Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier

AIM To investigate whether gut microbiota metabolite sodium butyrate(Na B)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...

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Published in:World journal of gastroenterology : WJG 2017-01, Vol.23 (1), p.60-75
Main Authors: Zhou, Da, Pan, Qin, Xin, Feng-Zhi, Zhang, Rui-Nan, He, Chong-Xin, Chen, Guang-Yu, Liu, Chang, Chen, Yuan-Wen, Fan, Jian-Gao
Format: Article
Language:English
Subjects:
Animals
Basic Study
Butyric Acid - pharmacology
Butyric Acid - therapeutic use
Cytokines - metabolism
Diet, High-Fat - adverse effects
Drug Evaluation, Preclinical
Dysbiosis - drug therapy
Gastrointestinal Microbiome - drug effects
Humans
Immunohistochemistry
Inflammation - drug therapy
Intestinal Mucosa - drug effects
Intestinal Mucosa - metabolism
Lactobacillus - drug effects
Lactobacillus - metabolism
Liver - drug effects
Liver - metabolism
Liver Function Tests
Male
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease - etiology
Non-alcoholic Fatty Liver Disease - therapy
Real-Time Polymerase Chain Reaction
Specific Pathogen-Free Organisms
Tumor Necrosis Factor-alpha
Zonula Occludens-1 Protein - metabolism
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Summary:AIM To investigate whether gut microbiota metabolite sodium butyrate(Na B)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 Na B 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 Na B corrected the HFD-induced gut microbiota imbalance in mice,while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae,Blautia and Lactobacil us.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-γin liver or epididymal fat were obviously downregulated after Na B intervention.Liver inflammation and fat accumulation were ameliorated,the levels of TG and cholesterol in liver were decreased after Na B 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.CONCLUSION Na B 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.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v23.i1.60