The Effects of Sweeteners in the Gut Microbiome
Introduction
By Matthew Nguyen
Within the last decade, sweeteners have begun to play a crucial role in today’s society. Many people have started to look into new forms of sweeteners, both artificial and natural, to help meet caloric intake goals as well as for overall enjoyment of food and beverages being consumed. From stevia to aspartame, more and more sweeteners are being discovered and being approved by the Food and Drug Administration (FDA). Though consuming these lower calorie sugars may be beneficial for meeting calorie goals, it may not be beneficial for gut health in the long-run. Many factors contribute to why a person chooses to consume artificial sweeteners, including socioeconomic status and health goals. There have been many pros and cons found related to the consumption of artificial sweeteners. Throughout this review, we will discuss what effects sweeteners can have on the human gut microbiome and discuss if sweeteners really are beneficial to humans or if it's just hurting their bodies. Understanding the effects that sweeteners can have on the gut microbiome is beneficial for understanding what foods should and should not be consumed on a daily basis.
Human Gut Microbiome
To understand the effects that sweeteners can have on the human body, we must first understand the human gut microbiome. The human gut microbiome can be defined as the complex community of microorganisms that inhabit the gastrointestinal tract[1]. This important organ that regulates metabolism, cellular immune response, and contributes to the host’s health is an extremely important element in the human body (Kasti et al, 2022). The bacteria and other microorganisms that make up the gut have an important role in maintaining immune and metabolic homeostasis as well as protecting against pathogens (Thursby et al, 2017). Though the gut is a very large and complex interface, the microbiota within provide many beneficial contributions. The microbiota strengthens the gut integrity, helps shape the intestinal epithelium, provides protection against pathogens, and regulates host immunity (Thursby et al, 2017). Researchers still do not fully understand the human gut microbiome as not all guts are the same. There are many people that eat a well-balanced diet, while there are others that consume high calorie food, like fast food restaurants. The amount of liquids a person consumes can also affect the gut microbiome, making it even more difficult for researchers to investigate.
There are many factors that contribute to the development of the gut including diet, environmental factors, and feeding methods throughout infancy. A persons’ diet contributes the most to the composition of the gut, due to many different types of bacteria being introduced to the already dense amount of bacteria. Diets that are high in resistant starch or non-starch polysaccharide fibre were shown to have much more bacterial diversity compared to diets that are more animal or plant based (Thursby et al, 2017). Another important factor that contributes to the development of the gut is feeding methods throughout a child’s infancy. Many babies are either fed via human milk (breast-feeding) or via formula. Studies have shown that there is an abundance of fucosylated oligosaccharides in breast milk that can be used by several bacteria species helping them to outcompete other more harmful bacteria (Thursby et al, 2017). When young infants are fed via formula, they lack these natural bacterias that breast milk contains, creating indifferences between babies fed via breast milk and babies fed via formula. When comparing these two feeding methods, there is no “right or wrong” method of feeding, as these bacterias found in breast milk are not essential for human growth.
Types of Sweeteners
There are two types of sweeteners that are used in food and beverage creation. Natural sweeteners are produced by nature, without any added chemicals (Neacsu et al, 2014). On the other hand, artificial sweeteners are substances that are used to replace natural sweeteners in foods and beverages with the goal to maintain a similar taste (Neacsu et al, 2014). Artificial sweeteners can be separated into two groups: nutritive sweeteners, which add some energy value to food and beverages, and non-nutritive sweeteners, which are used in very small amounts and add no energy value to food and beverages (Neacsu et al, 2014). Non-nutritive sweeteners are usually substituted in foods and beverages for a lower calorie intake. Many people counting calories will substitute foods and beverages containing non-nutritive sweeteners to be able to consume the foods that they enjoy, while still reaching their nutrition goals. Some examples of artificial sweeteners include acesulfame potassium, luo han guo, saccharin, and purified stevia leaf extracts ((Mayo Clinic Staff, 2023). These popular artificial sweeteners can be found in foods like baked goods, diet sodas, canned fruits, and flavored waters.
Impact of Sweeteners on Gut Microbiome
Both Natural and Artificial sweeteners have an impact on the human gut microbiome. The artificial sweeteners that are in most food and beverages can affect the gut microbiome by altering the microbial composition of the gut. The non-nutritive sweeteners formulation drives the development of glucose intolerance through the induction of compositional as well as functional alterations to intestinal microbiota (Ruiz-Ojeda et al, 2019). Non-nutritive sweeteners have been studied in detail due to their potential effects on possible insulin resistance, obesity, and inflammation. These studies have shown that the gut micro bacteria acts as a mediator of potential effects (Conz et al, 2023). Since non-nutritive sweeteners are synthetic, the gut micro bacteria must adjust to be able to metabolize the food and beverages being consumed with these sugars. When non-nutritive sweeteners enter the gut, they are used as a carbon source by certain strains of gut bacteria, which results in changes to their metabolic activity (Conz et al, 2023).
