Improved hemodynamic and liver function in portal hypertensive cirrhotic rats after administration of B. pseudocatenulatum CECT 7765

Purpose: Evaluating whether changes in gut microbiota induced by a bifidobacterial strain may have an effect on the hepatic vascular function in portal hypertensive cirrhotic rats.Methods: Bile duct ligation (BDL) was performed in rats. A subgroup of animals received B. pseudocatenulatum CECT7765 (109 cfu/daily ig.) for 1 week prior to laparotomy. Hemodynamic, biochemical and inflammatory markers were evaluated. Ileal microbiota composition was identified. Statistical analysis was performed.Results: Sham-operated (n = 6), BDL (n = 6) and BDL treated with bifidobacteria (n = 8) rats were included. B. pseudocatenulatum CECT7765 significantly decreased proteobacteria (p = 0.001) and increased Bacteroidetes (p = 0.001) relative abundance. The bifidobacteria decreased the Firmicutes/Bacteroidetes ratio in the BDL model (p = 0.03). BDL with bifidobacteria vs BDL rats showed: significantly reduced portal vein area, portal flow, congestion index, alkaline phosphatase and total bilirubin, significantly increased serum cytokines and nitric oxide levels, gene expression levels of bile acids receptor FXR and endothelial nitric oxide synthase. Quantitative changes in the Clostridiales and Bacteroidales orders were independently associated with variations in portal vein area and portal flow, while changes in the Proteobacteria phylum were independently associated with congestion. Variations in all liver function markers significantly correlated with total OTUs mainly in the Firmicutes, but only changes in the Clostridiales were independently associated with alkaline phosphatase in the ANCOVA analysis.Conclusion: Hemodynamic alterations and liver dysfunction induced by BDL in rats are partially restored after oral administration of B. pseudocatenulatum CECT7765. Results provide a proof-of-concept for the beneficial effect of this bifidobacterial strain in reducing complications derived from portal hypertension in cirrhosis

Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis

Short-chain fatty acids (SCFAs) are gut microbiota-derived products that participate in maintaining the gut barrier integrity and host's immune response. We hypothesize that reduced SCFA levels are associated with systemic inflammation, endotoxemia, and more severe hemodynamic alterations in cirrhosis. Patients with cirrhosis referred for a hepatic venous pressure gradient (HVPG) measurement (n = 62) or a transjugular intrahepatic portosystemic shunt placement (n = 12) were included. SCFAs were measured in portal (when available), hepatic, and peripheral blood samples by GC-MS. Serum endotoxins, proinflammatory cytokines, and NO levels were quantified. SCFA levels were significantly higher in portal vs. hepatic and peripheral blood. There were inverse relationships between SCFAs and the severity of disease. SCFAs (mainly butyric acid) inversely correlated with the model for end-stage liver disease score and were further reduced in patients with history of ascites, hepatic encephalopathy, and spontaneous bacterial peritonitis. There was an inverse relationship between butyric acid and HVPG values. SCFAs were directly related with systemic vascular resistance and inversely with cardiac index. Butyric acid inversely correlated with inflammatory markers and serum endotoxin. A global reduction in the blood levels of SCFA in patients with cirrhosis is associated with a more advanced liver disease, suggesting its contribution to disease progression.-Juanola, O., Ferrusquía-Acosta, J., García-Villalba, R., Zapater, P., Magaz, M., Marín, A., Olivas, P., Baiges, A., Bellot, P., Turon, F., Hernández-Gea, V., González-Navajas, J. M., Tomás-Barberán, F. A., García-Pagán, J. C., Francés, R. Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis

Epidemiological, Clinical and Genetic Study of Hypophosphatasia in A Spanish Population: Identification of Two Novel Mutations in The Alpl Gene

Hypophosphatasia (HPP) is a genetic disease caused by one or several mutations in ALPL gene encoding the tissue-nonspecific alkaline phosphatase affecting the mineralization process. Due to its low prevalence and lack of recognition, this metabolic disorder is generally confused with other more frequent bone disorders. An assessment of serum total alkaline phosphatase (ALP) levels was performed in 78,590 subjects. Pyridoxal-5′-phosphate (PLP) concentrations were determined and ALPL gene was sequenced in patients potentially affected by HPP. Functional validation of the novel mutations found was performed using a cell-based assay. Our results showed persistently low serum ALP levels in 0.12% of subjects. Among the studied subjects, 40% presented with HPP-related symptoms. Nine of them (~28%) had a history of fractures, 5 (~16%) subjects showed chondrocalcinosis and 4 (~13%) subjects presented with dental abnormalities. Eleven subjects showed increased PLP concentrations. Seven of them showed ALPL gene mutations (2 of the mutations corresponded to novel genetic variants). In summary, we identified two novel ALPL gene mutations associated with adult HPP. Using this protocol, almost half of the studied patients were diagnosed with HPP. Based on these results, the estimated prevalence of mild HPP in Spain could be up to double than previously reported.Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (with support from NIH P41-GM103311)grants from Alexion and FEIOMM, by Instituto de Salud Carlos III (grants PI18-00803 and PI18-01235)co-funding from FEDER and by Junta de Andalucía (grant PI-0207-2016)GM-N is supported by the predoctoral program from Instituto de Salud Carlos III (FI17/00178) and by the Research Initiation Grants for Official Master Students program from the University of Granada (2017)PJR is a Ramon y Cajal Researcher from the MINECO (RYC-2015-18383) at GENyO and University of Granada

