The intestinal milieu harbours the gut microbiota, consisting of a complex community of bacteria, archaea, fungi, viruses and protozoans that bring to the host organism an endowment of cells and genes more numerous than its own. In the last 10 years, mounting evidence has highlighted the prominent influence of the gut mutualistic bacterial communities on human health. Microbial colonization occurs alongside with immune system development and plays a role in intestinal physiology. The community of the gut microbiota does not undergo significant fluctuations throughout adult life. However, bacterial infections, antibiotic treatment, lifestyle, surgery and diet might profoundly affect it. Gut microbiota dysbiosis, defined as marked alterations in the amount and function of the intestinal microorganisms, is correlated with the aetiology of chronic noncommunicable diseases, ranging from cardiovascular, neurologic, respiratory and metabolic illnesses to cancer. In this review, we focus on the interplay among gut microbiota, diet and host to provide a perspective on the role of microbiota and their unique metabolites in the pathogenesis and/or progression of various human disorders. We discuss interventions based on microbiome studies, that is faecal microbiota transplantation, probiotics and prebiotics, to introduce the concept that correcting gut dysbiosis can ameliorate disease symptoms, thus offering a new approach towards disease treatment.

The in vivo activity of different 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (vastatins) on neointimal formation induced by insertion of a flexible collar around one carotid artery of normocholesterolemic rabbits was investigated. The contralateral carotid artery served as a sham control. Pravastatin, lovastatin, simvastatin, and fluvastatin were given mixed with food at daily doses of 20 ing/kg body wt for 2 weeks starting on the day of collar placement. The treatment with vastatins did not modify rabbit plasma cholesterol concentrations. The neointimal formation was assessed by measuring the cross-sectional thickness of intimal and medial tissues of fixed arteries with light microscopy. Fourteen days after collar placement, intimal hyperplasia (mostly cellular) was pronounced in treated carotid arteries. The intimal/medial (I/M) tissue ratio was 12-fold higher in treated arteries than in arteries without the collar (0.36±0.04 versus 0.03±0.02). Animals treated with lovastatin (R=12), simvastatin (n=12), and fluvastatin (R=12) showed significantly less neointimal formation; I/M tissue ratios were 0.24±0.03, 0.20±0.03, and 0.17±0.03, respectively. The inhibition elicited by pravastatin (n=12, 032 ±0.03) did not reach statistical significance. or-Actin antibody immunofluorescence analysis of serial sections revealed that cells present in the hyperplastic intima were mostly myocytes. Rates of intimal myocyte proliferation were also measured by incorporation of 5-bromo-2'-deoxyuridine, a thymidine analogue, into replicating DNA. Immunofluorescence analysis showed that 5-bromo-2'-deoxyuridine was actively incorporated into intimal myocytes after insertion of the collar, with a labeling index (percent of labeled myocytes) of 2.15 after 14 days. Labeling indexes for pravastatin-, lovastatin-, simvastatin-, and fluvastatin-treated carotid arteries were 2.01, 1.32,1.23, and 1.20, respectively, suggesting a direct effect of vastatins on arterial myocyte proliferation. The different responsiveness shown by the vastatins tested may be attributed to the differences in their capacity to penetrate cell membranes and their potency in inhibiting the HMG CoA reductase enzyme. We conclude that the inhibition of carotid intimal myocyte proliferation by these vastatins is independent of their effect on plasma cholesterol concentrations. -11 suggesting that the hypolipidemic effect is

Abstract-The ability of HDL to remove cholesterol from peripheral cells and drive it to the liver for excretion is believed to explain most of the strong inverse correlation between plasma HDL cholesterol levels and coronary heart disease.

Studies over several decades have documented the beneficial actions of n-3 polyunsaturated fatty acids (PUFAs), which are plentiful in fish oil, in different disease states. Mechanisms responsible for the efficacy of n-3 PUFAs include: (1) Reduction of triglyceride levels; (2) anti-arrhythmic and antithrombotic effects, and (3) resolution of inflammatory processes. The human microbiota project and subsequent studies using next-generation sequencing technology have highlighted that thousands of different microbial species are present in the human gut, and that there has been a significant variability of taxa in the microbiota composition among people. Several factors (gestational age, mode of delivery, diet, sanitation and antibiotic treatment) influence the bacterial community in the human gastrointestinal tract, and among these diet habits play a crucial role. The disturbances in the gut microbiota composition, i.e., gut dysbiosis, have been associated with diseases ranging from localized gastrointestinal disorders to neurologic, respiratory, metabolic, ocular, and cardiovascular illnesses. Many studies have been published about the effects of probiotics and prebiotics on the gut microbiota/microbioma. On the contrary, PUFAs in the gut microbiota have been less well defined. However, experimental studies suggested that gut microbiota, n-3 PUFAs, and host immune cells work together to ensure the intestinal wall integrity. This review discussed current evidence concerning the links among gut microbiota, n-3 PUFAs intake, and human inflammatory disease.