Unlike non-nutritive sweeteners, natural sweeteners can have a different effect on the human gut microbiome when consumed. Natural sweeteners, like stevia, have shown to have a potential benefit on the gut microbiome and human body overall. For example, stevia has shown antiglycemic action and antioxidant effects in adipose tissue and the vascular wall, reduced blood pressure levels and hepatic steatosis, stabilization of the atherosclerotic plaque, and ameliorates liver and kidney damage (Kasti et al, 2022). Steviol glycoside is the factor that gives stevia the super sweet taste. Steviol glycoside metabolism is dependent upon the microbiota, which breaks down glycosides into steviol that is then able to be absorbed by the host. In a study examining E. coli, researchers examined petri dishes containing non-nutritive sweeteners and natural sweeteners. To model the gut bacteria, the E. coli was diluted 1% and streaked across each petri dish of agar and then sweetener was added (Swift, 2019). The petri dishes were then placed in an incubator and were observed for four days, taking pictures of the dishes each day to observe the frequency of bacterial colonies across all of the available area (Swift, 2019). After the four days, the control petri dishes and the petri dish made with natural sweeteners showed a development of bacteria colonies, while the petri dish made with artificial sweeteners showed no development of bacteria colonies (Swift, 2019). These results tell us that artificial sweeteners inhibit the growth and development of E. Coli colonies while natural sweeteners allow for the growth and development to proceed. This information tells us that natural sweeteners can help with the development of the human gut microbiome while artificial sweeteners or non-nutritive sweeteners can have negative effects on the human gut microbiome (Swift, 2019). This knowledge is extremely useful for individuals trying to reduce their calorie intake as no negative effects were found with the consumption of natural sweeteners.
Examples of Sweeteners
There are many sweeteners that are being used in every-day lives, and eventually scientists will synthetically create many more. It is important to be familiar with a few of the important sweeteners and the effects that they have on the human gut. Aspartame is an extremely important sweetener that is found in many diet sodas and gums. Aspartame is a dipeptide consisting of aspartic acid and phenylalanine that has a carboxyl terminal group that becomes methylated (Ruiz-Ojeda et al, 2019). It is known to be approximately 200 times sweeter than sucrose and is required to be labeled, “contains aspartame (source of phenylalanine)” if being sold to consumers (Ruiz-Ojeda et al, 2019). When experimenting with the effects of aspartame, low doses were consumed by rats in a diet-induced obesity model. The rats were divided into four groups that all received different dosages of aspartame in their drinking water depending on their weight as well as differences in the fat percentages of their food. The results showed that rats that consumed aspartame had higher blood-sugar levels and changes in type of bacteria in the gut (Ruiz-Ojeda et al, 2019). It was also found that the aspartame was quickly broken down in the body and linked to certain fatty acids in the body (Ruiz-Ojeda et al, 2019). These results tell us that the consumption of aspartame should be monitored as too much consumption could lead to potential negative effects in the body.
Another important sweetener example found in our everyday lives is sucralose. Sucralose is found in a variety of foods like baked goods, frozen dairy desserts, and chewing gum. It is derived by the substitution of the three hydroxyl groups in sucrose and is approximately 320-1000 times sweeter than sucrose (Ruiz-Ojeda et al, 2019). In recent studies, rats were administered various amounts of sucralose over a twelve week period. The consumption of sucralose decreased the total number of anaerobic and aerobic bacteria, bifidobacteria, lactobacilli, Bacteroides, and Clostridium (Ruiz-Ojeda et al, 2019). The results produced modifications in the intestinal microbiota at 14 different taxonomic levels which was found to be related to inflammation within the host (Ruiz-Ojeda et al, 2019). This tells us more about how some synthetic sweeteners are able to slightly modify the gut microbiome and high consumption levels can be dangerous.
