HSD is demonstrated to add to the risk by altering the secretion of inflammatory cytokines mediated by innate immune cells, and by stimulating the Th17 and ILC3 response in intestines, but by suppressing the function of Treg cells [5,6,11]. This could be an un-DOI: 10.1159/000493096 derlying mechanism for a bland diet to be considered beneficial for illness rehabilitation and is frequently prescribed to patients with GI disease.…”

“…Increasing studies concentrate on characterizing the effects of HSD on GI disorders from an immune-based perspective [5,6]. Recent studies showed that HSD exacerbated colitis in mice by affecting the gut microbiota and intestinal immune homeostasis [5,11,26].…”

“…Recent studies showed that HSD exacerbated colitis in mice by affecting the gut microbiota and intestinal immune homeostasis [5,11,26]. Actually, an HSD has long been demonstrated to disrupt intestinal immunity and increase the risk of IBD [12], exacerbating experimental colitis in both the ceca and colon while increasing immune infiltration, epithelial hyperplasia, and extensive goblet cell loss [12].…”

“…Actually, an HSD has long been demonstrated to disrupt intestinal immunity and increase the risk of IBD [12], exacerbating experimental colitis in both the ceca and colon while increasing immune infiltration, epithelial hyperplasia, and extensive goblet cell loss [12]. The HSD stimulates the Th17 response in both the small and large intestines, increasing the production of IL-17A but suppressing the function of Treg cells, inhibiting the secretion of IL-10 [5] and altering epithelial signaling cascades to promote inflammation. Given that ILC3 is abundant in the gut mucosa, the latest research revealed that the increased IL-17 dependent inflammatory effects of HSD may partially stem from ILC3 [11].…”

“…People in Turkey consume sodium 308 mmol/day have higher risk for coronary heart disease [4]. Importantly, a highsalt diet (HSD) is proved to have adverse effects on the gastrointestinal (GI) functions [5][6][7][8], also with a regional variability. Salting and pickling, as traditional popular ways for preparing food in Japan and some parts of Asia, increase the risk of stomach cancer in these areas [9].…”