The case against processed food just keeps getting stronger. But, amazingly, we still don’t understand exactly why it’s so bad for us.

In two papers published in the BMJ in May 2019, the more ultraprocessed — or industrially manufactured — foods a person ate, the more likely they were to get sick and even die. In one study, they were more likely to suffer from cardiovascular problems. The other linked an ultraprocessed diet to a higher risk of death from all causes.

Those studies followed a first-of-its-kind randomized controlled trial, out of the National Institutes of Health: Researchers found people following an ultraprocessed diet ate about 500 more calories per day than those consuming minimally processed, whole foods. Then, a December paper in JAMA Internal Medicine found that the more ultraprocessed food a person ate, the higher their risk of Type 2 diabetes.

Sure, potato chips, cookies, and hot dogs are chock-full of salt, sugar, fat, and calories. They can cause us to gain weight and put us at a higher risk of diseases such as obesity.

But why? What if there’s something unique about ultraprocessed foods that primes us to overeat and leads to bad health?

A new, intriguing hypothesis offers a potential answer. Increasingly, scientists think processed foods, with all their additives and sugar and lack of fiber, may be formulated in ways that disturb the gut microbiome, the trillions of diverse bacteria lining our intestines and colon. Those disturbances, in turn, may heighten the risk of chronic disease and encourage overeating.

The idea sheds new light on why ultraprocessed foods seem to be so bad for us. But to understand the hypothesis, we need to first look at what ultraprocessed foods are, and how they shape the community of bacteria in our gut that’s so intimately linked to our health.

Ultraprocessed foods, explained

More than half of the calories Americans consume now come from ultraprocessed foods. But what exactly are they?

For starters, ultraprocessed foods look a lot different from the foods our great-great-great-grandmothers ate, as author Michael Pollan would say. They’re the frozen chicken nuggets at McDonald’s, the soda and sports drinks in just about every beverage fountain across the country, and the milkshakes masquerading as coffee at Starbucks.

According to a widely used scientific definition, they’re:

industrial formulations made entirely or mostly from substances extracted from foods (oils, fats, sugar, starch, and proteins), derived from food constituents (hydrogenated fats and modified starch), or synthesized in laboratories from food substrates or other organic sources (flavor enhancers, colors, and several food additives used to make the product hyper-palatable).

In other words, ultraprocessed foods are created in factories. They’re pumped full of chemicals and other additives for color, flavor, texture, and shelf life. This processing generally increases the flavor and caloric density of the foods, while stripping away the fiber, vitamins, and nutrients. So these foods are distinct from whole foods (like apples and cucumbers) and processed foods (like vegetables pickled in brine, or canned fish in oil) that rely on only salt, sugar, and oil — rather than a range of complicated additives — to preserve them or make them tastier.

Carlos Monteiro, a professor of nutrition and public health at the University of Sao Paulo, helped write the “ultraprocessed” definition in 2009, when he was working with the Brazilian government to understand how the emergence of a global industrial food system changed Brazilians’ eating habits. People started cooking less, eating out more, and relying on packaged products for their calories. “We realized that people were replacing freshly prepared dishes and meals,” he told Vox, “[with] ready-to-consume products based on sugar, fats and salt plus many ingredients of exclusive industrial use,” such as protein isolates, modified starches, and color additives.

That’s why pinpointing exactly what in ultraprocessed foods may increase the risk of disease is difficult. It’s hard to disentangle, for example, whether it’s the chemical additives in these foods, the calories they deliver, or the stuff they generally don’t contain, such as fiber. Or maybe it’s the contaminants in them, like plastics that leach from packaging. People who eat lots of processed foods may also be fundamentally different from people who avoid them. “We are dealing with something very complex,” Monteiro added.

What we eat shapes our gut flora

Considering the arrival of ultraprocessed foods fundamentally changed how we eat, researchers recently began to wonder what that was doing to our gut microbiome.

The majority of bacteria in our gut are benign or good for our health. They evolved with us to do things such as aid digestion and regulate the immune system. We’re only just beginning to understand how integral the microbiome is to our health. And to date, much of the science on the relationships between these bacteria and our health is focused on mice. Of the studies we have in humans, most of the findings are correlational.

