Maternal-prenatal gut microbiome-systemic metabolome perturbations and TH2-skewed immunity link to offspring gut microbiome disruption and atopic dermatitis susceptibility

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dc.contributor.authorNg, Daniel Zhi Wei
dc.contributor.authorYap, Gaik Chin
dc.contributor.authorTay, Carina Jing Xuan
dc.contributor.authorHuang, Chiung Hui
dc.contributor.authorZhao, Siyan
dc.contributor.authorLow, Adrian
dc.contributor.authorTham, Elizabeth Huiwen
dc.contributor.authorLoo, Evelyn Xiu Ling
dc.contributor.authorShek, Lynette P.
dc.contributor.authorGoh, Anne
dc.contributor.authorChong, Kok Wee
dc.contributor.authorGoh, Si Hui
dc.contributor.authorCheng, Zai Ru
dc.contributor.authorVan Bever, Hugo P.S.
dc.contributor.authorTeoh, Oon Hoe
dc.contributor.authorLee, Yung Seng
dc.contributor.authorYap, Fabian
dc.contributor.authorTan, Kok Hian
dc.contributor.authorChong, Yap Seng
dc.contributor.authorChan, Shiao Yng
dc.contributor.authorEriksson, Johan Gunnar
dc.contributor.authorGodfrey, Keith M.
dc.contributor.authorLay, Christophe
dc.contributor.authorKnol, Jan
dc.contributor.authorSchuster, Stephan C.
dc.contributor.authorLai, Jun Shi
dc.contributor.authorChong, Mary Foong Fong
dc.contributor.authorLee, Jonathan Wei Jie
dc.contributor.authorLee, Bee Wah
dc.contributor.authorChan, Eric Chun Yong
dc.contributor.authorTa, Le Duc Huy
dc.contributor.funderMinistry of Health, Government of Singapore
dc.date.accessioned2026-07-09T09:50:02Z
dc.date.available2026-07-09T09:50:02Z
dc.date.issued2026-04-17
dc.description.abstractBackground Emerging evidence suggests that maternal-prenatal gut microbiome disturbances shape offspring allergic outcomes through modulation of the in utero immune environment. Yet, no comprehensive clinical studies in human mother–offspring dyads have deconvoluted the maternal-prenatal gut microbiome and systemic immune-metabolome signatures underlying offspring allergic predisposition. Methods We performed a longitudinal nested case–control study involving 128 well-characterized mother–offspring dyads from defined cases (offspring with atopic dermatitis (AD); n = 64) and controls (offspring without AD; n = 64). Maternal stool and blood samples were collected at multiple time points during gestation for multi-omic profiling. Structural and functional gut microbiome composition was characterized via metagenomic sequencing, while systemic metabolome and serum immune milieu were profiled using targeted plasma metabolomics and Olink proximity extension assays, respectively. In offspring early-life, stool samples were collected longitudinally up to 6 months of age for gut microbiome and metabolome analyses. Results Mothers of AD infants exhibited longitudinal enrichments of gut Klebsiella pneumoniae, Roseburia intestinalis, Clostridioides difficile and Bilophila sp. 4_1_30, alongside depletions in gut Clostridium sp. CAG:678, Romboutsia timonensis, Akkermansia muciniphila, Blautia hansenii and Alistipes ihumii during pregnancy. These taxonomic shifts were associated with systemic metabolomic alterations, including elevated branched-chain amino acids and immune-related metabolites (e.g., creatine, ornithine), and a concurrent pro-inflammatory TH2-skewed immunological milieu marked by increased interleukin-4 (IL-4) and IL-5 and decreased CXCL11. In early life, AD infants harbored a dysbiotic gut microbiome characterized by persistent enrichments of potentially pathogenic Escherichia coli and K. pneumoniae, along with depletion of short chain fatty acid-producing Bacteroides species and beneficial colonizers. Integrated multi-omic analyses across the prenatal-postnatal axis indicated that the impaired establishment of gut microbiome in AD infants may, in part, be attributed to the (1) potential transmission of maternally originated Klebsiella and (2) immunomodulatory effects of a maternal-prenatal pro-inflammatory, TH2-skewed milieu during gestation. Conclusions Our study uncovers a distinct maternal-prenatal gut microbiome and systemic metabolome–immune signature that predisposes offspring to AD by disrupting early-life gut microbial establishment. These findings highlight the gestational period as a critical window for preventive strategies targeting the maternal microbiome or systemic immune-metabolic axes to mitigate allergic disease susceptibility in offspring.en
dc.description.versionPublished Version
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dc.identifier.articleid72
dc.identifier.authororcidNg, Daniel Zhi Wei
dc.identifier.authororcidYap, Gaik Chin
dc.identifier.authororcidTay, Carina Jing Xuan
dc.identifier.authororcidHuang, Chiung Hui
dc.identifier.authororcidZhao, Siyan
dc.identifier.authororcidLow, Adrian
dc.identifier.authororcidTham, Elizabeth Huiwen
dc.identifier.authororcidLoo, Evelyn Xiu Ling
dc.identifier.authororcidShek, Lynette P.
