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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,11]]},"abstract":"<jats:p>\n                    Plant-based diets are associated with both positive health outcomes and a diverse gut microbiome. Such diets alter the microbiome\u2019s metabolic outputs, including increasing phenylalanine-derived phenols associated with beneficial health outcomes (hippuric acid and 3-phenylpropionate), while decreasing tyrosine-derived phenols considered uremic toxins (phenol sulfate and p-cresol sulfate). The mechanisms linking plant eating to these phenol metabolites are not known. Plant-based foods are fiber and phytochemical rich. They also contain proteins that are resistant to host digestion and thus reach the gut microbiome. Here, we show that fiber and digestion-resistant protein work in concert to shift the phenol profile by altering gut microbiome nutrient supply. Through isotope-tracing studies, we reveal that host secreted proteins are a source for phenol sulfate and p-cresol sulfate, while digestion-resistant dietary protein is the source for hippuric acid and 3-phenylpropionate. Fiber decreases bacterial digestion of host secreted proteins (e.g., mucins) and thus suppresses tyrosine-derived phenol sulfate and p-cresol sulfate, whose levels correlate with the mucin-digesting bacterial family\n                    <jats:italic toggle=\"yes\">Oscillospiraceae.<\/jats:italic>\n                    Digestion-resistant dietary protein increases bacterial access to phenylalanine and thereby boosts phenylalanine-derived hippuric acid and 3-phenylpropionate. Thus, digestion-resistant plant protein modulates microbiome metabolism and, together with fiber, supports healthy metabolite profiles associated with plant-based diets.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2605226123","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:47:21Z","timestamp":1785181641000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Digestion-resistant proteins support the healthy metabolite profiles associated with plant-based diets"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5870-6984","authenticated-orcid":false,"given":"Jenna E.","family":"AbuSalim","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hx57361","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology, Princeton 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