Effects of the Artificial Sweetener Neotame on the Gut Microbiome and Fecal Metabolites in Mice

Effects of the Artificial Sweetener Neotame on the Gut Microbiome and Fecal Metabolites in Mice

Although artificial sweeteners are widely used in food industry, their effects on human health remain a controversy. It is known that the gut microbiota plays a key role in human metabolism and recent studies indicated that some artificial sweeteners such as saccharin could perturb gut microbiome and further affect host health, such as inducing glucose intolerance. Neotame is a relatively new low-caloric and high-intensity artificial sweetener, approved by FDA in 2002. However, the specific effects of neotame on gut bacteria are still unknown. In this study, we combined high-throughput sequencing and gas chromatography–mass spectrometry (GC-MS) metabolomics to investigate the effects of neotame on the gut microbiome and fecal metabolite profiles of CD-1 mice. We found that a four-week neotame consumption reduced the alpha-diversity and altered the beta-diversity of the gut microbiome. Firmicutes was largely decreased while Bacteroidetes was significantly increased. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis also indicated that the control mice and neotame-treated mice have different metabolic patterns and some key genes such as butyrate synthetic genes were decreased.....
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To put such a study in context, we would need to examine the effects of sugars (such as sucrose or fructose) on the microbiome. This paper says:
a diet enriched in fructose not only induced NAFLD [non-alcoholic fatty liver disease] but also negatively affected the gut barrier and the microbiota, leading to dysbiosis.

In addition, the microbiota itself was shown to contribute to the progression of liver disease and injury and diet-induced NAFLD resulted in dysbiosis and a strong decrease in microbial diversity.

Although the underlying mechanisms are not fully discovered yet, fructose is known to be highly involved in the development of NAFLD by altering gut metabolites. Fructose increased the intestinal translocation of endotoxins and endotoxin levels in plasma contributing to inflammation and degrading of the mucosa barrier. Consequently, acute and chronic exposure to high fructose increased circulating endotoxin in patients with NAFLD, accompanied by markers of insulin resistance and inflammation.
Microbial diversity significantly decreases when consuming a high sugar diet already after 1 week
Fructose consumption causes dysbiosis in the microbiota, leading to an increased permeability of the gut barrier, hepatic inflammation, progressive development of metabolic syndrome, and insulin resistance.
These health issues arising from fructose are amplified in the US, due to the fact that fructose is used to sweeten soft drinks.