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      Poor Adherence to Mediterranean Diet and Serum Lipopolysaccharide Are Associated with Oxidative Stress in Patients with Non-Alcoholic Fatty Liver Disease

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          Abstract

          Oxidative stress plays a pivotal role in non-alcoholic fatty liver disease (NAFLD). Factors inducing oxidative stress in NAFLD may be several; however, a relationship with the adherence to Mediterranean Diet (Med-diet) and with serum lipopolysaccharide (LPS) has been poorly investigated in this setting. The aim was to investigate factors associated with impaired oxidative stress in NAFLD, focusing on the potential role of LPS and Med-diet. We enrolled 238 consecutive outpatients from the PLINIO study, in whom we measured the soluble Nox2-derived peptide (sNox2-dp), a marker of systemic oxidative stress, and serum LPS. Adherence to Med-diet was investigated by a nine-item validated dietary questionnaire. Serum sNox2-dp and LPS were higher in patients with NAFLD compared to those without (25.0 vs. 9.0 pg/mL, p < 0.001 and 62.0 vs. 44.9 pg/mL, p < 0.001, respectively). In patients with NAFLD, the highest sNox2-dp tertile was associated with the top serum LPS tertile (Odds Ratio (OR): 4.71; p < 0.001), APRI > 0.7 (OR: 6.96; p = 0.005) and Med-diet-score > 6 (OR: 0.14; p = 0.026). Analyzing individual foods, the daily consumption of wine (OR: 0.29, p = 0.046) and the adequate weekly consumption of fish (OR: 0.32, p = 0.030) inversely correlated with the top sNox2-dp tertile. In conclusion, patients with NAFLD showed impaired oxidative stress. Levels of sNox2 correlated with serum LPS and with low adherence to Med-Diet.

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          The role of the gut microbiota in NAFLD.

          NAFLD is now the most common cause of liver disease in Western countries. This Review explores the links between NAFLD, the metabolic syndrome, dysbiosis, poor diet and gut health. Animal studies in which the gut microbiota are manipulated, and observational studies in patients with NAFLD, have provided considerable evidence that dysbiosis contributes to the pathogenesis of NAFLD. Dysbiosis increases gut permeability to bacterial products and increases hepatic exposure to injurious substances that increase hepatic inflammation and fibrosis. Dysbiosis, combined with poor diet, also changes luminal metabolism of food substrates, such as increased production of certain short-chain fatty acids and alcohol, and depletion of choline. Changes to the microbiome can also cause dysmotility, gut inflammation and other immunological changes in the gut that might contribute to liver injury. Evidence also suggests that certain food components and lifestyle factors, which are known to influence the severity of NAFLD, do so at least in part by changing the gut microbiota. Improved methods of analysis of the gut microbiome, and greater understanding of interactions between dysbiosis, diet, environmental factors and their effects on the gut-liver axis should improve the treatment of this common liver disease and its associated disorders.
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            The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation.

            Nonalcoholic fatty liver disease (NAFLD) is closely associated with the metabolic syndrome. We evaluated the association among the metabolic syndrome, visceral fat accumulation, and the severity of fatty liver with a new scoring system of ultrasonographic findings in apparently healthy Japanese adults. Subjects consisted of 94 patients who received liver biopsy and 4,826 participants who were selected from the general population. Two hepatologists scored the ultrasonographic findings from 0 to 6 points. We calculated Cohen's kappa of within-observer reliability and between-observer reliability. We evaluated the predictive value of the score by the area under a conventional receiver operating characteristic curve (AUC). Within-observer reliability was 0.95 (95% CI 0.93-0.97, P<0.001) and between-observer reliability was 0.95 (95% CI 0.93-0.97, P<0.001). The AUC to diagnose NAFLD was 0.980. The sensitivity was 91.7% (95% CI 87.0-95.1, P<0.001) and the specificity was 100% (95% CI 95.4-100.0, P<0.001). The AUC to diagnose visceral obesity was 0.821. The sensitivity was 68.3% (95% CI 51.9-81.9, P=0.028) and the specificity was 95.1% (95% CI 86.3-99.0, P<0.001). Adjusted odds ratio of the score for the metabolic syndrome was 1.37 (95% CI 1.26-1.49, P<0.001). The scoring system with abdominal ultrasonography could provide accurate information about hepatic steatosis, visceral obesity, and the metabolic syndrome in apparently healthy people who do not consume alcohol.
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              Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis.

