Artificial sweeteners, gut microbiota and metabolic health: an interaction requiring close examination
By Pr. Karine Clément
Sorbonne University, Inserm, Unité de recherche nutrition et obésités ; approches systémiques [Nutrition and Obesity Research Unit (systemic approaches)], Paris, France; Nutrition Department, Assistance-Publique - Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
About this article
Sweeteners are considered as a worthy alternative to the excessive use of simple sugars, which are considered to be harmful to cardiometabolic health . Sweeteners can be consumed directly or in processed products  In Cell, Suez et al. reported the results of a randomised controlled trial which showed that, paradoxically, some sweeteners may disturb glucose tolerance and that some effects are mediated by changes in the gut microbiota .
How do you explain that only two sweeteners have an effect on blood sugar levels (saccharin and sucralose) while the four sweeteners tested had an impact on the composition and functions of the gut microbiota?
The use of sweeteners can be suggested in people with metabolic diseases to help them reduce their calorie intake, lose weight and improve their metabolic risk . However, over time, concerns have emerged due to the fact that sweeteners do not have a neutral effect [5, 6]. In 2014, the authors of this publication had already shown that mice consuming high doses of aspartame, saccharin and sucralose developed glucose intolerance due to disturbances in the gut microbiota . In this new research, they have gone one step further by carrying out a well-conducted clinical study in humans. In 120 healthy participants, the researchers assessed the effects on glucose tolerance of sucralose, saccharin, stevia and aspartame administered for 14 days (5 study arms, 20 participants per group and one control group). Sweeteners were used at levels lower than the recommended daily intake. The ingestion of sucrose and sucralose aggravated glucose tolerance, while aspartame and stevia had a neutral effect. These sweeteners had distinct effects on the composition of the oral and faecal microbiota and on key functions (such as purine and pyrimidine metabolism, glycolysis, and amino-acid metabolism). The most significant effect was observed with sucralose. Microbiota transfer studies (human to mouse) have established the causality of effects. Animals colonised with samples from sweetener-supplemented subjects showed varying degrees of altered glucose tolerance. The chemical composition of sweeteners appears to influence the microbiota; however, the precise mechanism by which they exert these variable effects on the host through changes in the faecal microbiota requires further detailed study. More specifically, sucralose, saccharin and stevia are partially metabolised in the upper digestive tract and only a tiny proportion reaches the colon.
Does this mean you recommend that your patients should not use non-nutritive sweeteners, since they may not be physiologically inert?
In my clinical practice, we do not systematically suggest patients use sweeteners, as there is no evidence that they are an effective weight-loss tool. Although, in patients who are unable to lose their sweet tooth, we prefer suggesting the use of natural sweeteners such as steviol glucoside, which can be used on a short-term and reasonable basis. However, the above discussed results highlight the need for a rigorous assessment of the short- and longterm impact of the available sweeteners on human health before deciding whether or not to recommend their continued use as an aid to reducing metabolic risks.
1. Andrade L, Lee KM, Sylvetsky AC, Kirkpatrick SI. Low-calorie sweeteners and human health: a rapid review of systematic reviews. Nutr Rev 2021 ; 79 : 1145-64.
2. Carocho M, Morales P, Ferreira ICFR. Sweeteners as food additives in the XXI century: A review of what is known, and what is to come. Food Chem Toxicol 2017 : 107 : 302-17.
3. Suez J, Cohen Y, Valdés-Mas R, et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell 2022 ; 185 : 3307-28.e19.
4. McGlynn ND, Khan TA, Wang L, et al. Association of low- and no-calorie sweetened beverages as a replacement for sugar-sweetened beverages with body weight and cardiometabolic risk: a systematic review and meta-analysis. JAMA Netw Open 2022 ; 5 : e222092.
5. Humphries P, Pretorius E, Naudé H. Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr 2008 ; 62 : 451-62.
6. Wu GD, Chen J, Hoffman C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011 ; 334 : 105-8.
7. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014 ; 514 : 181-6.