Sugar substitutes may alter gut microbiome and affect blood glucose tolerance in humans: study

Many of us tend to drink a diet drink or stir a sachet of sweetener into our coffee in an attempt to reduce our sugar intake.

Key Points:

  • Artificial and natural sweeteners, such as sucralose and stevia, are often used as an alternative to sugar.
  • Commonly used sweeteners could change the composition of gut microbiomes in healthy people, study finds
  • This, in turn, slowed their ability to process sugar, but how it affects the microbiome is not yet known.

But in an ironic twist, a trial has found that some healthy adults had less control over their blood sugar levels after two weeks of consuming less than the recommended daily amount of sugar substitutes.

Published in the journal Cell, the study also found that the microbial species inhabiting the participants’ gut, known collectively as the gut microbiome, changed in composition and began to function like a person’s microbiome with diabetes

“We were able to demonstrate why [sweeteners] that supposedly have no effect on the human body … alters the gut microbiome, which is enough to alter human metabolic health,” said Johns Hopkins microbiome researcher and study lead author Jotham Suez.

One sweetener in particular, sucralose, caused the biggest change in the microbiome among study participants.

But that doesn’t mean everyone should stop using sweeteners immediately, Dr. Suez added.

It is not true to say that sugar substitutes are safe or harmful for everyone.

“It’s a middle ground, and we’re working on it, but the truth is that the literature is still complicated and the jury is still out.

“But if you can stop drinking [sugar substitutes] without increasing your sugar intake, that’s obviously the safest thing to do.”

‘Stealth Sweeteners’

Sugar substitutes may seem like a fairly new addition to our diet, but they’ve been around since the 1800s.

Many are “non-nutritive,” meaning they contain no carbohydrates and are low in calories, and were generally considered “inert,” delivering their sweet hit and then passing safely through the body without interacting with anything downstream of the mouth

Although research over the past two decades has yielded mixed results, some studies suggest that they are not as inert as we once thought.

And the consumption of sugar substitutes, especially artificial sweeteners, has been linked to conditions such as type 2 diabetes, but this has not been enough to say that the sweeteners cause the disease. It could be that people with diabetes simply choose to consume more sugar substitutes.

In 2020-21, almost a quarter of Australian adults report drinking diet drinks at least once a week, with 7% consuming daily.

The global market for food sweeteners is expected to reach $152 billion by 2030. (Unsplash: Towfiqu barbhuiya)

Even if you don’t go out of your way to consume them, you probably do anyway, said Richard Young, a microbiome researcher at the University of South Australia who was not involved in the study.

“There are many ‘stealth sweeteners’ in the food chain that we don’t know about.”

Only in recent years have researchers conducted interventional studies like the one led by Dr. Suez to see what effects, if any, sugar substitutes have on the human body.

A spoonful of sucralose helps reduce glucose tolerance

Dr. Suez and colleagues at Israel’s Weizmann Institute of Science recruited about 120 healthy people who completely avoided sugar substitutes (no mean feat, given how ubiquitous they are in processed foods) and divided them into six groups.

Four groups received sachets of a commonly used sweetener – aspartame, saccharin, sucralose or stevia – which they consumed with their usual food every day for fifteen days.

The fifth group only received glucose sachets, while the sixth group received nothing, for them it was business as usual.

Everyone had stool samples taken before starting the trial to analyze the species that make up their usual gut microbiome and compared them to samples taken after the two weeks had passed.

Dr. Suez and his crew found distinct changes in the gut microbiome composition of participants who consumed sweeteners, particularly sucralose.

This may be because sucralose doesn’t leave the digestive tract until we expel it, so it has a better chance of interacting with our microbiome than other sweeteners, which can be broken down and absorbed into the bloodstream further up the gut.

Throughout the trial, participants also regularly tested how well their bodies could clear blood sugar after drinking a glucose-concentrated drink.

This process, called glucose tolerance, was significantly impaired in the sucralose and saccharin groups, with blood sugar levels remaining higher for longer after the drink.

The groups that had only glucose, or no intervention, had no change.

Next, the researchers wanted to establish causality and see if the microbiome changes driven by the sweeteners at least contributed to impaired glucose tolerance.

