1-Deoxynojirimycin improves high fat diet-induced nonalcoholic steatohepatitis by restoring gut dysbiosis

J Nutr Biochem. 2019 Sep:71:16-26. doi: 10.1016/j.jnutbio.2019.05.013. Epub 2019 Jun 8.

Abstract

Non-alcoholic steatohepatitis (NASH) is associated with chronic inflammation and gut bacterial dysbiosis. Studies show that 1-deoxynojirimycin (DNJ) may improve NASH, yet the role of gut microbiota in protective effect of DNJ on NASH remains to be known. In present study, we aimed to examine how DNJ ameliorated high-fat diet (HFD)-induced mouse NASH through the regulation of gut microbiota dysbiosis. C57BL/6 J mice fed with HFD were treated with DNJ (0.1 mg/mL, in drinking water) for 4 months. The results by using histochemical staining and qPCR confirmed that DNJ remarkably modulated glucose intolerance and hyperlipidemia, attenuated hepatic steatosis and systemic chronic inflammation in HFD-induced mice. Moreover, DNJ greatly reshaped the structure of disbalanced intestinal flora, as indicated by the enhanced bacterial richness and diversity, the decreased Firmicutes-to-Bacteroidetess ratio and the increased Akkermansia level. The prediction algorithm suggests that DNJ may extensively dampen the bacterial motility and bacterial energy metabolism. Consistently, the altered gut microbiota was closely correlated with metabolic biomarkers of mice with NASH. Based on our studies, DNJ could alleviate the progress of HFD-induced NASH by rebuilding the gut microbial community structure, suggesting that DNJ may serve as a functional food to prevent or treat NASH clinically.

Keywords: 1-Deoxynojirimycin; Akkermansia; Gut microbiota; High fat diet; Non-alcoholic steatohepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / pharmacology*
  • Animals
  • Diet, High-Fat / adverse effects*
  • Dysbiosis / drug therapy*
  • Dysbiosis / microbiology
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / physiology
  • Glucose Intolerance / drug therapy
  • Hepatitis / drug therapy
  • Hepatitis / etiology
  • Insulin / metabolism
  • Lipids / blood
  • Male
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / microbiology

Substances

  • Insulin
  • Lipids
  • 1-Deoxynojirimycin