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Dysregulation of secondary bile acid metabolism precedes islet autoimmunity and type 1 diabetes
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Örebro University, School of Medical Sciences. Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.ORCID iD: 0000-0003-0475-2763
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; Department of Chemistry, University of Turku, Turku, Finland.
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; Walter Mors Institute of Research on Natural Products, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
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2022 (English)In: Cell Reports Medicine, E-ISSN 2666-3791, Vol. 3, no 10, article id 100762Article in journal (Refereed) Published
Abstract [en]

The gut microbiota is crucial in the regulation of bile acid (BA) metabolism. However, not much is known about the regulation of BAs during progression to type 1 diabetes (T1D). Here, we analyzed serum and stool BAs in longitudinal samples collected at 3, 6, 12, 18, 24, and 36 months of age from children who developed a single islet autoantibody (AAb) (P1Ab; n = 23) or multiple islet AAbs (P2Ab; n = 13) and controls (CTRs; n = 38) who remained AAb negative. We also analyzed the stool microbiome in a subgroup of these children. Factor analysis showed that age had the strongest impact on both BA and microbiome profiles. We found that at an early age, systemic BAs and microbial secondary BA pathways were altered in the P2Ab group compared with the P1Ab and CTR groups. Our findings thus suggest that dysregulated BA metabolism in early life may contribute to the risk and pathogenesis of T1D.

Place, publisher, year, edition, pages
Cell Press , 2022. Vol. 3, no 10, article id 100762
Keywords [en]
Bile acid, genome-scale metabolic modeling, gut microbiome, islet autoimmunity, lipid metabolism, lipidomics, metabolomics, microbial metabolism, type 1 diabetes
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-101663DOI: 10.1016/j.xcrm.2022.100762ISI: 000875228300007PubMedID: 36195095Scopus ID: 2-s2.0-85140084328OAI: oai:DiVA.org:oru-101663DiVA, id: diva2:1701179
Funder
Novo Nordisk, NNF20OC0063971Academy of Finland, 333981Swedish Research Council, 2016-05176Swedish Research Council Formas, 2019-00869
Note

Funding agencies:

Academy of Finland postdoctoral grant 323171

Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research 250114

Medical Research Funds, Helsinki University Hospital

Available from: 2022-10-05 Created: 2022-10-05 Last updated: 2024-01-16Bibliographically approved

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Sen, ParthoHyötyläinen, TuuliaOresic, Matej

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