Microbiome-derived bile acid signatures in early life and their association with islet autoimmunity
Abstract
Abstract 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.
Article Details
Authors (29)
Santosh Lamichhane
Alex M. Dickens
Tanja Buchacher
Tianai Lou
Vincent Charron-Lamoureux
Roosa Kattelus
Pragya Karmacharya
Lucas Pinto da Silva
Matilda Kråkström
Omid Rasool
Partho Sen
Corinn Walker
Abubaker Patan
Emily C. Gentry
Simone Zuffa
Aron Arzoomand
Tadepally Lakshmikanth
Jaromir Mikeš
Aman Mebrahtu
Tommi Vatanen
Manuela Raffatellu
Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics
Karsten Zengler
Department of Pediatrics, University of California
Tuulia Hyötyläinen
Ramnik J. Xavier
Petter Brodin
Riitta Lahesmaa
Pieter C. Dorrestein
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego
Mikael Knip
Matej Oresic