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We analyzed fecal 16\u2009s rRNA microbiome profiling and fecal metabolomic profiling from stool samples collected from mothers during the third trimester of pregnancy (<jats:italic>n<\/jats:italic>\u00a0=\u00a0120) and offspring at ages 3\u20136\u00a0months (<jats:italic>n<\/jats:italic>\u00a0=\u00a0265), 1 (<jats:italic>n<\/jats:italic>\u00a0=\u00a0436) and 3\u2009years (<jats:italic>n<\/jats:italic>\u00a0=\u00a0506) in a total of 657 mother\u2013child pairs participating in the Vitamin D Antenatal Asthma Reduction Trial. We used clinical data from birth to age 6\u2009years to characterize subjects with asthma as having early, transient or active asthma phenotypes. In addition to identifying specific genera that were robustly associated with asthma phenotypes in multiple covariate\u2010adjusted models, we clustered subjects by their longitudinal microbiome composition and sought associations between fecal metabolites and relevant microbiome and clinical features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven maternal and two infant fecal microbial taxa were robustly associated with at least one asthma phenotype, and a longitudinal gut microenvironment profile was associated with early asthma (Fisher exact test <jats:italic>p<\/jats:italic>\u00a0=\u00a0.03). Though mode of delivery was not directly associated with asthma, we found substantial evidence for a pathway whereby cesarean section reduces fecal <jats:italic>Bacteroides<\/jats:italic> and microbial sphingolipids, increasing susceptibility to early asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, our results suggest that the early\u2010life, including prenatal, fecal microbiome modifies risk of asthma, especially asthma with onset by age 3\u2009years.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15516","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T16:02:51Z","timestamp":1663257771000},"page":"418-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["The maternal prenatal and offspring <scp>early\u2010life<\/scp> gut microbiome of childhood asthma phenotypes"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0550-1640","authenticated-orcid":false,"given":"Kathleen A.","family":"Lee\u2010Sarwar","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Allergy and Clinical Immunology Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yih\u2010Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Allergy and Clinical Immunology Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita\u00a0L.","family":"Kozyrskyj","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piush J.","family":"Mandhane","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart E.","family":"Turvey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmaja","family":"Subbarao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics &amp; Physiology Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4131-7592","authenticated-orcid":false,"given":"Hans","family":"Bisgaard","sequence":"additional","affiliation":[{"name":"COPSAC, Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen  Gentofte Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4989-9769","authenticated-orcid":false,"given":"Jakob","family":"Stokholm","sequence":"additional","affiliation":[{"name":"COPSAC, Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen  Gentofte Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6846-6243","authenticated-orcid":false,"given":"Bo","family":"Chawes","sequence":"additional","affiliation":[{"name":"COPSAC, Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen  Gentofte Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren J.","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"COPSAC, Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen  Gentofte Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-1822","authenticated-orcid":false,"given":"Rachel\u00a0S.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lasky\u2010Su","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Zeiger","sequence":"additional","affiliation":[{"name":"Department of Clinical Science Kaiser Permanente Bernard J. Tyson School of Medicine  Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George T.","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Pulmonary Center and Department of Medicine Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan T.","family":"Sandel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Boston Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard B.","family":"Bacharier","sequence":"additional","affiliation":[{"name":"Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics Monroe Carell Jr Children's Hospital at Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avraham","family":"Beigelman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics Washington University School of Medicine, St Louis, MO and St Louis Children's Hospital  St Louis Missouri USA"},{"name":"The Kipper Institute of Allergy and Immunology Schneider Children's Medical Center of Israel, Tel Aviv University  Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent\u00a0J.","family":"Carey","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Harshfield","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Laranjo","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane R.","family":"Gold","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Environmental Health Harvard T.H. 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