Gut bacteria need to eat, and if you don’t feed them, they’ll find something else to feed on, including you. Two new studies from the Ludwig Institute for Cancer Research’s Princeton branch, led by Jenna AbuSalim and Joshua Rabinowitz, dig into what actually happens when plant-based diets influence the gut microbiome, and the picture is more nuanced, and stranger than “fiber is good.”

Two families of metabolites, two very different outcomes

The first study, published in Proceedings of the National Academy of Sciences, looked at phenol metabolites, compounds gut bacteria produce while breaking down the amino acids tyrosine and phenylalanine. Not all phenols are equal. Phenylpropionate and hippuric acid, made from phenylalanine, are linked to gut health and healthy body weight. P-cresol sulfate and phenol sulfate, made from tyrosine, are linked to worse outcomes in cancer patients and toxicity in people with kidney disease.

Using stable isotope labeling to trace exactly where these compounds come from in the mouse gut, the researchers found something unexpected: the harmful tyrosine-derived phenols were largely produced when bacteria broke down proteins belonging to the host, including proteins in the protective mucus lining of the gut itself. The beneficial phenols, on the other hand, came almost entirely from indigestible plant proteins in the diet.

Meet “Prif”, protein imitating fiber

Fiber has long had the spotlight in gut health advice, but this research points to an overlooked co-star: indigestible plant proteins, which the team is calling Prif (“proteins imitating fiber”). Fiber suppressed bacterial breakdown of the gut’s mucus lining, cutting down production of the harmful phenols. Prif gave gut microbes more dietary protein to work with, feeding the production of the beneficial phenols instead. Working together, fiber and Prif shifted the overall balance of gut chemistry toward the healthier profile. As Rabinowitz put it, “food packaging may eventually list Prif right below fiber.”

Not everything credited to microbes actually comes from microbes

The second study, published in Nature Metabolism, challenges a longstanding assumption: that phenol and indole metabolites (indoles come from the amino acid tryptophan, and have been linked to inflammatory bowel disease, neurodegeneration, and cancer) are made exclusively by gut bacteria. Using isotope tracing in mice, rats, and human cells, the team found that mammalian metabolism can independently produce many of these same compounds, including indole-3-lactate and indole-3-acetate.

The clearest evidence came from antibiotic treatment. In both mice and human cancer patients on antibiotics, levels of metabolites made exclusively by microbes (like indole-3-propionate and p-cresol sulfate) dropped as expected. But levels of indole-3-lactate and indole-3-acetate stayed high, because the body itself, not just bacteria, was still making them.

Why it matters

Together, the two studies sharpen a picture that’s been blurry for years: which gut metabolites come from diet, which come from bacteria, and which the body can make on its own regardless of what’s happening in the microbiome. That distinction matters for anyone designing a probiotic, dietary, or drug-based strategy to raise or lower specific metabolites, targeting the microbiome won’t help if the body is producing the compound independently, and ignoring diet won’t help if bacteria are quietly cannibalizing the gut lining for lack of better fuel.

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