Ludwig Princeton studies link plant fiber and Prif proteins to healthier gut metabolites

Two Ludwig Princeton studies led by Jenna AbuSalim and Joshua Rabinowitz find that plant fiber and indigestible plant proteins they call Prif can steer gut microbes away from consuming the intestine's protective mucus and toward metabolites tied to better gut health and body weight. In work published in the Proceedings of the National Academy of Sciences, isotope tracing in mice showed beneficial phenols such as phenylpropionate and hippuric acid came almost entirely from dietary indigestible proteins, while harmful phenols such as p-cresol sulfate and phenol sulfate arose largely when bacteria broke down host proteins in the mucus lining. Fiber suppressed mucus breakdown; Prif boosted the more favorable phenylalanine pathway. A companion Nature Metabolism paper found mammalian cells can produce many indoles and phenols on their own, including indole-3-lactate and indole-3-acetate, so antibiotic disruption did not clear those compounds from blood the way it cleared microbe-exclusive metabolites. Rabinowitz said diet remains a path to control microbiome outputs, but therapies must match whether a metabolite is mainly microbial or host-made. The papers list DOI 10.1073/pnas.2605226123 and DOI 10.1038/s42255-026-01550-8.