These days, grocery store shelves are piled high with products containing artificial, or non-nutritive, sweeteners.
Although the United States Food and Drug Administration (FDA) has approved some of them, experts are still discussing their effects on the human body.
Some, including the companies that produce these sweeteners, believe they are harmless. Others think they might have a subtle influence on our metabolic health.
At this stage, no one has fully unraveled the details.
Over recent years, some scientists have started focusing on how they might influence your gut microbiome — the trillions of bacteria and other microbes that live in your gut.
At ZOE, we know that harboring a thriving, diverse community of these bugs is associated with positive health outcomes. We also know that certain “bad” bugs are linked to negative health outcomes.
Before diving into the details, we should clarify that scientists are still collecting evidence. So far, there are no hard and fast conclusions about artificial sweeteners and the gut microbiome.
First up, what are artificial sweeteners?
Introducing artificial sweeteners
These compounds are designed to be sweet but contain few or no calories.
Manufacturers add them to all manner of foods, from cakes to cereals and from breads to chili sauce.
Currently, the FDA has approved six artificial sweeteners:
acesulfame potassium (Ace-K)
They vary in sweetness from 200 times the sweetness of table sugar to 20,000 times as sweet.
Although they taste sweet, they’re all chemically different. Food manufacturers often use a combination of sweeteners in their products to improve the overall flavor.
Saccharine, which was first discovered in 1879, is the oldest on this list. Initially, it was used as a medicinal product for people with type 2 diabetes.
However, when World War 2 caused sugar shortages, it became a sweet treat for the population at large.
It wasn’t until the 80s and 90s that scientists discovered aspartame, Ace-K, and sucralose. From then, artificial sweeteners really took off.
What’s the drama?
Because we consume artificial sweeteners so regularly, scientists need to understand if there are any health concerns.
For instance, from 2005–2009, by volume, 15% of the food purchased in the U.S. contained artificial sweeteners.
Over the years, controversy has plagued these sweet compounds.
Glucose control refers to your body’s ability to keep blood sugar levels within safe boundaries.
If there’s too much sugar in your blood for long periods of time, it can damage your health. If there’s too little, your body won’t have enough energy to run, which is also dangerous.
We’ll talk a little more about glucose control later on.
To make matters more complex, the food industry has muddied the water. After all, artificial sweeteners are big business. By 2025, experts expect the market to be worth $20.6 billion.
And where there’s oodles of cash, there’s oodles of intrigue.
For instance, one study reviewed research into the effects of artificial sweeteners on weight.
The authors found that when studies are sponsored by companies that make artificial sweeteners, they are more likely to find these compounds effective for weight loss. Quelle surprise.
They also found that industry-sponsored papers were more likely to put a positive “spin” on the findings regardless of the study's outcome.
The authors provide a telling example:
“[A]mong a sample of studies of aspartame, 100% of the industry-sponsored studies concluded that aspartame was safe, and 92% of the independently funded studies identified adverse effects of aspartame consumption.”
We’re not going to get into this sticky business here, though. Instead, we’ll focus on whether artificial sweeteners affect your gut bacteria.
The gut microbiome
As you read this, trillions of microbes are busy at work in your gut. These bugs play an important role in helping you digest food — but there’s more to them than that.
Studies have linked a thriving, diverse microbiome to better health outcomes. But not all gut bugs are equal.
ZOE’s research has identified 15 “good” bugs associated with positive health outcomes and 15 “bad” bugs linked to poor health outcomes.
Experts believe a healthy, balanced gut microbiome is vital for maintaining good health.
Your gut bacteria shift over time, and food can influence these shifts.
For instance, scientists have shown that people who stick to a Mediterranean diet have higher numbers of “good” bacteria than those who follow it less closely.
Historically, experts considered artificial sweeteners to be inert and, therefore, unable to affect your body.
This is because your digestive enzymes can’t break down artificial sweeteners, so most of them exit your body in poop or urine, unchanged.
More recently, though, scientists have started to wonder whether these sweeteners interact with gut bacteria on their way through your gut.
