The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice

Abstract

Artificial sweeteners have been widely used in the modern diet, and their observed effects on human health have been inconsistent, with both beneficial and adverse outcomes reported. Obesity and type 2 diabetes have dramatically increased in the U.S. and other countries over the last two decades. Numerous studies have indicated an important role of the gut microbiome in body weight control and glucose metabolism and regulation. Interestingly, the artificial sweetener saccharin could alter gut microbiota and induce glucose intolerance, raising questions about the contribution of artificial sweeteners to the global epidemic of obesity and diabetes. Acesulfame-potassium (Ace-K), a FDA-approved artificial sweetener, is commonly used, but its toxicity data reported to date are considered inadequate. In particular, the functional impact of Ace-K on the gut microbiome is largely unknown. In this study, we explored the effects of Ace-K on the gut microbiome and the changes in fecal metabolic profiles using 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. We found that Ace-K consumption perturbed the gut microbiome of CD-1 mice after a 4-week treatment. The observed body weight gain, shifts in the gut bacterial community composition, enrichment of functional bacterial genes related to energy metabolism, and fecal metabolomic changes were highly gender-specific, with differential effects observed for males and females. In particular, ace-K increased body weight gain of male but not female mice. Collectively, our results may provide a novel understanding of the interaction between artificial sweeteners and the gut microbiome, as well as the potential role of this interaction in the development of obesity and the associated chronic inflammation.

Consumption of artificially sweetened beverages during pregnancy impacts infant gut microbiota and body mass index

“…To our knowledge, this is the first human study to report the impact of maternal consumption of ASB on the infant gut microbiome, and its potential influence on infant BMI. In light of recent data showing that ASB can drive dysregulation of energy metabolism in mice through changes in the gut microbiome 24,25,38,39 , our study suggests that infants exposed to ASB through their mothers may be at higher risk of shifts in microbial community structure related to early-life predisposition to metabolic diseases 40,41 .…”

“…As reported by Bian et al 38,39 in two studies with adult mice, and by Nettleton et al 43 in a study on dams and their offspring, ASB have been shown to alter gut bacterial community composition (increase of Bacteroides and reductions of Lactobacillus and Clostridium ) and increase body weight in parallel with an enrichment of energy metabolism bacterial genes. The functional cluster analyses by Bian et al 38,39 revealed activation of genes related to carbohydrate absorption and increases in metabolic pathways related to glycolysis and sugar and xylose transport 38 . Sucralose treatment resulted in an increase in bacterial pro-inflammatory mediator genes in mice 39 .…”

“…that were enriched (3 ASVs) or depleted (6 ASVs) at high levels of maternal ASB consumption, suggesting a mechanism of influence on infant weight gain involving specific taxa of the gut microbiome. The taxa Akkermansia municiphila and genus Bacteroides have previously been identified by various studies to be respectively decreased and enriched as a consequence of ASB consumption 25,38,39,42 . Our results differ from previous findings for A. municiphila and suggest that Bacteroides patterns of enrichment or depletion might be species- or strain-specific, warranting further research with deeper resolution.…”

Dietary Exposures to Common Emulsifiers and Their Impact on the Gut Microbiota: Is There a Cause for Concern?

“…Another recent study suggests that conventional cleaners and eco-friendly cleaners modulate the composition of the gut microbiota of infants leading to obesity at 3 years of age (Tun, Tun, & Mahoney et al, 2018). Likewise, exposure to artificial sweeteners (sucralose, acesulfame potassium, saccharin) has been associated with an altered gut microbiota and, ultimately, gut and intestinal inflammation, obesity, and diabetes (Bian et al, 2017a(Bian et al, , 2017bSuez, Korem, Zilberman-Schapira, Segal, & Elinav, 2015). Evidently there is a clear pattern in that the composition of the gut microbiota is shifted in different disease states; however, the exact mechanism by which this occurs remain unknown.…”

The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease

“…These sweeteners have also not been tested for effects on the gut microbiota prior to approval. Effects from rodent studies include altered composition of microbes leading to impaired glucose tolerance [28,59,60], as well as increased pro-inflammatory potential [61,62] and liver inflammation [61]. NAS-induced alterations in microbiota composition leading to adverse metabolic outcomes should give rise to concern, especially because the demand for NAS containing products are increasing, and persons suffering from metabolic disorders could be more likely to choose such products for health benefits.…”