{"doi":"10.1101/2025.03.04.640785","title":"Human Milk Oligosaccharides Modulate Inflammatory Responses and Lipid Metabolism in a Human Intestinal Organoid Model","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>Human milk oligosaccharides (HMOs) are a major component of human breast milk and have significant protective effects on infant gut health. HMOs are also present in the amniotic fluid surrounding the developing fetus in the womb. Beginning at 10 weeks of gestational age, HMOs enter the fetal gut through the swallowing of amniotic fluid. The effects of this earliest exposure to HMOs on the gut epithelium, which pre-term infants partially miss, remains unknown. In this study, we investigate the effect of a blend of HMOs, including 2’-fucosyllactose (2’FL), 3’-sialyllactose (3’SL), and difucosyllactose (DFL), on intestinal epithelial cells, examining their role in steady-state conditions and during inflammation. By utilizing advanced intestinal epithelial organoid models derived from fetal and pediatric donors, we reveal developmental-stage-specific responses to this HMO blend, as well as its potential to mitigate inflammatory damage. These findings offer important insights into the role of HMOs in early-life nutrition and gut health, lending compelling evidence to support their inclusion in infant nutrition strategies.</jats:p>","journal":null,"year":null,"id":673313,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"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":12448,"name":"Jaesub Park","orcid":"0000-0002-4905-5980","position":1,"is_corresponding":false},{"id":1759177,"name":"Thomas Dennison","orcid":"0000-0002-1449-7965","position":2,"is_corresponding":false},{"id":1759178,"name":"Tim Mak","orcid":null,"position":3,"is_corresponding":false},{"id":1759179,"name":"Igor Bendik","orcid":null,"position":4,"is_corresponding":false},{"id":571381,"name":"Ateequr Rehman","orcid":"0000-0002-5664-4628","position":5,"is_corresponding":false},{"id":1759180,"name":"Bernd Mussler","orcid":null,"position":6,"is_corresponding":false},{"id":1759181,"name":"Frank Wiens","orcid":null,"position":7,"is_corresponding":false},{"id":1759182,"name":"Komal Nayak","orcid":null,"position":8,"is_corresponding":false},{"id":60537,"name":"Matthias Zilbauer","orcid":"0000-0002-7272-0547","position":9,"is_corresponding":false},{"id":1759176,"name":"Ellie Slater","orcid":"0000-0002-6538-7790","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Human Milk Oligosaccharides Modulate Inflammatory Responses and Lipid Metabolism in a Human Intestinal Organoid Model","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>Human milk oligosaccharides (HMOs) are a major component of human breast milk and have significant protective effects on infant gut health. HMOs are also present in the amniotic fluid surrounding the developing fetus in the womb. Beginning at 10 weeks of gestational age, HMOs enter the fetal gut through the swallowing of amniotic fluid. The effects of this earliest exposure to HMOs on the gut epithelium, which pre-term infants partially miss, remains unknown. In this study, we investigate the effect of a blend of HMOs, including 2’-fucosyllactose (2’FL), 3’-sialyllactose (3’SL), and difucosyllactose (DFL), on intestinal epithelial cells, examining their role in steady-state conditions and during inflammation. By utilizing advanced intestinal epithelial organoid models derived from fetal and pediatric donors, we reveal developmental-stage-specific responses to this HMO blend, as well as its potential to mitigate inflammatory damage. These findings offer important insights into the role of HMOs in early-life nutrition and gut health, lending compelling evidence to support their inclusion in infant nutrition strategies.</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":"19162232","pmcid":null,"openalex_id":"https://openalex.org/W4408251474","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2025/03/04/2025.03.04.640785.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2025/03/04/2025.03.04.640785.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2025.03.04.640785","host_type":"publisher"},{"url":"https://doi.org/10.1101/2025.03.04.640785","host_type":"repository"},{"url":"https://www.repository.cam.ac.uk/handle/1810/395218","host_type":"repository"},{"url":"https://www.repository.cam.ac.uk/bitstreams/829d031e-2438-401f-b197-543d005663ab/download","host_type":"repository"}],"fields_of_study":["Infant Nutrition and Health","Neonatal Respiratory Health Research","Birth, Development, and Health"],"mesh_terms":[],"keywords":["Amniotic fluid","Organoid","Fetus","Physiology","Intestinal epithelium","Biology","Breast milk","Inflammation","Embryonic stem cell","Breast feeding","Medicine","Pregnancy","Epithelium","Immunology","Cell biology","Pathology","Pediatrics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T13:00:17.718449Z","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":[]}