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Trajectories of microbiome-derived bile acids in early life: nsights into the progression to islet autoimmunity
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; Department of Chemistry, University of Turku, Turku, 20500, Finland.
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland.
Medical Research Council Laboratory of Medical Sciences (MRC LMS), Imperial College Hammersmith Campus, London, UK; Department of Immunology and Inflammation, Imperial College London, W12 0NN, London, UK.
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2025 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Recent studies reveal that gut microbes produce diverse bile acid conjugates, termed microbially conjugated bile acids (MCBAs). However, their regulation and health effects remain unclear. Here, we analyzed early-life MCBA patterns and their link to islet autoimmunity. We quantified 110 MCBAs in 303 stool samples collected longitudinally (3-36 months) from children who developed one or more islet autoantibodies and controls who remained autoantibody-negative. Stool MCBAs showed distinct age-dependent trajectories and correlated with gut microbiome composition. 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 MCBAs influence immune development and type 1 diabetes risk.

Place, publisher, year, edition, pages
2025. article id 2025.02.18.25322275
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Microbiology in the Medical Area Endocrinology and Diabetes
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URN: urn:nbn:se:oru:diva-120093DOI: 10.1101/2025.02.18.25322275PubMedID: 40061321OAI: oai:DiVA.org:oru-120093DiVA, id: diva2:1946436
Note

MedRxiv. Article id 2025.02.18.25322275

Available from: 2025-03-21 Created: 2025-03-21 Last updated: 2025-03-21Bibliographically approved

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Hyötyläinen, TuuliaOresic, Matej

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