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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
  1. Jodi E Nettleton1,
  2. Nicole A Cho1,
  3. Teja Klancic1,
  4. Alissa C Nicolucci1,
  5. Jane Shearer1,2,
  6. Stephanie L Borgland3,
  7. Leah A Johnston1,
  8. Hena R Ramay4,
  9. Erin Noye Tuplin1,
  10. Faye Chleilat1,
  11. Carolyn Thomson5,
  12. Shyamchand Mayengbam1,
  13. Kathy D McCoy5,
  14. Raylene A Reimer1,2
  1. 1Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
  2. 2Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  3. 3Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
  4. 4International Microbiome Centre, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  5. 5Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  1. Correspondence to Dr Raylene A Reimer, Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada; reimer{at}


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.

  • diet
  • glucose metabolism
  • intestinal bacteria
  • obesity
  • energy metabolism

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  • Contributors JEN designed research, carried out experiments, collected data, analysed data, generated figures and wrote paper. NAC, TK and LAJ helped carry out experiments. ACN and HRR helped analyse 16S rRNA sequencing data. JS and SLB provided input into research design. ENT, FC, CT and KDM helped perform the faecal microbiota transplant experiment. SM performed short chain fatty acids analysis. RAR designed research, wrote paper and had primary responsibility for final content. All authors read and approved the final manuscript.

  • Funding This work was supported by a Canadian Institutes of Health Research grant (MOP115076). JEN is supported by Alberta Children’s Hospital Research Institute and Canadian Institutes of Health Research. NAC was supported by a Talisman Energy Fund Healthy Living and Injury Prevention Studentship. TK is supported by an Alberta Innovates Health Solutions Doctoral Scholarship, Eye’s High Doctoral Scholarship and Vanier Canada Graduate Scholarship. LAJ was supported by an Alberta Children’s Hospital Research Institute Summer Studentship. FC is supported by a Faculty of Kinesiology Dean’s Doctoral Scholarship and Alberta Children’s Hospital Research Institute scholarship. SM is supported by an Alberta Innovates Postgraduate Fellowship and Eye’s High Postdoctoral Fellowship.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The University of Calgary Animal Care Committee granted ethical approval for this study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request up until 3 years after publication.

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