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

• Published in: World journal of gastroenterology : WJG Vol. 23; no. 1; pp. 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: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 07.01.2017
• 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; Gut microbiota; Sodium butyrate; Non-alcoholic fatty liver disease; Endotoxin; Gastrointestinal barrier
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v23.i1.60

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.