Social Disparities
Consuming a balanced diet is crucial for living a long and healthy life, but this is not often available to everyone. Socioeconomic inequalities lead to a variety of indifferences in diets among many people, not by choice. People with a lower socioeconomic status are more at risk to consume poorer diets, with lower fruit and vegetable intake, and more consumption of unhealthy snacks and artificially processed foods (Bolt-Evensen et al, 2018). In comparison, people with higher socioeconomic status tend to live longer and have reduced health problems due to availability of more healthy and natural foods (Bolt-Evensen et al, 2018). In a study conducted in Norway, researchers studied the frequency of consumption of sugar-sweetened beverages and artificially sweetened beverages in regards to socioeconomic groups (Bolt-Evensen et al, 2018). The study concluded that participants with high socioeconomic status were consuming less sugar-sweetened beverages, but not artificially sweetened beverages compared to those with lower socioeconomic status who consumed higher amounts of sugar-sweetened beverages (Bolt-Evensen et al, 2018). Researchers believe this could be due to relatively low prices on sugar-sweetened beverages and explains why people with lower socioeconomic status tend to live shorter lives than people with higher incomes. The availability of more nutritious foods and beverages is an important and overlooked factor for families in lower socioeconomic statuses. The foods consumed play an important role in an individuals gut microbiome and the consumption of less nourishing foods can affect the microbiome negatively.
Experiments
In a study conducted in December of 2023, researchers looked into the impact sweeteners have on the human gut microbiome. In the experiment conducted by Cedars-Sinai investigators, results showed artificial sweeteners are not benign for the microbiome of the gut (Mathur, 2024). To obtain these results, subjects were chosen from a small group of adults undergoing standard of care esophagogastroduodenoscopy without colon prep. The subjects were then asked to provide duodenal luminal aspirates and fasting blood samples to be analyzed. Stool samples were optional (Mathur, 2024). Scientists analyzed the subject samples with three different categories to be tested including non-aspartame non-sugar sweeteners, aspartame only, and controls. The results of these tests showed that compared to the controls within the study, there were significant differences in both stool and microbial diversity and composition in subjects who consumed both non-aspartame non-sugar sweeteners and aspartame alone (Mathur, 2024). Ruchi Mathur MD, who was a lead scientist in the study stated, “We found that the richness of the bacteria in the small bowel was less in those subjects consuming non-aspartame non-sugar sweeteners when compared to controls, whereas bacterial richness in those consuming aspartame was similar to control (Mathur, 2024).” This information tells us sweeteners are having an effect on the human gut microbiome and that it's important to dive deeper into what long term effects this can have to the body.
In another study, scientists looked into the short and long-term effects of non-caloric artificial sweeteners in humans. To test the long term effects, scientists conducted a clinical nutritional study with data collected from 381 non-diabetic individuals (Suez et al, 2014). The results showed a positive correlation between non-caloric artificial sweeteners consumption and several metabolic-syndrome-related parameters, including increased weight and waist-to-hip ratio, glycosylated hemoglobin and glucose tolerance test, higher fasting blood glucose, and elevated serum alanine aminotransferase (Suez et al, 2014). These results show the potential for imbalance of the gut microbiome which could contribute to glucose intolerance. To understand the effects of non-caloric artificial sweeteners in the short run, seven volunteers who normally do not consume non-caloric artificial sweeteners participated in a one-week study. On days 2-7 of the study, the participants consumed the maximal acceptable amount of commercial saccharin per the FDA, and were monitored daily for glucose measurements (Suez et al, 2014). The results showed in most of the individuals, there were significantly poorer glycaemic responses developed after 5-7 days of the FDA approved amount of non-caloric artificial sweeteners (Suez et al, 2014). This information provides evidence that non-caloric artificial sweeteners have an effect on the human gut microbiome in the short-run as well as the long-run. When consuming sugary foods and beverages, it is important to note the amount of artificial sweeteners in the product to make sure you are intaking the FDA approved amount.
Why or Why Not Sweeteners?
The debate on whether or not artificial sweeteners should be consumed by humans is still very much controversial. Research shows many pros and cons for and against the consumption of artificial sweetener substitutes. The FDA in the United States, only allows eight sugar substitutes to be used in produced foods and beverages (Mayo Clinic Staff, 2023). The amount of artificial sweeteners that should be consumed by a single person depends on the height and weight of the individual. Researchers suggest that individuals living with the rare disease, phenylketonuria, foods and drinks with aspartame can lead to serious health problems (Mayo Clinic Staff, 2023). Researchers also suggest that if you are suffering from a bowel disease, the use of artificial sweetener substitutes may cause a flare up of symptoms (Mayo Clinic Staff, 2023).
