Plant-based foods may do more for the gut than simply provide fiber.
Two new studies suggest that parts of plants that resist normal digestion can change what gut bacteria eat and, in turn, influence the chemicals those bacteria release into the body.
The research was led by Jenna AbuSalim and Joshua Rabinowitz of Ludwig Princeton. One study was published in the Proceedings of the National Academy of Sciences, while a related study appeared in Nature Metabolism in June.
Scientists have known for years that diets rich in vegetables, fruits, beans, whole grains, nuts, and seeds are associated with many health benefits. These foods provide vitamins and minerals, but they also contain fiber and thousands of natural plant compounds that interact with the digestive system.
The human intestine is home to trillions of bacteria and other microorganisms, collectively called the gut microbiome. These microbes help process parts of food that human digestive enzymes cannot completely break down.
When microbes feed on these leftovers, they produce small chemicals called metabolites. Some metabolites may support the intestinal lining, immune system, and metabolism, while others can become harmful when produced in large amounts or when the body cannot remove them efficiently.
The first new study focused on chemicals called phenol metabolites. Gut microbes can produce these substances when they process two amino acids, phenylalanine and tyrosine, which are building blocks of proteins.
Not all phenol metabolites have the same effects. Phenylpropionate and hippuric acid, which can arise from phenylalanine, have been associated with healthier body weight and better gut health.
Other compounds have a less favorable reputation. P-cresol sulfate and phenol sulfate, which are connected with tyrosine metabolism, can build up in people with poor kidney function and have been linked with toxic effects in the body.
The Princeton-led researchers found that plant fiber could shift this chemical balance. But they also discovered that certain plant proteins that pass through the upper digestive system without being fully digested may have an important role.
The team calls these proteins “proteins imitating fiber,” or Prif. Like fiber, they reach the lower intestine, where they become food for gut microbes.
The researchers found that fiber and Prif together encouraged microbial activity that favored more of the potentially beneficial phenols derived from phenylalanine. At the same time, they reduced production of the less desirable compounds linked to tyrosine.
To understand why, the scientists needed to determine exactly what the bacteria were eating. They used stable isotope labels, which act like harmless chemical tracking tags, to follow proteins as they moved through the digestive system of mice.
The experiment revealed an unexpected difference. The more favorable phenols came largely from indigestible proteins supplied by the diet, while harmful phenols were produced when bacteria consumed proteins belonging to the animal itself.
Some of those host proteins came from mucus lining the intestine. This mucus forms a protective barrier between gut microbes and the cells underneath.
When microbes begin using the gut’s own mucus as a food source, the relationship between the body and its microbial residents can change. The study found that dietary fiber reduced bacterial breakdown of this mucus and therefore reduced production of some harmful phenols.
Prif appeared to help in a different way. By carrying more dietary protein into the lower intestine, it gave microbes an alternative source of material that could be turned into more favorable metabolites.
This finding expands the traditional view of plant nutrition. Fiber has received enormous attention, but indigestible plant proteins may represent another important part of food that shapes the microbiome.
The second study challenged another common assumption about gut metabolites. Scientists have often treated several phenol and indole compounds as products made almost entirely by intestinal bacteria.
Indoles are produced from tryptophan, another amino acid found in proteins. Researchers are interested in these compounds because they have been connected with inflammation, immune function, cancer, inflammatory bowel disease, and diseases affecting the brain.
Using isotope tracking in mice, rats, and human cells, the researchers found that the body’s own cells can produce substantial amounts of several indole and phenol metabolites. These included indole-3-lactate and indole-3-acetate.
The team also studied what happened when antibiotics greatly disrupted gut bacteria. If a metabolite came only from microbes, its level should fall sharply when those microbes disappeared.
Some compounds did exactly that. Indole-3-propionate and p-cresol sulfate dropped after antibiotic treatment, supporting the idea that they depend strongly on gut bacteria.
But other metabolites remained at substantial levels despite disruption of the microbiome. Similar patterns appeared in samples from people taking antibiotics, including cancer patients, suggesting that human metabolism can also be an important source.
These findings matter because scientists are trying to develop diets, probiotics, and medicines that change specific microbial metabolites. Such treatments will be difficult to design if researchers incorrectly assume that every target chemical comes from gut bacteria.
Taken together, the two studies show that the relationship between food, microbes, and human metabolism is more complicated than a simple idea that “fiber feeds good bacteria.” Different plant components can change what microbes consume, while the body itself can produce chemicals once credited mainly to microbes.
The work is promising because it points toward more precise nutrition research. In the future, scientists may be able to identify which foods increase helpful metabolites or reduce harmful ones rather than giving broad dietary advice alone.
However, much of the detailed tracing work was performed in animals and laboratory systems, so the findings do not yet prove that increasing a particular plant protein will prevent disease in people. The health effects of individual metabolites also remain complex and can depend on dose, disease, and other biological factors.
The strongest conclusion is therefore about mechanism rather than treatment.
The studies reveal new ways plant fiber and hard-to-digest proteins shape gut chemistry and show that scientists must distinguish microbial metabolism from the body’s own metabolism before designing therapies around these compounds.
