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      Beneficial Effect of a Multistrain Synbiotic Prodefen ® Plus on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A

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          Abstract

          A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available Prodefen ® Plus . MtS was induced by HFD (45%) in male Wistar rats. Half of the MtS animals received Prodefen ® Plus for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. Prodefen ® Plus supplementation did not affect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. Prodefen ® Plus supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with Prodefen ® Plus could be considered an interesting non-pharmacological approach in MtS.

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          Diabetes, obesity and gut microbiota.

          The gut microbiota composition has been associated with several hallmarks of metabolic syndrome (e.g., obesity, type 2 diabetes, cardiovascular diseases, and non-alcoholic steatohepatitis). Growing evidence suggests that gut microbes contribute to the onset of the low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. Recently, enteroendocrine cells and the endocannabinoid system have been shown to control gut permeability and metabolic endotoxaemia. Moreover, targeted nutritional interventions using non-digestible carbohydrates with prebiotic properties have shown promising results in pre-clinical studies in this context, although human intervention studies warrant further investigations. Thus, in this review, we discuss putative mechanisms linking gut microbiota and type 2 diabetes. These data underline the advantage of investigating and changing the gut microbiota as a therapeutic target in the context of obesity and type 2 diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.
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            Vascular oxidative stress, nitric oxide and atherosclerosis.

            In the vascular wall, reactive oxygen species (ROS) are produced by several enzyme systems including NADPH oxidase, xanthine oxidase, uncoupled endothelial nitric oxide synthase (eNOS) and the mitochondrial electron transport chain. On the other hand, the vasculature is protected by antioxidant enzyme systems, including superoxide dismutases, catalase, glutathione peroxidases and paraoxonases, which detoxify ROS. Cardiovascular risk factors such as hypercholesterolemia, hypertension, and diabetes mellitus enhance ROS generation, resulting in oxidative stress. This leads to oxidative modification of lipoproteins and phospholipids, mechanisms that contribute to atherogenesis. In addition, oxidation of tetrahydrobiopterin may cause eNOS uncoupling and thus potentiation of oxidative stress and reduction of eNOS-derived NO, which is a protective principle in the vasculature. This review summarizes the latest advances in the role of ROS-producing enzymes, antioxidative enzymes as well as NO synthases in the initiation and development of atherosclerosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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              Monostrain, multistrain and multispecies probiotics--A comparison of functionality and efficacy.

              This literature review was carried out to make a comparison of functionality and efficacy between monostrain, multistrain and multispecies probiotics. A monostrain probiotic is defined as containing one strain of a certain species and consequently multistrain probiotics contain more than one strain of the same species or, at least of the same genus. Arbitrarily, the term multispecies probiotics is used for preparations containing strains that belong to one or preferentially more genera. Multispecies probiotics were superior in treating antibiotic-associated diarrhea in children. Growth performance and particularly mortality in broilers could be improved with multistrain probiotics. Mice were better protected against S. Typhimurium infection with a multistrain probiotic. A multispecies probiotic provided the best clearance of E. coli O157:H7 from lambs. Rats challenged with S. Enteritidis showed best post-challenge weight gains when treated with a multispecies probiotic. Possible mechanisms underlying the enhanced effects of probiotic mixtures are discussed. It is also emphasized that strains used in multistrain and multispecies probiotics should be compatible or, preferably, synergistic. The design and use of multistrain and multispecies probiotics should be encouraged.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                01 January 2020
                January 2020
                : 12
                : 1
                : 117
                Affiliations
                [1 ]Department of Physiology, School of Medicine, Universidad Autónoma de Madrid, Calle de Arzobispo Morcillo 4, 28029 Madrid, Spain; pablollevenes@ 123456gmail.com (P.L.); croslaia@ 123456gmail.com (L.C.-B.); gloria.balfagon@ 123456uam.es (G.B.)
                [2 ]Department of Pharmacology and Therapeutics, School of Medicine, Universidad Autónoma de Madrid, Calle de Arzobispo Morcillo 4, 28029 Madrid, Spain; raquel.rodrigues@ 123456uam.es
                [3 ]Center for Biomedical Research Network (CIBER) in Cardiovascular Diseases, Calle de Melchor Fernández Almagro 3, 28029 Madrid, Spain
                [4 ]Research Institute University Hospital la Paz (IdIPaz), Calle de Pedro Rico 6, 28029 Madrid, Spain; iprieto@ 123456intermic.com
                [5 ]Department of General and Digestive Surgery, Hospital Universitario la Paz, Paseo de la Castellana 261, 28046 Madrid, Spain
                [6 ]Research Institute of Santa Creu i Sant Pau Hospital, Carrer de Sant Quintí 77–79, 08041 Barcelona, Spain; lcasani@ 123456santpau.cat
                Author notes
                [* ]Correspondence: javier.blanco@ 123456uam.es ; Tel.: +34-91-497-5446
                Author information
                https://orcid.org/0000-0003-1925-7204
                https://orcid.org/0000-0002-6348-1505
                https://orcid.org/0000-0002-0139-4588
                https://orcid.org/0000-0001-7232-2314
                Article
                nutrients-12-00117
                10.3390/nu12010117
                7019517
                31906276
                e84648a1-bdb7-43c3-ae5b-7b6624cc205e
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 December 2019
                : 18 December 2019
                Categories
                Article

                Nutrition & Dietetics
                metabolic syndrome,synbiotic,hypertension,superior mesenteric artery,perivascular nitrergic innervation,nitric oxide,neuronal nitric oxide synthase,protein kinase a

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