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.
Highlights
Changes 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
Given that gut microbiota composition has been implicated in the pathophysiology of multiple immune-related disorders, such as inflammatory bowel disease (IBD), diabetes, or asthma [20], and taking into account that diet shapes the gut microbiota, we investigated the ability of high salt diet (HSD) to modulate gut microbial composition and metabolism, and to influence vulnerability to intestinal inflammatory stimuli
Mice were divided into two groups: (1) control diet—mice were fed with control diet for the entire course of the experiment; (2) HSD—mice received the same diet supplemented with 4% NaCl, plus 1% NaCl sterile water, ad libitum, during 4 weeks
Summary
Changes 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. 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. Previous studies have shown that a high fat diet may have a direct pro-inflammatory effect, increasing the production of pro-inflammatory cytokines TNFα, IL-1β, and IL-6 [7]. Others have shown direct interactions between animal fat consumption, altered bile acid metabolism, and specific alteration in the gut microbiota, leading to increased colitis severity [8]. One characteristic element in the western diet that has been overlooked until recently is its high salt (sodium chloride, NaCl) content
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