{"doi":"10.3390/toxins18030149","title":"Human Organoids and Organ-on-Chip for Biotoxin Assessment: Applications, Best Practices, and a Translational Roadmap","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–kidney 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–organ coupling is expected to change the interpretation.</jats:p>","journal":"Toxins","year":2026,"id":609077,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1553927,"name":"Shuhong Huang","orcid":"0000-0003-2302-4200","position":1,"is_corresponding":false},{"id":1565141,"name":"Jinze Jia","orcid":null,"position":2,"is_corresponding":false},{"id":1565142,"name":"Yixing Feng","orcid":null,"position":3,"is_corresponding":false},{"id":500806,"name":"Jing Zhang","orcid":"0000-0002-4823-4629","position":4,"is_corresponding":false},{"id":711501,"name":"Mingzhu Li","orcid":"0000-0001-7217-2045","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Human Organoids and Organ-on-Chip for Biotoxin Assessment: Applications, Best Practices, and a Translational Roadmap","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–kidney 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–organ coupling is expected to change the interpretation.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41893572","pmcid":"PMC13030031","openalex_id":null,"authors":[],"funders":[{"funder_name":"Beijing Natural Science Foundation","grant_id":"7254471","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"22576021","title":null},{"funder_name":"Beijing High-Level Innovation and Entrepreneurship Talent Support Program—Young Top Talent Projects","grant_id":"20250598","title":null}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2072-6651/18/3/149/pdf?version=1773930397","host_type":"publisher"},{"url":"https://www.mdpi.com/2072-6651/18/3/149/pdf","host_type":"publisher"},{"url":"https://doaj.org/article/2776fef1fe9c4844b713e85598bc16c3","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13030031/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC13030031","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC13030031?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["Organoids","Animals","Humans","Mycotoxins","Microphysiological Systems"],"keywords":["Mycotoxins","Enterotoxins","Organ-on-chip","Algal Biotoxins","Human Organoids"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T02:56:14.362018Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}