Let's unpack some research | 10 min. read
Artificial sweeteners are nothing new to the food and beverage industry. They have been pushed as a weight loss and anti-diabetes replacement for regular, sugar-sweetened products. With all the ‘diet’ options out there employing artificial sweeteners, not to mention these additives being snuck into tons of foods from yogurt to salad dressing, it’s important that we monitor and evaluate how these sweeteners affect our bodies.
You might be craving an answer to all your questions about non-sugar sweeteners, so we’re here to help. We’ve done all the research and come up with some answers for you, from how artificial sweeteners pass through the body, to how they affect gut microbiota, glucose tolerance, and body weight, and putting this all together to understand what it actually means for your health.
Just like how a diet coke may satisfy your sweet tooth, we hope that this article satisfies all your curiosities on the subject of sweeteners and gut health. So… are you ready to put your scientist hat on and do some investigating with us?
What are Artificial Sweeteners?
Some sugar substitutes with their chemical structure and a common food product that they are found in. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363527/.
Artificial sweeteners are products created to mimic sugar. They are low in calories and generally have more potent sweetness, meaning you can use less of them but still enjoy a sugary flavour. There are lots of different types of artificial sugars: aspartame, acesulfame K, saccharin, sucralose, and sugar alcohols like maltitol, xylitol, isomalt, and sorbitol are just some of the most popular ones. Natural sweeteners such as stevia are also placed in the sugar replacement category. The list goes on and on, which can make the prospect of figuring out how to manage your diet according to the current science a daunting task.
The stevia plant and powder. Retrieved from https://www.livescience.com/39601-stevia-facts-safety.html.
There’s lots of research out there on processed foods and sugars like high-fructose corn syrup, sucrose, and glucose, among others. Science has a solid understanding of the dangers of these products and how they work in the body. However, when it comes to other sweeteners like aspartame and stevia, there’s a lot more unknowns. One of the most prominent inquiries is what impact artificial sweeteners have on gut health. To address this inquiry, we have to consider the role of metabolism for diet and health.
How are Sweeteners Digested?
Metabolism is the process of how food is turned into energy for cells. This also creates byproducts, known as metabolites, that promote gut health through countless properties such as controlling appetite, inflammation, cholesterol levels, heart and bone health, and many other processes.
There are various types of metabolic functions throughout the body, but one that is at the core of sugar consumption is carbohydrate metabolism, since, after all, sugar is just a type of carbohydrate. The smallest carb, the glucose molecule, is an essential part of life, playing key roles in biochemical reactions that feed cells, help them grow, and allow them to execute functions such as regulating blood sugar levels. But this begs the question--if artificial sweeteners aren’t made up of real sugar molecules, how are they processed?
That is indeed a very good question--one that researchers are still trying to answer. It appears that artificial sweeteners are metabolized in different ways, with different effects on gut bacteria and metabolite production. Some sweeteners go right through the digestive tract and are excreted when you use the washroom, but others interact more directly with gut bacteria in the colon. By virtue of this fact, some artificial sweeteners have an effect on the gut microbiome and thus intestinal health. For instance, sugar alcohols, also known as polyols, can be absorbed into the bloodstream from the small intestine or make it all the way to the large intestine before being processed by gut bacteria . In fact, sugar alcohols such as isomalt, maltitol, lactitol, and xylitol have been shown to increase populations of Bifidobacteria in the human gut, which can have some implications for health by causing an imbalance in the gut microbiome . Sugar alcohols are known to trigger symptoms such as diarrhea, which is already a common symptom that impacts nearly 80% of people with inflammatory bowel disease [2,3]. How this works mechanistically is yet to be determined, but knowing that these sweeteners can trigger laxative effects is enough for scientists to advise that people with inflammatory bowel disease or irritable bowel syndrome avoid sugar alcohols.
Many studies have looked at the effects of artificial sweetener consumption, with the majority being done on rodents. While animal studies aren’t a clear indicator of how things work in humans, they can still hint at issues in our health. There are a smaller number of studies done on humans, but certainly more are required to make stronger claims about the effects of artificial sweeteners on human health and disease. With that in mind, let’s discuss what animal studies have revealed about the impact of artificial sweeteners on gut health.
