Gut bacteria are often credited with producing a wide range of compounds linked to digestion, immunity and other aspects of health. New research suggests the human body may produce some of those compounds on its own, complicating efforts to control them through food, probiotics or other microbiome-focused approaches.
The findings come from two separate studies involving mice, rats, human cells and patient samples. Neither study tested a diet in people nor showed that changing these compounds improves health. Instead, the research helps clarify where certain substances found in the body come from and how diet may influence their production.
“There’s growing interest across medical disciplines in manipulating the human microbiome or using its metabolic products themselves for therapy,” said Joshua Rabinowitz, director of the Princeton Branch of the Ludwig Institute for Cancer Research. “Diet holds great promise for controlling the microbiome and its outputs. But to devise effective therapeutic interventions, we need to understand what aspects of the diet control which microbial outputs.”
One study, published in Nature Metabolism, examined compounds known as indole and phenol metabolites. These substances are produced when amino acids, the building blocks of protein, are broken down.
Scientists have often assumed that many of these compounds are made primarily or exclusively by gut bacteria. That assumption has fueled interest in diets, probiotics and other treatments intended to alter their levels.
The researchers found that mammalian cells could also produce several of the compounds. In mice, some remained in circulation even after antibiotic treatment disrupted the gut microbiome. Similar patterns appeared in samples from patients taking antibiotics.
Other compounds did fall after antibiotic treatment, indicating that gut bacteria remained important to their production.
The findings do not mean the microbiome is unimportant. Rather, they suggest that scientists may need to distinguish more carefully between compounds produced by microbes, compounds produced by the body and compounds produced by both.
That distinction matters because a diet or probiotic designed to influence gut bacteria may have less effect on a compound if the body is producing much of it independently.
The second study, published in the Proceedings of the National Academy of Sciences, looked at how fiber and certain hard-to-digest plant proteins affected gut bacteria in mice.
The researchers used specially labeled proteins to track what happened as the proteins moved through the digestive system. They found that some plant proteins reached the lower digestive tract without being fully broken down, allowing gut bacteria to use them.
The researchers call these proteins “proteins imitating fiber,” or Prif, because they appear to reach gut microbes in a way that resembles fiber.
In the mice, fiber and these plant proteins shifted the balance of compounds produced by gut bacteria. Fiber also appeared to reduce the breakdown of proteins found in the gut’s protective mucus layer.
“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,” said Jenna AbuSalim, a researcher at Ludwig Princeton.
The researchers described some of the resulting compounds as potentially more favorable than others, but those labels require caution. A compound associated with better or worse health outcomes does not necessarily cause those outcomes, and its effects may differ depending on the amount, location and health of the person involved.
The research also does not establish Prif as a recognized nutrient category. Rabinowitz suggested food labels could someday include it alongside fiber, but that possibility remains speculative. Scientists would first need to determine which foods contain meaningful amounts, how the proteins behave in people and whether they produce measurable health benefits.
For now, the studies offer a more detailed picture of the relationship among food, gut bacteria and the body’s own metabolism.
They do not provide a reason to seek out a particular supplement, probiotic or plant protein. They also do not change established guidance encouraging people to eat a varied diet that includes fiber-rich plant foods.
Instead, the findings show why microbiome claims deserve careful scrutiny. A substance detected in the blood or digestive system may not come from a single source, and changing gut bacteria may not automatically change every compound associated with them.
“A clearer picture of how different foods interact with the microbiome to modulate the production of bacterial metabolites will help sharpen the guidance nutritionists and doctors can give to people for disease prevention and therapy,” Rabinowitz said.
The studies were supported by the Ludwig Institute for Cancer Research, the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, the Princeton Alliance for Collaborative Research and Innovation and Princeton University.