title: Clostridium butyricum B1 alleviates high-fat diet-induced steatohepatitis in mice via enterohepatic immunoregulation.
abstract: OBJECTIVE
  Enterohepatic immunologic derangement is associated with non-alcoholic steatohepatitis. Here, we investigated whether Clostridium butyricum B1 (CB) would be an effective immune-targeted substance to attenuate steatohepatitis in mice.
  
  
  METHODS
  Thirty mice were randomized into a control group fed with common forage, a high-fat diet (HFD) group fed an HFD for 16 weeks, and an HFD + CB group treated with CB for the latter 8 weeks. Inflammation-associated or metabolism-associated genes in the liver or epididymal fat tissue were quantified; intrahepatic and intestinal immune factors were detected. Further short-chain fatty acids in the cecal contents or liver were measured, and differentiations of T cells in vitro were analyzed.
  
  
  RESULTS
  Characteristics of non-alcoholic steatohepatitis in the HFD group were obvious and were significantly attenuated in the HFD + CB group. The messenger RNA levels of monocyte chemotactic protein-1 and tumor necrosis factor-α in the liver and epididymal fat tissue were increased in the HFD group compared with the control group and were downregulated in the HFD + CB group. Intrahepatic and intestinal interferon-γ and interleukin (IL)-17 were significantly increased, whereas forkhead box P3, IL-4, and IL-22 were significantly decreased in the HFD group compared with the control group. However, these intrahepatic or intestinal immune changes were reversed after CB intervention. Furthermore, butyrate in the cecal content and liver of the HFD + CB group was significantly elevated. An in vitro investigation showed that sodium butyrate promoted CD4+T cell differentiation into Th2, Th22, or Treg, whereas it inhibited CD4+T cell differentiation into Th1 or Th17 under a cytokine milieu, which was mimicked by Trichostatin A.
  
  
  CONCLUSIONS
  Clostridium butyricum B1 could attenuate HFD-induced steatohepatitis in mice partially through butyrate-induced enterohepatic immunoregulation.
authors.affiliation: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Da
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Liu
authors.affiliation: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Rui-Xu
authors.initials: RX
authors.lastname: Yang
authors.affiliation: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yuan-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian-Gao
authors.initials: JG
authors.lastname: Fan
mesh_terms: D000818:Animals; D002087:Butyrates / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes; D002454:Cell Differentiation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D046972:Clostridium butyricum / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology* / Q000276:immunology / Q000628:therapy*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D002087:Butyrates; D018932:Chemokine CCL2; D016207:Cytokines; D005232:Fatty Acids, Volatile; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: Clostridium butyricum B1; NASH; butyrate; histone deacetylase inhibition; immunity