Sweeteners Have An Effect on Gut Microbiota
As a core aspect of human health, there needs to be a diverse and balanced population of gut microbiota. But given the fact that there are so many factors that affect gut bacteria, it comes as no surprise that sweeteners could be one such factor.
How this works is another story that is still being written, but regardless, we’ve found plenty of research on how non-sugar sweeteners affect gut microbiota. Just because most artificial sweeteners aren’t metabolized by the human body like sugar molecules are doesn’t mean they have no effect, since they interact with gut microbiota in many cases . Microbiome science can be a heavy and complicated topic for anyone to digest (pun intended), so we’ve distilled the main points from fascinating research on this topic in a more accessible way. The bottom line is that aspartame, acesulfame K, saccharin, sucralose, and stevia can all cause changes in the composition of gut bacteria. Here’s some of the research currently out there on this:
Comparing how acesulfame K affects male and female mice
A study compared how male and female mice reacted after consuming acesulfame K for one month. The conclusion was that acesulfame K can affect the composition of the gut microbiome and lead to challenges with energy balance in the body and trigger inflammatory responses.
More specifically, both male and female mice had changes in gut microbiota populations, including an increase in bacteria linked to energy metabolism, but only male mice experienced changes in body weight. Having high amounts of bacteria like Bacteroides and Anaerostipes is actually linked to obesity, and this sort of change occurred in the gut microbiome of male mice after acesulfame K consumption. There were different changes in gut bacteria observed by sex, but overall, consumption of acesfulfame K resulted in more genes related to chronic inflammation. Chronic inflammation may occur due to changes in gut bacterial composition, increasing inflammatory chemicals and impeding metabolites.
Other research has linked the development of colitis in mice to Bacteroides species such as B. thetaiotaomicron and B. vulgatus, and Sutterella to increased inflammation and the ability to influence the person’s immune system. 
Studying the effects of saccharin on different animals
Another study found that the sweetener saccharin led to changes in gut microbiota diversity in mice, rats, piglets, and humans across different studies. In one case, the changes were associated with liver inflammation triggered by saccharin consumption in mice . In the same vein, scientists found that mice who ate saccharin had genetically and functionally different microbiomes than a normal mouse and that antibiotics contributed further to glucose intolerance onset by saccharin consumption .
The impact of sucralose on rats
A 12-week study on the effect of sucralose consumption on the microbiome has been conducted. Scientists discovered a gradual decrease in diversity and balance of the gut bacteria of rats. They found that beneficial gut bacteria such as Bifidobacteria, Lactobacilli, and Bacteroides were diminished whereas Enterobacteria, which can be bad for gut health, were allowed to grow and reproduce more than usual .
There’s also lots that we can discuss from results on humans
Some studies have suggested that there is no major negative effect of sweeteners on gut health, but they don’t tell the whole story.
Aspartame is quickly broken down into products that are absorbed before they can get into contact with bacteria in the colon, so it’s hard to accurately evaluate how this sweetener affects our gut microbiome .
Erythritol seems to have insignificant effects on human gut microbiota. Many tests on its toxicity, cancer-causing capacity, and reproductive risks proved that it’s safe as well .
A clinical trial compared how volunteers’ bodies reacted to either isomalt or sucrose, and results showed that isomalt supports gut microbiota because once it’s fermented in the colon by bacteria, it can increase the population of beneficial Bifidobacteria. This can be a positive for colon health. These effects on Bifidobacteria populations have also been demonstrated with consumption of other sugar alcohols like xylitol, lactitol, and maltitol, but as mentioned, they also tend to trigger diarrhea and more gas and are not recommended for inflammatory bowel disease patients .
Lactitol promotes the production of the anti-inflammatory short chain fatty acid butyrate and IgA antibody secretion, which defends the body against infections .
While research has pointed to aspartame and sucralose as safe, with no measurable effect on gut bacteria or their byproducts, these findings were quite short-term: the randomized, double-blinded crossover clinical trial (can’t get anymore unbiased and rigorous than that) only looked at 2 weeks’ worth of regular artificial sweetener intake in humans. There aren’t many other studies out there like this; more research with longer timelines, different dosages of sweeteners, and comparisons to regular sugars should be conducted before we make any solid conclusions . Scientists argue that short-term studies hide the impact of extended, cumulative use of artificial sweeteners, so more observational, interventional, epidemiological studies must be conducted to see the bigger picture of what’s really going on. We also have to start comparing artificial sweeteners directly to sugar sweeteners rather than healthy participants not consuming any type of sweetener.
