Editors' ChoiceMetabolism

A Bug in the System for Artificial Sweeteners

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Science Translational Medicine  08 Oct 2014:
Vol. 6, Issue 257, pp. 257ec170
DOI: 10.1126/scitranslmed.3010419

A quick trip to the local supermarket reveals the pervasive access to sugar-free products in every aisle. These reduced-calorie foods and beverages, which contain noncaloric artificial sweeteners (NASs) such as saccharin and aspartame, are widely used by individuals who are trying lose weight or are suffering from metabolic syndrome. But some studies have demonstrated an association between NAS consumption and increased risk of weight gain and type II diabetes. Now, Suez et. al. report that consumption of commonly used NASs drive the development of glucose intolerance in an unsuspected manner—by altering the gut microbiome.

The investigators fed mice with common NAS formulations (saccharin, aspartame, or sucralose) versus glucose at doses within the range of intake allowed for humans by the U.S. Food and Drug Administration. Lean mice that consumed NASs developed marked glucose intolerance compared with glucose-consuming mice, an effect that was also observed in mice on a high-fat diet. Intriguingly, NAS-induced glucose intolerance was abrogated when mice were treated with broad-spectrum antibiotics, suggesting that the host microbial flora was required for this pathology. Fecal or microbial transplantation experiments demonstrated that transfer of microbiota exposed to NASs was sufficient to cause glucose intolerance in normal chow–consuming, germ-free mice. Genomic and metabolomic profiling revealed that NAS consumption caused distinct functional alterations in the gut microbiome of mice, including alterations in glycan degradatory pathways. In an attempt to translate their findings, the authors conducted a retrospective analysis of 381 nondiabetic human subjects and discovered that long-term NAS consumption was independently associated with several biomarkers of metabolic syndrome. In fact, 1 week of NAS consumption by healthy human volunteers was associated with glucose intolerance and dysbiosis of gut microbiota in a subset of individuals.

This study reveals that ingestion of certain NAS formulations can cause glucose intolerance via functionally altering the gut microbiome, prompting further study of the metabolic effects of these food additives. Future research to define the precise molecular effectors of this complex pathobiology may elucidate new disease mechanisms and provide previously unrecognized therapeutic opportunities for metabolic syndrome.

J. Suez et al., Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 10.1038/nature13793 (2014). [Full text]

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