Two Princeton-led studies found that insufficient dietary fiber can push gut microbes toward breaking down proteins in the intestine’s protective mucus layer, while fiber and indigestible plant proteins may redirect microbial metabolism toward compounds associated with more favorable health effects.
By yourNEWS Media Newsroom.
Researchers studying the relationship between diet and the gut microbiome have identified a mechanism that may help explain why diets lacking fiber can be harmful to intestinal health: When preferred dietary nutrients become scarce, certain gut microbes may begin consuming proteins belonging to their host, including those within the mucus barrier protecting the intestinal lining.
Two studies led by scientists at the Ludwig Institute for Cancer Research at Princeton University examined how dietary components influence the production of metabolites formed from amino acids in the digestive system. Published in the Proceedings of the National Academy of Sciences and Nature Metabolism, the research also identified a previously underappreciated group of indigestible plant proteins that can influence the chemicals generated by gut microbes.
Researchers termed these compounds “proteins imitating fiber,” or Prif.
The findings suggest that fiber and Prif can alter microbial activity through different but complementary mechanisms. Dietary fiber appears to reduce bacterial consumption of the intestinal mucus layer, while indigestible plant proteins provide material that reaches gut microbes and can be converted into potentially beneficial metabolites.
Together, those processes shifted the balance away from compounds including p-cresol sulfate and phenol sulfate and toward metabolites such as phenylpropionate and hippuric acid.
Researchers Trace Harmful Metabolites Back to the Host
The Proceedings of the National Academy of Sciences study was led by Jenna AbuSalim and Joshua Rabinowitz of Ludwig Princeton and focused on phenol metabolites generated from the amino acids tyrosine and phenylalanine.
Using isotope tracing experiments in mice, researchers were able to investigate where those metabolites originated rather than simply measuring their concentrations.
The experiments revealed an important distinction.
Phenols characterized by the researchers as harmful were produced when intestinal bacteria metabolized proteins originating from the host itself. Those protein sources included components of the mucus lining that forms a protective barrier along the gut.
When dietary fiber was available, however, bacterial degradation of that mucus barrier declined. The corresponding levels of harmful phenol metabolites also fell.
Indigestible plant proteins appeared to operate through another pathway. Because Prif proteins survive digestion and reach the intestinal microbiome, they provide bacteria with a dietary protein source that can produce a different metabolic profile.
Researchers found that these plant proteins increased production of phenylalanine-derived metabolites considered more favorable.
“Our studies showed that both the fiber and indigestible proteins from plants — which we call ‘proteins imitating fiber,’ or Prif — shift the balance of phenol metabolites from the harmful kind made from tyrosine to the healthful variety derived from phenylalanine,” AbuSalim said in a statement.
Fiber has long been recognized as an important dietary component for intestinal health, while the potential significance of indigestible plant proteins has received considerably less attention.
Earlier research has likewise indicated that restricting dietary fiber can compromise the intestinal mucus barrier. A 2018 study, later discussed by author Dave Asprey in his book “Super Human,” reported that a low-fiber diet could contribute to leaks developing in the mucus layer protecting the gut.
The Princeton research offers additional detail about what may be occurring metabolically under those conditions, suggesting that bacteria deprived of sufficient dietary substrates can turn toward host-derived proteins instead.
Second Study Challenges Assumptions About Microbiome Metabolites
A separate study published in Nature Metabolism in June 2026 examined another fundamental question: whether metabolites commonly associated with the gut microbiome necessarily originate from microbes.
Researchers used isotope tracing in mice, rats and human cells to determine the origins of several indole and phenol metabolites.
The results showed that mammalian cells themselves can generate many of the compounds previously associated primarily with bacterial metabolism.
For example, circulating concentrations of indole-3-lactate and indole-3-acetate remained elevated even after antibiotic treatment substantially disrupted the microbiome. Researchers said that pattern resembled what has been observed in patients taking antibiotics.
Other metabolites responded very differently.
Compounds produced exclusively by microbes, including indole-3-propionate and p-cresol sulfate, declined following antibiotic treatment.
