Bifidobacterium pseudocatenulatum CECT7765 promotes a TLR2-dependent anti-inflammatory response in intestinal lymphocytes from mice with cirrhosis

Eur J Nutr. 2016 Feb;55(1):197-206. doi: 10.1007/s00394-015-0837-x. Epub 2015 Feb 6.

Abstract

Background: Intestinal homeostasis plays an important role in bacteria-derived complications in cirrhosis. Intestinal lymphocytes are responsible for immune effector functions and can be modulated by certain probiotics. We evaluate the interaction between Bifidobacterium pseudocatenulatum CECT7765 and intestinal lymphocytes in mice with cirrhosis.

Animals and methods: Cirrhosis was induced by intragastrical administration of carbon tetrachloride in Balb/C mice. One week prior to laparotomy, animals received B. pseudocatenulatum CECT7765 (10(7), 10(9) or 10(10) cfu/daily) or placebo. Chemokine receptor and cytokine expression were evaluated in intestinal lymphocytes. Gut permeability was studied by FITC-LPS recovery in vivo. Luminal antigens, inflammation and functional markers were evaluated in liver samples.

Results: Bifidobacterium pseudocatenulatum CECT7765 decreased the expression of pro-inflammatory chemokine receptors CCR6, CCR9, CXCR3 and CXCR6 in intestinal lymphocytes from cirrhotic mice in a concentration-dependent manner. The bifidobacterial strain induced a shift towards an anti-inflammatory cytokine profile in this cell subset. B. pseudocatenulatum CECT7765-induced inflammatory modulation was TLR2-mediated, as in vitro TLR2 blockade inhibited the reduction of TNF-alpha and its receptors and the increase of IL-10 and IL-10 receptor secretion. The recovery rate of administered fluorescence-labelled endotoxin was significantly and dose-dependently lowered with the bifidobacterial strain. The reduced intestinal permeability was associated with a decreased burden of bacterial antigens in the liver of mice treated with B. pseudocatenulatum CECT7765. Liver function and inflammation were improved with the use of the bifidobacterial strain at the highest dose tested (10(10) cfu).

Conclusion: Bifidobacterium pseudocatenulatum CECT7765 improves gut homeostasis and prevents gut-derived complications in experimental chronic liver disease.

Keywords: B. pseudocatenulatum CECT7765; Cirrhosis; Endotoxin; Inflammation; Intestinal lymphocytes; Toll-like receptor 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bifidobacterium*
  • Carbon Tetrachloride / administration & dosage
  • Carbon Tetrachloride / toxicity
  • Disease Models, Animal
  • Female
  • Gastrointestinal Microbiome*
  • Homeostasis
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Intestines / cytology
  • Intestines / microbiology
  • Liver / metabolism
  • Liver / microbiology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / therapy*
  • Lymphocytes / metabolism
  • Lymphocytes / microbiology*
  • Mice
  • Mice, Inbred BALB C
  • Permeability
  • Probiotics / administration & dosage*
  • Receptors, CCR / genetics
  • Receptors, CCR / metabolism
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / metabolism
  • Receptors, CXCR / genetics
  • Receptors, CXCR / metabolism
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism
  • Receptors, CXCR6
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 2 / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CC chemokine receptor 9
  • CCR6 protein, mouse
  • Cxcr3 protein, mouse
  • Cxcr6 protein, mouse
  • IL10 protein, mouse
  • Receptors, CCR
  • Receptors, CCR6
  • Receptors, CXCR
  • Receptors, CXCR3
  • Receptors, CXCR6
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Carbon Tetrachloride