Food additives commonly found in ultraprocessed foods may disrupt gut health through a variety of mechanisms, but the end result appears to be the same: dysbiosis and damage to the intestinal epithelial barrier, which normally helps protect the host from chronic inflammation.

Some emulsifiers can erode the mucus layer, certain food colorings may be metabolized by commensal bacteria into pro-inflammatory compounds, artificial sweeteners may promote microbial imbalance, and nanoparticles may impair goblet cell function.

Taken together, these additives may contribute to an altered gut microbiome and weakened barrier integrity, potentially setting the stage for ongoing inflammatory effects.

“It has already been scientifically proven that changes in the function and composition of the microbiota increase the risk of disease. What we are highlighting is that excessive consumption of ultraprocessed foods can promote a proinflammatory microbiota,” stated Ligia Yukie Sassaki, MD, a gastroenterologist in the Department of Clinical Medicine at the São Paulo State University (Unesp) School of Medicine in Sao Paulo, Brazil.

She is among the authors of a critical review published in Nutrients by researchers from Unesp, Unicamp, and Aalborg University in Aalborg, Denmark. The review outlined the mechanisms by which additives in ultraprocessed foods can alter the composition and function of the gut microbiota, and how this disruption may help drive the development of inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis.

Regular consumption of ultraprocessed foods is associated with consistent changes in the gut microbiota, including a reduction in butyrate-producing bacteria, such as Faecalibacterium prausnitzii, an increase in opportunistic pathogens, and a decrease in the production of short-chain fatty acids — metabolites essential for the integrity of the epithelial barrier. This imbalance facilitates the translocation of bacterial lipopolysaccharides into the bloodstream, activating inflammatory pathways such as NF-κB and elevating proinflammatory cytokines such as TNF-alpha and interleukin (IL)-6 — mechanisms central to the pathophysiology of IBD.

Among the most extensively studied additives are emulsifiers. Carboxymethylcellulose and polysorbate 80, which are used in products such as margarine, processed breads, and desserts, can promote bacterial adhesion to the intestinal epithelium, reduce beneficial taxa such as F prausnitzii and Ruminococcus, and increase proinflammatory Pseudomonadota.

Polysorbate 80 may also help Escherichia coli translocate through M cells and Peyer’s patches, further undermining intestinal barrier integrity.

Synthetic azo dyes, such as Red 40 and Yellow 6, found in soft drinks and processed foods, are metabolized by commensal bacteria, such as Bacteroides ovatus and Enterococcus faecalis, into metabolites that activate CD4+ lymphocytes via the IL-23 axis, inducing colitis in genetically susceptible animal models.

Artificial sweeteners, such as saccharin, sucralose, and aspartame, alter glucose tolerance through dysbiosis and elevate inflammatory markers such as TNF-alpha and IL-6. Maltodextrin, in turn, reduces the expression of mucin 2 — a protein essential for mucus layer formation — thereby increasing the adhesion of pathogenic bacteria to the epithelium. Titanium dioxide, used as a bleaching agent, impairs the function of goblet cells and induces reactive oxygen species, which have genotoxic potential with prolonged exposure.

To guide patients in practice, the researchers used the NOVA system, which classifies foods into four groups based on their degree of industrial processing.

“Ultraprocessed foods are the ones that cause the most harm to the gut microbiota, and their consumption should be limited. Processed foods can be included in the diet as occasional treats, such as a slice of cheese for breakfast. But they should not form the basis of our diet,” recommended Amanda Spiller, a nutritionist at Unesp, and the lead author of the article.

“There is a lot of marketing that suggests that, for a food to be healthy, it must contain protein. But excessive protein does not guarantee safety. For example, people have been replacing fruit with protein bars. They can serve as a supplement, but they contain many flavorings as food additives,” she added. “We consume many products without knowing what they are or what they’re for. The first three ingredients listed are the ones present in the greatest quantities. If the first is sugar or fat, we need to consider whether it’s really a good food.”

The Role of Diet

Diets rich in fiber and minimally processed foods have the opposite effect. Regular consumption of fruits, vegetables, grains, and seeds stimulates the growth of butyrate-producing bacteria — the main energy source for intestinal epithelial cells — and increases the production of secretory immunoglobulin A, which helps defend the mucosa. This dietary pattern reduces proinflammatory species such as E coli and Ruminococcus gnavus, promotes greater microbial diversity, and improves the integrity of the intestinal barrier, reducing epithelial permeability and circulating levels of inflammatory cytokines such as TNF-alpha and IL-6.

“Although it is not the only factor, diet is one of the key factors in prevention, so it is important to highlight the role of a healthy diet in reducing the risk of developing these diseases,” added Sassaki.

Genetic factors, however, remain an important part of the picture. “Even if you don’t smoke, exercise regularly, and follow a completely healthy diet, a strong family history can still put you at risk for developing one of these diseases because of genetic factors. But among the factors that can be modified over the course of a lifetime, diet is one of the most important,” the gastroenterologist said.

Limitations

Most of the studies supporting these associations were conducted on animals and in vitro models. “Results from animal studies do not translate to humans, especially when it comes to the microbiota, which varies from person to person,” noted Márcia Terra, a board member of the Brazilian Society of Food and Nutrition, who did not participate in the study.

The NOVA classification, central to the study, is not without controversy. “The ‘ultraprocessed food’ category is too broad. It groups fortified bread, soda, and yogurt under the same label. When you lump so many different things together, some statistical association will always emerge, but that doesn’t point to any specific mechanism. It’s the dose that matters, not the category,” Terra pointed out.

For her, the concept itself is debatable. “There are processed and unprocessed foods; food is food, whether it’s made at home, in a restaurant, or in a cafeteria. What prevents disease is dietary patterns over time, not the degree of processing.”

Spiller acknowledges the limitations but defends the tool’s clinical utility. “When we’re advising a patient, we need to use what’s in the literature. I understand that we shouldn’t lump everything together, but there is indeed a difference between fortified store-bought bread — which contains additives to extend its shelf life — and homemade bread.”

According to Spiller, consumption should be avoided, not prohibited. “Can these foods be part of the diet? Yes, they can. But they cannot form the basis of one’s diet,” she emphasized.

“In Brazil, where processed foods are a staple due to convenience and cost, telling someone to give them all up is advice that ignores reality. The answer lies in balance. Low consumption isn’t harmful,” added Terra.

Washington Castilhos has been a science and health journalist for more than 20 years. He holds a master’s degree in science, health, and technology communication from the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil, and a doctorate in education and biosciences communication from the Federal University of Rio de Janeiro, which included a doctoral internship at Paris 8 University, Saint-Denis, France.

This story was translated from Medscape’s Portuguese edition.