But there’s one thing researchers already agree on: “Diet is the No. 1 influencer and determinant of our gut microbiome composition,” said Suzanne Devkota, director of microbiome research at the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. They also generally agree that the more diversity of bacteria in the gut microbiome, the better for our health.

Devkota is among the researchers exploring how the influx of processed meats, cereals, and sugars into our diet has influenced both the type of bacteria and variety of them in the microbiome. Their findings are potential cause for concern.

When researchers have compared the microbiomes of mice eating a bland, low-fiber, high-fat diet (one that resembles Western-style, ultraprocessed food) to mice eating a fiber-enriched high-fat diet, the two sets of rodents had distinctly different microbiomes: Mice on the low-fiber diet had a marked reduction in the total numbers of bacteria in their gut and a less diverse microbiome compared to the mice on the high-fiber diet.

The mouse findings echo the few studies we have in humans. Researchers who analyzed stool samples from people living in less industrialized hunter-gatherer cultures — where ultraprocessed foods are uncommon — and compared them with stool samples from people in industrialized countries, uncovered a strong pattern: The further away people were from industrialization and ultraprocessed foods, the more diverse their gut micriobiome was.

Similarly, when researchers sequenced the DNA of calcified dental plaque, they found the bacterial colony in the oral cavities of humans from Neolithic and medieval times were a lot more diverse than postindustrial modern humans. “Major changes in carbohydrate intake in human history appear to have impacted the ecosystem of the mouth,” the researchers wrote.

“The thing you can generally say is that in states of health, the microbiota has a high level of diversity in a wide variety of different species,” said Andrew Gewirtz, a professor at Georgia State University’s Center for Inflammation Immunity and Infection. “And a lot of these [bacteria] tend to get lost in diets that are highly processed.”

The possible problem with emulsifiers and refined sugars in junk food

There’s also a link between diets heavy in ultraprocessed foods and harmful inflammation — when the body’s inflammatory response goes into overdrive, making it harder to fight off viruses and disease. One measure of inflammation is a blood marker called C-reactive protein (CRP). Researchers have found associations between higher levels of CRP and various chronic illnesses, including cancer, arthritis, cardiovascular disease, and diabetes. And people who eat an unhealthy diet tend to have higher levels of CRP in their bodies.

So why exactly are these foods linked to less diversity in the microbiome, and more inflammation and disease?

One theory: Key ingredients, such as emulsifiers and refined sugars, impair the microbial life in our gut, instead of helping it flourish.

Emulsifiers are additives used to stabilize ultraprocessed foods. They help the oil and vinegar in a bottled salad dressing stay mixed, and keep ice cream from forming ice and crystallizing in the freezer. For a study that was published in 2015, Gewirtz and his colleagues hypothesized that widely used emulsifiers — specifically carboxymethylcellulose and polysorbate-80 — might disturb the microbiome and increase inflammation.

And that’s exactly what they found. Mice that had a genetic predisposition to colitis, a chronic, inflammatory bowel disease, developed the disease faster when exposed to emulsifiers. Mice that didn’t have that predisposition but were also emulsifier-exposed developed low-grade inflammation and mild obesity. Gewirtz said he thinks the friendly microbes in the gut may view emulsifiers as a toxic chemical that “antagonizes” the microbiome and causes it “not to live well with the host.”

“As best we can tell, at doses that seem to be reasonable mimics of exposure to emulsifiers in humans, the emulsifiers promoted inflammatory diseases in mice,” said Gewirtz, who is now working on a similar study in humans. But the mouse evidence was compelling enough that forthcoming dietary recommendations for inflammatory bowel disease suggest people avoid emulsifiers.

Another theory, outlined in a recent review paper on the effects of the Western diet on the microbiome, is that the sugar in ultraprocessed foods may feed harmful bacteria in the gut, causing them to bloom.

“These refined carbohydrates could be feeding the bad bacteria in the small intestine,” said the paper’s lead study author, Marit Zinocker, “and that’s where inflammation starts. Animal studies have shown that if you increase the amount of simple sugars in the diet, that’ll change the growth potential of [pathogenic] bacteria in the gut.”

