loading page

Gut Akkermansia muciniphila ameliorates non-alcoholic fatty liver disease by L-aspartate via interaction with liver
  • +13
  • Yong Rao,
  • Zhi-qi Kuang,
  • Chan Li,
  • Shi-Yao Guo,
  • Yao-Hao Xu,
  • Dan-Dan Zhao,
  • Yu Hu,
  • Bing-Bing Song,
  • Zhi Jiang,
  • Zhen-Huang Ge,
  • Xi-Yuan Liu,
  • Cheng-Dao Li,
  • Shuo-Bin Chen,
  • Ji-Ming Ye,
  • Yong-jun Lu,
  • Zhi-Shu Huang
Yong Rao
Sun Yat-sen University
Author Profile
Zhi-qi Kuang
Sun Yat-Sen University
Author Profile
Chan Li
Sun Yat-Sen University
Author Profile
Shi-Yao Guo
Sun Yat-sen University
Author Profile
Yao-Hao Xu
Sun Yat-Sen University
Author Profile
Dan-Dan Zhao
Sun Yat-Sen University
Author Profile
Yu Hu
Sun Yat-Sen University
Author Profile
Bing-Bing Song
Sun Yat-Sen University
Author Profile
Zhi Jiang
Sun Yat-Sen University
Author Profile
Zhen-Huang Ge
Sun Yat-Sen University
Author Profile
Xi-Yuan Liu
Sun Yat-Sen University
Author Profile
Cheng-Dao Li
Sun Yat-Sen University
Author Profile
Shuo-Bin Chen
Sun Yat-Sen University
Author Profile
Ji-Ming Ye
RMIT University
Author Profile
Yong-jun Lu
Sun Yat-Sen University
Author Profile
Zhi-Shu Huang
Sun Yat-Sen University
Author Profile

Abstract

Background and Purpose The human gut bacterium Akkermansia muciniphila has been increasingly recognized for its therapeutic potential in treating metabolic disorders. However, its efficacy in preventing non-alcoholic fatty liver disease (NAFLD) and the mechanism involved in its well-known metabolic actions are unknown. The present study explored the therapeutic effect and novel mechanism of A. muciniphila in intervening NAFLD. Experimental Approach The anti-NAFLD activity of A. muciniphila was evaluated in an obese mouse model induced by high-fat and cholesterol (HFC) diets using three different interventions. The gut microbiota composition, beneficial metabolic effects in the gut-liver axis were explored. The level and beneficial metabolic effects of L-aspartate in vitro and in vivo were further determined. Key Results Mice treated with A. muciniphila efficiently reversed NAFLD in the liver, such as hepatic steatosis, inflammatory, and liver injury. These therapeutic effects persisted after long-term drug withdrawal and were slightly weakened in a germ-free mouse model. A. muciniphila treatment efficiently increased mitochondrial oxidation and bile acid metabolism in the gut-liver axis, ameliorated oxidative stress- induced cell apoptosis in the gut, leading to the reshaping of the gut microbiota composition. These metabolic improvements occurred with increased L-aspartate levels in the liver that transported from the gut. The administration of L-aspartate in vitro or in mice displayed the similar beneficial metabolic effects mentioned above. Conclusion and Implications The anti-NAFLD activity of A. muciniphila correlated with lipid oxidation and improved gut-liver interactions through regulating L-aspartate metabolism. A. muciniphila would be a potent agent for clinical intervention in NAFLD.