dc.identifier.authororcidGoh, Anne
dc.identifier.authororcidChong, Kok Wee
dc.identifier.authororcidGoh, Si Hui
dc.identifier.authororcidCheng, Zai Ru
dc.identifier.authororcidVan Bever, Hugo P.S.
dc.identifier.authororcidTeoh, Oon Hoe
dc.identifier.authororcidLee, Yung Seng
dc.identifier.authororcidYap, Fabian
dc.identifier.authororcidTan, Kok Hian
dc.identifier.authororcidChong, Yap Seng
dc.identifier.authororcidChan, Shiao Yng
dc.identifier.authororcidEriksson, Johan Gunnar
dc.identifier.authororcidGodfrey, Keith M.
dc.identifier.authororcidLay, Christophe
dc.identifier.authororcidKnol, Jan
dc.identifier.authororcidSchuster, Stephan C.
dc.identifier.authororcidLai, Jun Shi
dc.identifier.authororcidChong, Mary Foong Fong
dc.identifier.authororcidLee, Jonathan Wei Jie
dc.identifier.authororcidLee, Bee Wah
dc.identifier.authororcidChan, Eric Chun Yong
dc.identifier.authororcidTa, Le Duc Huy
dc.identifier.citationNg, D Z W, Yap, G C, Tay, C J X, Huang, C H, Zhao, S, Low, A, Tham, E H, Loo, E X L, Shek, L P, Goh, A, Chong, K W, Goh, S H, Cheng, Z R, Van Bever, H P S, Teoh, O H, Lee, Y S, Yap, F, Tan, K H, Chong, Y S, Chan, S Y, Eriksson, J G, Godfrey, K M, Lay, C, Knol, J, Schuster, S C, Lai, J S, Chong, M F F, Lee, J W J, Lee, B W, Chan, E C Y & Ta, L D H 2026, 'Maternal-prenatal gut microbiome-systemic metabolome perturbations and T H 2-skewed immunity link to offspring gut microbiome disruption and atopic dermatitis susceptibility', Genome Medicine, vol. 18, no. 1, 72. https://doi.org/10.1186/s13073-026-01655-5
dc.identifier.doi10.1186/s13073-026-01655-5
dc.identifier.issn1756-994X
dc.identifier.issued1
dc.identifier.journaltitleGenome Medicine
dc.identifier.urihttps://hdl.handle.net/10468/19035
dc.identifier.volume18
dc.language.isoen
dc.publisherBioMed Central Ltd
dc.relation.urihttps://www.scopus.com/pages/publications/105040561317
dc.rights© 2026, the Author(s) . Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.accessrightsopen access
dc.rights.licensenameAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.statusPeer reviewed
dc.subjectAtopic dermatitis
dc.subjectDevelopmental biology
dc.subjectMicrobiome-metabolome-immunity
dc.subjectMother–offspring interface
dc.subjectMulti-omic analyses
dc.subjectPaediatric allergy
dc.subjectPrenatal-maternal biological signature
dc.subjectS-PRESTO Birth Cohort
dc.subject[Microbiology]
dc.titleMaternal-prenatal gut microbiome-systemic metabolome perturbations and TH2-skewed immunity link to offspring gut microbiome disruption and atopic dermatitis susceptibilityen
dc.typeArticle (peer-reviewed)
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