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.

The HDL receptor, scavenger receptor class B type I (SR-BI), is expressed on the surface of multiple cell types and has been shown to mediate both HDL-dependent atheroprotective © 2014 American Heart Association, Inc.Arterioscler Thromb Vasc Biol is available at http://atvb.ahajournals.org DOI: 10.1161/ATVBAHA.114.304200Objective-Deficiency of the high-density lipoprotein receptor, scavenger receptor class B, type I (SR-BI), in apolipoprotein E knockout or hypomorphic mice, respectively, results in spontaneous or diet-inducible occlusive coronary artery (CA) atherosclerosis, myocardial infarction, and early death. Here, we examine effects of SR-BI deficiency on cardiovascular phenotypes in low-density lipoprotein receptor (LDLR) knockout mice fed different atherogenic diets. Approach and Results-SR-BI/LDLR double knockout and control LDLR knockout mice were fed atherogenic diets containing different amounts of fat, cholesterol, and sodium cholate. Double knockout mice fed atherogenic diets high in cholesterol exhibited significantly reduced survival compared with LDLR knockout mice fed the same diets. In addition to increased diet-accelerated aortic sinus atherosclerosis, we observed significant diet-induced CA atherosclerosis in double knockout mice and diet-dependent accumulation of platelets in CA atherosclerotic plaques. This was accompanied by substantial myocardial fibrosis in double knockout mice fed high cholesterol diets. Atherogenic diet fed double knockout mice also exhibited higher circulating cytokine levels, monocytosis with increased proportions of Ly6C hi and Ly6C int monocytes, and higher adhesion molecule expression in CA endothelial cells compared with control LDLR knockout mice. Conclusions-Diet-accelerated atherosclerosis and occlusive, platelet-rich CA disease in SR-BI/LDLR double knockout mice is affected by amounts of cholesterol and cholate in atherogenic diets and is accompanied by increased expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in CAs and increased Ly6C hi and Ly6C Fuller et al Coronary Atherosclerosis in SR-BI/LDLR dKO Mice 2395signaling 8,9 and selective lipid transfer between HDL and cells, which is critical for functional reverse cholesterol transport, the major avenue for cholesterol removal from peripheral tissues.8,10 Deficiency of SR-BI not only accelerates atherosclerosis in the aortic sinus of apoE knockout mice 11 but also renders these mice susceptible to spontaneous occlusive CA atherosclerosis, myocardial infarction, and ultimately early death. 12 A related model, the SR-BI knockout/apoE hypomorphic mouse, develops a similar phenotype when fed high fat, high cholesterol (HFC) diets. 13,14 We have previously shown that SR-BI deficiency increases atherosclerosis in the aortas of LDLR knockout mice fed a high-fat (HF) Western-type diet; however, reduced survival was not observed in these mice, and CA atherosclerosis was not assessed. 15In the current study, we tested the effects of feeding SR-BI/ LDLR double knockout (dKO) mic...