Aspartame consumption is implicated in the development of
obesity and
metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose
aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose
aspartame (A, 5-7 mg/kg/d in
drinking water) treatments for 8 week (nā=ā10-12 animals/treatment). Animals on
aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this,
aspartame elevated fasting
glucose levels and an
insulin tolerance test showed
aspartame to impair
insulin-stimulated
glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed
aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and
aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF,
aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed
aspartame to be rapidly metabolized and to be associated with elevations in the
short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on
insulin tolerance. How
aspartame influences gut microbial composition and the implications of these changes on the development of
metabolic disease require further investigation.