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 d...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.展开更多
基金the State Key Development Program for Basic Research of China,No.2012CB517501National Natural Science Foundation of China,No.81070322,No.81270491,No.81470840 and No.31400001100 Talents Program,No.XBR2011007h
文摘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.
