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. 2014 Oct 14;9(10):e109841.
doi: 10.1371/journal.pone.0109841. eCollection 2014.

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

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Free PMC article

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

Marie S A Palmnäs et al. PLoS One. .
Free PMC article

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Measures of glucose tolerance and insulin sensitivity.
A. Blood glucose from the oral glucose tolerance test (OGTT) from 0–120 min. B. Total area under the curve for OGTT over 120 min. C. Blood glucose following an insulin tolerance test (ITT). D. Total area under the curve for the ITT over 120 min. Data represents means ± SE, n = 9–12 per treatment. † p<0.05 for fluid (water vs.aspartame) within diet (chow, high fat). Statistics (p values) for area under the curve data (diet, fluid) and their interactions are also shown, p<0.05 being considered significant. Data from the water controls (chow, high fat) were part of a shared control group that has been previously published . Permission to reuse the data in this figure was obtained from Elsevier. Abbreviations are as follows; CHW, chow water; CHA, chow aspartame; HFW, high fat water; HFA, high fat aspartame.
Figure 2
Figure 2. Gut microbiota analyses of diet and fluid treatments.
A. Graphical representation of the absolute changes in the Firmicutes:Bacteroidetes ratio in fresh fecal matter resulting from dietary (chow or high fat) or fluid (water or aspartame) treatment. HFW has elevated levels in comparison to the other groups, with the data representing absolute number (106) of 16S rRNA gene copies per 20 ng DNA. The numerical value above each bar represents the Firmicutes:Bacteroidetes value. B. Relative bacterial abundance within the Firmicutes phyla. Data is based on 16S rRNA gene copies (106/20 ng DNA), on a relative (100%) scale. Consistent with the absolute results ( Table 2 ), APM treatment within HF (HFA) increased the relative proportion of Clostridium leptum and attenuated high fat- increased in Clostridium cluster XI. Data from the water controls (chow, high fat) were part of a shared control group that has been previously published . Permission to reuse the data in this figure was obtained from Elsevier. Abbreviations are as follows: CHW, chow water; CHA, chow aspartame; HFW, high fat water; HFA, high fat aspartame. Data represents means ± SE, n = 9–12 per treatment.
Figure 3
Figure 3. Short-chain fatty acid concentrations from serum metabolomics analysis.
Relative changes in the serum short chain fatty acids using 1H NMR spectroscopy. Data represents means ± SE, n = 9–12 per treatment. Data are shown relative to chow water, set as a value of 1.0. * p<0.05 for diet (chow vs. high fat) within fluid treatments (water, aspartame); † p<0.05 for fluid (water vs. aspartame) within diet (chow, high fat).

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Grant support

Research was funded by a National Science and Engineering Council of Canada Discovery Grant. H. J. V. currently holds the Lance Armstrong Chair for Molecular Cancer Research. J. S. is an Alberta Innovates Health Solutions Scholar. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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