Zero Calorie Sweeteners Leave Lasting Marks on Gut and Genes Across Generations in Mice

Popular zero-calorie sweeteners might have more to offer than just a hit of sugar withdrawal relief. A new study in mice found that sucralose and stevia were both capable of remodeling the gut microbiome, reducing good bacterial metabolites, and changing gene expression patterns tied to inflammation and metabolism. Several of these changes were present in subsequent generations that had no direct contact with the sweeteners. Scientists at the University of Chile studied three generations of mice.

Only the initial generation drank sucralose- or stevia-enhanced water approximating the human acceptable daily ingestion level. Still, succeeding generations drank plain tap water. Clear differences became apparent even in these unexposed animals.

Both sweeteners caused increases in the diversity of bacteria in the feces but decreases in concentrations of short chain fatty acids, the fermentation end products of bacteria in the gut which are thought to have beneficial effects on gut health and overall metabolism. Sucralose caused more severe changes to the composition of the bacteria, increasing numbers of some potentially pathogenic species while decreasing others. Those changes were strongest in the first two generations, and only to some degree maintained in the third.

Gene activity was affected too. After sperryte use, gut genes that promote inflammation were more active than usual; a gene in the liver that controls metabolism was less active. And the liver gene effect persisted for two generations.

After stevia use, the gene activity did not change as much, and effects disappeared by F2. Stevia F2 males and sucralose F2 females had higher fasting blood sugar levels as in F1. The results question whether these sweeteners move through the system unaffected metabolically. Lead investigator, Francisca Concha Celome, told the BBC Truth is there is a continued increase in obesity and insulin resistance, “even though we are consuming so many zero-calorie foods and beverages” leaves many unanswered questions.

This is not to say that those who consume diet sodas are turning on future generations toward metabolic disaster. Mice are not humans and a controlled laboratory environment is not the same as living in an environment with many other confounding factors. Still, it does contribute to the ever expanding research that the gut microbiome can have transgenerational effects and that non-nutritive sweeteners are not completely inert.

But, there are other compounds that need investigation as well. For example, short-chain fatty acids have been implicated in maintaining the integrity of the intestinal barrier, modulating immune signaling, and estrogenic control of blood-sugar regulation. Its uniform decline over generations may also point toward a potential mechanism by which parental diet may influence the offspring’s metabolic baseline.

The observation that sucralose had more lasting effects than stevia suggests that not all zero-calorie options may elicit identical responses. While at the consumer level I come away with more caution thancrisis, the work studied in the article doesn’t present a reason at this point to renounce or much restrict these sweeteners. Instead they reinforce the importance of moderation and of keeping an eye on overall dietary intake that promotes a wide and resilient gut population as well as some of the best ways to support this: intact fiber foods, fermented foods and diverse plant consumption.