High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production

Abstract

BackgroundChanges in hygiene and dietary habits, including increased consumption of foods high in fat, simple sugars, and salt that are known to impact the composition and function of the intestinal microbiota, may explain the increase in prevalence of chronic inflammatory diseases. High salt consumption has been shown to worsen autoimmune encephalomyelitis and colitis in mouse models through p38/MAPK signaling pathway. However, the effect of high salt diet (HSD) on gut microbiota and on intestinal immune homeostasis, and their roles in determining vulnerability to intestinal inflammatory stimuli are unknown. Here, we investigate the role of gut microbiota alterations induced by HSD on the severity of murine experimental colitis.ResultsCompared to control diet, HSD altered fecal microbiota composition and function, reducing Lactobacillus sp. relative abundance and butyrate production. Moreover, HSD affected the colonic, and to a lesser extent small intestine mucosal immunity by enhancing the expression of pro-inflammatory genes such as Rac1, Map2k1, Map2k6, Atf2, while suppressing many cytokine and chemokine genes, such as Ccl3, Ccl4, Cxcl2, Cxcr4, Ccr7. Conventionally raised mice fed with HSD developed more severe DSS- (dextran sodium sulfate) and DNBS- (dinitrobenzene sulfonic acid) induced colitis compared to mice on control diet, and this effect was absent in germ-free mice. Transfer experiments into germ-free mice indicated that the HSD-associated microbiota profile is critically dependent on continued exposure to dietary salt.ConclusionsOur results indicate that the exacerbation of colitis induced by HSD is associated with reduction in Lactobacillus sp. and protective short-chain fatty acid production, as well as changes in host immune status. We hypothesize that these changes alter gut immune homeostasis and lead to increased vulnerability to inflammatory insults.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0433-4) contains supplementary material, which is available to authorized users.

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

“…HSD, as the substance that comes in direct contact with GI, has been studied for effects on the secretion and function of GI hormones. Research have proven that an 8-week HSD caused both exocrine and endocrine pancreatic insufficiency in rats, which significantly decreased plasma levels of α-amylase and lipase, insulin while significantly increasing TGF-β1 and IL6, resulting in pancreatic fibrosis [26]. An insulin decrease has also been observed with HSD-fed Wistar rats [26,51].…”

“…increased after an HSD [45]. And the study by sequencing the V4 region of 16S ribosomal RNA gene found that HSD increased the Firmicutes/Bacteroidetes ratio, that is, increased the abundances of gen-DOI: 10.1159/000493096 era Lachnospiraceae and Ruminococcus (p < 0.05) but decreased the abundance of Lactobacillus (p < 0.05) [26]. As the onset of Lactobacillus depletion is quick and remarkable, the Lactobacillus murinus is the most strongly associated with HSD [46].…”

“…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]. Alternatively, HSD affects the colonic and small intestine mucosal immunity in mouse models by enhancing the expression of pro-inflammatory genes such as Rac1, Map2k1, Map2k6, Atf2, while suppressing cytokine and chemokine genes like Ccl3, Ccl4, Cxcl2, Cxcr4, Ccr7 [26]. In addition, studies also identified HSD as a risk factor for gastritis in models of mouse and human [7,8], also human functional dyspepsia [27], and gastric cancer of human [28][29][30][31].…”

“…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].…”

“…This study also found that reducing intestinal survival of Lactobacillus spp. after high salt challenge would increase pathogenic Th17 cells [46], increase blood pressure [46], and increase colitis in mice [26].…”