title: Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier.
abstract: OBJECTIVE
  To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms.
  
  
  METHODS
  Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation- or metabolism-associated genes were quantified by real-time PCR.
  
  
  RESULTS
  NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteriaChristensenellaceae,BlautiaandLactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-α, IL-1, IL-2, IL-6 and IFN-γ in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group.
  
  
  CONCLUSIONS
  NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.
authors.affiliation: Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Yuan-Wen Chen, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Da
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Yuan-Wen Chen, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Yuan-Wen Chen, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Feng-Zhi
authors.initials: FZ
authors.lastname: Xin
authors.affiliation: Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Yuan-Wen Chen, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Rui-Nan
authors.initials: RN
authors.lastname: Zhang
authors.affiliation: Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Yuan-Wen Chen, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Chong-Xin
authors.initials: CX
authors.lastname: He
authors.affiliation: Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Yuan-Wen Chen, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Chen
authors.affiliation: Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Yuan-Wen Chen, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Yuan-Wen Chen, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yuan-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Yuan-Wen Chen, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Jian-Gao
authors.initials: JG
authors.lastname: Fan
mesh_terms: D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D064806:Dysbiosis / Q000188:drug therapy; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007778:Lactobacillus / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000628:therapy*; D060888:Real-Time Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*
chemical_list: D016207:Cytokines; C569043:Tjp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D020148:Butyric Acid
keywords: Endotoxin; Gastrointestinal barrier; Gut microbiota; Non-alcoholic fatty liver disease; Sodium butyrate