Zero-calorie sweeteners may alter intestinal flora, liver toxicity during pregnancy

Exposure to sucralose and acesulfame-K in the womb and via breastmilk leads to altered intestinal flora and liver toxicity in mice, according to a new study published in the Frontiers in Microbiology.

Scientists exposed pregnant and lactating mice to sucralose and acesulfame-K, a common combination in soda, sports supplements, and other sweetened products. They fed mouse moms one of three sweetener solutions throughout pregnancy and lactation and analyzed the effects on their pre-weaned pups. The solutions contained a mixture of sucralose and acesulfame-K at the acceptable daily intake (ADI), double the ADI, or a control (water). The ADI is the maximum consumption deemed safe in humans based on toxicology studies.

Analysis of blood, feces, and urine from a total of 226 mice pups found that both sweeteners are transmitted prenatally and affect the metabolism and microbiome of the offspring.

While the pups' exposure was low, the researchers found significant metabolic changes in both the ADI and double ADI groups versus the control group. Specifically, these changes indicated impaired liver functioning in clearing toxins from the blood, and a dramatic shift in bacterial metabolites in the gut. In both sweetener groups, the researchers observed the loss of a major beneficial species of gut bacteria, Akkermansia muciniphila. Similar microbiome alterations in humans have been linked to type 2 diabetes and obesity, researchers said.

The degree of metabolic change was greater in the double ADI than the ADI group. Further changes in sweetener-exposed pups, including lower weight and fasting blood glucose, only became prevalent in the double ADI group. However, the microbiome changes were drastic even at the acceptable daily intake level.

Current recommendations for artificial sweetener use during pregnancy state that they may be used in moderation, except for saccharin, which should be avoided entirely. However, artificial sweeteners are now found in more products than ever, including mouthwash, toothpaste, and medicines, as well as food and drink. Since labels do not specify the amounts of added sweeteners, it is impossible to accurately track our intake, according to John Hanover, PhD, a glycobiologist and senior author of the study, which was supported by the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health.

"The perinatal period is a critical developmental stage for the microbiome and emerging detoxification systems in the rodent and human neonate alike, and our study defines potentially adverse consequences of early exposure to sweeteners,” said Hanover in a statement. “Therefore, based on our findings, zero-calorie sweeteners warrant further investigation in humans in this critical developmental window."