Artificial sweeteners are synthetic sugar substitutes that are commonly consumed in the diet. In the past couple of decades, artificial sweeteners have become increasingly popularised as a noncaloric additive to sweeten foods and drinks.
As well as being incorporated into many food products and beverages, they are also components of pharmaceutical products. Artificial sweetener consumption in the diet continues to increase, its effects on the microbiota and how to mitigate any damaging effects are becoming increasingly studied.
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The increased uptake of artificial sweetness
Sweeteners are sugar substitutes that mimic the taste of sugar while having a negligible effect on energy intake. Examples of sweeteners include sucralose, sorbitol, mannitol, erythritol, and aspartame. Typically sweeteners have a very high sweetening intensity relative to sugar which has a greater caloric impact per gram. Sweetness can be synthetic or natural in origin come out with the latter form a preferred choice.
While epidemiological studies have evidenced the benefit of sweetness in weight loss for patients with glucose intolerance and type 2 diabetes, there are some conflicting reports parent artificial sweetener consumption has been linked to conditions that culminate in metabolic disease development - this effect is mediated through the gut microbiota.
Sweeteners include:
- Non-nutritive sweeteners: defined as having sweetening intensity and lower calorie content per gram compared with nutritive sweeteners – derived from natural sources
- Low-calorie sweeteners: typically polyols or sugar alcohols, which are low digestible carbohydrates derived from hydrogenating sugar or syrup; these sugar alcohols have a lower caloric content relative to sugar and do not promote tooth decay or spike blood glucose
The consumption of commonly used non-nutritive artificial sweeteners has driven the development of glucose intolerance by inducing changes in the composition and function of the intestinal microbiota.
Intestinal microbial communities are unknown to play a significant and central role in human disease and health. The intestinal microbiome is involved in several physiological processes including metabolism, immunity, anabolism (growth) add cognitive function. There is a very intimate connection between the gut microbiota on the immune system; microbial communities provide signals that promote the education and maturation of immune cells.
Alongside artificial sweeteners, the composition and function of the microbiome are also modulated and rapidly changed by diet. The potential link between artificial sweeteners and their downstream effects on human health are currently being addressed due to these well-known interactions between various elements of human health, diet, and intestinal microbiota.
Alterations in the gut microbiota and consequent changes in metabolism, weight, and metabolic disorder
Studies have shown that artificial sweeteners may favor the growth of bacteria that increase the bioavailability of calories.
A study that examined the effect of aspartame, sucralose, or saccharin on mice revealed that that circulating blood glucose levels were greater relative to mice ingesting sugar.
This is due to the alteration in the composition of two types of bacterial species that comprise approximately 90% of the bacterial species in the gut. These are Bacteroidetes and Firmicutes. Studies have shown that genetically obese mice have, on average, 50% less of the Bacteroidetes and 50% greater Firmicutes relative to their normal-weight counterparts.
As a proof of principle, when a sample of Firmicutes was transferred to the normal weight mouse population, the normal mice became obese. The basis for this change is a consequence of increased production of enzymes from the Firmicutes species that promote greater energy extraction. Moreover, Firmicutes can manipulate gene expression to promote fat storage relative to breakdown for energy.
This finding suggests that the bacteria in the human gut may not only influence the ability to extract calories and store energy from the diet but also affect the balance of hormones, such as leptin, that shape eating behavior, leading to increased caloric consumption.
Similar effects have been shown across several studies, which show positive correlations between artificial sweetener consumption and changes in specific species of bacteria. Moreover, these effects have been seen to be reflected in glycemic response and glucose tolerance. Invariably, these studies have shown a deleterious effect on glucose tolerance as a consequence of changes in the intestinal microbiota.
It is important to note that while these patterns correlate, they are not causative. Obese people may have a greater likelihood of consuming artificial sweeteners relative to a normal population.
However, direct testing of the association in a small group of lean and healthy volunteers demonstrated that after consuming the maximum dose of saccharin over five days, four of the seven subjects showed a reduction in glucose response as well as an abrupt change in their gut microbes. The three volunteers who were resistant to changes in glucose tolerance did not experience a change in the composition or function of the gut microbiome.
Beyond weight, glucose tolerance, and metabolic disorder: The effect of sweeteners on pathogenetic characteristics of the gut microbiome
A recent study published this year has shown that sweetness can also affect the pathogenicity of gut bacterial species. In this study, the model gut bacteria were exposed to several concentrations of the artificial sweetness saccharin, sucralose, and aspartame, and their pathogenicity and changes and interactions with intestinal cell types were measured using in vitro studies. Results demonstrated that sweeteners increase the ability of these bacteria to form a biofilm (namely Escherichia coli and Enterococcus faecalis). Consequently, these bacteria were able to adhere to, invade, and kill host epithelium.
While analysis has shown that the consumption of artificial sweeteners changes the composition and abundance of several of the gut microbiota populations, further studies are necessary. This is because changes observed in the intestinal microbiota have been predominantly observed in animals rather than human subjects.
As a consequence, well-designed, long-term, double-blind, placebo-controlled, randomized clinical trials are necessary to determine the effects of artificial sweetener consumption on intestinal microbiota in humans and how this could affect health outcomes and determine the biomarkers related to chronic disease.
References
- Ruiz-Ojeda FJ, Plaza-Díaz J, Sáez-Lara MJ, Gil A. (2020) Effects of Sweeteners on the Gut Microbiota: A Review of Experimental Studies and Clinical Trials. Adv Nutr. doi:10.1093/advances/nmy037.
- Konstantinidi M, Koutelidakis AE. (2019) Functional Foods and Bioactive Compounds: A Review of Its Possible Role on Weight Management and Obesity's Metabolic Consequences. Medicines. doi:10.3390/medicines6030094.
- Shil A, Chichger H. (2021) Artificial Sweeteners Negatively Regulate Pathogenic Characteristics of Two Model Gut Bacteria, E. coli and E. faecalis. Int J Mol Sci. doi:10.3390/ijms22105228.
Further Reading
Penn State study examines how a person's telomeres are affected by caloric restriction