Non-nutritive sweeteners alter microbiome composition, glycemia in healthy adults
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Non-nutritive artificial sweeteners may alter the intestinal and oral microbiome as well as glycemic levels of healthy adults with no cardiometabolic complications, according to a study published in Cell.
“Our work provides evidence of human microbiome responsiveness to non-nutritive sweeteners and its ability to transmit, in specific configurations, downstream effects on the host glucose tolerance,” Eran Elinav, MD, PhD, professor in the department of systems immunology at Weizmann Institute of Science in Rehovot, Israel, and colleagues wrote. “As such, and in contrast to the common notion suggesting that non-nutritive sweeteners are metabolically inert, these data suggest that the human gut microbiome may constitute a ‘responsiveness hub’ enabling, in some individuals, the transmission of non-nutritive effects on human physiology.”
Researchers conducted a multi-arm randomized controlled trial in which they enrolled 120 adults in good metabolic health (65% women; median age, 29.95 years). Participants were randomly assigned to a supplement of aspartame, saccharin, sucralose or stevia daily; a 5 g supplement of glucose daily; or no supplement. Supplementation began after 7 days of baseline measurements of metabolic, metabolomic and microbial parameters. Supplementation lasted for 14 days, followed by 7 additional days of measurements. Participants wore a continuous glucose monitor throughout the trial. Glucose tolerance tests, anthropometrics and blood tests were conducted. Microbiome samples from the stool and oral cavity were collected and analyzed.
Saccharin, sucralose enhance glycemic response
In an analysis of glucose tolerance tests, participants in the saccharin group had an elevated glycemic response compared with those receiving glucose only (P = .042) and those receiving no supplement (P = .018). Similarly, adults receiving sucralose had a higher glycemic response compared with the glucose group (P = .004) and the no supplement group (P = .001). No significant association was found with aspartame or stevia supplementation.
Researchers normalized the incremental area under the curve on glucose tolerance tests for each participant with their average baseline value. During the first week after randomization, the sucralose group had a higher glycemic response compared with the glucose and no supplement groups, and the saccharin group had a higher glycemic response than the glucose group. The elevated glycemic responses continued during the second week of supplementation but declined during follow-up.
“Taken together, these findings indicate that short-term consumption of sucralose and saccharin in doses lower than the average daily intake can impact glycemic responses in healthy individuals,” the researchers wrote.
Microbiome features altered by non-nutritive sweeteners
At baseline, stool microbiome composition and function were similar between all six groups. After supplementation, all four sweetener types had an effect on microbiome function, and sucralose and saccharin had an effect on microbiome composition. No significant changes were observed in the glucose and no supplement groups.
In an analysis of microbiome features correlating with non-nutritive sweeteners, researchers found 22 metabolites correlated with an increase in glycemic response in the sucralose group that were not associated with changes in the glucose or no supplement groups. In the saccharin group, baseline levels of Prevotella copri and uridine monophosphate biosynthesis were positively associated with incremental area under the glucose curve and gradually increased during the exposure, whereas levels of Bacteroides xylanisolvens were negatively associated with glucose AUC and also increased during the trial. Among the stevia group, two Prevotella species were positively associated with glucose AUC and decreased during the trial, whereas Bacteroides coprophilus, Parabacteroides goldsteinii and Lachnospira species were positively associated with glycemic response and increased during the trial. Among those taking aspartame, B. fragilis and B. acidifaciens were positively associated with glucose AUC and B. coprocola was negatively associated. Levels of kynurenine, a metabolite associated with diabetes, increased among the aspartame group.
Changes in most of the microbiome features started as early as the first week of sweetener exposure and reverted to baseline after sweetener exposure ended during follow-up.
“These results should not be interpreted as calling for consumption of sugar, which is strongly linked to cardiometabolic diseases and other adverse health effects,” the researchers wrote. “Unraveling molecular mechanisms and clinical consequences of non-nutritive sweetener consumption on the human host and microbiome may enable to optimize dietary recommendations in preventing and treating hyperglycemia and its metabolic ramifications.”
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