Microbiome-derived bile acid signatures in early life and their association with islet autoimmunity
Emerging studies reveal that gut microbes can conjugate diverse amino acids to bile acids, known as microbially conjugated bile acids. However, their regulation and health effects remain unclear. Here, we analyzed early-life microbially conjugated bile acid patterns and their link to islet autoimmunity. We quantified 110 microbial bile acids in 303 stool samples collected longitudinally (3-36 months) from children who developed one or more islet autoantibodies and controls who remained autoantibody-negative. We identified distinct age-dependent trajectories of these bile acid amidates and correlated them with gut microbiome composition. We found that altered levels of ursodeoxycholic and deoxycholic acid conjugates were linked to islet autoimmunity as well as modulated monocyte activation in response to immunostimulatory lipopolysaccharide and Th17/Treg cell balance. These findings suggest that microbially conjugated bile acids influence immune development and type 1 diabetes risk.
Authors
- Mikael Knip (ORCID: https://orcid.org/0000-0003-0474-0033)
- Omid Rasool (ORCID: https://orcid.org/0000-0002-1286-4725)
- Partho Sen (ORCID: https://orcid.org/0000-0003-0475-2763)
- Alex M. Dickens (ORCID: https://orcid.org/0000-0002-3178-8449)
- Aman Mebrahtu
- Aron Arzoomand
- Tuulia Hyötyläinen (ORCID: https://orcid.org/0000-0002-1389-8302)
- Riitta Lahesmaa (ORCID: https://orcid.org/0000-0002-4782-9567)
- Tadepally Lakshmikanth (ORCID: https://orcid.org/0000-0001-7256-5770)
- Santosh Lamichhane (ORCID: https://orcid.org/0000-0002-9292-3595)
- Lucas Pinto da Silva
- Manuela Raffatellu (ORCID: https://orcid.org/0000-0001-6487-4215)
- Roosa Kattelus (ORCID: https://orcid.org/0000-0002-5620-6978)
- Tommi Vatanen (ORCID: https://orcid.org/0000-0003-0949-1291)
- Jaromír Mikeš (ORCID: https://orcid.org/0000-0002-9941-7855)
- Ramnik J. Xavier (ORCID: https://orcid.org/0000-0002-5630-5167)
- Karsten Zengler (ORCID: https://orcid.org/0000-0002-8062-3296)
- Petter Brodin (ORCID: https://orcid.org/0000-0002-8103-0046)
- Emily C. Gentry (ORCID: https://orcid.org/0000-0002-0016-8132)
- Matilda Kråkström (ORCID: https://orcid.org/0000-0001-7956-958X)
- Pieter C. Dorrestein (ORCID: https://orcid.org/0000-0002-3003-1030)
- Matej Orešič (ORCID: https://orcid.org/0000-0002-2856-9165)
- Vincent Charron‐Lamoureux (ORCID: https://orcid.org/0000-0001-9440-7036)
- Tianai Lou (ORCID: https://orcid.org/0009-0004-2794-368X)
- Simone Zuffa (ORCID: https://orcid.org/0000-0001-7237-3402)
- Tanja Buchacher (ORCID: https://orcid.org/0000-0003-1937-2202)
- Abubaker Patan
- Corinn Walker
- Pragya Karmacharya
Institutions
- Broad Institute (US)
- Åbo Akademi University (FI)
- La Jolla Institute for Immunology (US)
- University of Helsinki (FI)
- University of Auckland (NZ)
- University of Turku (FI)
- Turku Centre for Computer Science (FI)
- Örebro University (SE)
- Hammersmith Hospital (GB)
- Karolinska Institutet (SE)
- University of California San Diego (US)
- Tampere University Hospital (FI)
- Tampere University (FI)
- Institute for Molecular Medicine Finland (FI)
- Turku Centre for Biotechnology (FI)
- MRC London Institute of Medical Sciences (GB)
- Imperial College London (GB)
- University of Montana (US)
- Virginia Tech (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-03
- DOI
- https://doi.org/10.1038/s41467-025-66619-6
- Citations
- 3
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- European Commission
- Svenska Forskningsrådet Formas
- Jane ja Aatos Erkon Säätiö
- Novo Nordisk
- Vetenskapsrådet
- Novo Nordisk Fonden
- HORIZON EUROPE Framework Programme