Maternal Exposure to Non‐nutritive Sweeteners Impacts Progeny’s Metabolism and Microbiome

Non‐nutritive sweeteners (NNS e.g. Splenda, Sweet’N’Low, Equal, Stevia, …) are highly prevalent in the diet of United States adults and children and are found in beverages, yogurt, cocoa powder, coffee sweeteners, medicine and kid electrolyte solution (Pedialyte). They are marketed as sugar alternatives providing sweet taste with few or no calories. First thought to be harmless, a growing number of research studies now questioning the safety of NNS consumption. In the past decades, NNS have been shown to alter gut hormonal secretion, glucose absorption, appetite, kidney function, insulin secretion, adipogenesis and gut microbiota. The wide range of action associated by NNS exposure is likely linked to their binding to the sweet taste receptor, found not only on the tongue but also in the intestines, lungs, bones, adipose tissue and testis. However, to date, the effects of NNS on early development are incompletely understood. In critical stage such as embryonic/ fetal development, small exposures can be serious as demonstrated for alcohol consumption or smoking. While there are many specific recommendations during pregnancy or lactation for various products, there are no guidelines for NNS consumption. Furthermore, it is interesting to know that only one of four parents are able to correctly identify NNS on food product suggesting that many are consuming NNS involuntarily Interestingly, at least 10 different studies demonstrated an association between increased BMI and NNS consumption suggesting a significant association in children. Furthermore, despite known transmission through amniotic fluid and breast milk, the impact of NNS on early metabolic development remains largely unknown. To answer this question, we exposed pregnant and lactating mice to NNS (sucralose, acesulfame‐K) at doses relevant for human consumption (Acceptable Daily Intake). While the pups’ exposure seemed minimal, metabolic changes were drastic, indicating extensive down‐regulation of hepatic detoxification mechanisms and changes in bacterial metabolites. Microbiome profiling confirmed a significant increase in firmicutes and a striking decrease of Akkermansia muciniphila . Similar microbiome alterations in humans have been linked to metabolic disease and obesity. Our finding corroborates the existing literature but required considerably shorter NNS exposure (only ~40 days). Therefore, we concluded that pregnancy is a vulnerable time for exposing offspring to NNS. While our findings need to be reproduced in humans, they suggest that NNS consumption during pregnancy and lactation have adverse effects on infant metabolism and potential predisposition to metabolic deregulation later in life.Summary figure of the effect of sucralose and acesulfame‐K consumption during pregnancy and lactation.