Studies all find different things in terms of the impact on the gut microbiome and what effect that has, but a solid takeaway that scientists are pulling from this collection of findings is that healthy people have a “core microbiome” with similar characteristics for processing sugars that can be affected by artificial sweetener consumption. This has the impact of shifting the body to a state of improper carbohydrate metabolism that can lead to issues such as prediabetes. It’s thought that even low amounts of artificial sweeteners regularly consumed long-term can cause increased predisposition to metabolic disorders. 
Effects on Glucose Tolerance and Body Weight
First off, what is glucose intolerance? Considered to be an indicator of prediabetes, glucose intolerance refers to metabolic disorders that are characterized by challenges with processing glucose, meaning that there can be abnormally high blood sugar levels. It’s thought that this result is mediated by changes in the composition and thus functions of gut microbiota (yes, gut bacteria can even be involved in glucose processing). This relates back to body weight control as well. The bottom line for studies on this topic is that sweeteners can encourage glucose intolerance. Here’s some evidence to demonstrate this point:
In mice, by changing the composition and functions of gut microbiota, research shows that artificial sweeteners can lead to glucose intolerance. This leaves them at higher risk of developing a metabolic disease such as diabetes, an effect that is mirrored in tests on healthy human participants. In this study, saccharin induced changes to a diverse array of gut bacteria, which impacted how the microbiome functions, affecting metabolic processes in mice and directly inhibiting proper blood sugar control in humans. 
This research suggested that all humans have unique responses to artificial sweeteners in the short- and long-term, as we all have a different microbiome makeup. They also found that two bacterial profiles (more Bacteroides and less Clostridiales) linked to type 2 diabetes occurred in humans following artificial sweetener use. 
Given that these were short-term studies on healthy human volunteers who didn’t normally have artificial sweeteners in any form, it’s actually a meaningful result that participants developed issues processing glucose properly in such a short time. However, more studies that also utilize the appropriate recommended daily intake of artificial sweeteners and that study these effects on a longer timeline are needed to figure out what this means for long-term saccharin consumers.
Despite one motivating factor for use of alternative sweeteners being to manage weight through reducing sugar intake, many studies on rats and mice have found the opposite; saccharin, acesulfame K, stevia, and aspartame have all been linked to weight gain and/or obesity. These findings only add to other research that has shown that saccharin and aspartame can impede blood sugar control and trigger issues with insulin release. 
What Are the Implications of Changes to Microbiome Composition, Diversity, and Balance?
With all the mention of the types of bacteria that are affected by artificial sweeteners, we can’t finish off without tying it all back to what kinds of physiological consequences this may cause. For starters, when it comes to intestinal health, changing the makeup of the microbiome is an important factor related to the development of inflammatory bowel disease . However, although we have some indications of which sweeteners lead to changes in gut bacteria, the mechanisms by which these processes are affected and lead to poor health outcomes are yet to be determined.
So while a lot of research is saying that sweeteners like aspartame are safe, there’s also enough evidence to point to risks, from short-term issues like laxative effects to long-term challenges with managing glucose metabolism and all the health conditions that can come with that. At this point, there’s no need to be afraid of some sucralose here and some xylitol there, but if you have inflammatory bowel disease or are worried about how diet may be affecting your gut microbiome, try to avoid artificial sweeteners. As you can probably tell after reading this entire synthesis of various research studies, the science is evolving but there’s a lot of research pointing at effects on gut bacteria.
As passionate microbiome lovers, we always advocate for the importance of a strong army of bacteria in the gut. Despite all the research accumulating over the years, it’s still early days of these investigations into artificial and natural sweeteners--on gut health and beyond--so we encourage you to keep following this topic as it continues to grow! You have the ability to decide what makes the most sense for your health, which can be empowering even when there is uncertainty about how your body will react. You are an expert on your own body, so continue to be curious, ask questions, and do your research--this will help you make the most informed and confident decisions for you and your gut health. Speaking of making informed decisions, one great way to kickstart the process of navigating and monitoring your diet and microbiome health is through Phyla’s health app and microbiome test kit. With this test, you’ll get an in-depth analysis of your gut bacteria, possibly including those mentioned in this article. There’s no better way to monitor your gut health from the comfort of your home!