Fiber intake and all-cause mortality in the Prevención con Dieta Mediterránea (PREDIMED) study

Background: Few observational studies have examined the effect of dietary fiber intake and fruit and vegetable consumption on total mortality and have reported inconsistent results. All of the studies have been conducted in the general population and typically used only a single assessment of diet. Objective: We investigated the association of fiber intake and whole-grain, fruit, and vegetable consumption with all-cause mortality in a Mediterranean cohort of elderly adults at high cardiovascular disease (CVD) risk by using repeated measurements of dietary information and taking into account the effect of a dietary intervention. Design: We followed up 7216 men (55-75 y old) and women (60-75 y old) at high CVD risk in the Prevención con Dieta Mediterránea (PREDIMED) trial for a mean of 5.9 y. Data were analyzed as an observational cohort. Participants were initially free of CVD. A 137-item validated food-frequency questionnaire administered by dietitians was repeated annually to assess dietary exposures (fiber, fruit, vegetable, and whole-grain intakes). Deaths were identified through the continuing medical care of participants and the National Death Index. An independent, blinded Event Adjudication Committee adjudicated causes of death. Cox regression models were used to estimate HRs of death during follow-up according to baseline dietary exposures and their yearly updated changes. Results: In up to 8.7 y of follow-up, 425 participants died. Baseline fiber intake and fruit consumption were significantly associated with lower risk of death [HRs for the fifth compared with the first quintile: 0.63 (95% CI: 0.46, 0.86; P = 0.015) and 0.59 (95% CI: 0.42, 0.82; P = 0.004), respectively]. When the updated dietary information was considered, participants with fruit consumption .210 g/d had 41% lower risk of all-cause mortality (HR: 0.59; 95% CI: 0.44, 0.78). Associations were strongest for CVD mortality than other causes of death. Conclusion: Fiber and fruit intakes are associated with a reduction in total mortality. PREDIMED was registered at controlled-trials.com as ISRCTN35739639. © 2014 American Society for Nutrition.Peer Reviewe

The Emerging Relevance of AIM2 in Liver Disease

Absent in melanoma 2 (AIM2) is a cytosolic receptor that recognizes double-stranded DNA (dsDNA) and triggers the activation of the inflammasome cascade. Activation of the inflammasome results in the maturation of inflammatory cytokines, such as interleukin (IL)-1 β and IL-18, and a form of cell death known as pyroptosis. Owing to the conserved nature of its ligand, AIM2 is important during immune recognition of multiple pathogens. Additionally, AIM2 is also capable of recognizing host DNA during cellular damage or stress, thereby contributing to sterile inflammatory diseases. Inflammation, either in response to pathogens or due to sterile cellular damage, is at the center of the most prevalent and life-threatening liver diseases. Therefore, during the last 15 years, the study of inflammasome activation in the liver has emerged as a new research area in hepatology. Here, we discuss the known functions of AIM2 in the pathogenesis of different hepatic diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), hepatitis B, liver fibrosis, and hepatocellular carcinoma (HCC)

Gut bacterial DNA translocation is an independent risk factor of flare at short term in patients with crohn's disease

OBJECTIVES We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variant-NOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P<0.001), steroids startup (OR 8.5 (2.7-27.1); P<0.001), and switch of treatment (OR 3.5 (1.6-7.7); P=0.002) at 6 months. No relationship was observed between bactDNA and mucosal lesions in patients with colonoscopy at admission. Serum pro-inflammatory cytokines were significantly increased in patients with bactDNA or a variant-NOD2 genotype. The combination of both factors induced decreased anti-TNF-α levels and a higher percentage of patients on intensified anti-TNF therapy. CONCLUSIONS BactDNA is an independent risk factor of relapse at 6 months in CD patients. BactDNA is also independently associated with an increased risk of hospitalization, switch of treatment, and steroids initiation

Colour assesment of red wine by sensory analysis. Correlation of phisical-chemical parameters with sensory attributes

Póster presentado en el X Congreso Nacional del Color, celebrado en Valencia del 26 al 28 de junio de 2013.N

Efecto del tiempo y la concentración de oxígeno en la evolución del color de vinos jóvenes

Póster presentado en el XII Congreso de los Grupos de Investigación Enológica (GIENOL 2013, Nuevas perspectivas en investigación vitivinícola), celebrado en Madrid del 18 al 21 de junio de 2013.Peer Reviewe