Published online Jan 7, 2017. doi: 10.3748/wjg.v23.i1.60
Peer-review started: September 12, 2016
First decision: October 20, 2016
Revised: October 25, 2016
Accepted: November 15, 2016
Article in press: November 16, 2016
Published online: January 7, 2017
Processing time: 115 Days and 10.7 Hours
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.
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.
NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. 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.
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.
Core tip: Non-alcoholic fatty liver disease (NAFLD) is a global epidemic metabolic health crisis that lacks effective therapeutic strategies. We found that NaB could correct the high-fat diet (HFD)-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, improved tight junction structure, reduced gut endotoxin into liver, leading to attenuate HFD induced liver inflammation and lipid accumulation, which may be a potential gut microbiota modulator and therapeutic substance for NAFLD.