What the Research Says
A landmark randomized controlled trial in 120 healthy adults found that two weeks of consumption of saccharin, sucralose, aspartame, or stevia (at doses below the acceptable daily intake) each distinctly altered stool and oral microbiome composition and plasma metabolome, with saccharin and sucralose significantly impairing glycemic responses [1]. Gnotobiotic mice transplanted with microbiomes from human responders replicated these glycemic changes, confirming a causal role of the microbiome [1].
Pre-clinical studies in rats show mixed results: a 28-day study of acesulfame potassium and saccharin found only minor effects on fecal microbiota and metabolome, though saccharin significantly altered plasma amino acids, lipids, and bile acids [5]. In contrast, maternal consumption of aspartame or stevia in obese dams altered the cecal microbiome of offspring, with changes in propionate/lactate metabolism correlating with increased body weight and fat in weanlings [4].
Long-term (20-week) exposure to five common non-nutritive sweeteners in mice on regular or high-fat diets did not induce adverse metabolic effects; sucralose and steviol glycoside (Reb M) even improved insulin sensitivity and reduced weight gain under obesogenic conditions, with Reb M increasing colonic Lachnospiracea bacteria [6]. However, aspartame decreased glucose tolerance on a regular diet [6].
Caveats and Conflicting Evidence
The scientific community has no unanimous consensus on the effects of non-nutritive sweeteners on the gut microbiota, as results vary widely between studies due to differences in administration methods, animal species, human dietary habits, and baseline microbiome composition [3]. Some human randomized controlled trials report a lack of significant impacts on gut microbiota composition, while others observe dysbiosis [3].
Person-specific responses are a key factor: in the human trial, glycemic responses to the same sweetener varied among individuals, and these differences were microbiome-dependent [1]. Additionally, sex-specific effects have been observed in rats, with acesulfame potassium causing larger alterations in glycine-conjugated bile acids in males than females [5].
The mechanisms by which sweeteners affect the microbiome and host metabolism remain unclear, though changes in bile acid profiles and metabolome suggest adaptive rather than toxic responses [5][7]. Long-term clinical implications, including associations with cardiovascular and cancer risks, require further study [2].
本文引用的文献
Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance
In a randomized trial of 120 healthy adults, saccharin, sucralose, aspartame, and stevia each altered stool and oral microbiome and plasma metabolome, with saccharin and sucralose impairing glycemic responses; effects were person-specific and microbiome-dependent [1].
Is the Use of Artificial Sweeteners Beneficial for Patients with Diabetes Mellitus? The Advantages and Disadvantages of Artificial Sweeteners
Artificial sweeteners alter gut microbiota composition and worsen glycemic control in some studies, and high intake is associated with increased all-cause mortality and cardiovascular risk in large cohort studies [2].
Effect of Non-Nutritive Sweeteners on the Gut Microbiota
Pre-clinical and clinical studies show conflicting results on the dysbiotic effect of non-nutritive sweeteners, with many randomized controlled trials reporting no significant impacts on gut microbiota composition [3].
A Metagenomics Investigation of Intergenerational Effects of Non-nutritive Sweeteners on Gut Microbiome
Maternal consumption of aspartame (5–7 mg/kg/day) or stevia (2–3 mg/kg/day) in obese dams altered offspring cecal microbiome and propionate/lactate metabolism, correlating with increased body weight and fat in weanlings [4].
Investigating the gut microbiome and metabolome following treatment with artificial sweeteners acesulfame potassium and saccharin in young adult Wistar rats
In Wistar rats, 28-day treatment with acesulfame potassium (40 and 120 mg/kg) and saccharin (20 and 100 mg/kg) showed only minor effects on fecal microbiota and metabolome, but saccharin significantly altered plasma bile acids and other metabolites [5].
Long-term metabolic effects of non-nutritive sweeteners
Long-term (20-week) consumption of five non-nutritive sweeteners in mice did not induce adverse metabolic effects; sucralose and Reb M improved insulin sensitivity and reduced weight gain under high-fat diet, while aspartame decreased glucose tolerance on regular diet [6].
Interactions of Non-Nutritive Artificial Sweeteners with the Microbiome in Metabolic Syndrome
Evidence from human and animal trials indicates that non-nutritive artificial sweeteners can alter gut microbiome composition, function, and metabolome, but mechanisms remain unclear and outcomes vary with individual microbiome variation [7].