Throughout research and studies, it has been found that there are some positive effects that sweeteners can have on the human body. For people struggling with obesity, the use of sugar substitutes can help to manage weight loss in the short term due to the lower amount of calories found in artificial sweeteners. Sugar substitutes have also been found to lower your risk of getting tooth decay compared to the use of normal added sugars (Mayo Clinic Staff, 2023). Experiments have also shown that the use of sugar substitutes do not raise the levels of sugar in the blood (Mayo Clinic Staff, 2023). This is very beneficial for individuals because it gives them more flexibility in their diets, allowing for more sugary foods to be consumed if desired. Artificial sweeteners not raising the levels of sugar in the blood is even more beneficial for individuals with diabetes. People with diabetes are required to maintain a healthy blood-sugar level to survive, and artificial sweeteners can help them to be able to still enjoy sweet foods while maintaining a healthy blood-sugar level.
Though health agencies have clarified that artificial sweeteners do not cause any serious health problems, there have been some potential long-term effects when including sugar substitutes in your everyday diet (Mayo Clinic Staff, 2023). Research suggests that daily consumption of artificial sweeteners is linked to a higher risk of stroke, heart disease, and death overall (Mayo Clinic Staff, 2023). Certain sugar alcohols, like stevia and luo han guo, can cause bloating, gas, and diarrhea in some individuals, but the severity of these symptoms depends on the amount of the specific sugar alcohol consumed (Mayo Clinic Staff, 2023). At the end of the day, whether an individual chooses to consume artificial sweeteners or not is completely up to them. As more research continues, hopefully a definite solution will be found. If choosing to consume artificial sweeteners, it is important to consume the FDA’s recommended amount according to an individual's height and weight for the safest effects.
Conclusion
Though many researchers have been intrigued on the effects that sweeteners can have on the human gut microbiome, there is still so much information that is unknown. Researchers are able to run experiments to better understand any short-term effects, but this new research is still hard to fully understand in the long term. What makes this research complicated as well, is that no human’s gut microbiome is the same. The gut microbiome differs by what food and beverages are consumed by an individual. When looking at the research with E.Coli, we learned that natural sweeteners can help with the development of the gut microbiome, while artificial sweeteners can negatively impact the gut microbiome. Comparing these results to the other experiments looked at in this research paper, evidence shows that artificial sweeteners can have effects on the human gut microbiome. Though moderate amounts of artificial sweetener intake can be neutral for the body, trying to consume as little amounts of artificial sweeteners is the most beneficial for your body and for your gut health.
References
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[2] Thursby, E. and Juge, N. (2017) Introduction to the human gut microbiota, The Biochemical journal. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433529/.
[3] Bolt-Evensen, K. et al. (2018) Consumption of sugar-sweetened beverages and artificially sweetened beverages from childhood to adulthood in relation to socioeconomic status – 15 years follow-up in Norway - international journal of behavioral nutrition and physical activity, SpringerLink. Available at: https://link.springer.com/article/10.1186/s12966-018-0646-8.
[4] Neacsu, N.A. and Madar, A. (2014) ARTIFICIAL SWEETENERS VERSUS NATURAL SWEETENERS , View of artificial sweeteners versus natural sweeteners. Available at: https://webbut.unitbv.ro/index.php/Series_V/article/view/4911/3800.
[5] Conz, A., Salmona, M. and Diomede, L. (2023) Effect of non-nutritive sweeteners on the gut microbiota, MDPI. Available at: https://www.mdpi.com/2072-6643/15/8/1869.
[6] Mathur, R. (2024) Research alert: Artificial sweeteners significantly alter the small bowel microbiome. Available at: https://www.cedars-sinai.org/newsroom/research-alert-artificial-sweeteners-significantly-alter-the-small-bowel-microbiome/#:~:text=We%20found%20that%20the%20richness,Cedars%2DSinai%20and%20the%20lead.
[7] Suez, J. et al. (2014) Artificial sweeteners induce glucose intolerance by altering the gut microbiota, Nature News. Available at: https://www.nature.com/articles/nature13793.
[8] Mayo Clinic Staff (2023) Pros and cons of artificial sweeteners, Mayo Clinic. Available at: https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/artificial-sweeteners/art-20046936#:~:text=In%20general%2C%20artificial%20sweeteners%20are,lead%20to%20serious%20health%20problems.
[9] Kasti, A.N. et al. (2022a) The effects of stevia consumption on gut bacteria: Friend or foe?, MDPI. Available at: https://www.mdpi.com/2076-2607/10/4/744.
[10] Swift, J. (2019) The effects of natural and artificial sweeteners on gut bacteria as modeled by E. coli., NASA/ADS. Available at: https://ui.adsabs.harvard.edu/abs/2019AGUFMED41B1088S/abstract.
