Acesulfame Potassium, Gut Microbiome Disruption, and Weight Gain

by | May 6, 2018 | 2017, Obesity

Written by Joyce Smith, BS. The artificial sweetener, acesulfame potassium, differentially disrupted the gut microbiome of mice and contributed to obesity only in male mice.

Artificial sweeteners have been a popular weight control product; yet in spite of their perceived role as a calorie-restrictive sugar substitute, the prevalence of obesity and diabetes has risen dramatically over the past 20 years 1. The artificial sweetener saccharin has been shown to alter gut microbiota and induce glucose intolerance in both mice and human subjects 2; thus lending credence to a potential role in today’s global epidemic of obesity and diabetes 1. The functional impact of the artificial sweetener acesulfame-potassium (ACE-K), while FDA approved, has not been well studied, thus prompting researchers to investigate the effects of ACE-K on the gut microbiome in a mouse model.3

Twenty CD-1 mice were randomly assigned to a 4-week dose of 37.5mg/kg bodyweight/day of either water (control) or artificial sweetener (ACE-K). Weight was taken before and after treatment and fecal metabolic profiles were established using 16SrRNA sequencing and gas chromatography- mass spectrometry (GC-MS.)

Interestingly, Ace-K consumption affected the male and female mice quite differently. Researchers found that Ace-K consumption altered the gut microbiome of the CD-1 mice causing only male mice to gain weight. Specifically, Ace-K significantly increased the body Ace-K consumption increased the weight in male mice [10.28 g vs 5.44g, (p<0.01)] but not in female mice relative to their respective controls. Ace-K-treated male mice also had significantly increased Bacteroides (associated with obesity) 4, (p<0.01), Anaerostipes (p<0.05) and Sutterella (p<0.05) colonies; female mice had significant decreases in Lactobacillus (p<0.05), Clostridium (p<0.001), a Ruminococcaceae genus (p<0.05) and an Oxalobacteraceae genus (p<0.01), while Mucispirillum (p<0.05) were increased.

Ace-K consumption altered functional genes of the bacterial community and induced fecal changes that were highly gender dependent. Functional genes involved in energy metabolism and carbohydrate absorption were activated in male mice only, thus increasing genes involved in sugar and xylose transport, glycolysis and the TCA cycle (tricarboxylic acid cycle, commonly known as Krebs cycle) (p<0.05). The significant increases in Bacterioides and Anaerostipes in their microbiome reflects a high capacity for energy harvesting and is associated with obesity 4. The also significantly abundant key metabolite, pyruvate, ferments to produce the short-chain fatty acids propionate and butyrate 5 further suggesting that these microbiota help facilitate the male mice to extract calories from their diet and contribute to obesity. However, in female mice, Ace-K consumption decreased genes involved in energy metabolism pathways and impaired polysaccharide digestion and fermentation in the female gut microbiome as witnessed by the absence of weight gain.

Common to both male and female mice, Ace-K increased the abundance of genes related to lipopolysaccharide (LPS) synthesis (p<0.05). LPSs, consisting of fats (lipids) and sugar, are both structural and protective to bacteria; however, when released into the bloodstream by a disrupted gut microbiome, LPS become a potent endotoxin that drives a sudden and acute inflammatory reaction 6. Prominent in both genders was a bacterial toxin synthesis gene, Thiol-activated cytolysin, a gram-positive bacterial toxin and an important virulence factor 7 that can stimulate the expression of inflammatory mediators such as cytokines, and induce inflammatory responses 7.

Overall, Ace-K significantly altered fecal metabolomes containing metabolites, which serve as signaling molecules for the complex crosstalk that occurs between the host and gut bacteria 8. This study demonstrated the significant and unique impact of Ace-K on specific metabolites in male and female mice, with the majority of metabolites being down-regulated in female mice and up-regulated in male mice, emphasizing the importance of gender in mediating the gut microbiome and host response to artificial sweeteners. Collectively, these results may provide novel insights into understanding the functional interaction between artificial sweeteners and the gut microbiome and the role of this interaction in the development of obesity and chronic inflammation.

Source: Bian X, Chi L, Gao B, Tu P, Ru H, Lu K (2017) The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLoS ONE 12(6):e0178426. https://doi.org/10.1371/journal.pone.0178426l.

© 2017 Bian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Posted May 5, 2018.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

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  3. Bian X, Chi L, Gao B, Tu P, Ru H, Lu K. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PloS one. 2017;12(6):e0178426.
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The tricarboxylic acid cycle (TCA cycle) is a series of enzyme-catalyzed chemical reactions that form a key part of aerobic respiration in cells. This cycle is also called the Krebs cycle and the citric acid cycle. The greatly simplified cycle below starts with pyruvate, which is the end product of gylcolysis, the first step of all types of cell respiration.