Maternal low-dose aspartame and stevia consumption with an obesogenic diet alters metabolism, gut microbiota and mesolimbic reward system in rat dams and their offspring

Gut. 2020 Oct;69(10):1807-1817. doi: 10.1136/gutjnl-2018-317505. Epub 2020 Jan 29.

Abstract

Objective: We examined the impact of maternal low-dose aspartame and stevia consumption on adiposity, glucose tolerance, gut microbiota and mesolimbic pathway in obese dams and their offspring.

Design: Following obesity induction, female Sprague-Dawley rats were allocated during pregnancy and lactation to: (1) high fat/sucrose diet (HFS) +water (obese-WTR); (2) HFS +aspartame (obese-APM; 5-7 mg/kg/day); (3) HFS +stevia (obese-STV; 2-3 mg/kg/day). Offspring were weaned onto control diet and water and followed until 18 weeks. Gut microbiota and metabolic outcomes were measured in dams and offspring. Cecal matter from offspring at weaning was used for faecal microbiota transplant (FMT) into germ-free (GF) mice.

Results: Maternal APM and STV intake with a HFS diet increased body fat in offspring at weaning and body weight long-term with APM. Maternal APM/HFS consumption impaired glucose tolerance in male offspring at age 8 weeks and both APM and STV altered faecal microbiota in dams and offspring. Maternal obesity/HFS diet affected offspring adiposity and glucose tolerance more so than maternal LCS consumption at age 12 and 18 weeks. APM and STV altered expression of genes in the mesolimbic reward system that may promote consumption of a palatable diet. GF mice receiving an FMT from obese-APM and obese-STV offspring had greater weight gain and body fat and impaired glucose tolerance compared with obese-WTR.

Conclusion: Maternal low-calorie sweetener consumption alongside HFS may disrupt weight regulation, glucose control and gut microbiota in dams and their offspring most notably in early life despite no direct low-calorie sweetener consumption by offspring.

Keywords: diet; energy metabolism; glucose metabolism; intestinal bacteria; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / drug effects*
  • Animals
  • Animals, Newborn
  • Aspartame* / metabolism
  • Aspartame* / pharmacology
  • Body Weight / drug effects
  • Diet, High-Fat / methods
  • Energy Metabolism / drug effects*
  • Fecal Microbiota Transplantation / methods
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Glucose / metabolism*
  • Glucose Intolerance / metabolism
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Stevia / metabolism*
  • Sweetening Agents / metabolism
  • Sweetening Agents / pharmacology

Substances

  • Sweetening Agents
  • Glucose
  • Aspartame

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