Maternal sucralose intake alters gut microbiota of offspring and exacerbates hepatic steatosis in adulthood

Gut Microbes. 2020 Jul 3;11(4):1043-1063. doi: 10.1080/19490976.2020.1738187. Epub 2020 Mar 31.


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.

Keywords: Sucralose; butyrate; gut barrier function; gut microbiota; hepatic steatosis; lactation; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / classification*
  • Bacteria / growth & development
  • Bacteria / metabolism
  • Butyrates / metabolism
  • Clostridium butyricum / physiology
  • Cytokines / metabolism
  • Diet, High-Fat
  • Dietary Sugars / administration & dosage*
  • Dysbiosis
  • Female
  • Gastrointestinal Microbiome*
  • Inflammation
  • Intestine, Large / metabolism
  • Intestine, Large / microbiology
  • Intestines / growth & development
  • Intestines / microbiology*
  • Intestines / physiology*
  • Lipid Metabolism
  • Male
  • Maternal Nutritional Physiological Phenomena
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Pregnancy
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Sucrose / administration & dosage
  • Sucrose / analogs & derivatives*


  • Butyrates
  • Cytokines
  • Dietary Sugars
  • Ffar2 protein, mouse
  • Receptors, G-Protein-Coupled
  • Sucrose
  • trichlorosucrose

Grants and funding

This study is supported by the grants [81741075 and 81970477] from the National Natural Science Foundation of China, the grants [17JCYBJC24900] from Tianjin Research Program of Application Foundation and Advanced Technology of China, the grant [2019M651049] from China Postdoctoral Science Foundation.