Those contrasting responses allowed researchers to distinguish metabolic products that depend on gut bacteria from those the host can produce independently.
The findings challenge a broader assumption that the presence of certain indole and phenol metabolites in the body necessarily means they were generated by the microbiome.
That distinction could be particularly important as researchers investigate therapies intended to manipulate intestinal microbes or administer their metabolic products.
Joshua Rabinowitz, director of Ludwig Princeton, said there is “growing interest across medical disciplines in manipulating the human microbiome or using its metabolic products themselves for therapy.”
Determining precisely where individual metabolites originate and how diet influences their production will therefore be important when developing interventions intended to increase helpful compounds or suppress potentially harmful ones.
Fiber and Prif Could Shape Future Dietary Strategies
Viewed together, the two studies provide a more detailed picture of the connections among food, intestinal bacteria, host metabolism and the compounds circulating through the body.
Rather than treating all microbiome-associated metabolites as products of the same biological process, the findings show that different compounds can originate through substantially different routes.
Some depend directly on microbial activity. Others can be produced by mammalian metabolism without bacterial involvement. Still others can change depending on whether microbes are metabolizing dietary material or proteins derived from their host.
Diet can influence that balance.
Fiber appears to help prevent intestinal microbes from turning toward proteins in the protective mucus layer as an alternative nutrient source. Prif, meanwhile, supplies indigestible plant-derived protein to the microbiome and can favor production of different phenylalanine-derived metabolites.
The discovery of Prif raises the possibility that indigestible proteins could eventually be considered a distinct nutritional category alongside dietary fiber.
Rabinowitz suggested that “food packaging may eventually list Prif right below fiber.”
Understanding those distinctions could eventually allow scientists to develop more precise dietary or probiotic strategies designed to alter individual metabolites rather than broadly attempting to change the microbiome.
Such approaches might seek to increase particular beneficial compounds, decrease undesirable metabolites or provide microbial communities with dietary substrates that discourage them from consuming host tissue.
Those possibilities remain areas for future research, and additional studies will be necessary before the findings can be translated into specific clinical recommendations.
Findings Add to Evidence on the Importance of Fiber
The research also provides a possible biological explanation for observations made in earlier studies examining low-fiber diets.
Previous work has suggested that when gut microorganisms do not receive adequate dietary fiber, they can begin utilizing host-derived material as an alternative source of nutrients. Dr. Mercola highlighted that concept in 2016, warning that microbes deprived of adequate fiber may effectively begin feeding on their host and emphasizing the importance of prebiotic fiber.
The new research demonstrates one mechanism through which that process can occur, identifying proteins within the gut’s mucus barrier as a bacterial nutrient source under certain dietary conditions.
The findings also contribute to the broader scientific discussion surrounding fiber and health beyond the digestive tract.
A report from NaturalNews.com has cited multiple peer-reviewed studies associating greater dietary fiber consumption with improved cognitive function and a reduced risk of depression.
Although such associations do not establish that fiber alone produces those outcomes, the Princeton research further illustrates the extensive metabolic consequences that can result from differences in the nutrients reaching intestinal microbes.
Research Points Toward More Precise Understanding of Diet and the Microbiome
The two studies indicate that the effects of plant-based foods on the gut extend beyond conventional definitions of dietary fiber.
Fiber can influence whether microorganisms consume dietary material or turn toward the body’s own protective proteins, while indigestible plant proteins can provide another substrate for microbial metabolism and alter the resulting chemical compounds.
At the same time, the Nature Metabolism findings show that researchers must distinguish metabolites genuinely produced by bacteria from those generated independently by the human body before attempting to manipulate them through microbiome-based treatments.
The research was supported by the Ludwig Institute for Cancer Research, the National Institutes of Health and other agencies.
Further research will be required to determine how the findings translate from experimental systems into clinical nutrition and medical treatment. The studies nevertheless provide a foundation for more targeted investigation of how particular foods, fiber and indigestible plant proteins can influence the microbiome, the intestinal barrier and the metabolites produced throughout the body.
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