              Increased exposure to intestinal bacterial products may contribute to the pathogenesis of non alcoholic steatohepatitis (NASH). Bifidobacteria are predominant bacterial species in the human gut microbiota and have been considered to exert a beneficial effect on human health by maintaining the equilibrium of the resident microbiota. To evaluate the effects of Bifidobacterium longum with fructo-oligosaccharides (Fos) in the treatment of NASH. A total of 66 patients were randomly and equally divided into two groups receiving Bifidobacterium longum with Fos and lifestyle modification (i.e., diet and exercise) versus lifestyle modification alone. The following variables were assessed at -4 (beginning of the dietary lead-in period), 0 (randomization), 6, 12, 18, and 24 weeks: aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, albumin, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting plasma glucose, insulin, C-peptide, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homeostasis model assessment of insulin resistance (HOMA-IR), and serum endotoxins. Liver biopsies were performed at entry and repeated after 24 weeks of treatment. At the end of study period, we observed that the Bifidobacterium longum with Fos and lifestyle modification group versus the lifestyle modification alone group showed significant differences in the AST -69.6 versus -45.9 IU/mL (P < 0.05), LDL cholesterol -0.84 versus -0.18 mmol/L (P < 0.001), CRP -2.9 versus -0.7 mg/L (P < 0.05), TNF-α -0.45 versus -0.12 ng/mL (P < 0.001), HOMA-IR -1.1 versus -0.6 (P < 0.001), serum endotoxin -45.2 versus -30.6 pg/mL (P < 0.001), steatosis (P < 0.05), and the NASH activity index (P < 0.05). Bifidobacterium longum with Fos and lifestyle modification, when compared to lifestyle modification alone, significantly reduces TNF-α, CRP, serum AST levels, HOMA-IR, serum endotoxin, steatosis, and the NASH activity index.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                10 June 2020
                June 2020
                : 12
                : 6
                : 1732
                Affiliations
                [1 ]I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; francesco.baratta@ 123456uniroma1.it (F.B.); daniele.pastori@ 123456uniroma1.it (D.P.); simona.bartimoccia@ 123456uniroma1.it (S.B.); vittoria.cammisotto@ 123456uniroma1.it (V.C.); nicholas.cocomello@ 123456gmail.com (N.C.); alessandracolantoni@ 123456libero.it (A.C.); cristina.nocella@ 123456uniroma1.it (C.N.); domenico.ferro@ 123456uniroma1.it (D.F.); francesco.violi@ 123456uniroma1.it (F.V.); maria.delben@ 123456uniroma1.it (M.D.B.)
                [2 ]Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04015 Latina, Italy; roberto.carnevale@ 123456uniroma1.it
                [3 ]Mediterranea Cardio Centro, 80122 Napoli, Italy
                [4 ]Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Roma, Italy
                Author notes
                [* ]Correspondence: francesco.angelico@ 123456uniroma1.it ; Tel.: +39-064-997-2249
                [†]

                These authors are joint first authors and contributed equally to this work.

                [‡]

                These authors are joint last authors and contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-1708-272X
                https://orcid.org/0000-0001-6357-5213
                https://orcid.org/0000-0002-4922-4318
                https://orcid.org/0000-0003-4330-6379
                https://orcid.org/0000-0002-6216-9595
                https://orcid.org/0000-0002-9372-3923
                https://orcid.org/0000-0003-1199-8454
                Article
                nutrients-12-01732
                10.3390/nu12061732
                7352324
                32531941
                184860b1-74ed-4399-9730-c35391ae4192
                © 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
                : 22 April 2020
                : 07 June 2020
                Categories
                Article

                Nutrition & Dietetics
                non-alcoholic fatty liver disease,mediterranean diet,oxidative stress,lipopolysaccharide,nox2-derived peptide

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