Artificial sweeteners such as aspartame (NutraSweet®, Equal®), sucralose (Splenda®), and saccharin (Sweet’N Low®) are ubiquitous in processed foods and beverages; and are regularly consumed by 1/3 of all Americans in a variety of “diet” products.[i]  While designed to be low calorie alternatives to sugar, research has repeatedly shown that consumption of these artificial sweeteners is still linked to metabolic derangements such as weight gain, impaired glucose tolerance and increased incidence of type 2 diabetes.[ii],[iii] Now, research has discovered that while most of these synthetic sweeteners are excreted unchanged in either the urine or feces, they affect metabolism through alterations of the gut microbiota.

In an animal model, Suez et al. showed aspartame, sucralose and saccharin induced glucose intolerance over eight and eleven weeks; further study of saccharin demonstrated the effects were mediated through compositional and functional changes to the gut microbiota, with more than 40 operational taxonomic units altered in the saccharin-fed group.[iv]  Interestingly, Akkermansia muciniphila was underrepresented in the mice fed saccharin. Using antibiotics and transplanting fecal microbiota samples into germ-free mice, the group linked the impaired glucose tolerance to an altered microbiome.

The group then studied the effects of artificial sweeteners in a small-scale human intervention study. Seven subjects (who did not normally consume artificial sweeteners) consumed a regular diet supplemented with the upper limit of daily saccharin dose (5 mg/kg/day) for one week. Four of the seven volunteers showed an elevated glycemic response (responders), and the other three individuals showed no response. The researchers transplanted the four responders’ microbiota into germ-free mice and replicated the impaired glucose response, again linking the metabolic effects to the altered microbiota.  The responder/non-responder effect suggests that not all individuals are affected equally by artificial sweetener consumption, and the response may depend on an individual’s baseline microbiota.[v] Although this is one of the few human intervention trials available to show the effect of artificial sweeteners on the microbiome, other animal studies using these ingredients (at relevant dietary doses) suggests that this phenomena is an important link between artificial sweeteners and metabolic dysregulation.[vi],[vii]

Ironically, many “light” yogurt products include these artificial sweeteners as a key ingredient in the effort to retain palatability while reducing total sugars and calories. Consuming yogurt products in an effort to favorably modify the microbiome while consuming these “light” or “reduced calorie” additives may detrimentally undermine any beneficial changes to the microbiome the consumer anticipates.


[This is a short excerpt from the “Supporting the Microbial Ecosystem of the Gut” section of our newest Road map Functional Strategies for the Management of Gastrointestinal Disorders, which is now (finally) ready to be ordered.]


[i] Sylvetsky AC, Welsh JA, Brown RJ, Vos MB. Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr. 2012 Sep;96(3):640-6.

[ii] Suez J, Korem T, Zilberman-Schapira G, et al. Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes. 2015;6(2):149-55.

[iii] Spencer M, Gupta A, Dam LV, et al. Artificial Sweeteners: A Systematic Review and Primer for Gastroenterologists. J Neurogastroenterol Motil. 2016 Apr 30;22(2):168-80.

[iv] Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6.

[v] Nettleton JE, Reimer RA, Shearer J. Reshaping the gut microbiota: Impact of low calorie sweeteners and the link to insulin resistance? Physiol Behav. 2016 Apr 15. pii: S0031-9384(16)30164-0.

[vi] Palmnäs MS, Cowan TE, Bomhof MR, et al. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PLoS One. 2014 Oct 14;9(10):e109841.

[vii] Abou-Donia MB1, El-Masry EM, Abdel-Rahman AA, et al. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71(21):1415-29.

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