{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T23:44:07Z","timestamp":1793490247412,"version":"4.5.0"},"reference-count":97,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7254471"],"award-info":[{"award-number":["7254471"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22576021"],"award-info":[{"award-number":["22576021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing High-Level Innovation and Entrepreneurship Talent Support Program\u2014Young Top Talent Projects","award":["20250598"],"award-info":[{"award-number":["20250598"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Human organoids and organ-on-chip\/microphysiological systems (OoC\/MPS) are increasingly used as new-approach methodologies for biotoxin assessment. They retain human-relevant tissue organization and enable interpretable analysis of exposure geometry, barrier transport, perfusion, and (when needed) multi-organ coupling. In this review, we synthesize primary evidence across major toxin classes, including bacterial enterotoxins (e.g., cholera toxin, heat-stable enterotoxins, Shiga toxins), mycotoxins (e.g., aflatoxin B1, ochratoxin A, deoxynivalenol), and algal\/cyanobacterial toxins (e.g., saxitoxin, domoic acid, microcystins, biliatresone). We emphasize studies that clearly define toxin identity and exposure context and that demonstrate mechanism-critical model competencies under assay conditions. We highlight decision-informative functional endpoints that align with the dominant pathophysiology. These include cystic fibrosis transmembrane conductance regulator (CFTR)-dependent secretion in human enteroids\/colonoids, transporter-linked proximal tubular injury in kidney MPS, gut\u2013kidney axis injury from Shiga toxin-producing E. coli in microfluidic systems, and multi-electrode array (MEA) network readouts in human 3D neural tissues. We then summarize best practices that improve cross-study comparability. These include reporting delivered versus nominal exposure, assessing recovery\/mass balance and device\/material interactions, applying proportional biological qualification (polarity, transporter\/enzymatic competence, functional stability), defining a minimal comparable endpoint core, and preserving QIVIVE readiness in reporting. Finally, we outline near-term priorities for the field, including chronic low-dose and mixture designs, harmonized reference panels and acceptance criteria, and fit-for-purpose escalation to coupled OoC\/MPS only when perfusion or organ\u2013organ coupling is expected to change the interpretation.<\/jats:p>","DOI":"10.3390\/toxins18030149","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:38:01Z","timestamp":1773934681000},"page":"149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Human Organoids and Organ-on-Chip for Biotoxin Assessment: Applications, Best Practices, and a Translational Roadmap"],"prefix":"10.3390","volume":"18","author":[{"given":"Mingzhu","family":"Li","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing 100013, China"},{"name":"School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinze","family":"Jia","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing 100013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixing","family":"Feng","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing 100013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing 100013, China"},{"name":"School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110489","DOI":"10.1016\/j.cellsig.2022.110489","article-title":"The manipulation of cell signaling and host cell biology by cholera toxin","volume":"100","author":"Christopher","year":"2022","journal-title":"Cell. 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