Artificial Sweeteners and the Microbiome

Obesity, hyperglycemia (high blood sugar), and type 2 diabetes are major medical concerns whose prevalence among adults and children has risen in recent decades, at least in part due to our sugar-rich diets. To reduce sugar intake, a variety of artificial sweeteners have been developed and marketed, including saccharin (e.g. Sweet’N Low), sucralose (e.g. Splenda), aspartame (e.g. Equal), and stevia (e.g. Truvia). Collectively, these compounds are known as non-nutritive sweeteners (NNS) because they taste sweet but are metabolized either very little or not at all by human cells. Being metabolically inactive they do not contribute calories to the foods and drinks containing them. Because of these properties, NNSs are considered harmless substitutes for sugar and a convenient way to reduce sugar consumption with its ill effects on our weight and metabolic health. Given this noncaloric benefit, NNSs have soared in popularity and are now ubiquitous in many products.

As NNS intake increases among the general public, more and more animal and human studies are being conducted to examine the effects and consequences of consuming these compounds. There is no clear answer yet as different studies have reported contradictory results with some finding improved metabolic markers, some showing no health impact, and others reporting a negative effect where NNSs may actually contribute to obesity and diabetes. Some of this discrepancy is likely due to the experimental constraints. Animal studies can always be criticized for failing to adequately reflect what would happen in humans, and human studies are inherently difficult to control given the heterogeneity in humans and their lifestyles. Still, one common issue that has arisen from some of these studies is the potential effect of NNS compounds on the human gut microbiome. While humans can’t metabolize the NNSs, certain gut microbes can and do utilize them, producing metabolic byproducts that are excreted and which may affect other bacteria and/or the human host. As humans vary widely in the types and ratios of different bacteria in the gastrointestinal tract, studying the effects of NNS compounds on our microbial flora has become an important concern.  

A recent study published in the journal Cell used 120 human volunteers to examine the effects of 4 NNSs on glucose tolerance and the microbiome. The volunteers were all healthy and non-overweight adults who had not used artificial sweeteners prior to the study. They were divided into 6 groups of 20 with 4 groups being the experimental groups and 2 groups being the controls. Each experimental group received a different NNS, either aspartame, sucralose, saccharin, or stevia, given 3 times a day for two weeks (amounts of the 4 NNSs varied from 0.1 to 0.24 grams/day total, well below accepted daily limits). The first control group received an equivalent amount of glucose 3 times a day and the second control group just maintained their normal, NNS-free diet. All participants had their blood glucose levels monitored, were given glucose tolerance tests, and had their oral and fecal microbiomes analyzed. Significantly, all 4 NNSs altered the oral and stool microbiomes of the test subjects, causing increases and decreases in certain bacterial families. In contrast, there was no change in the microbiomes for the glucose-only control group or the normal diet group over the two-week test period. These results raise the concern that NNS compounds are not truly inert and might affect health indirectly through alterations in our microbiomes. As microbiome composition can significantly vary between individuals, whether or not NNS effects might be very different from person to person must be investigated in a much larger cohort. 

In addition to the impact on microbiomes, saccharin and sucralose were also found to impair the glucose response (the ability of the body to remove glucose from the blood). Groups ingesting aspartame and stevia showed no effect on the glucose response similar to the 2 control groups. Importantly, when fecal bacteria from the saccharin and sucralose subjects were transplanted into germ-free mice the mice also developed impaired glucose regulation in their blood. This directly establishes a microbial cause for this dysregulation and suggests that saccharin/sucralose ingestion in humans can alter the microbiome in ways that negatively impact our glucose tolerance. These are worrisome results although there are 2 significant limitations to this study. First, the cohort size (20 people per group) was small and only involved individuals with normal weight and metabolism so the results could change in populations with different weights and health levels. Second, this was only a short-term study of 2 weeks duration. Whether or not these changes in the microbiome and/or glucose response would persist, worsen, or return to baseline cannot be predicted from this study. Much additional work is needed to fully understand the potential consequence of ingesting different NNSs so that we can accurately assess the risk-benefit ratios for these compounds.

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