Zinocker emphasized that the emulsifier and refined carbohydrate hypotheses are just two potential explanations for why ultraprocessed foods are unhealthy — and there’s still a lot scientists have to learn. For now, though, researchers have figured out that it’s not just what’s added to processed foods that may hurt the gut microbiome. It’s also what’s missing.

The lack of fiber in ultraprocessed foods may harm us too

Because our intestines can’t directly digest fiber, we’ve long seen fiber as beneficial for relieving constipation by adding bulk to stool and promoting regular bowel movements. But that “was before people [realized] how much the non-digestible things we eat impact our gut bacteria,” said University of Michigan microbiologist Eric Martens when I spoke to him for a feature on fiber.

Researchers now consider fiber’s role in nourishing our gut microbiome to be one of its main health benefits. They don’t yet fully understand why fiber is so good for our gut, but they have some ideas.

Fermentable fibers, which include all soluble fibers and some insoluble fibers, are metabolized or fermented by bacteria in the gastrointestinal tract. That process produces chemicals, including short-chain fatty acids, that are important food sources for our gut bacteria.

They also carry health benefits, Martens said. Short-chain fatty acids have been shown to promote insulin production so we can better manage the spikes of sugar (or glucose) in our blood, for example, helping to manage Type 2 diabetes. In addition, they seem to have anti-inflammatory properties.

“When we don’t consume enough fiber, we are essentially starving our gut microbiome,” Jens Walter, a researcher who studies fiber at the University of Alberta, told me, “which is likely detrimental for a variety of reasons. We also probably lose [microbiome] diversity.”

That lack of diversity linked with a low-fiber diet might affect the mucus layer in the gut. Mucus acts as a protective barrier between us and the outside world. It’s constantly being replenished by secretions from the cells that make up our intestines, and it’s covered with a layer of bacteria, part of our microbiome. Fiber feeds the bacteria on top of the mucus layer as it passes through, helping keep our microbiomes robust, Gewirtz said.

Another fiber study, again in mice, showed what happens when the bacteria in the digestive tract don’t get any fiber. Researchers, including Martens, found the bacteria begin to eat away at the mucus layer, bringing them into closer contact with the intestinal tissue. “The hypothesis is if we stop feeding the microbiome [fiber], the bacteria will resort more frequently to digesting that mucus barrier as a source of nutrients.”

If bacteria eating up the mucus layer sounds bad, well, it is. The mucus layer keeps out pathogens, and the researchers were able to show that if they introduced a pathogen in the context of a low-fiber diet, it had an easier time getting into the intestine and causing an infection. “The lack of a mucus barrier made the disease get much worse much quicker,” Martens added. “It may irritate the [intestinal] tissue or provoke immune responses,” leaving the mice more vulnerable to disease.

Why microbiome disturbances may cause people to eat more

The microbiome idea may also help explain why highly processed diets cause people to eat more, Gewirtz said. “Antagonizing the microbiota by highly processed diets — starving it by removing fiber and attacking it [with emulsifiers] — promotes inflammation.” That can hamper the body’s ability to feel satiated and result in overeating. For example, he explained, eating causes the body to release the hormone leptin, which quells hunger. But inflammation interferes with leptin’s action.

“Put another way, our results do not question the notion that the obesity epidemic is driven by overeating,” he added. “Rather, it suggests that such overeating is driven, in part, by alterations in the microbiome inducing inflammation.”

Researchers still have a lot to untangle here. But should we wait to better understand precisely why ultraprocessed food is bad for us before we start regulating it?

Brazil’s Monteiro thinks lawmakers should act now and figure out how to make unprocessed foods more accessible and affordable, while taxing ultraprocessed foods and regulating the marketing around them.

“We started to have policies to make people smoke less or to avoid smoking before we knew all the problems caused by smoking,” he said. Similarly, with ultraprocessed foods, he argued, health authorities shouldn’t wait until every mechanism is known. “We’re in a situation where you have so many ultraprocessed foods and so many diseases related to ultraprocessed foods,” Monteiro said. If we try to answer every question about these products, we’ll never regulate them. And given the mounting evidence of harm, delayed action increasingly looks like it’ll cost health dollars and lives.