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

• Published in: Gut Vol. 69; no. 10; pp. 1807 - 1817
• Main Authors: Nettleton, Jodi E, Cho, Nicole A, Klancic, Teja, Nicolucci, Alissa C, Shearer, Jane, Borgland, Stephanie L, Johnston, Leah A, Ramay, Hena R, Noye Tuplin, Erin, Chleilat, Faye, Thomson, Carolyn, Mayengbam, Shyamchand, McCoy, Kathy D, Reimer, Raylene A
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.10.2020; BMJ Publishing Group
• Series: Original research
• Subjects: Adipose tissue; Adiposity - drug effects; Age; Animals; Animals, Newborn; Aspartame - metabolism; Aspartame - pharmacology; Body composition; Body fat; Body weight; Body Weight - drug effects; Body weight gain; Breastfeeding & lactation; Calories; Cecum; Diabetes; Diet; Diet, High-Fat - methods; Energy Metabolism - drug effects; Fecal Microbiota Transplantation - methods; Female; Females; Food; Gastrointestinal Microbiome - drug effects; Gene expression; Germfree; Glucose; Glucose - metabolism; Glucose Intolerance - metabolism; Glucose tolerance; Gut Microbiota; High fat diet; Immunological tolerance; Intestinal microflora; Lactation; Mesolimbic system; Metabolism; Mice; Microbiota; Nutrition research; Obesity; Offspring; Overweight; Potassium; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Reinforcement; Rodents; Statistical analysis; Stevia - metabolism; Sucrose; Sweetening Agents - metabolism; Sweetening Agents - pharmacology; Variance analysis; Weaning; Womens health; intestinal bacteria; diet; glucose metabolism; energy metabolism; obesity
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2018-317505

ObjectiveWe 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.DesignFollowing 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.ResultsMaternal 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.ConclusionMaternal 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.