{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:09:52Z","timestamp":1780319392813,"version":"3.54.1"},"reference-count":200,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: The translocation of diet-derived antigens from the maternal intestine to breast milk represents a primary gateway for neonatal immune priming, yet the structural basis for why certain proteins survive this transit while others do not remains poorly understood. This review introduces the \u201cSurvivor Peptide\u201d hypothesis, proposing that specific food allergens possess intrinsic \u201cstability architectures\u201d that enable them to resist maternal digestion and navigate the gut\u2013mammary axis to reach the infant in an immunologically active form. Methods: We analyzed the current literature regarding the detection and structural characteristics of food allergens in human milk. Integrating evidence from 26 major sources, we performed an in silico structural analysis of five representative \u201csurvivor\u201d proteins: Gal d 1 (egg white), Bos d 5 (cow\u2019s milk), Gal d 6 (egg yolk), Tri a 19 (wheat), and tropomyosin (Der p 10-mite\/shellfish). High-resolution 3D models were retrieved from the Protein Data Bank and AlphaFold2, and then visualized in UCSF ChimeraX to map stability anchors, including disulfide bonds and hydrophobic clusters, against solvent-accessible IgE-binding epitopes. Results: We identified and categorized allergens into distinct Molecular Resilience Architectures: the \u201cCovalent Cage\u201d (Gal d 1), defined by dense disulfide stapling, the \u201cGlycoprotein Shield\u201d (Gal d 6), utilizing yolk-matrix structural anchors, the \u201cTopological Shield\u201d (Bos d 5), characterized by a stable \u03b2-barrel, and \u201cCoiled-Coil Rigidity\u201d (Der p 10). These frameworks protect large, immunogenic fragments that maintain the spatial arrangement required for IgE cross-linking. Conclusions: Allergen persistence in the gut\u2013mammary axis is dictated by a protein\u2019s intrinsic structural architecture. Identifying these stability fingerprints provides a unified theory for allergen persistence and offers a path for refining component-resolved diagnostics and neonatal oral tolerance strategies.<\/jats:p>","DOI":"10.3390\/nu18111757","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:19:42Z","timestamp":1780316382000},"page":"1757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The \u201cSurvivor Peptide\u201d Hypothesis: Structural Resilience and Immunological Persistence of Food Allergens in the Gut\u2013Mammary Axis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8004-4615","authenticated-orcid":false,"given":"Madalina","family":"Coman-Stanemir","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-4005","authenticated-orcid":false,"given":"Mariana Catalina","family":"Ciornei","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Burtescu","sequence":"additional","affiliation":[{"name":"Independent Researcher, 060011 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana Raluca","family":"Papacocea","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41577-022-00821-1","article-title":"The Therapeutic Age of the Neonatal Fc Receptor","volume":"23","author":"Pyzik","year":"2023","journal-title":"Nat. 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