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Healthy Sweeteners and the Gut-Brain Axis

Here's how sweeteners can affect your mental state via the gut-brain axis.

Key points

  • Sugar and some artificial sweeteners can negatively affect your gut microbes.
  • Some natural sugar substitutes can act as prebiotics.
  • The prebiotic effect of oligosaccharides can improve beneficial gut microbes.
  • An improved gut microbiota can boost mood and cognition.

A human being has a natural desire to have more of a good thing than he needs. —Mark Twain

Can a sweetener be healthy?
Source: vitaliymateha/iStock

Sugar is ridiculously delicious, but it hides a depressing secret. Sugar disturbs the gut microbes that normally protect us against metabolic disorders, a doorway to obesity and diabetes. Lately, we’ve learned that due to the gut-brain connection, sugar intake can also lead to depression. That has convinced many people to skip the sugar and go for a low-calorie substitute. Sadly, as discussed in my last article, new research finds that some artificial sweeteners raise insulin levels and disrupt gut microbes just as much as the sugar they are replacing.

So, for people with metabolic syndrome or insulin resistance, sugar is out, and artificial sweeteners are suspect. What options are left?

Natural Sweeteners

In this article, we’ll look at some alternative sweeteners that are all-natural and, as a bonus, are also healthy for you. First, we need some definitions. There are several categories of natural sweeteners, and we’ll look at each of them.

  • Natural nonnutritive super sweeteners include thaumatin, stevia, glycyrrhizin, and monk fruit.
  • Nutritive sweeteners, or sugar alcohols, include erythritol, xylitol, and maltitol.
  • Oligosaccharides include inulin, fructooligosaccharide (FOS), galactooligosaccharides (GOS), and xylooligosaccharides (XOS).

Super Sweeteners

Natural sugar substitutes, such as stevia and monk fruit, are hundreds of times sweeter than sucrose. That means you only consume a fraction of the amount, making them essentially zero-calorie. Better yet, they may enhance the microbiota—but in such small doses, probably not much.

Monk fruit is generally lightly refined, but stevia requires more processing to differentiate the two active sugars in the plant: stevioside and rebaudioside. The first sugar has bitterness associated with it, and so rebaudioside is the more popular of the two.

The amounts you need to use are silly, though. For a teaspoon of sugar, an equivalent amount of monk fruit would be a tiny teaspoon 200 times smaller. So typically, these super sweeteners are compounded with sugar alcohol to give them the equivalent bulk of sugar.

Sugar Alcohols

Sugar alcohols are natural sweeteners derived from fruits and berries. They include erythritol, xylitol, mannitol, maltitol, and sorbitol. Some, such as maltitol and xylitol, can reach the colon and feed microbes. That makes them prebiotics, supporting such beneficial bacteria as bifidobacteria, which can improve mood and cognition via the gut-brain axis.

Erythritol is quite popular with makers of sugar substitutes. Most of it gets absorbed in the small intestines and then excreted in the urine, so it’s not much of a prebiotic, but it is essentially calorie-free. It is often the major component of stevia and monk fruit sweeteners.

A caveat: although xylitol has a good reputation for killing oral pathogens (thus its ubiquity in chewing gum), it can be dangerous for dogs, so it may be best for dog owners to avoid this one.


Simple sugars like glucose and fructose are monosaccharides. There are a mystifyingly large number of them; apparently, mother nature can’t get enough. They are the basic building blocks of other, more complex sugars.

Disaccharides have two monosaccharides stuck together. Table sugar is an example. Technically called sucrose, table sugar is composed of a glucose molecule glued to a fructose molecule. It is the most popular of the disaccharides. Much of it comes from sugar cane, the largest crop in the world and a sobering measure of our decadence. Other disaccharides include lactose (glucose and galactose) and maltose (two of glucose).

Oligosaccharides, from the Latin for “a few sugars,” have three or more sugar links. They are also known as fiber, and they are all more or less sweet tasting. For some people, fiber conjures up tree bark—and they aren’t completely wrong. Fibers are the sturdy building blocks of plants capable of growing 300-foot redwood trees. A pretty impressive showing for simple chains of sugar.

Oligosaccharides are composed of a mixture of monosaccharides, including glucose, fructose, mannose, galactose, lactose, and more. That means there are millions of different oligosaccharides of varying lengths and compositions.

