Scientists are discovering that the health value of plant foods may depend partly on a hidden competition inside the gut.
When the right plant material reaches intestinal bacteria, the microbes may feed on the diet instead of turning to proteins in the gut’s protective lining.
That shift could change the chemicals produced inside the intestine, according to two studies led by Jenna AbuSalim and Joshua Rabinowitz at Ludwig Princeton. The studies were published in the Proceedings of the National Academy of Sciences and Nature Metabolism.
Plant-rich diets have repeatedly been linked with better heart and metabolic health and with a healthier digestive system. Researchers have often credited fiber, which humans cannot fully digest but many gut bacteria can use as food.
Yet plants contain far more than fiber. They also contain proteins, natural pigments, and many other compounds, and scientists are still learning what happens to these substances after they enter the complex ecosystem of the intestine.
The gut microbiome contains an enormous community of microorganisms. Rather than simply sitting inside the digestive tract, these microbes constantly transform food molecules into new chemicals that can enter the bloodstream or interact with intestinal cells.
These chemicals are called metabolites. Some may be useful to the body, while others can contribute to problems when they accumulate, particularly in people whose kidneys cannot remove them effectively.
In one of the new studies, researchers investigated a family of metabolites known as phenols. Gut bacteria can make different phenols depending on whether they are processing the amino acid phenylalanine or the related amino acid tyrosine.
That difference matters because the resulting chemicals are not biologically identical. Phenylpropionate and hippuric acid have been linked in previous research with healthier body weight and gut health.
By comparison, p-cresol sulfate and phenol sulfate have been associated with toxicity in kidney disease and poorer outcomes in some people with cancer. The researchers wanted to understand what determines which group of compounds microbes produce.
Fiber turned out to be part of the answer, but the study uncovered another player. Some proteins in plant foods are difficult for human digestive enzymes to break down, allowing them to travel farther through the intestine.
AbuSalim and colleagues describe these substances as “proteins imitating fiber,” shortened to Prif. Although they are proteins rather than fiber, their resistance to digestion means they can reach gut bacteria and become microbial food.
Experiments showed that Prif and plant fiber changed microbial metabolism in complementary ways. Together, they shifted production away from tyrosine-related harmful phenols and toward phenylalanine-related compounds considered more favorable.
The researchers then asked a deeper question: where were the bacteria getting the raw materials for the harmful compounds? To answer it, they tagged proteins with stable, non-radioactive isotopes and tracked them through the digestive system of mice.
The results suggested that harmful phenols were often made when bacteria broke down proteins belonging to the host animal. Importantly, some of those proteins came from the mucus coating that protects the intestinal wall.
This mucus is not simply waste. It helps create a physical and chemical barrier that separates a dense population of microbes from the body’s intestinal tissue.
Dietary fiber appeared to reduce the microbes’ need to consume that protective material. With more fiber available, bacterial breakdown of mucus decreased, and production of harmful phenols also fell.
Prif supplied another source of food. Because these plant proteins survived digestion long enough to reach the microbes, bacteria could use dietary protein to make more of the favorable phenylalanine-derived compounds.
The discovery suggests that nutrition labels may eventually need to consider more than conventional fiber when scientists evaluate how foods feed the microbiome. Rabinowitz even suggested that Prif could someday become a recognized dietary category.
A second study from the same research group complicated the picture further. It asked whether several metabolites commonly described as products of gut bacteria are really made only by microbes.
The team focused on both phenols and indoles. Indoles are chemicals related to the amino acid tryptophan and have attracted attention because of possible roles in immune responses, intestinal disease, cancer, and disorders of the nervous system.
Many efforts to manipulate the microbiome assume that increasing or decreasing certain bacteria will change the amount of a desired metabolite. That strategy only works as expected if microbes are actually the main source of the chemical.
Using isotope tracing in mice, rats, and human cells, the researchers discovered that mammalian cells themselves could make several important compounds. Indole-3-lactate and indole-3-acetate were among those produced in meaningful amounts without relying entirely on gut bacteria.
Antibiotic experiments provided another test. When antibiotics disrupted the microbiome, some supposedly microbial metabolites remained surprisingly abundant in the circulation.
Researchers observed a similar pattern in samples from people taking antibiotics, including patients being treated for cancer. This strengthened the evidence that the human body itself can contribute substantially to production of some of these chemicals.
Other metabolites behaved differently. Indole-3-propionate and p-cresol sulfate fell after antibiotic treatment, indicating that these compounds depend much more strongly on microbial production.
This distinction could have practical consequences. If scientists want to raise a potentially helpful metabolite with probiotics or lower a harmful one by changing the microbiome, they first need to know whether bacteria are actually controlling most of its production.
The two studies therefore change the story in two ways. First, they suggest that hard-to-digest plant proteins can act alongside fiber to influence what bacteria eat and which metabolites they release.
Second, they show that some chemicals long treated as microbial products also come from normal metabolism in mammalian cells. The gut microbiome and the host body are both chemical factories, and their products can overlap.
From a health perspective, the findings offer a possible explanation for some benefits associated with plant-rich diets, but they are not yet a prescription for a specific food or supplement. Many experiments involved animals or cells, and scientists still need to determine how strongly these mechanisms affect human disease.
The research also warns against labeling every metabolite as simply “good” or “bad.” A chemical’s effects may vary with its concentration, the health of the person, where it is produced, and how efficiently the body removes it.
The most important advance is the clearer map of how diet, microbes, and the body’s own metabolism interact. That knowledge could eventually make nutrition and microbiome therapies more targeted, but clinical studies will be needed before these discoveries can be turned into specific advice for preventing or treating disease.
Source: Princeton University.
