GUT CHECK: Low-Calorie Sweeteners and the Gut Microbiome

We’re back again with another edition of Gut Check, our series on the relationship between food and the gut microbiome. So far, we’ve taken a closer look at how whole grains, fiber, and fermented foods affect our gut microbes. In this article we’re taking a closer look at low-calorie sweeteners (LCSs) and the growing body of research on their connection to our microbial communities.

LCSs (sometimes referred to as non-nutritive sweeteners, high-intensity sweeteners, artificial sweeteners or sugar substitutes) provide sweetness without adding a significant amount of calories. They have a long history of safe use in a variety of foods and beverages, ranging from soft drinks to candy to tabletop sweeteners. In the U.S., the most common LCSs are acesulfame potassium (ace-K), aspartame, monk fruit, saccharin, stevia and sucralose.

LCSs are some of the most studied and reviewed ingredients in the world today. And yet, research on their relationship to the gut microbiome is very much in its infancy.

Most LCSs are not metabolized by our digestive enzymes, so they travel through the digestive system intact and pass out of the body unchanged. Because of this, scientists have long thought they have no effects on the body. However, recent research has revealed that some LCSs may influence the bacteria in our gut.

Most of these studies have been done in animal models and have shown wide-ranging results—from reductions in total bacterial count to increases in short-chain fatty acids, which are made by gut bacteria and are thought to be beneficial for gut health. The translation of these results to humans can be tricky and, in many cases, it’s just plain impractical. A primary reason? Lab animals are often genetically identical to each other and live their lives in the same environments, while in humans the microbiome is reflective of widely variable lifestyle habits and genetic differences.

So when it comes to studies in humans, things get a lot more complex. It’s much more difficult to control and/or accurately measure food and beverage intake in people than it is in animals. We tend to have more diverse and variable diets and, unlike lab animals, we don’t usually rely on researchers to provide all of our meals and snacks.

Intentionally or unintentionally, we’re prone to inaccurately reporting our dietary intake, which makes assessment of food intake very tricky. This can be avoided if researchers control all of the foods and beverages that research participants eat and drink (called a controlled feeding study), but they’re very expensive and place an added burden on participants, so they aren’t often done.

One tiny study from 2014 attempted to classify the effects of saccharin on glucose tolerance and the gut microbiome by having human research participants consume the acceptable daily intake (ADI) of saccharin for one week (but didn’t otherwise control their diet). Only four of the seven volunteers showed changes in glucose response and the profile of their gut microbes, while the other three showed none.

The researchers then transplanted the responders’ microbiota into mice, which also exhibited changes in their glucose response. These results suggest that the gut microbiome may be involved in how our body responds to LCSs but very clearly demonstrate that not all individuals are affected equally by LCS consumption. The response likely depends on a person’s microbial profile at baseline, which is heavily influenced by genetics and the environments we live in, along with our habitual LCS consumption.

Another very small study in humans compared the microbial profiles of aspartame and ace-K consumers and non-consumers. These two groups didn’t differ in the relative abundance of gut bacteria, which is a measure of the amount of a specific type of bacteria that’s usually expressed as a percentage of the total population of bacteria. The larger the percentage, the more real estate that microbe occupies in the gut. More than 90 percent of the bacterial species in the gut come from just two subgroups: Bacteroidetes and Firmicutes.

However, the diversity of bacteria differed between groups. Having a diverse microbiome is generally thought to be indicative of a “healthy” gut. Because relative abundance was the same between groups, it’s likely that the differences in diversity were driven by small groups of more rare bacteria.

Researchers dove a little deeper to look at the functional capabilities of the microbes that were present and found no differences, meaning that there weren’t any outward, noticeable alterations in metabolism between groups. In a nutshell, even though distinct bacteria were present in each group (in small numbers), it probably didn’t matter in the big picture.

So far, this is about as much scientific information as we have when it comes to how LCSs affect our gut microbes. Clearly, more research needs to be done on this emerging issue, and major limitations abound.

Different types of LCSs are metabolized differently, so we can’t make broad statements about how all LCSs affect the microbiome. Take aspartame, for example. Because it’s digested in the small intestine, it’s unlikely that intact aspartame reaches gut microbes, which predominantly cluster at the end of the digestive tract. Therefore, it’s unclear how aspartame would affect most of the gut microbiota.

Other types of LCSs (like sucralose) pass through the digestive tract mostly unmetabolized. We don’t know how — or if — these intact compounds might influence microbes before they’re excreted. And in the case of stevia, gut microbes are directly involved in its metabolism: They snip off glucose sections from the stevia molecule, which allows it to be absorbed into the bloodstream. However, it’s not clear how this might affect the bacterial community or its functions.

There are also huge differences in the dose of LCSs that researchers use in these kinds of studies, which can range from the ADI (which is much, much more than what most people consume) on down to zero, which makes it difficult to compare results between studies.

Perhaps the biggest caveat of them all is that a great deal of research is still needed to identify a microbiome profile and degree of diversity considered to be optimal in populations and in individuals. If we can’t pinpoint what’s considered to be a “healthy” gut, it’s pretty tough to give any food a thumbs-up or -down.

It’s far too soon to know how LCSs impact the gut microbiome, but you can bet that we’ll continue to learn more as research continues.

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