Effects of Low-Dose Non-Caloric Sweetener Consumption on Gut Microbiota in Mice
Non-caloric artificial sweeteners (NASs) provide sweet tastes to food without adding calories or glucose. NASs can be used as alternative sweeteners for controlling blood glucose levels and weight gain. Although the consumption of NASs has increased over the past decade in Japan and other countries, whether these sweeteners affect the composition of the gut microbiome is unclear. In the present study, we examined the effects of sucralose or acesulfame-K ingestion (at most the maximum acceptable
... daily intake (ADI) levels, 15 mg/kg body weight) on the gut microbiome in mice. Consumption of sucralose, but not acesulfame-K, for 8 weeks reduced the relative amount of Clostridium cluster XIVa in feces. Meanwhile, sucralose and acesulfame-K did not increase food intake, body weight gain or liver weight, or fat in the epididymis or cecum. Only sucralose intake increased the concentration of hepatic cholesterol and cholic acid. Moreover, the relative concentration of butyrate and the ratio of secondary/primary bile acids in luminal metabolites increased with sucralose consumption in a dose-dependent manner. These results suggest that daily intake of maximum ADI levels of sucralose, but not acesulfame-K, affected the relative amount of the Clostridium cluster XIVa in fecal microbiome and cholesterol bile acid metabolism in mice. Nutrients 2017, 9, 560 2 of 11 the effects of NASs, particularly sucralose and acesulfame-K, on metabolism are important to provide guidance on the amount of NASs that can be consumed. In the past decade, several studies examined the effects of NASs on appetite, weight gain, incidence of obesity, and metabolic disorders, but the results were not consistent [3, 5] . In a systematic review, Imamura et al. found that individuals who consumed higher amounts of beverages made with artificial sweeteners had an 8% increased incidence of type 2 diabetes, even after adjustment for adiposity , whereas Kim et al. and Cheungpasitporn et al. showed that these beverages were associated with an increased risk of hypertension [7,8]. Meanwhile, Cheungpasitporn et al. reported that the pooled risk ratios (RR) of five study samples of chronic kidney disease in patients who consumed artificially sweetened soda were not statistically significant (RR: 1.33, 95% confidence intervals 0.82-2.15) , although it should be noted that neither the Cheungpasitporn et al. study nor the Kim et al. study made adjustments for adiposity. Recently, a study by Suez J et al. suggested that saccharin, aspartame, or sucralose consumption could induce glucose intolerance by promoting gut dysbiosis  . Sucralose is rarely absorbed in the mammalian gut, but this NAS can affect non-mammalian cells, including gut bacteria  . Sucralose has been shown to increase serotonin, which initiates peristaltic and secretory activity [12, 13] . In rats, consumption of sweeteners containing sucralose (e.g., Splenda) reduced the numbers of intestinal bacteria  . In addition, chronic consumption of sucralose triggered increased food intake in mice and flies  . However, because this study used high amounts of NASs, particularly sucralose (approximately 20-fold higher than the acceptable daily intake (ADI) ), whether lower doses of sucralose or acesulfame-K (at most the maximum ADI levels of 15 mg/kg body weight) also affect the gut microbiome and food intake are unclear. In the present study, we examined the effect of low-dose pure sucralose or acesulfame-K consumption on the gut microbiome and host metabolism in mice.