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

  • Isabel Gómez-Hurtado
  • Pedro Zapater
  • Kevin Portune
  • Oriol Juanola
  • Anabel Fernández-Iglesias
  • José M. González-Navajas
  • Jordi Gracia-Sancho
  • Yolanda Sanz
  • Rubén Francés
Original Contribution

Abstract

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.

Keywords

Liver damage Bile duct ligation Liver hemodynamics Liver function Bifidobacterium Microbiota 

Notes

Funding

This work has been partially funded by Grants PI16/0967 from Instituto de Salud Carlos III, Madrid, Spain, PROMETEO/2016/001 from Generalitat Valenciana, Valencia, Spain, by FEDER funds and by the European Union’s Seventh Framework Program under the grant agreement no 613979 (MyNewGut).

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

394_2018_1709_MOESM1_ESM.pdf (61 kb)
Supplementary material 1 (PDF 61 KB)
394_2018_1709_MOESM2_ESM.pdf (53 kb)
Supplementary material 2 (PDF 53 KB)
394_2018_1709_MOESM3_ESM.docx (1.1 mb)
Supplementary material 3 (DOCX 1124 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Isabel Gómez-Hurtado
    • 1
  • Pedro Zapater
    • 1
    • 2
    • 3
  • Kevin Portune
    • 4
  • Oriol Juanola
    • 1
    • 3
  • Anabel Fernández-Iglesias
    • 1
    • 5
  • José M. González-Navajas
    • 1
    • 2
  • Jordi Gracia-Sancho
    • 1
    • 5
  • Yolanda Sanz
    • 4
  • Rubén Francés
    • 1
    • 2
    • 3
  1. 1.CIBERehd, Instituto de Salud Carlos IIIMadridSpain
  2. 2.Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO)AlicanteSpain
  3. 3.Dpto. Medicina ClínicaUniversidad Miguel HernándezSan JuanSpain
  4. 4.Grupo de Ecofisiología BacterianaIATA-CSICValenciaSpain
  5. 5.Liver Vascular Biology Research GroupIDIBAPSBarcelonaSpain

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