A recent study out of the University of Calgary and the University of Alberta found that pregnant rats fed stevia or aspartame gave birth to pups with altered gut microbial communities, higher body fat percentages and increased risk of obesity.
While low-calorie sweeteners are widely used and considered non-toxic in adults, the specific changes in microbial populations and their potential link to obesity were not previously well understood.
“In this study, we were interested in determining how consuming low calorie sweeteners during pregnancy, specifically the artificial sweetener aspartame or the natural alternative stevia, affected the gut bacteria and obesity risk of offspring,” explained Professor Raylene Reimer of the University of Calgary, and senior author on the study.
The research team fed aspartame, stevia, or plain water to pregnant rats. Once the rats gave birth, they weighed the rat pups and analyzed their gut microbiomes using shotgun metagenomics and 16S rRNA gene sequencing. These tools allowed the researchers to examine connections between key microbes, metabolic functions, and the physiological outcomes of the offspring.
According to the report, published in Frontiers in Nutrition, the goal was to identify the possible mechanisms by which this intergenerational risk is transmitted by assessing the metagenomic reconstruction of intestinal metabolism of dietary carbohydrates in the offspring alongside host parameters including weight gain, body fat, liver weight, and bone mineral density.
The findings revealed that sweeteners had minimal effects in the rat mothers, however they did have significant effects in their offspring. Pups born to sweetener-fed mothers gained more weight, had a higher body fat percentage, and showed key changes in their gut microbiomes, with increases in propionate- and butyrate-producing microbes and reductions in lactose-fermenting species, which could explain the weight gain.
“We found that aspartame and stevia intake during pregnancy significantly altered the composition and function of the gut microbiota in their 3-week offspring, which was significantly correlated with their increased body fat percentage and liver weight but decreased bone mineral density,” explained first author Weilan Wang, PhD, Post-doctoral Associate Faculty of Kinesiology, University of Calgary. “When we looked at changes in the composition and metabolic pathways of their gut microbiomes, we did find some differences between aspartame and stevia. For example, aspartame specifically enriched Akkermansia muciniphila (the species primarily involved in succinate/propionate conversion), while reducing the abundance of pyruvate/lactate-transforming lactobacilli, compared with stevia and controls.”
Wang told NutraIngredients-USA that this is not the first study investigating the potential side effects of long-term consumption of low-calorie sweeteners (LCS). Previous research has suggested that maternal prenatal consumption of LCS affects infant obesity risk, in which changes in gut microbiota composition may play a significant role. “However, our understanding of how the function of the bacteria in the infant's intestine changed following exposure to maternal sweetener intake remains limited. By reconstructing the alterations in the offspring's microbiome, we were able to identify the connections between key microbes, metabolic functions, and the obesity-related outcomes of offspring. Our findings could improve our understanding of the mechanism or pathway by which maternal aspartame and stevia consumption exert effects on offspring that never directly consumed the sweeteners themselves, which is quite meaningful for future research, but not so surprising.”
He added that typically only extreme diet changes or long-term changes to dietary patterns can cause significant abnormalities in gut microbiota composition and functions, probably due to the complexity of habitual diets and resilience of the intestinal bacterial community. However, some food ingredients or dietary habits in pregnancy, e.g., low-calorie sweeteners consumption, may have unexpected adverse effects on offspring.
Unanswered questions remain
“Our study still does not answer all questions about the intergenerational effects of low-calorie sweeteners consumption, such as the mechanisms by which microbial /metabolic abnormalities are transmitted from mother to offspring and how these abnormalities influence the offspring, such as whether and how they affect the offspring's appetite and food-seeking behavior,” said Wang.
He added that follow-up research in humans will help to understand if the same effects occur in human pregnancy and further investigation on a wider scale is still highly warranted to inform guidelines for maternal diet during pregnancy.
Currently, senior author Dr. Raylene Reimer is analyzing data from a human pregnancy cohort to determine if the bodyweight of young children differs between those whose mothers consumed diet soft drinks during pregnancy and those who did not.
International Sweeteners Association responds
In response to the reported findings, the International Sweeteners Association (ISA) issued the following statement: “The collective evidence which suggests that maternal exposure to low/no calorie sweeteners, during both pregnancy and lactation, does not increase body weight in offspring. In fact, a review by Morahan et al. considered the totality of available animal studies looking into the metabolic and behavioural effects of exposure to low/no calorie sweeteners during pregnancy and lactation. The authors concluded that the balance of evidence suggests maternal exposure to low/no calorie sweeteners in the diet does not increase body weight in offspring.
“Furthermore, it is important to highlight that the study by Wang et al. has several issues and limitations that need to be considered when interpreting the study results and especially their biological relevance to humans. Importantly, also, and in the case of aspartame, the study results cannot be supported by the well understood pathways of aspartame metabolism in the human body. Research investigating the impact of steviol glycosides on the gut microbiota does not confirm any negative effect either.
“At a time when obesity and non-communicable diseases including diabetes and dental diseases remain major global health challenges, and in light of current public health recommendations to reduce overall sugar intake, low/no calorie sweeteners can be helpful in creating healthier food environments. They provide a wide choice of sweet-tasting options with low or no calories, and thus can be a useful tool, when used in place of sugar and as part of a balanced diet, in helping reduce overall sugar and calorie intake, as well as in managing blood glucose levels, including for pregnant women who may be at risk of gestational diabetes. Low/no calorie sweeteners are also not fermentable by oral bacteria, which means that they do not contribute to tooth demineralization, which is one of the reasons for tooth decay. This can be helpful during pregnancy which often puts a strain on the overall mouth health and ensuring healthy teeth is all the more important.”
Source: Frontiers in Nutrition
14 January 2022 DOI 10.3389/fnut.2021.795848
“A Metagenomics Investigation of Intergenerational Effects of Non-nutritive Sweeteners on Gut Microbiome”
Authors: W. Wang et al.