Xin Dai1, Zixuan Guo1, Danfeng Chen1, Lu Li1, Xueli Song1, Tianyu Liu1, Ge Jin1, Yun Li2, Yi Liu3,4, Aihemaiti Ajiguli4, Cheng Yang5, Bangmao Wang1, Hailong Cao1,4,5. 1. Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University , Tianjin, China. 2. Department of Pharmacy, General Hospital, Tianjin Medical University , Tianjin, China. 3. Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital , Tianjin, China. 4. Department of Gastroenterology and Hepatology, Hotan District People's Hospital, Xinjiang Uygur Autonomous Region , Xinjiang, China. 5. Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine ,Tianjin.
Abstract
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is considered to be associated with diet and gut dysbiosis. Excessive sucralose can induce gut dysbiosis and negatively affect host health. Maternal diet shapes the microbial communities of neonate and this effect continues in later life. We aimed to investigate the effects of maternal sucralose (MS) intake on the susceptibility of offspring to hepatic steatosis in adulthood. METHODS: C57BL/6 pregnant mice were randomized into MS group (MS during gestation and lactation) and maternal control (MC) group (MC diet). After weaning, all offspring were fed a control diet until 8 weeks of age, and then treated with a high-fat diet (HFD) for 4 weeks. The intestinal development, mucosal barrier function, and gut microbiota were assessed in the 3-week-old offspring. Moreover, the severity of hepatic steatosis, serum biochemistry, lipid metabolism, and gut microbiota was then assessed in the 12th week. RESULTS: MS significantly inhibited intestinal development and disrupted barrier function in 3-week-old offspring. MS also induced intestinal low-grade inflammation, significantly changed the compositions and diversity of gut microbiota including reducing butyrate-producing bacteria and cecal butyrate production with down-regulation of GPR43. Mechanically, blocking GPR43 blunted the anti-inflammatory effect of one of the butyrate-producing bacteria, Clostridium butyricum in vitro. After HFD treatment, MS exacerbated hepatic steatosis, and disturbed fatty acid biosynthesis and metabolism, accompanied by inducing gut dysbiosis compared with MC group. CONCLUSIONS: MS intake inhibits intestinal development, induces gut dysbiosis in offspring through down-regulation of GPR43, and exacerbates HFD-induced hepatic steatosis in adulthood.
BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is considered to be associated with diet and gut dysbiosis. Excessive sucralose can induce gut dysbiosis and negatively affect host health. Maternal diet shapes the microbial communities of neonate and this effect continues in later life. We aimed to investigate the effects of maternal sucralose (MS) intake on the susceptibility of offspring to hepatic steatosis in adulthood. METHODS: C57BL/6 pregnant mice were randomized into MS group (MS during gestation and lactation) and maternal control (MC) group (MC diet). After weaning, all offspring were fed a control diet until 8 weeks of age, and then treated with a high-fat diet (HFD) for 4 weeks. The intestinal development, mucosal barrier function, and gut microbiota were assessed in the 3-week-old offspring. Moreover, the severity of hepatic steatosis, serum biochemistry, lipid metabolism, and gut microbiota was then assessed in the 12th week. RESULTS: MS significantly inhibited intestinal development and disrupted barrier function in 3-week-old offspring. MS also induced intestinal low-grade inflammation, significantly changed the compositions and diversity of gut microbiota including reducing butyrate-producing bacteria and cecal butyrate production with down-regulation of GPR43. Mechanically, blocking GPR43 blunted the anti-inflammatory effect of one of the butyrate-producing bacteria, Clostridium butyricum in vitro. After HFD treatment, MS exacerbated hepatic steatosis, and disturbedfatty acid biosynthesis and metabolism, accompanied by inducing gut dysbiosis compared with MC group. CONCLUSIONS: MS intake inhibits intestinal development, induces gut dysbiosis in offspring through down-regulation of GPR43, and exacerbates HFD-induced hepatic steatosis in adulthood.
Entities:
Keywords:
Sucralose; butyrate; gut barrier function; gut microbiota; hepatic steatosis; lactation; pregnancy