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

Abstract

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.

Plausible Biological Interactions of Low- and Non-Calorie Sweeteners with the Intestinal Microbiota: An Update of Recent Studies

“…Moreover, fecal transplantation from offspring to germ-free mice produced an altered gut microbiota, causing impaired adiposity and glucose tolerance. In addition, increased concentrations of Porphyromonadaceae in males and females obese-aspartame and obese-stevia offspring were found [14]. In contrast, in the study by Suez et al, food intake in mice assigned to a water group with LNCS (aspartame, sucralose, and saccharin) was reduced by up to 50%.…”

Maternal consumption of artificially sweetened beverages during pregnancy is associated with infant gut microbiota and metabolic modifications and increased infant body mass index

“… 30 , 31 in two studies with adult mice, and by Nettleton et al . 45 in a study on dams and their offspring, ASB has been shown to alter gut bacterial community composition (increase of Bacteroides and reductions of Lactobacillus and Clostridium ) and increase body weight in parallel with an enrichment of energy metabolism bacterial genes. The functional cluster analyses by Bian et al .…”

Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet

“…SCFAs were extracted from cecal matter and assessed using reverse-phase HPLC on a c18 column as previously described [ 83 ].…”