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Sugar Can Keep Good Microbes From Colonizing Your Gut

Simple sugars like fructose and glucose aren't just nutrients. They can also halt the production of proteins that foster the growth of beneficial gut microbes.

ByKatherine J. WuNOVA NextNOVA Next
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Eating too much sugar could negatively impact your gut microbes in unexpected ways, including preventing certain species from settling down in the colon. Photo Credit: Magone, iStock

When it comes to sweets, the verdict has long been in: Overindulging can really mess with your body. Eating too much sugar boosts your chances of succumbing to heart disease, diabetes, obesity, cavities—the list goes on and on.

But your body is home to far more than just human cells—and the trillions of bacteria that inhabit your gut might also be taking a considerable hit from your chronic sweet tooth. According to a new study, sugar can directly deter beneficial microbes from gaining a foothold in the guts of mice.

The report, published today in the journal PNAS, demonstrates that hefty doses of fructose and glucose—the building blocks of sucrose, or table sugar—impede the production of proteins that foster the growth of a bacterial species often found in lean, healthy people. Though the results still await confirmation in humans, they provide some of the first evidence that when it comes to diet, sugar’s not just a nutrient: It’s a signal—and that signal may be prompting some of the most important microbes in the gut to abandon ship.

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“This is a whole new level of showing the interactions between diet and microbes,” says Se Jin Song, who studies gut bacteria at the University of California San Diego, but did not contribute to the study.

In recent years, it’s become increasingly apparent that human bodies aren’t entirely human. Trillions of bacteria inhabit the human colon—a population often referred to as the gut microbiota. These microbes are essential players in daily function, aiding everything from digestion to immunity. Without them, humans would get fewer calories out of their food, struggle to absorb essential minerals, and be constantly plagued by infectious disease.

To power their performance, these industrious little critters rely on the same source of food that their human hosts do: whatever meals enter the gastrointestinal tract. No matter what state a human body is in, every time it eats, it’s feeding a few extra trillion little cells—which really ups the ante on watching one’s diet.

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Sucrose, or table sugar, is a combination of fructose and glucose. Added sugars make up a big proportion of the American diet, and are thought to contribute to cardiovascular disease and obesity, among other issues. Photo Credit: George Hodan

One of the most important players in the human gut is Bacteroides thetaiotaomicron (B. theta for short), a bacterial species that’s typically found in individuals who enjoy fiber-rich diets and maintain a healthy weight. In overweight and obese people, on the other hand, bacteria in the Bacteroides group are often far scarcer. Although having B. theta around isn’t a guarantor of health and longevity, it’s thought that these bugs confer a few benefits by fermenting the dietary fiber found in fruits, vegetables, whole grains, and beans into nourishing molecules that the human body can’t make on its own.

Study authors Guy Townsend, a microbiologist at Pennsylvania State University, and Eduardo Groisman, a microbiologist at Yale University, originally set out to assess how diet affected the ability of B. theta to set up shop in the intestines of mice. Previous research had pointed to the possibility that eating a lot of sugary foods favors the growth of some bacterial species over others—so Townsend wasn’t terribly surprised to see that B. theta wasn’t sweet on sugar. What floored him was the fact that sugar’s effects had nothing to do with what the microbes were munching on.

To inhabit the guts of mice, B. theta produces a protein called Roc—an acronym for “regulator of colonization.” The aptly-named Roc confers the ability to establish residence in, or colonize, a specific locale, like the large intestine; without Roc, B. theta can get flushed out of the system. When Townsend grew B. theta in the presence of fructose or glucose, he found that the bacteria abruptly stopped manufacturing Roc. It seemed that simple sugars were somehow acting as an environmental cue, halting the progression of the bacterial cells’ Roc-making assembly line.

“There’s real novelty here,” says Seth Rakoff-Nahoum, who studies how gut microbes utilize sugar at Boston Children’s Hospital and Harvard Medical School, but was not involved in the new research. “The bacteria aren’t sensing a sugar to use a sugar. They’re using the sugar to shut something down… and repressing a factor that’s important for them to live in the gut.”

Fructose and glucose are both common in the typical American diet. They’re both found naturally in fruits, vegetables, grains, and pretty much anything else that falls into the category of carbohydrates. But one of the most concerning sources of fructose and glucose is table sugar, or sucrose, which contains the two simple sugars bound together. Digestion breaks sugar complexes like sucrose apart, liberating its fructose and glucose units.

So far, the silencing of Roc seemed responsive only to fructose and glucose. When the researchers exposed B. theta to galactose—another simple sugar with a slightly different structure that’s found in milk—the bacteria kept churning out gobs of Roc. But when they next fed B. theta fructose-galactose or glucose-galactose mixtures, Roc disappeared once again. The same held true when galactose was swapped out for other, more complex sugars, including fructo-oligosaccharides, which are often consumed as a prebiotic, or a dietary additive that’s thought to feed populations of beneficial gut microbes (not to be confused with probiotics, or bacteria that are directly ingested in the hopes that they’ll seed the colon). For some reason, Roc seemed highly sensitive to a particular subset of simple sugars—and these sugars were capable of overriding whatever else was around.

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The researchers are still figuring out how exactly Roc is getting put out of commission. But Groisman thinks it’s likely to be at the step at which the bacterial cell’s protein-producing machinery is getting ready to read the genetic instructions for Roc.

In the future, the team also hopes to suss out why Roc and other, similar proteins are so important for B. theta and other gut microbes to settle down in the gut. There’s no guarantee that all species will behave in the same way—but simply knowing that sugar is a signal could be valuable. The researchers have already engineered a version of Roc that’s undeterred by sugar, and B. theta cells with this modification can safely take hold, even in the colons of mice eating high-sugar meals. Taking advantage of these genetic tools could eventually inform the production of future probiotics that are compatible with a multitude of diets.

These results can’t yet be extrapolated to human populations, however, Groisman cautions. The mice used in these studies lacked gut microbes, or were germ-free, before being introduced to B. theta. Also, what’s observed in mice doesn’t always translate over to humans—and several of the mouse diets tested, including one that was mostly table sugar, weren’t realistic representations of even the worst American eating habits.

The researchers also still aren’t certain that fructose and glucose are present in appreciable amounts in the human colon, which is home to the majority of our gut microbes. Not many sugars make it past the small intestine, where most nutrients are absorbed. But Townsend and others have shown that, at least in rodents, fructose is detectable in this far-flung locale—especially in mice feasting on sweets.

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Simple sugars like fructose and glucose, which are present in high amounts in food with added sugar, may halt the production of important proteins in beneficial gut microbes. Photo Credit: Rebecca Siegel, flickr

Even if the same phenomenon is observed in humans, Rakoff-Nahoum says, research like this isn’t prescriptive. For one thing, B. theta is already common in human guts—and there’s no evidence that sugars can destroy already-existing populations of beneficial bacteria. Once the microbes have colonized, sugar won’t necessarily jettison them from the gut.

As a whole, though, these findings point to yet another reason simple sugars might not be good for us, Groisman says. Sugar’s never been a superfood—but if it’s actually altering the ability of bacteria to pump out protein, its role may go far beyond nutrition.

“Based on this study alone, I wouldn’t give up fructose and glucose,” says Hannah Wexler, who studies bacteria in the Bacteroides group at the University of California, Los Angeles, but was not involved in the study. “But you have to look at the big picture [of sugar]. So, based on everything we know, it’s a maybe.”