What does the science say?
Much of the research into artificial sweeteners and gut bacteria has focused on laboratory and animal studies.
For instance, in one study, scientists fed Splenda to rats for 12 weeks. Splenda is an artificial sweetener that contains sucralose. The authors concluded that, after 12 weeks, the rats had fewer beneficial gut bacteria.
In another study, scientists fed Ace-K to rats for 4 weeks. They also noted changes in gut bacteria — but the shifts differed between male and female rats.
Interestingly, male rats experienced weight gain when taking Ace-K, but the females did not.
In fact, several animal studies have identified changes in gut bacteria after consuming artificial sweeteners. But what happens inside a rat doesn’t always match up with what happens inside a human.
Also, as ZOE’s Senior Nutrition Scientist and Registered Dietitian, Dr. Emily Leeming explains:
“The amount of artificial sweeteners they give mice is usually in far larger quantities relative to body size than what we would normally consume as humans. So, it can be hard to draw strong conclusions from this.”
Evidence in humans
When we look at human research, the evidence gets a little patchier. These studies tend to include just a handful of participants and last a relatively short time.
And the results are conflicting.
Some human studies haven’t identified any effect of artificial sweeteners on gut bacteria. For instance, one study recruited 34 healthy individuals and ran for 7 days.
Half of the participants received sucralose; the other half received a placebo.
At the end of the trial, the authors found no overall differences in glucose control, insulin resistance, or the gut microbiome.
Another study looked at high doses of saccharin in humans and mice. After 2 weeks, the researchers concluded that saccharin did not impact the gut bacteria of either mice or humans.
Similarly, a study that involved two 14-day exposures to sucralose and aspartame also concluded that there was no change in participants’ gut microbiomes.
Some researchers have identified shifts in gut bacteria in response to artificial sweeteners.
One study, which ran tests on animals and humans, did find changes in gut bacteria related to artificial sweeteners — but it’s complicated.
They followed seven people who didn’t usually consume artificial sweeteners for 1 week. On days 2 through 7, they consumed the FDA’s maximum acceptable daily saccharin intake.
They found that four of the seven people had poorer blood sugar responses on days 5–7 compared with days 1–4.
The authors call them “responders.” However, there was no change in the other three people, which they refer to as “non-responders.”
The scientists analyzed the gut microbiome of the four responders before and after consuming saccharin. They found these individuals had markedly different gut microbiomes than the three non-responders even before taking saccharin.
Also, at the end of the 7-day study, the gut microbiome of non-responders had not changed, whereas the responders’ gut microbiomes changed significantly over the course of the study.
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The scientists didn’t stop there. Next, they transferred poop from responders into germ-free mice — these are animals that scientists have raised in such a way that they don’t have a gut microbiome.
They found that when they transferred stool from day 7 — after the saccharin — the mice also developed a poorer response to glucose.
However, when they transferred stool from the same responder, but from day 1 — before the saccharin — the mice didn’t develop glucose intolerance.
In contrast, when they transferred poop from non-responders into germ-free mice, whether from day 1 or 7, the mice had normal glucose tolerance.
So, overall, some people were sensitive to saccharin: Their gut microbiome was different to start with, and it changed during the trial. This was linked to a poorer blood sugar response.
Other people, though, were not affected at all.
Perhaps this helps explain why the evidence is so patchy: Whether our gut bacteria shifts in response to artificial sweeteners may depend on our initial gut microbiome.
And as we all have a distinct gut microbiome, there could be a huge variety in how artificial sweeteners affect our individual gut bugs.
At ZOE, we know everyone responds differently to food. Even identical twins have different blood sugar responses to food. That’s why we believe personalized nutrition is the future — you need to eat the right way for your body.
Following on from the research outlined above, the same group of scientists ran another study on 120 people who rarely consumed sweeteners.
They gave participants sachets with saccharin, sucralose, aspartame, stevia, or a placebo.
Each sweetener had measurable and distinct effects on the gut and oral microbiome. The scientists also showed that saccharin and sucralose negatively affected participants’ blood sugar responses.
