Inulin alleviates inflammation of alcoholic liver disease via SCFAs-inducing suppression of M1 and facilitation of M2 macrophages in mice

Int Immunopharmacol. 2020 Jan;78:106062. doi: 10.1016/j.intimp.2019.106062. Epub 2019 Dec 9.

Abstract

Background: Alcoholic liver disease (ALD) presents one of the leading causes of cirrhosis worldwide. We have demonstrated that inulin alleviates ALD in mice. However, the exact role of hepatic macrophages in effects of inulin on ALD remains largely unclear.

Methods: In vivo, mice were divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with inulin (INU) group (PF/INU) and AF with INU group (AF/INU). Each group was fed modified Lieber-DeCarli liquid diet with or without alcohol. In vitro, RAW264.7 cell lines were polarized to M1 macrophage (Mψ) or M2 Mψ subsets with lipopolysaccharide (LPS) or interleukin-4 (IL-4) stimulation, respectively. The effects of propionate, butyrate and valeric on macrophage M1/M2 were investigated.

Results: The contents of propionate, butyrate and valeric were significantly increased in AF/INU group compared with that in the AF/CON group. M1 Mψ, inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) in AF/INU group were significantly lower than those in AF/CON group. In contrast, M2 Mψ, arginase-1 (Arg-1), and interleukin-10 (IL-10) were notably increased in AF/INU group. In vitro, sodium propionate, sodium butyrate and sodium valerate can suppress M1 Mψ and increase M2 Mψ polarization.

Conclusion: In ALD, inulin ameliorates the inflammation via SCFAs-inducing suppression of M1 and facilitation of M2 Mψ, which may potentially contribute to the control of the disease.

Keywords: ALD; Inflammation; Inulin; Macrophage; SCFA.

MeSH terms

  • Administration, Oral
  • Animals
  • Coculture Techniques
  • Disease Models, Animal
  • Ethanol / administration & dosage
  • Ethanol / toxicity
  • Fatty Acids, Volatile / analysis
  • Fatty Acids, Volatile / immunology
  • Fatty Acids, Volatile / metabolism*
  • Feces / chemistry
  • Gastrointestinal Microbiome / immunology*
  • Inflammation / diet therapy*
  • Inflammation / immunology
  • Inflammation / pathology
  • Intestinal Mucosa / microbiology
  • Inulin / administration & dosage*
  • Liver / cytology
  • Liver / immunology
  • Liver / pathology
  • Liver Diseases, Alcoholic / diet therapy*
  • Liver Diseases, Alcoholic / immunology
  • Liver Diseases, Alcoholic / pathology
  • Macrophage Activation
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Mice
  • Primary Cell Culture
  • RAW 264.7 Cells

Substances

  • Fatty Acids, Volatile
  • Ethanol
  • Inulin