ReviewReshaping the gut microbiota: Impact of low calorie sweeteners and the link to insulin resistance?
Introduction
On any given day, it is estimated that 11% of healthy-weight, 19% of overweight, and 22% of obese adults drink diet beverages, prevalent products containing low calorie sweeteners [5]. Women and children are now reported to be the greatest consumers of low calorie sweeteners in the United States. In 2008, it was estimated that nearly 15% of children and 33% of women consume food and beverages containing low calorie sweeteners, a large increase compared to 1999–2000 intake reports [68]. With obesity continuing to rise on a global scale [77], low calorie sweeteners have become a popular sugar substitute, particularly in ‘diet’ and ‘light’ foods, allowing a variety of products to retain their palatability without the associated calories, creating a perception of a ‘healthier’ product. Low calorie sweeteners are ubiquitous within current food products, such as desserts, gum, breakfast foods, and (diet) beverages, and therefore may be unintentionally consumed. For example, saccharin, sucralose, and acesulfame-potassium have all been found in the breast milk of women who did not explicitly report consuming these low calorie sweeteners [69].
The three most popular low calorie sweeteners are sucralose, followed by acesulfame-potassium and aspartame [82]. Although the common characteristic of low calorie sweeteners is to provide sweetness without associated calories, it is important to note that each one is metabolically and chemically distinct. For example, sucralose is a chlorinated disaccharide of which 65–95% is excreted in feces, whereas aspartame is a dipeptide and the majority is hydrolyzed into its three moieties (phenylalanine, methanol, and aspartic acid) and absorbed within the small intestine [50], [53]. Acesulfame potassium is an acidic cyclic sulphonamide derivative and is primarily excreted in urine [52].
Low calorie sweeteners have been approved for human consumption by regulatory agencies worldwide [24], [27] and found to be ‘safe’ for human consumption. Although low calorie sweeteners may have value in reducing the energy density of the diet, their impact on health requires further investigation. There is growing recognition that ‘safe’ and ‘healthy’ are different considerations. While safety considers disease (e.g. causative in cancer) and/or injury (e.g. toxicity), healthy implies a continued state of optimal physiological functioning (e.g. lack of insulin resistance). However, there is accumulating evidence that changes in gut microbiota may contribute to the development of certain diseases in susceptible individuals, as discussed below. Therefore, observations that low calorie sweetener consumption may result in alterations in the gut microbiota calls to question whether they may still be classified as ‘safe’.
Section snippets
Epidemiological data
Epidemiological, observational and biomedical evidence show regular low calorie sweetener consumption over a prolonged period may promote obesity, glucose intolerance, and its related comorbidities [17], [20], [41], [46]. Swithers evaluated and summarized longitudinal prospective cohort studies that examined low calorie sweetened beverage consumption in relation to health outcomes, including weight change, type 2 diabetes, cardiovascular disease and the metabolic syndrome [67]. In this paper,
Gut microbiota
Collectively, the human gut consists of trillions of microorganisms, a number far exceeding the total number of our somatic cells [40], [55]. The dynamic and diverse microorganisms that inhabit the gut are capable of quick adaptation to varied pathological, dietary and metabolic conditions. This is evident in examination of its biochemical capabilities; the human microbiota has evolved to contain upwards of 60,000 glycoside hydrolases and polysaccharide lyases that are capable of digesting
Involvement of the gut microbiota in obesity and insulin resistance
The severity and prevalence of obesity has dramatically increased on a global scale, and nearly 39% and 13% of adults are now considered overweight or obese respectively [78]. These statistics are cause for concern since obesity is a known contributor to many chronic disease states including type 2 diabetes and cardiovascular disease, which is increasing in developed and developing countries alike [78]. There is now abundant evidence that the microbiota is an environmental factor actively
Low calorie sweeteners and the gut microbiota
Our inherent craving for sweet foods starts at birth and is shared with many other animal species [43]. Some of the best work to recognize an impact of low-calorie sweeteners on both feeding behaviour and the gut microbiota is derived from the agricultural sector where low calorie sweeteners are added to starter feeds. Although results are variable, the inclusion of either sugar based sweeteners or low calorie sweeteners in a number of species helps to establish gut microbiota and modulate
Potential mechanistic considerations and knowledge gaps
At present, the exact mechanisms by which low calorie sweeteners perturb the gut microbiota are not known. Although we have grouped sweeteners into one class in this review, it is important to recognize that each one has a distinct structure, metabolism and acceptable daily intake level. Going forward, studies assessing each individual sweetener and their impact in health, pregnancy, and metabolic disease states are required. In this section we briefly highlight the potential mechanisms that
Conclusions
Accumulating evidence suggests that low calorie sweetener consumption perturbs the gut microbiota and disrupts metabolic health in susceptible individuals. This concern was echoed by the US Scientific Report of the 2015 Dietary Guidelines Advisory Committee that provides the US Federal government with a foundation for developing national nutrition policy. These recommendations acknowledge a potential relationship between low calorie sweetened soft drinks and type 2 diabetes risk. Their
Conflicts of interest
The authors have no conflicts of interest to declare.