Once again, the researchers found that these effects depended on the participants’ gut microbiome at the start of the study — there were responders and non-responders.
As in the previous study, when responders’ poop was transferred into germ-free mice, the animals' blood sugar responses became poorer.
Talking about the study, ZOE’s Chief Scientist Dr. Sarah Berry says:
“This study confirms what has been previously shown in mice in relation to the impact of sweeteners on the microbiome and adds to the body of evidence that some sweeteners have an unfavorable effect on blood glucose control.”
Dr. Berry would also like to see longer studies to understand whether “these unfavorable effects are sustained after long-term intake and if there are also subsequent effects on other health outcomes in the long term, such as blood pressure, insulin resistance, and body weight.”
So, in conclusion, we don’t know for sure whether artificial sweeteners influence gut bacteria. But it’s looking likely.
That’s not the zinger of an ending we’d hoped, but that’s the state of play at the moment: A lot of animal studies identify changes in the gut microbiome in response to sweeteners, but human studies are few and far between.
Although scientists are likely to continue investigating this question, there are stumbling blocks to contend with.
One challenge is finding people who don’t consume artificial sweeteners. Food manufacturers add them to an increasingly wide range of foods.
Without people who rarely eat them, it’s difficult to run experiments to assess their effects in isolation.
Also, as the world of the gut microbiome is slowly dissected, its complexity is revealed.
Trillions of microorganisms interact with each other, our bodies, and the food we eat. This produces a nearly infinite range of variables.
The picture will undoubtedly grow clearer, but we have barely left the starting blocks.
Artificial sweeteners: History and new concepts on inflammation. Frontiers in Nutrition. (2021). https://www.frontiersin.org/articles/10.3389/fnut.2021.746247/full
Artificial sweeteners a place in the field of functional foods? Focus on obesity and related metabolic disorders. Current Opinion in Clinical Nutrition and Metabolic Care. (2012). https://journals.lww.com/co-clinicalnutrition/Abstract/2012/11000/Artificial_sweeteners__a_place_in_the_field_of.13.aspx
Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. (2014). https://www.nature.com/articles/nature13793
Gut microbiota bacterial species associated with Mediterranean diet-related food groups in a northern Spanish population. Nutrients. (2021). https://www.mdpi.com/2072-6643/13/2/636/htm
High-intensity sweeteners. (2017). https://www.fda.gov/food/food-additives-petitions/high-intensity-sweeteners
High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome. (2021). https://link.springer.com/article/10.1186/s40168-020-00976-w
Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PLOS One. (2014). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109841
Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. (2022). https://www.sciencedirect.com/science/article/pii/S0092867422009199
Relationship between research outcomes and risk of bias, study sponsorship, and author financial conflicts of interest in reviews of the effects of artificially sweetened beverages on weight outcomes: A systematic review of reviews. PLOS One. (2016). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162198
Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. British Journal of Nutrition. (2019). https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/shortterm-impact-of-sucralose-consumption-on-the-metabolic-response-and-gut-microbiome-of-healthy-adults/BF3E70C09C5514E4078DB3ED3E8D39B3
Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Journal of Toxicology and Environmental Health. (2008). https://pubmed.ncbi.nlm.nih.gov/18800291/
Sugar substitutes market by type, composition, application, and region - global forecast to 2025. (n.d.). https://www.marketsandmarkets.com/Market-Reports/sugar-substitute-market-1134.html
The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLOS One. (2017). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178426
The effects of non-nutritive artificial sweeteners, aspartame and sucralose, on the gut microbiome in healthy adults: Secondary outcomes of a randomized double-blinded crossover clinical trial. Nutrients. (2020). https://www.mdpi.com/2072-6643/12/11/3408/htm
Trends in the consumption of low-calorie sweeteners. Physiology & Behavior. (2017). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578610/
Use of caloric and noncaloric sweeteners in U.S. consumer packaged foods, 2005-2009. Journal of the Academy of Nutrition and Dietetics. https://pubmed.ncbi.nlm.nih.gov/23102182/