Researchers from Israel recently published in Nature how NAS [Non-caloric artificial sweeteners] affect glucose tolerance.
In an initial experiment, researchers found mice that consumed water, glucose, or sucrose had comparable glucose tolerance curves, but all 3 mouse groups consuming NAS (either saccharin, sucralose, or aspartame) developed marked glucose intolerance.
They focused on saccharin for the next series of experiments, since it was associated with the most pronounced response. For mice on a high-fat diet, those consuming saccharin showed glucose intolerance compared to those consuming glucose. The groups had similar food and liquid consumption and energy expenditure.
Next, the researchers did two things to test whether the microbiota were responsible for the observed effects: (1) They treated mouse groups with antibiotics and found that differences in glucose intolerance between NAS and control mice were abolished; (2) They transferred feces of NAS-consuming mice and control mice into germ-free mice and found that only the recipients of microbiota from NAS consumers showed impaired glucose tolerance.
Microbiota analysis revealed that mice drinking saccharin, and those who got a fecal microbiota transplantation from saccharin-consuming donors, had a distinct microbiota after 11 weeks.
Researchers then performed shotgun metagenomic sequencing of fecal samples and found that saccharin consumption was associated with the largest change in microbial relative species abundance; saccharin appeared to affect microbiota function. Glucose transport pathways, for example, were underrepresented in these mice.
In vitro, too, the saccharin induced changes in the bacterial types, and transferring this mixture into germ-free mice made the mice glucose intolerant compared to controls.
In humans, researchers looked at questionnaire data from a clinical nutritional study. They found positive correlations between long-term NAS consumption and increased weight and waist-to-hip ratio, higher fasting blood glucose, and other clinical parameters.
Next, the scientists took a subgroup of high NAS consumers and non-NAS consumers and randomly selected some individuals for microbiota analysis. They found positive correlations between multiple taxonomic entities and NAS consumption, but these OTU [operational taxonomic unit] abundances did not correlate with body mass index.
Finally, seven healthy volunteers were selected who did not normally consume NAS. After one week of consuming the Food and Drug Administration’s maximum acceptable daily intake of saccharin, 4 out of 7 developed poorer glycaemic responses (i.e. the ‘responders’) and the rest showed no significant changes. The responders showed compositional changes in their microbiota. Stool from these subjects was transferred into mice both before and after the NAS consumption; only the stool from after NAS consumption induced glucose intolerance in the recipient mice.
Authors summarized by saying that NAS consumption increases the risk of glucose intolerance, and this is mediated by changes in the composition and function of the microbiota. They also said that this reaction is not present in all humans: the personalized response to NAS is probably because of initial differences in microbiota composition and function.
These discoveries are under debate due to confounding factors and a low number of human subjects.