To do this, they took stool samples before and after the sweetener from the participants who had the biggest change in glucose tolerance during the experiment and transplanted that poop into mice with no microbiome.

The glucose tolerance of these mice mirrored the glucose tolerance of their human poop donor at the time the stool sample was taken.

“In all cases, we have seen [blood sugar levels] exactly as we saw in humans: that blood glucose was higher in the group of mice that received it [poo transplants] taken on the last day of the experiment, compared to the first day of the experiment,” Dr. Suez said.

So how can sweeteners change the way we process blood sugar?

The short answer is: we don’t know. It’s something Dr. Suez’s lab is trying to figure out, but he has some ideas.

The primary function of our gut microbiome is to help us break down food, but it can affect our bodies from head to toe.

For example, different bacteria secrete different chemicals into our blood, and these compounds can affect how our organs function.

What happens to blood glucose after eating?

  • When you eat digestible carbohydrates like starches, your digestive system breaks them down into glucose, a type of sugar that your body’s cells use for energy.
  • This glucose enters the blood, raising blood sugar levels.
  • Soon after, your body secretes insulin, a hormone that lowers blood sugar levels to pre-meal levels.
  • If blood sugar levels remain too high for too long, as can be the case in people with untreated diabetes, they can damage nerves and organs in the body, including the eyes, kidneys and heart.

“We don’t know why some groups of bacteria die out in the presence of each sweetener; maybe the sweeteners are toxic, or maybe they affect some specific energy metabolism of the bacteria,” Dr Suez said.

Sweeteners can change the cells in the gut lining, making it more habitable for some bacteria than others, and thus change the composition of the microbiome.

Dr. Suez and his colleagues suspect that changes in the microbiome affect the signals the gut sends to the brain, which in turn tells the pancreas to release less insulin, thereby slowing the rate at which removes sugar from the blood.

Changes in the gut microbiome are likely part of the puzzle, Dr. Young said. Sweeteners also directly affect our gut.

“The gut wall is a sensory organ, like our eyes, our ears, our skin,” he said.

We have sweet taste receptors on our tongues, but they are also found throughout our intestinal tract, “tasting” our blended food as it travels through us.

“And we found that glucose absorption is much faster in healthy people who take sweeteners, because they tend to prepare the intestinal wall to absorb the sugars. [to our blood] faster,” he said.

“So not only are sweeteners susceptible to affecting bacteria, but we have good evidence to suggest that they’re also getting sugars into the bloodstream more quickly.

“There could be a double whammy of sweetness that we didn’t really appreciate before.”

What does this mean for me?

The results of this trial cannot be generalized to everyone, Dr. Suez said.

“This was an Israeli cohort, and I would like to see people repeating this experiment in other parts of the world and for longer exposure periods to really try to relate what we saw to a real-world scenario.”

Dr. Young called the trial “a well-constructed study that answered the questions that needed to be asked,” but agreed that it focused on one part of the population and did not truly reflect life as a free-living person.

Ideally, the experiment would be repeated in groups more likely to consume sweeteners: people who are prediabetic or living with diabetes.

The main constituent of white sugar, and of many such delicacies, is sucrose. (Unsplash: Heather Ford)

Also, most products that contain sweeteners don’t use just one.

“By themselves, sweeteners have properties that tend to cross into the bitter taste range,” he said.

“So by pairing them with another sweetener, manufacturers can create a sweeter mouthfeel.”

Different countries also favor different types of sweeteners.

While diet drinks in the United States typically use sucralose combined with a sweetener called acesulfame K or Ace-K, Australian ones use an aspartame-plus-Ace-K combination.

Ace-K was not tested in the study, probably because it is quickly cleared from the gut into the bloodstream, so it has very little contact with the microbiome. We basically rule it all out, Dr. Young said.

Participants in the sweetener cohorts who saw changes in their microbiome and their ability to handle blood sugar began to return to pre-sweetener levels after the two weeks were up.

Next, Dr. Suez said, he would like to find out why some people responded strongly to sweeteners while others had almost no effect.

“We could use this information to predict which microbiome will respond to sweeteners … and perhaps develop a tool or an algorithm to predict who will and will not respond to sweeteners.”

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