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Although multiple aspects of these diet types are believed to confer their respective effects, the role of their protein component is less well understood. Here, we conducted a randomized crossover-controlled feeding trial wherein healthy subjects consumed 70% of their daily protein intake in the form of pea protein (PP) or egg white protein (EWP) isolate (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05619939\">NCT05619939<\/jats:ext-link>\n                  ). Individuals who consumed EWP reported increased GI symptoms and exhibited elevated intestinal permeability. In contrast, these endpoints did not change following PP consumption. Fecal analysis showed increased diet-derived peptides only following EWP consumption, which was associated with resistance of EWP isolate to degradation by digestive enzymes\n                  <jats:italic>in vitro<\/jats:italic>\n                  . Metagenomic, metaproteomic and metabolomic analyses of stool after the EWP-based diet showed reduced abundance of multiple gut-protective bacterial species and increased bacterial amino acid utilization compared to samples following the PP-based diet. Dietary peptides in the gut luminal content of EWP-fed subjects reduced metabolic function of intestinal epithelial cell in culture. Providing an amino acid-based diet mimicking EWP composition to mice prevented colonic accumulation of diet-derived proteins and GI dysfunction associated with EWP diet consumption. Collectively, these findings demonstrate that dietary protein source is a key mediator of GI function, revealing a modifiable lifestyle factor that impacts human health.\n                <\/jats:p>","DOI":"10.64898\/2026.07.27.741049","type":"posted-content","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:10:19Z","timestamp":1785431419000},"source":"Crossref","is-referenced-by-count":0,"title":["Diet-derived peptides mediate the effects of dietary protein source on gastrointestinal health"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9826-4175","authenticated-orcid":false,"given":"Shrey D.","family":"Thaker","sequence":"first","affiliation":[{"name":"Department of Pathology Renaissance School of Medicine, Stony Brook University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Danowski","sequence":"additional","affiliation":[{"name":"Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine, Stony Brook University"},{"name":"Stony Brook Cancer Center, Stony Brook, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotiria","family":"Everett","sequence":"additional","affiliation":[{"name":"Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine, Stony Brook University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine, Stony Brook University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xaioyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biostatistical Consulting Core, Renaissance School of Medicine, Stony Brook University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine, Stony Brook University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn R.","family":"Dweck","sequence":"additional","affiliation":[{"name":"Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine, Stony Brook University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Aroniadis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonah S.","family":"Vadakkan","sequence":"additional","affiliation":[{"name":"Department of Pathology Renaissance School of Medicine, Stony Brook University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7638-5849","authenticated-orcid":false,"given":"J. 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