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Gut–liver axis, cirrhosis and portal hypertension: the chicken and the egg

  • Special Issue - Portal Hypertension
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Abstract

The term gut–liver axis is used to highlight the close anatomical and functional relationship between the intestine and the liver. The intestine has a highly specialized epithelial membrane which regulates transport across the mucosa. Due to dysbiosis, impairment of the intestinal barrier and altered immunity status, bacterial products can reach the liver through the portal vein, where they are recognized by specific receptors, activate the immune system and lead to a proinflammatory response. Gut microbiota and bacterial translocation play an important role in the pathogenesis of chronic liver diseases, including alcoholic and non-alcoholic fatty liver disease, cirrhosis, and its complications, such as portal hypertension, spontaneous bacterial peritonitis and hepatic encephalopaty. The gut microbiota also plays a critical role as a modulator of bile acid metabolism which can also influence intestinal permeability and portal hypertension through the farnesoid-X receptor. On the other hand, cirrhosis and portal hypertension affect the microbiota and increase translocation, leading to a “chicken and egg” situation, where translocation increases portal pressure, and vice versa. A myriad of therapies targeting gut microbiota have been evaluated specifically in patients with chronic liver disease. Further studies targeting intestinal microbiota and its possible hemodynamic and metabolic effects are needed. This review summarizes the current knowledge about the role of gut microbiota in the pathogenesis of chronic liver diseases and portal hypertension.

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Abbreviations

ACLF:

Acute-on-chronic liver failure

APC:

Antigen-presenting cells

BAs:

Bile acids

BDL:

Bile-duct ligation

DAMPs:

Damage-associated molecular patterns

DDAH-2:

Dimethylarginine dimethylaminohydrolase 2

eNOS:

Endothelial nitric oxide synthase

FXR:

Farnesoid-X receptor

IFN-Υ:

Interferon gamma

IL-6:

Interleukin-6

MLCK:

Myosin-light chain kinase

NAFLD:

Non-alcoholic liver disease

NLR:

Nucleotide-binding oligomerization domain like receptors

NSBB:

Non-selective beta-blockers

LPS:

Lipopolysaccharide

OCA:

Obeticholic acid

PAMPs:

Pathogen-associated molecular patterns

PP2A:

Protein phosphatase 2A

PPI:

Proton-pump inhibitors

PRRs:

Pattern recognition receptors

SIBO:

Small intestine bacterial overgrowth

TNF-α:

Tumor necrosis factor-α

TLRs:

Toll-like receptors

ZO-1:

Zonula occludens-1

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Acknowledgements

This work was supported by grant(s) NIH DK59615 and AA021171 (VHS), the Clinical Core of the Mayo Clinic Center for Cell Signaling in Gastroenterology (P30DK084567). Arab JP was funded by an award from AASLD Foundation (AASLD/LIFER Clinical and Translational Research Fellowship in Liver Diseases). The authors also thanks Mrs. Terri Johnson for her secretarial assistance.

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  1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First ST SW, Rochester, MN, USA

    Juan P. Arab, Rosa M. Martin-Mateos & Vijay H. Shah

  2. Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile

    Juan P. Arab

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Arab, J.P., Martin-Mateos, R.M. & Shah, V.H. Gut–liver axis, cirrhosis and portal hypertension: the chicken and the egg. Hepatol Int 12 (Suppl 1), 24–33 (2018). https://doi.org/10.1007/s12072-017-9798-x

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