JULY 27, 2026, NEW YORK – Plant-based diets are good for you. They promote gut, immune, metabolic and cardiovascular health, in part by cultivating a diverse community of intestinal bacteria. These benefits have long been known to stem partly from the fiber in plant-based foods, which are processed by our commensal gut bacteria, and the often brightly colored “phytochemicals” plants produce to protect themselves from environmental threats. But much remains to be learned about how exactly the bugs in our bellies process the constituents of veggies to such salubrious effect.
A pair of studies led by Ludwig Princeton’s Jenna AbuSalim and Director Joshua Rabinowitz —one in the current issue of the Proceedings of the National Academy of Sciences , the other published in Nature Metabolism in June—shed new light on the matter. One study reveals that plant fibers and proteins reprogram microbial metabolism to boost production of a healthful species of metabolites, while suppressing that of their harmful counterparts. The other demonstrates that many physiologically important metabolites generally attributed to intestinal microbes are, in fact, produced abundantly by mammalian metabolism as well.
“There’s growing interest across medical disciplines in manipulating the human microbiome or using its metabolic products themselves for therapy,” said Rabinowitz. “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.”
For the PNAS study, Rabinowitz, AbuSalim and their colleagues explored how plant-based foods affect levels of phenol metabolites. Produced by the bacterial digestion of the amino acids tyrosine and phenylalanine, these phenols have sharply divergent health effects. One set, phenylpropionate and hippuric acid, made from the bacterial processing of phenylalanine, supports gut health and healthy body weight. The other, p-cresol sulfate and phenol sulfate, derives from tyrosine and is associated with worse outcomes for cancer patients and systemic toxicity in patients with kidney disease.
“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,” said AbuSalim.
While the benefits of plant fibers are well known, indigestible proteins from plants have so far been largely overlooked. AbuSalim, Rabinowitz and colleagues report here that such proteins are processed by gut microbes, reshaping microbiome composition and host metabolism. They further act in concert with indigestible plant fiber to rewire the metabolic programs of gut bacteria in a manner that favors the production of “good” phenols.
By labeling proteins with stable (non-radioactive) isotopes and tracking their digestion in the mouse gut, the researchers discovered that the “bad” phenols are made by the bacterial consumption of host proteins, such as those in the mucus lining the gut, while the good phenols are made almost exclusively from the indigestible dietary proteins (Prif). Fiber suppresses bacterial catabolism of the gut mucus lining, decreasing production of the bad phenols. Prif enhances the amount of dietary protein reaching gut microbes and thus the production of the good phenols.
“We think Prifs represent an emerging class of dietary nutrients that shape the composition of the gut microbiome and could have a far-reaching influence on metabolic health,” said AbuSalim.
“Food packaging may eventually list Prif right below fiber,” said Rabinowitz.
The Nature Metabolism study explored the sources of phenol metabolites and that of indole metabolites, which are derived from the amino acid tryptophan. Like phenols, they are being actively investigated for their therapeutic potential. Indole metabolites have been implicated in diseases ranging from inflammatory bowel disease to neurodegenerative disorders to cancer, where they’ve been found to influence cancer metastasis and anti-tumor immune responses, among other things.
Both phenols and indoles were generally believed to be produced solely by gut bacteria, an assumption AbuSalim and Rabinowitz and colleagues thought they’d put to the test. There has been much interest in developing dietary or probiotic-based strategies to boost the levels of healthy indole metabolites. But if mammalian metabolism contributes most to their circulating levels, alternative approaches need to be considered.
As it turned out, isotope-tracing studies in mice, rats and human cells revealed that mammalian metabolism is perfectly capable of producing many indole and phenol metabolites, including several physiologically important ones like indole-3-lactate and indole-3-acetate. In mice, circulating levels of the metabolites remained robust following treatment with antibiotics, which disrupt the microbiome. This was reflected also in samples from patients, including cancer patients, on antibiotics. Meanwhile, metabolites produced exclusively by microbes, such as indole-3-propionate and p-cresol sulfate, decreased following antibiotic treatment.
Taken together, the findings of the two studies make important contributions to our understanding of the source and production of phenol and indole metabolites and have implications for the design of tools and strategies to manipulate their levels for therapy.
“Beyond that,” said Rabinowitz, “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.”
These studies were funded 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, Princeton University.
Aside from his post as Director of the Princeton Branch of the Ludwig Institute for Cancer Research, Joshua Rabinowitz is Professor in the Department of Chemistry & Lewis-Sigler Institute for Integrative Genomics and a member of the Rutgers Cancer Institute.
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Ludwig Cancer Research is an international collaborative network of acclaimed scientists that has pioneered cancer research and landmark discovery for more than 50 years. Ludwig combines basic science with the translation and clinical evaluation of its discoveries to accelerate the development of new cancer diagnostics, therapies and prevention strategies. Since 1971, Ludwig has invested nearly $3 billion in life-changing science through the not-for-profit Ludwig Institute for Cancer Research and the six U.S.-based Ludwig Centers. To learn more, visit www.ludwigcancerresearch.org .
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Proceedings of the National Academy of Sciences