The results of research in rats suggest that maternal diet during pregnancy can significantly impact the gut microbial communities, and affect the obesity risk, of their offspring. The study, by a team at the University of Calgary and the University of Alberta, found that pregnant rats fed with either of the sweeteners stevia or aspartame gave birth to pups that had higher body fat percentages, and a higher risk of obesity. The pups also demonstrated changes to their gut microbial communities, which might lead to alterations in microbial fermentation that could explain the weight gain.

The scientists suggest that their findings highlight the importance of maternal nutrition during pregnancy. “Even though the offspring never consumed the low-calorie sweeteners themselves, their gut bacteria and obesity risk were influenced by the sweeteners that their mothers consumed during pregnancy,” said Raylene Reimer, PhD, who is senior author of the researchers’ published study in Frontiers in Nutrition. “We found that specific bacteria and their enzymes were linked to how much weight the offspring gained and how much body fat they accumulated.”

Reimer and colleagues reported their findings in a paper titled, “A metagenomics investigation of intergenerational effects of non-nutritive sweeteners on gut microbiome,” in which they concluded, “Compositional and functional shifts in the microbiome with non-nutritive sweetener consumption should be investigated further in human cohorts to inform guidelines for maternal diet during pregnancy.”

Low-calorie—or non-nutritive—sweeteners have been used for decades as sugar replacements. Aspartame and stevia are just two examples. Many people use low-calorie sweeteners as a healthier alternative to sugar, but while they are largely nontoxic in adults, previous research suggests that prenatal consumption by mothers can affect obesity risk and the microbiome in infants. As the authors noted, “ … detrimental effects, including disrupted gut microbiota, impaired glucose homeostasis, and higher risk of obesity have been observed in offspring of rodents consuming non-nutritive sweeteners and infants of pregnant women consuming beverages with non-nutritive sweeteners.” However, no one has previously examined this in detail to understand the specific changes in microbial populations and their potential link to obesity.

“We know that a mother’s diet during pregnancy plays an extremely important role in determining whether their offspring will develop certain diseases later in life,” said Reimer. “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.”

To investigate this, the researchers fed aspartame, stevia, or plain water to pregnant rats. Once the rats gave birth, the researchers weighed the rat pups and analyzed their gut microbiomes to assess how the sweeteners had affected them. The team used techniques including shotgun metagenomics and 16S rRNA gene sequencing to try to find connections between key microbes, metabolic functions, and the physiological outcomes of the offspring. The aim was to uncover potential mechanisms by which maternal aspartame and stevia consumption might exert effects on offspring that had never directly consumed the sweeteners themselves. “To identify possible mechanisms by which this intergenerational risk is transmitted, we assessed 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,” they wrote.

Strikingly, the scientists found that while the sweeteners had minimal effects in the rat mothers, 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. These changes in microbial fermentation in the gut may have caused weight gain in the pups, the investigators suggested. “The resultant altered propionate and lactate production could explain increased body weight and body fat in offspring from aspartame and stevia consuming dams.”

So, what do the findings mean for expectant mothers? While the study was performed in rats, and so isn’t directly applicable to humans, previous human studies have shown a similar link between consuming sweeteners during pregnancy and higher infant body mass index. “ … detrimental effects, including disrupted gut microbiota, impaired glucose homeostasis, and higher risk of obesity have been observed in offspring of rodents consuming non-nutritive sweeteners and infants of pregnant women consuming beverages with non-nutritive sweeteners.”

The newly reported results, the authors maintain, thus have “… important implications for human health because the diet of mothers during pregnancy and lactation likely also impacts the gut microbiota, microbial metabolites, and the metabolic fitness to their children. Compositional and functional shifts in the microbiome with non-nutritive sweetener consumption should be investigated further in human cohorts to inform guidelines for maternal diet during pregnancy.”

“A mother’s diet during pregnancy is very important for the short- and long-term health of their infants,” said Reimer. “Following dietary guidelines and staying within the recommended weight gain guidelines for pregnancy are key steps to take.”

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