Bifidobacterium adolescentis CGMCC 15058 alleviates liver injury, enhances the intestinal barrier and modifies the gut microbiota in D-galactosamine-treated rats

Appl Microbiol Biotechnol. 2019 Jan;103(1):375-393. doi: 10.1007/s00253-018-9454-y. Epub 2018 Oct 22.

Abstract

Acute liver failure is a drastic, unpredictable clinical syndrome with high mortality. Various preventive and adjuvant therapies based on modulating the gut flora have been proposed for hepatic injury. We aimed to explore the preventive and therapeutic effects of Bifidobacterium adolescentis CGMCC15058 on rat liver failure, as well as the potential microecological and immunological mechanisms of those effects. B. adolescentis CGMCC15058 (3 × 109 CFU), isolated from healthy human stool, was gavaged to Sprague-Dawley rats for 14 days. Acute liver injury was induced on the 15th day by intraperitoneal injection of D-galactosamine. After 24 h, liver and terminal ileum histology, liver function, plasma cytokines, bacterial translocation and gut microbiota composition were assessed. We found that pretreatment with B. adolescentis significantly relieved elevated serum levels of alanine aminotransferase (ALT), total bile acid and lipopolysaccharide-binding protein and enhanced the expression of mucin 4 and the tight junction protein zonula occludens-1. B. adolescentis exhibited anti-inflammatory properties as indicated by decreased levels of mTOR and the inflammatory cytokines TNF-α and IL-6, as well as elevated levels of the anti-inflammatory cytokine interleukins-10 in the liver. Similar anti-inflammatory signs were also found in plasma. B. adolescentis significantly altered the microbial community, depleting the common pathogenic taxon Proteus and markedly enriching the taxa Coriobacteriaceae, Bacteroidales and Allobaculum, which are involved in regulating the metabolism of lipids and aromatic amino acids. Our findings not only suggest B. adolescentis acts as a prospective probiotic against liver failure but also provide new insights into the prevention and treatment of liver disease.

Keywords: Acute liver failure; Bifidobacterium adolescentis; D-galactosamine; Gut microbiota.

MeSH terms

  • Acute-Phase Proteins
  • Animals
  • Bifidobacterium adolescentis* / isolation & purification
  • Carrier Proteins / blood
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / therapy*
  • Cytokines / blood
  • Dysbiosis / microbiology
  • Dysbiosis / therapy
  • Feces / microbiology
  • Galactosamine / adverse effects
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Intestines / physiology*
  • Lipopolysaccharide-Binding Protein
  • Liver / pathology
  • Male
  • Membrane Glycoproteins / blood
  • Rats, Sprague-Dawley

Substances

  • Acute-Phase Proteins
  • Carrier Proteins
  • Cytokines
  • Galactosamine
  • Membrane Glycoproteins
  • Lipopolysaccharide-Binding Protein