Plants assemble these structural sugars using enzymes, and generally, there is a specialized enzyme that can glue any two given sugars together. Likewise, there is another enzyme to cleave a sugar chain between any two given sugars.

Humans don’t produce most of these enzymes, but microbes do. They are experts at eking out the last erg of energy from a sugar chain, link by link. Since oligosaccharides can’t be broken down by our stomach acids or pancreatic enzymes, they make it all the way to the colon, where they are happily digested by expert gut microbes. In turn, the microbes create fatty acids, like butyrate, that nourish and heal the gut lining. And that is how fiber contributes to a healthy gut and why they are called prebiotics: “an indigestible food ingredient that promotes the growth of beneficial microorganisms.” This sugar doesn’t just help the medicine go down; it is the medicine.

In addition, oligosaccharides like fructooligosaccharide (FOS) and galactooligosaccharide (GOS) have been found to have psychobiotic properties, namely the ability to encourage gut microbes to generate metabolites that act as antidepressants.


These sugars are not for everyone. People with IBS or Crohn’s flare-ups should be cautious: Oligosaccharides can exacerbate the situation. Many of these people are on a low FODMAP diet and must forgo these exact sugars: FODMAP stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (sugar alcohols). This is a depressing list for those who crave sweets.

Many of the high-fiber foods that have been shown to improve mental health and gut health, like asparagus, artichokes, onions, beans, and berries, are prohibited by this draconian diet. However, the low FODMAP diet is meant to be temporary in acknowledgment of how restrictive it is. When your gut feels better, and you end the diet, a slow introduction of high-fiber foods is what you want to help heal your gut.

We have to mention farting. You may notice some extra gassiness when you switch to oligosaccharides. This is a sign that your good bacteria are happy and producing mostly odorless hydrogen and methane. Many people live in a narrow dietary groove, and the addition of fiber can be disruptive, so start slowly.

Before we had “refined” foods, there was a lot more flatulence in the world. Today’s refined food, with all the gas-producing fiber removed, is a false Eden. Farting is funny; diabetes is not.

Bottom Line

These natural sugar substitutes don’t have the same problems that are associated with many artificial sweeteners, but they are still understudied. As prebiotics, they may be helpful to your gut—even as they lower calories and minimize sugar spikes. Manufacturers are starting to market some of these natural sweeteners with varying degrees of success.

Perhaps a better path for our health is to consume fewer sweets in general. I know I’m on thin ice here. Some people will put up a fight if you try to take away their candy bar. But treating sweets as a staple may be overdoing it. If you must have a candy bar, try one with an alternative natural sweetener and see if it hits that sweet spot.

There was a time when we consumed a heroic amount of salt, but most of the world has learned to eat less. It is a matter of recalibrating our taste buds, which takes just a few weeks. Once we tame our sweet tooth, it’s no longer a huge disappointment to forego a little sugar. Delicious dark chocolate is an example of how little justification we have for complaining. Lower your sugar intake, and it just might add some healthy years to your life. A little less sugary, but no less sweet.


Chi, Liandi, Imran Khan, Zibei Lin, Jiwen Zhang, M. Y. Simon Lee, Waikit Leong, W. L. Wendy Hsiao, and Ying Zheng. “Fructo-Oligosaccharides from Morinda Officinalis Remodeled Gut Microbiota and Alleviated Depression Features in a Stress Rat Model.” Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 67 (February 2020): 153157.

Johnstone, Nicola, Chiara Milesi, Olivia Burn, Bartholomeus van den Bogert, Arjen Nauta, Kathryn Hart, Paul Sowden, Philip W. J. Burnet, and Kathrin Cohen Kadosh. “Anxiolytic Effects of a Galacto-Oligosaccharides Prebiotic in Healthy Females (18–25 Years) with Corresponding Changes in Gut Bacterial Composition.” Scientific Reports 11, no. 1 (April 15, 2021): 8302.

Zhu, Zhen-Hua, Xu-Yuan Yin, Tu-Sun Xu, Wei-Wei Tao, Guang-Da Yao, Pei-Jie Wang, Qi Qi, et al. “Morinda Officinalis Oligosaccharides Mitigate Chronic Mild Stress-Induced Inflammation and Depression-like Behaviour by Deactivating the MyD88/PI3K Pathway via E2F2.” Frontiers in Pharmacology 13 (2022).

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