Featured Article - November 2014
Short description: Artificial sweeteners alter metabolism through shifts in the distribution of gut microbiota species.
Non-caloric artificial sweeteners (NAS) are widely consumed due to the perceived health benefits of reducing the intake of “empty calories” in refined sugars. Six NAS products are currently approved by the FDA, despite conflicting data regarding their effects on glycemic response, weight gain and the risk of diabetes.
The impact of diet on intestinal microbiota that affect weight control and disease has been documented, prompting Elinav, Segal and colleagues to test for the potential effects of NAS on gut microbiota metabolism. Whereas the addition of glucose or sucrose did not alter glucose tolerance in mice, artificial sweeteners (saccharin, sucralose or aspartame) led to marked glucose intolerance within weeks, in both lean mice and those fed a high-fat diet. NAS-induced glucose intolerance was likely due to alterations in gut microbiota, as it was reversed by treatment with antibiotics and could be transferred to NAS-naive mice via transplant of fecal matter from NAS-treated mice or matter cultured in NAS.
By analyzing species representation among gut microbiota, the authors showed NAS treatment or fecal transplant from NAS-treated mice caused similar population shifts, favoring a specific subset of species at the expense of others. Shifts in species representation coincided with changes in gene abundance, decreasing glucose transport pathways in favor of pathways metabolizing other sugars, glycans, starch and sphingolipids. Genes in pathways for biosynthesis of folate, glycerolipids and fatty acids were also elevated, and products of these pathways were enriched in stool.
NAS use likely has similar effects on human metabolism, as a long-term study of 383 non-diabetic patients showed BMI-independent positive correlations between self-reported NAS use, clinical measures of glucose intolerance and gut microbiota species distribution. In healthy human NAS non-consumers, less than a week of daily saccharin caused significant negative effects on glycemic response and shifts in microbiota species in 4 out of 7 volunteers, and post-treatment feces from responders induced glucose intolerance in NAS-naive mice.
These results support that NAS use causes glucose intolerance due to shifts in microbiota composition and function. These changes may be linked to an increased risk of diabetes and obesity.
J. Suez et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota.
Nature. (17 September 2014). doi:10.1038/nature13793