These results confirm the efficacy of ETC-216 for atherosclerosis treatment and provide guidance for dose selection and frequency to obtain a significant reduction of plaque volume.

Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD)-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo) E−/− mice were divided into two groups and fed a high-fat diet with or without 5% (w/w) SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in the 12 apoE−/− mice fed 5% SPH for 12 weeks compared to the 12 casein-fed control mice. Immunohistochemical characterization of atherosclerotic lesions in aortic sinus displayed no differences in plaque composition between mice fed SPH compared to controls. However, reduced mRNA level of Icam1 in the aortic arch was found. The plasma content of arachidonic acid (C20∶4n-6) and oleic acid (C18∶1n-9) were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1β, IL-6, TNF-α and GM-CSF, whereas plasma cholesterol and triacylglycerols (TAG) were unchanged, accompanied by unchanged mitochondrial fatty acid oxidation and acyl-CoA:cholesterol acyltransferase (ACAT)-activity. These data show that a 5% (w/w) SPH diet reduces atherosclerosis in apoE−/− mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids or fatty acids.

The biological activities of a protein isolate from lupin (Lupinus albus) were studied in a rabbit model of atherosclerosis. Focal plaque development was induced at both common carotid arteries by perivascular injury. After surgery, animals were fed three different diets for 90 d, all with 1 % cholesterol, 15 % SFA and 20 % protein; the protein source was casein (CAS), lupin proteins (LUP) or 50 % CAS þ 50 % LUP (CAS þ LUP). Lower cholesterolaemia was detected in the LUP v. the CAS group at 60 and 90 d of treatment (2 40·3 and 233·5 %, respectively; P, 0·05). Cryosection analyses of the carotids indicated a significant reduction in focal lesion progression in the LUP v. the CAS group (2 37·4 %; P, 0·05). In summary, in a rabbit model of atherosclerosis, a protein isolate from L. albus reduced cholesterolaemia and exerted a remarkable protective activity against atherosclerosis progression. Lupinus albus: Protein isolates: Cholesterol: Atherosclerosis: RabbitsThe growing use of legume proteins in human nutrition for their nutraceutical properties (1 -4) has recently suggested detailed investigations on the possible clinical use of lupin proteins. Lupin beans are characterised by a lower content of antinutrients v. other legumes (5) and by an almost total absence of phyto-oestrogens (6,7) . This last feature, on the one hand, may avoid potential problems that have been recently indicated for these hormone-like components (8) ; on the other, it allows a direct evaluation of the activity of 'proteins', independent of other components. Lupin protein isolates are nutritionally satisfactory (9,10) and have a neutral flavour (11) , thus allowing the production of food items with optimal sensory characteristics (12) .A previous study from our group (7) investigated the potential hypolipidaemic effect of a total protein extract from Lupinus albus. When given to rats fed a classical cholesterol -cholic acid regimen, lupin proteins significantly reduced both plasma cholesterol and TAG levels v. control animals. The cholesterol reduction appeared to be associated with a mechanism shared with soya proteins, i.e. a direct up regulatory activity on LDL receptors (13 -15) .Based on recent data by our group (16) and others (17,18) suggesting an anti-atherosclerotic effect of soya proteins, also characterised by a cholesterol-lowering activity (1,13,15) , the impact on atherosclerosis progression of a diet containing L. albus proteins was tested in a rabbit model of focal lipid-rich soft plaques, generated at the common carotid arteries (19) .

Controversial data on the lipid-lowering effect of dietary pea proteins have been provided and the mechanisms behind this effect are not completely understood. The aim of the study was to evaluate a possible hypolipidemic activity of a pea protein isolate and to determine whether pea proteins could affect the hepatic lipid metabolism through regulation of genes involved in cholesterol and fatty acid homeostasis. Rats were fed Nath's hypercholesterolemic diets for 28 days, the protein sources being casein or a pea protein isolate from Pisum sativum. After 14 and 28 days of dietary treatment, rats fed pea proteins had markedly lower plasma cholesterol and triglyceride levels than rats fed casein (p<0.05). Pea protein-fed rats displayed higher hepatic mRNA levels of LDL receptor versus those fed casein (p<0.05). Hepatic mRNA concentration of genes involved in fatty acids synthesis, such as fatty acid synthase and stearoyl-CoA desaturase, was lower in pea protein-fed rats than in rats fed casein (p<0.05). In conclusion, the present study demonstrates a marked cholesterol and triglyceride-lowering activity of pea proteins in rats. Moreover, pea proteins appear to affect cellular lipid homeostasis by upregulating genes involved in hepatic cholesterol uptake and by downregulating fatty acid synthesis genes.