Eating more plants is widely associated with better health, but scientists are still discovering exactly why. New research suggests fiber is only part of the story. Certain plant proteins that resist digestion may also play a surprisingly important role in shaping gut bacteria and determining whether they produce beneficial or potentially harmful substances.
Plant-based diets support digestive health, immune function, metabolism and cardiovascular health. One reason is that they help maintain a diverse community of microorganisms in the intestines, collectively called the gut microbiome. Many of these bacteria are beneficial because they help break down food components that the human digestive system cannot process on its own.
Fiber is particularly important because it feeds gut microbes. Plants also contain phytochemicals, natural substances that often give fruits and vegetables their vibrant colors and help protect them from environmental threats. These compounds may also contribute to human health. Yet researchers are only beginning to understand the complex chemical interactions that occur when gut bacteria digest plant foods.
Two studies led by Jenna AbuSalim and Joshua Rabinowitz, director of the Princeton branch of the Ludwig Institute for Cancer Research, provide important new information. One, published in the Proceedings of the National Academy of Sciencesshows how plant fibers and certain proteins influence gut bacteria to promote the production of beneficial compounds rather than potentially harmful compounds. The other, published in Natural metabolism in June, challenges the long-held belief that many important chemical compounds circulating in the body come exclusively from gut microbes.
“There is growing interest across medical disciplines in manipulating the human microbiome or using its metabolic products themselves for therapeutic purposes,” Rabinowitz said. “Diet holds great promise for controlling the microbiome and its outputs. But to design effective therapeutic interventions, we need to understand which aspects of diet control which microbial outputs.”
How Plant Foods Change the Chemicals Your Gut Produces
In the PNAS In this study, researchers looked at a group of substances called phenol metabolites. Metabolites are chemicals formed when the body or microorganisms break down and process nutrients. Some are essential for normal biological functions, while others can contribute to health problems when they accumulate.
The phenol metabolites studied by the team are produced when gut bacteria process two amino acids, tyrosine and phenylalanine. Amino acids are the building blocks of proteins, but the compounds they produce can have very different effects on health.
Two phenylalanine-derived metabolites, phenylpropionate and hippuric acid, are associated with healthy body weight and better gut health. In contrast, two tyrosine-derived compounds, p-cresol sulfate and phenol sulfate, have been linked to worse outcomes in cancer patients and harmful effects throughout the body in people with kidney disease.
The researchers wanted to understand whether different components of plant foods could influence which of these substances are produced by gut microbes.
“Our studies have shown that fiber and indigestible proteins in plants – which we call ‘fiber-mimicking proteins’ or Prif – shift the balance of phenol metabolites, from the harmful kind made from tyrosine to the healthy variety derived from phenylalanine,” AbuSalim said.
An Overlooked Plant Protein Works Alongside Fiber
Although the health benefits of dietary fiber have been widely studied, scientists have paid much less attention to plant proteins that pass through the digestive system without being completely broken down.
The researchers found that these indigestible proteins, which they call Prif, can reach the gut microbiome and serve as material for bacterial metabolism. In doing so, they influence which microbes grow and which chemical compounds are produced.
It is important to note that these proteins do not work in isolation. They cooperate with plant fibers to change the way gut bacteria process nutrients, directing their activity toward the production of beneficial phenolic metabolites.
This finding suggests that the nutritional value of plant foods may depend on much more than their usual concentrations of fiber, vitamins and minerals. The amount and type of proteins that escape digestion could also help determine how foods influence the gut microbiome.
When gut bacteria lack fiber, they can feed on the protective mucus in your gut
One of the most intriguing findings concerns where gut bacteria obtain the raw materials used to produce harmful metabolites.
To investigate, the researchers labeled the proteins with stable (non-radioactive) isotopes, allowing them to track exactly where the proteins moved and how they were processed in the mice’s digestive systems. This technique works by giving molecules a detectable chemical signature without making them radioactive.
The experiments revealed a significant difference between beneficial and harmful sources of phenols.
The potentially harmful phenols came from gut bacteria breaking down proteins belonging to the host, including proteins found in the mucus layer that covers the intestines. This protective mucus helps separate intestinal microbes from the cells lining the intestine and is part of the body’s natural defenses.
During this time, beneficial phenols were produced almost entirely from indigestible proteins provided by foods.
Fiber helped suppress bacterial breakdown of the gut’s protective mucus, thereby reducing the production of harmful phenols. Non-digestible plant proteins (Prif), in turn, provided more dietary protein to gut bacteria, encouraging them to produce beneficial compounds.
Together, the results reveal two complementary ways that plant foods can influence gut chemistry. Fiber helps discourage bacteria from consuming the proteins in the gut’s protective mucus, while Prif provides an alternative source of nutrients that supports the production of healthier metabolites.
“We believe that Prifs represent an emerging class of dietary nutrients that shape the composition of the gut microbiome and could have a dramatic influence on metabolic health,” AbuSalim said.
The implications could eventually extend to nutrition labels and dietary recommendations.
“Food packaging could potentially include Prif just below the fiber,” Rabinowitz said.
Second discovery challenges what scientists thought about gut bacteria
The additional study in Natural metabolism addressed another important question: are gut bacteria actually responsible for producing all the metabolites traditionally attributed to them?
In addition to phenol metabolites, the researchers looked at indole metabolites, formed from tryptophan, another amino acid found in food proteins.
These substances attract considerable scientific interest because they participate in biological processes related to inflammation, immune activity and disease. Researchers have studied their involvement in inflammatory bowel diseases, neurodegenerative disorders and cancer. Certain indole metabolites have also been shown to influence the spread of cancer and the ability of the immune system to attack tumors.
Scientists generally assume that gut bacteria are the source of these compounds. This belief has encouraged efforts to develop probiotics and dietary interventions that increase the production of potentially beneficial indole metabolites.
However, this approach relies on an important assumption: Gut microbes are responsible for producing most, if not all, of the compounds that researchers want to influence.
If the body’s cells produce substantial amounts of these metabolites, changing the microbiome may not be the most effective way to control their levels.
Your body may produce compounds once attributed to gut microbes
To investigate, the research team used isotope tracing in mice, rats and human cells to track the production of different metabolites.
The results challenged conventional thinking. Mammalian cells were capable of generating many phenol and indole metabolites independently of gut bacteria.
These included indole-3-lactate and indole-3-acetate, two biologically important compounds previously thought to be products of microbial metabolism.
The researchers also looked at what happened when antibiotics disrupted the gut microbiome. If certain metabolites were entirely dependent on gut bacteria, their concentrations would decrease sharply when these bacteria were depleted.
But many metabolites remained at substantial levels in the blood of antibiotic-treated mice. A similar trend appeared in samples from patients receiving antibiotics, including people undergoing cancer treatment.
Other compounds behaved differently. Levels of indole-3-propionate and p-cresol sulfate, produced exclusively by microbes, decreased after antibiotic treatment.
These results provided further evidence that some metabolites depend on gut bacteria, while others can also be made by the body’s own metabolic processes.
The distinction is important because it could change how researchers develop treatments aimed at increasing beneficial metabolites or reducing harmful metabolites.
What these findings mean for nutrition and future treatments
Together, the two studies provide a more detailed understanding of how diet, gut microbes and the body’s metabolism interact.
The first identifies a neglected class of plant proteins that work with fiber to influence bacterial activity, potentially helping to shift the balance away from harmful metabolic products. The second demonstrates that the body itself can produce many compounds once thought to come exclusively from gut bacteria.
Both findings have implications for research into metabolic diseases, digestive health, cancer and other…
Gn Health
