Impaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice
Zunji Shi,
Hehua Lei,
Gui Chen,
Peihong Yuan,
Zheng Cao,
Hooi-Leng Ser,
Xuehang Zhu,
Fang Wu,
Caixiang Liu,
Manyuan Dong,
Yuchen Song,
Yangyang Guo,
Chuan Chen,
Kexin Hu,
Yifan Zhu,
Xin-an Zeng,
Jinlin Zhou,
Yujing Lu,
Andrew D. Patterson,
Limin Zhang
Affiliations
Zunji Shi
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Hehua Lei
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Gui Chen
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Peihong Yuan
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Zheng Cao
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Hooi-Leng Ser
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China
Xuehang Zhu
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Fang Wu
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Caixiang Liu
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Manyuan Dong
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Yuchen Song
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Yangyang Guo
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Chuan Chen
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Kexin Hu
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Yifan Zhu
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
Xin-an Zeng
School of Food Science and Engineering, South China University of Technology, Guangzhou, China
Jinlin Zhou
Engineering Research Academy of High Value Utilization of Green Plants, Meizhou, China
Yujing Lu
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China
Andrew D. Patterson
Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, Pennsylvania, USA
Limin Zhang
Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China
ABSTRACT Noncaloric artificial sweeteners (NAS) are extensively introduced into commonly consumed drinks and foods worldwide. However, data on the health effects of NAS consumption remain elusive. Saccharin and sucralose have been shown to pass through the human gastrointestinal tract without undergoing absorption and metabolism and directly encounter the gut microbiota community. Here, we aimed to identify a novel mechanism linking intestinal Akkermansia muciniphila and the aryl hydrocarbon receptor (AHR) to saccharin/sucralose-induced nonalcoholic fatty liver disease (NAFLD) in mice. Saccharin/sucralose consumption altered the gut microbial community structure, with significant depletion of A. muciniphila abundance in the cecal contents of mice, resulting in disruption of intestinal permeability and a high level of serum lipopolysaccharide, which likely contributed to systemic inflammation and caused NAFLD in mice. Saccharin/sucralose also markedly decreased microbiota-derived AHR ligands and colonic AHR expression, which are closely associated with many metabolic syndromes. Metformin or fructo-oligosaccharide supplementation significantly restored A. muciniphila and AHR ligands in sucralose-consuming mice, consequently ameliorating NAFLD. IMPORTANCE Our findings indicate that the gut-liver signaling axis contributes to saccharin/sucralose consumption-induced NAFLD. Supplementation with metformin or fructo-oligosaccharide is a potential therapeutic strategy for NAFLD treatment. In addition, we also developed a new nutritional strategy by using a natural sweetener (neohesperidin dihydrochalcone [NHDC]) as a substitute for NAS and free sugars.