Acknowledgements
J. S. and R. A. R. (RGPIN 238382-2011) receive research funding from the National Science and Engineering Research Council of Canada. J.E.N. is supported by an Alberta Children's Hospital Research Institute Studentship (Calgary, AB).
References (82)
Effect of saccharin ingestion on stool composition in relation to caecal enlargement and increased stool hydration
Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc.
(1983)- et al.
Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling
Cell Metab.
(2015) Origins and evolution of the Western diet: health implications for the 21st century
Am. J. Clin. Nutr.
(2005)Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits
Cell
(2014)Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidemiologique aupres des femmes de la Mutuelle Generale de l’Education Nationale-European prospective investigation into cancer and nutrition cohort
Am. J. Clin. Nutr.
(2013)- et al.
Robust scientific evidence demonstrates benefits of artificial sweeteners
Trends Endocrinol. Metab. TEM
(2014) - et al.
Diketopiperazines: biological activity and synthesis
Tetrahedron
(2007) Ontogeny of taste preferences: basic biology and implications for health12345
Am. J. Clin. Nutr.
(2014)Microbes in gastrointestinal health and disease
Gastroenterology
(2009)Bacteria in the gut: friends and foes and how to alter the balance
J. Nutr.
(2004)
Sucralose metabolism and pharmacokinetics in man
Food Chem. Toxicol.
Specialized metabolites from the microbiome in health and disease
Cell Metab.
Mucosal flora in inflammatory bowel disease
Gastroenterology
Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements
Trends Endocrinol. Metab.
Low-calorie sweetener consumption is increasing in the United States
Am. J. Clin. Nutr.
Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation
Cell Metab.
Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome
Cell Host Microbe
Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion
J. Biol. Chem.
Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome P-450 in male rats
J. Toxic. Environ. Health A
The gut microbiota as an environmental factor that regulates fat storage
Proc. Natl. Acad. Sci. U. S. A.
Diet-beverage consumption and caloric intake among US adults, overall and by body weight
Am. J. Public Health
Effects of methanol on the growth of gastrointestinal anaerobes
Can. J. Microbiol.
Antibiotics in early life alter the murine colonic microbiome and adiposity
Nature
Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain
Clin. Exp. Rheumatol.
Exercise and associated dietary extremes impact on gut microbial diversity
Gut
Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis
Nutr. Metab. (Lond.)
Dietary intervention impact on gut microbial gene richness
Nature
High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome
Gut
Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community
Circulation
Susceptibility to Campylobacter infection is associated with the species composition of the human fecal microbiota
mBio
Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity
Proc. Natl. Acad. Sci. U. S. A.
High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States
Ann. Epidemiol.
The stool microbiota of insulin resistant women with recent gestational diabetes, a high risk group for type 2 diabetes
Sci. Rep.
Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis
PLoS ONE
Contribution of diet to the composition of the human gut microbiota
Microb. Ecol. Health Dis.
Microbiome: the critters within
Nature
Structure, function and diversity of the healthy human microbiome
Nature
Cited by (100)
The effect of aspartame on accelerating caspase-dependent apoptosis of pancreatic islet via ZIPK/STAT3/caspase 3 signaling pathway
2024, Journal of Physiology and Biochemistry