文献类型： 外文期刊

作者： Zhang, Danni ¹ ; Wang, Huiying ¹ ; Liu, Ana ¹ ; Wang, Shan ¹ ; Xu, Cuifang ¹ ; Lan, Ke ³ ; Xiang, Wenqing ¹ ; Zhu, Kun ⁴ ; Xiao, Yingping ⁵ ; Fu, Junfen ¹ ; Jiang, Runqiu ⁶ ; Chen, Wenlian ⁸ ; Ni, Yan ¹ ;

作者机构： 1.Zhejiang Univ, Sch Med, Childrens Hosp, Natl Clin Res Ctr Child Hlth, Hangzhou, Peoples R China

2.Zhejiang Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Hangzhou, Peoples R China

3.Sichuan Univ, West China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Minist Educ, Chengdu, Peoples R China

4.Zhejiang Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth, Dept Pathol,Sch Med, Hangzhou, Peoples R China

5.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, State Key Lab Managing Biot & Chem Threats Qual &, Hangzhou, Peoples R China

6.Nanjing Univ, Affiliated Drum Tower Hosp, Med Sch, Dept Hepatobiliary Surg, Nanjing, Peoples R China

7.Nanjing Univ, Med Sch, Nanjing, Peoples R China

8.Shanghai Univ Tradit Chinese Med, Longhua Hosp, Canc Inst, Shanghai, Peoples R China

关键词： Fructose; NAFLD; bile acids; gut microbiome; Clostridium sp

期刊名称：JOURNAL OF NUTRITIONAL BIOCHEMISTRY （ 影响因子：5.6； 五年影响因子：5.9 ）

ISSN： 0955-2863

年卷期： 2023 年 121 卷

页码：

收录情况： SCI

摘要： Excessive fructose intake is associated with the rising prevalence of nonalcoholic fatty liver disease (NAFLD). The gut microbiome (GM) and bile acids (BAs) are involved in the pathogenesis of NAFLD, but the impact of fructose on their cross-talk is unclear. In this study, adult male C57BL/6J mice were fed a normal diet with tap water (ND) or with 4% fructose in the drinking water (Fru), 60% high-fat diet with tap water (HF) or with 4% fructose solution (HFF) for 12 weeks. Targeted BA analysis was performed in five anatomical sites including the liver, ileum contents, portal serum, cecum contents, and feces. Metagenomic sequencing was performed to explore gut dysbiosis. Within 12 weeks, the 4% fructose diet could initially stimulate gut dysbiosis and BA upregulation in the ileum, portal serum, and cecum when the intestinal and hepatic transport system remained stable without hepatic lipid accumulation. However, the chronic consumption of fructose promoted HF-induced NAFLD, with significantly increased body weight, impaired glucose tolerance, and advanced liver steatosis. BA transporters were inhibited in HFF, causing the block of internal BA circulation and increased BA secretion via cecum contents and feces. Notably, lithocholic acid (LCA) and its taurine conjugates were elevated within the enterohepatic circulation. Meanwhile, the Clostridium species were significantly altered in both Fru and HFF groups and were closely associated with fructose and BA metabolism. In summary, excessive fructose caused gut dysbiosis and BA alterations, promoting HF-induced NAFLD. The crosstalk between Clostridium sp. and LCA species were potential targets in fructose-mediated NAFLD.(c) 2023 Elsevier Inc. All rights reserved.