{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:50:30Z","timestamp":1791399030369,"version":"4.3.3"},"reference-count":78,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"870","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK078392"],"award-info":[{"award-number":["P30 DK078392"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 DK126108"],"award-info":[{"award-number":["U54 DK126108"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK116868"],"award-info":[{"award-number":["DK116868"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK137771"],"award-info":[{"award-number":["DK137771"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA218133"],"award-info":[{"award-number":["CA218133"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08 DK134884"],"award-info":[{"award-number":["K08 DK134884"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:p>\n                    Despite appreciation that neonatal immune responses differ markedly from those of adults, the mechanisms that enable early-life immunity remain poorly understood. Here, we find that healthy newborn mice express high concentrations of the S100 calcium-binding protein A8\/A9 (S100A8\/S100A9) antimicrobial heterodimer calprotectin and that this early up-regulation in the intestine is driven by initial exposure to commensal bacteria. Impaired calprotectin expression or microbiota colonization at birth increased susceptibility of neonatal mice to sepsis and death postinfection; however, calprotectin administration rescued microbiota-depleted pups from infection. Microbiota colonization induced S100A9 expression by intestinal epithelial cells (IECs), and epithelial cells represented the main source of calprotectin in the neonatal intestine. Consistent with a critical role in early-life defense, neonatal IEC-specific\n                    <jats:italic toggle=\"yes\">S100A9<\/jats:italic>\n                    knockout pups were highly susceptible to infection, phenocopying\n                    <jats:italic toggle=\"yes\">S100A8\/A9<\/jats:italic>\n                    full knockout and antibiotic-exposed neonatal mice. IEC-intrinsic S100A9 expression mediated microbiota-sensitive defense in neonatal mice, and commensal bacteria, such as\n                    <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                    , were sufficient to prime this epithelial defense pathway. Mechanistically, indole-3-lactic acid produced by initial colonizers directed IEC intrinsic up-regulation of S100A9 in both mice and human intestinal organoids. Thus, microbiota-epithelial dynamics that occur at birth are essential for programming early-life immunity and suggest that probiotic approaches targeting epithelial cells could prevent neonatal sepsis and death.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adx6147","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:58:16Z","timestamp":1791395896000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Early-life microbiota direct an epithelial S100 program required for neonatal immunity"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8028-715X","authenticated-orcid":true,"given":"Shikha","family":"Negi","sequence":"first","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."},{"name":"Center for Inflammation and Tolerance, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7501-1685","authenticated-orcid":true,"given":"Seika","family":"Hashimoto-Hill","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."},{"name":"Center for Inflammation and Tolerance, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Waddell","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."},{"name":"Center for Inflammation and Tolerance, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Engleman","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."},{"name":"Center for Inflammation and Tolerance, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Lutz","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."},{"name":"Center for Inflammation and Tolerance, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-7930","authenticated-orcid":true,"given":"Taylor","family":"Rice","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."},{"name":"Center for Inflammation and Tolerance, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8045-7198","authenticated-orcid":true,"given":"Lee A.","family":"Denson","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Vallance","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, BC Children\u2019s Hospital Research Institute and the University of British Columbia, Vancouver, BC V5Z 4H4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4969-1263","authenticated-orcid":true,"given":"Nurit P.","family":"Azouz","sequence":"additional","affiliation":[{"name":"Center for Inflammation and Tolerance, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."},{"name":"Division of Allergy and Immunology, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7177-7763","authenticated-orcid":true,"given":"Philippe A.","family":"Tessier","sequence":"additional","affiliation":[{"name":"Infectious and Immune Diseases Division, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Qu\u00e9bec, QC G1V 4G2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2987-0555","authenticated-orcid":true,"given":"Sergei I.","family":"Grivennikov","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Biomedical Sciences, Cedars-Sinai Cancer, Cedars-Sinai Health Sciences University, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9632-164X","authenticated-orcid":true,"given":"Hitesh","family":"Deshmukh","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4514-3710","authenticated-orcid":true,"given":"Theresa","family":"Alenghat","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA."},{"name":"Center for Inflammation and Tolerance, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","unstructured":"L. Liu K. Hill S. Oza D. Hogan Y. Chu S. Cousens C. Mathers C. Stanton J. Lawn B. E. Robert in Reproductive Maternal Newborn and Child Health: Disease Control Priorities Third Edition (Volume 2) R. E. Black R. Laxminarayan M. Temmerman N. Walker Eds. (International Bank for Reconstruction and Development\/World Bank 2016) pp. 71\u201383.","DOI":"10.1596\/978-1-4648-0348-2_ch4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldh029"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.03.009"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005616"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3542"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abh3816"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad2571"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1898-4"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0480-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315792111"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220839"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/ismejo\/wraf266"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002601107"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.06.005"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00984-19"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1560-1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-025-05907-y"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2024.11.001"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0640-y"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152449"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2008.63"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011493"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/315810"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.170019"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62423"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000639"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1638"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3745"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601083R"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.08.019"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01822"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-2217"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-9-88"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2012-0541"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60844-2"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52829-x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222195"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag2029"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050177"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201643483"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000597"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1329"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1939"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11020236"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3228"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3608"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1720"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.09.010"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071022"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0395-5"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2018.09.008"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.03.006"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.02.014"},{"key":"e_1_3_2_56_2","first-page":"525","article-title":"Perinatal antibiotic usage and changes in colonization and resistance rates of group B streptococcus and other pathogens","volume":"100","author":"Spaetgens R.","year":"2002","unstructured":"R. Spaetgens, K. DeBella, D. Ma, S. Robertson, M. Mucenski, H. D. Davies, Perinatal antibiotic usage and changes in colonization and resistance rates of group B streptococcus and other pathogens. Obstet. Gynecol. 100, 525\u2013533 (2002).","journal-title":"Obstet. Gynecol."},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e318225f765"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.01.006"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24628"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.05.024"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504757102"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11053"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0740-x"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.01.017"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27297-2"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29098-7"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.3389\/ftox.2021.787360"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2013.43"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-309059"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0221528"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-738005"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2022-222229"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204935200"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000902"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-306651"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00257-10"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1101\/027607"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt389"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-3-r46"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adx6147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:58:26Z","timestamp":1791395906000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adx6147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":78,"journal-issue":{"issue":"870","published-print":{"date-parts":[[2026,10,7]]}},"alternative-id":["10.1126\/scitranslmed.adx6147"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adx6147","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"2025-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-18","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadx6147"}}