Gut microbiome maturation in early childhood interacts with host genetics to predict type 1 diabetes risk
Prospective evidence linking early-life microbiome development and host genetics with type 1 diabetes (T1D) risk is limited. Here, we describe how gut microbiome maturation and host genetics influence T1D risk in the TEDDY study. We analysed 12,151 longitudinal metagenomes and host genetic data from 887 children at high genetic risk for T1D followed for up to 6 years. We identify three microbiome maturational patterns: Early Matured, Late Matured and Early Plateaued, driven primarily by non-linear changes in species from the Bifidobacterium and Ruminococcus genera. The Early Matured pattern is enriched in galactose metabolism and exhibits higher production of aromatic amino acids and B-group vitamins at early follow-ups, whereas the Early Plateaued pattern has increased microbial production of branched-chain amino acids. Notably, the Early Plateaued pattern is associated with a threefold elevated risk of T1D, whereas other patterns are not associated with T1D risk. Furthermore, we find that host genetic variants related to antimicrobial and antiviral immune responses modify the association between the Late Matured pattern and T1D risk. These findings highlight the role of early microbial exposures and host genetics in T1D susceptibility. In the prospective, multicentre TEDDY study, distinct patterns of gut microbiome maturation are associated with differential risk of type 1 diabetes, with host genetics modifying the strength of this association.
Authors
- Teija Mykkänen
- Jaakko J. Koskenniemi (ORCID: https://orcid.org/0000-0002-9348-3325)
- Pieta Kemppainen
- Jarita Kytölä
- Leena Hakola (ORCID: https://orcid.org/0000-0001-7115-6035)
- Merja Koskinen
- Michelle Hoffman (ORCID: https://orcid.org/0000-0003-1078-6740)
- Tiina Latva-aho
- Curtis Huttenhower (ORCID: https://orcid.org/0000-0002-1110-0096)
- Katja Kokkonen
- Mondher Khdhiri
- Heikki Hyöty (ORCID: https://orcid.org/0000-0003-0370-4145)
- Zhian Othmani
- Saori Itoshima (ORCID: https://orcid.org/0000-0002-9800-6747)
- Irene Viinikangas
- Markus Mattila (ORCID: https://orcid.org/0000-0002-7829-9474)
- Marisa Stahl
- Daniel Felipe-Morales
- Katri Lindfors (ORCID: https://orcid.org/0000-0001-7417-5151)
- George Weingart
- Laura Leppänen (ORCID: https://orcid.org/0009-0009-1953-9368)
- Taru Karjalainen
- Edwin Liu (ORCID: https://orcid.org/0000-0003-3591-8922)
- Sanna Jokipuu
- Aaron M. Walsh (ORCID: https://orcid.org/0000-0001-7058-728X)
- Nelli Rönkä
- Elina Mäntymäki
- Tiina Niininen
- Danyue Dong (ORCID: https://orcid.org/0009-0003-3256-2876)
- Minna-Liisa Koivikko
- Tommi Vatanen (ORCID: https://orcid.org/0000-0003-0949-1291)
- Kendra Vehik (ORCID: https://orcid.org/0000-0001-6243-6772)
- Marika Korpela
- Minna Romo
- Leena Karlsson
- Eeva Varjonen
- Satu Simell
- Noora Nurminen (ORCID: https://orcid.org/0000-0002-6798-7677)
- Eric A. Franzosa (ORCID: https://orcid.org/0000-0002-8798-7068)
- Judith Baxter
- Sandra Hummel (ORCID: https://orcid.org/0000-0001-6554-5974)
- Annika Adamsson (ORCID: https://orcid.org/0000-0003-1635-0331)
- Sirpa Pohjola
- Holly O’Donnell
- Maria Lönnrot (ORCID: https://orcid.org/0000-0002-2460-6221)
- Salla Kuusela (ORCID: https://orcid.org/0000-0003-4945-3089)
- Miia Kähönen
- Annette Knopff
- Rachel Karban
- Jenna Rautanen
- Anja Heublein (ORCID: https://orcid.org/0000-0002-1092-2485)
- Juulia Rönkä
- Mirva Koreasalo
- Maija E. Miettinen (ORCID: https://orcid.org/0000-0002-5587-7227)
- Paula Ollikainen
- Dong D. Wang (ORCID: https://orcid.org/0000-0002-0897-3048)
- Siiri Leisku
- Hanna-Leena Oinas
- Mari Vähä-Mäkilä (ORCID: https://orcid.org/0000-0003-2216-4607)
- Sari Niinistö (ORCID: https://orcid.org/0000-0003-2041-6241)
- Percy Gordon
- Randi Johnson
- Jill Norris
- Melissa Gardiner
- Anette G. Ziegler (ORCID: https://orcid.org/0000-0002-6290-5548)
- Andrea Steck
- Suvi Ahonen
- Cigdem Sanverdi
- Sanni Heikura
- Noora Ruotsalainen
- Mari Åkerlund (ORCID: https://orcid.org/0009-0005-3780-3821)
- Desmond Schatz
- Kalle Kurppa (ORCID: https://orcid.org/0000-0003-4757-2164)
- Jukka Kero
- Jorma Ilonen
- Laura Jacobsen (ORCID: https://orcid.org/0000-0002-5144-7836)
- KIMBERLY BAUTISTA
- Jennifer Hosford
- Kathleen Waugh
- Olli G. Simell
- Patricia Gesualdo
- Diane Hopkins
- Richard McIndoe
- Brigitte I. Frohnert
- Päivi Tossavainen
- Ashok Sharma
- Marian Rewers
- Jorma Toppari
- Suvi M. Virtanen
- Sirpa Anttila
- Meir J. Stampfer
- Tiia Honkanen
- Mia Rein
- Sami Oikarinen
- Ezio Bonifacio
- Jutta Laiho
- Mikael Knip
- The TEDDY Study Group
- Michael Haller
- Riitta Veijola
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- University of Helsinki (FI)
- Harvard University (US)
- University of Auckland (NZ)
- University of Turku (FI)
- Tampere University (FI)
- Augusta University (US)
- University of South Florida (US)
- Oulu University Hospital (FI)
- Turku University Hospital (FI)
- Helmholtz Zentrum München (DE)
- University of Florida (US)
- Finnish Institute for Health and Welfare (FI)
- Tampere University Hospital (FI)
- Northern Ostrobothnia Hospital District (FI)
- Tampere University (FI)
- German Center for Diabetes Research (DE)
- Center for Regenerative Therapies Dresden (DE)
- University of Colorado Anschutz Medical Campus (US)
- Technische Universität Dresden (DE)
- University of Oulu (FI)
Publication Details
- Journal
- Nature Metabolism
- Published
- 2026-09-21
- DOI
- https://doi.org/10.1038/s42255-026-01614-9
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00