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

Gómez-Hurtado, Isabel, Zapater, Pedro, Portune, Kevin, Juanola, Oriol, Fernández-Iglesias, Anabel, González-Navajas, José M., Gracia-Sancho, Jordi, Sanz, Yolanda, Francés, Rubén
European journal of nutrition 2019 v.58 no.4 pp. 1647-1658
Bacteroidales, Bifidobacterium, Clostridiales, Proteobacteria, alkaline phosphatase, analysis of covariance, bile acids, bile ducts, bilirubin, blood serum, cytokines, endothelial nitric oxide synthase, gene expression, hemodynamics, ileum, intestinal microorganisms, laparotomy, liver, liver function, nitric oxide, oral administration, portal hypertension, portal vein, rats
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.