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

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-weekold 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 antiinflammatory 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.

Lactobacillus rhamnosus GG Colonization in Early Life Ameliorates Inflammaging of Offspring by Activating SIRT1/AMPK/PGC‐1α Pathway

“…An adequate physical gut barrier consists of a mucous layer, intestinal epithelial cells, and tight junctions [ 29 ]. It is pivotal for protection against the potentially harmful compounds and microorganisms while promoting the absorption of nutrients, electrolytes, and water.…”

Perinatal High-Salt Diet Induces Gut Microbiota Dysbiosis, Bile Acid Homeostasis Disbalance, and NAFLD in Weanling Mice Offspring

“…NAFLD in children is a major risk factor for the development of cirrhosis and hepatocellular carcinoma in adult [ 2 , 3 ], and it is also an early predictor of hypertension and type 2 diabetes [ 4 , 5 ]. Pregnancy is a critical period for fetal organ development [ 6 ], and maternal diet during pregnancy plays an important role in protecting against or exacerbating the offspring’s risk of developing NAFLD [ 7 , 8 ]. Emerging evidence from human and animal studies has revealed that a high-salt (HS) diet in adulthood is not only a major risk factor for hypertension [ 9 ] and cardiovascular disease [ 10 ], but also exerts effects on hypertriglyceridemia [ 11 ], oxidative stress, and inflammation [ 12 ], which are well-known pathological features of the development of NAFLD [ 13 , 14 ].…”

Role of the Gut Microbiota in Regulating Non-alcoholic Fatty Liver Disease in Children and Adolescents

“…Maternal obesity and high-fat diet consumption both alter the gut microbiota of their offspring and increase their risk of developing NAFLD (168,169). Therefore, interventions that target mothers are one approach for preventing NAFLD in children.…”