Microbiome-derived bile acid signatures in early life and their association with islet autoimmunity
: Lamichhane, Santosh; Dickens, Alex M.; Buchacher, Tanja; Lou, Tianai; Charron-Lamoureux, Vincent; Kattelus, Roosa; Karmacharya, Pragya; Pinto da Silva, Lucas; Kråkström, Matilda; Rasool, Omid; Sen, Partho; Walker, Corinn; Patan, Abubaker; Gentry, Emily C.; Zuffa, Simone; Arzoomand, Aron; Lakshmikanth, Tadepally; Mikeš, Jaromir; Mebrahtu, Aman; Vatanen, Tommi; Raffatellu, Manuela; Zengler, Karsten; Hyötyläinen, Tuulia; Xavier, Ramnik J.; Brodin, Petter; Lahesmaa, Riitta; Dorrestein, Pieter C.; Knip, Mikael; Orešič, Matej
Publisher: Springer Nature
: 2026
Nature Communications
: 38
: 17
: 2041-1723
DOI: https://doi.org/10.1038/s41467-025-66619-6
: https://doi.org/10.1038/s41467-025-66619-6
: https://research.utu.fi/converis/portal/detail/Publication/505811785
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
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Open access funding provided by Örebro University.