Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat

Abstract

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 (n = 10–12 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.

Nutritional and biochemical effects of aspartame intake in rats under an experimental diet

“…However, the aspartame intake avoids the high body weight as observed in the E group. The weight loss by aspartame has been reported extensively (Ishii et al, 1981;Butchko et al, 2002;de la Hunty et al, 2006;Palmnäs et al, 2014). In this case, the reduction of the body mass cannot be explained by a significant loss of adipose tissue.…”

“…It is important to note that the serum creatinine is a reliable marker for the evaluation of the muscle mass if the kidney function and dietary protein intake is undertaken as was done for the E versus EA data (Perrone et al, 1992;Patel et al, 2013). Changes in muscle mass or serum creatinine during loss of body weight due to aspartame were not evaluated previously (Ishii et al, 1981;Butchko et al, 2002;de la Hunty et al, 2006;Palmnäs et al, 2014). Creatinine results of the rat groups.…”

“…A study assaying the aspartame intake under a similar pattern of the society feeding relating to the WHO/FAO recommended limits has not been reported (Frey, 1976;Knopp et al, 1976;Ishii et al, 1981;Stegink et al, 1983;Shahangian et al, 1984;Stegink, 1987;Colagiuri et al, 1989;Gupta et al, 1989;Butchko et al, 2002;Gougeon et al, 2004;Roberts, 2004;de la Hunty et al, 2006;Soffritti et al, 2006;Gombos et al, 2007;Magnuson et al, 2007;Soffritti et al, 2007;Roberts, 2008;Anton et al, 2010;Abhilash et al, 2011;Aune, 2012;Schernhammer et al, 2012;Feijó et al, 2013;Palmnäs et al, 2014). Therefore, the aim of this study was to evaluate the nutritional and biochemical effects of aspartame in Wistar rats consuming a fat plus sucrose enriched diet relating to the WHO/FAO values.…”

Non-Nutritive Sweeteners: Evidence on their Association with Metabolic Diseases and Potential Effects on Glucose Metabolism and Appetite

“…This was associated with an increase in gut total bacteria, Enterobacteriaceae, Clostridium leptum, and Roseburia ssp. In addition, in rats fed with a high-fat diet, aspartame attenuated the increase in the Firmicutes:Bacteroidetes ratio 24 .…”

The Western Diet&ndash;Microbiome-Host Interaction and Its Role in Metabolic Disease

“…These sweeteners have also not been tested for effects on the gut microbiota prior to approval. Effects from rodent studies include altered composition of microbes leading to impaired glucose tolerance [28,59,60], as well as increased pro-inflammatory potential [61,62] and liver inflammation [61]. NAS-induced alterations in microbiota composition leading to adverse metabolic outcomes should give rise to concern, especially because the demand for NAS containing products are increasing, and persons suffering from metabolic disorders could be more likely to choose such products for health benefits.…”