TY - JOUR TI - The Crohn’s disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1/Th17 response AU - Lavoie, Sydney AU - Conway, Kara L AU - Lassen, Kara G AU - Jijon, Humberto B AU - Pan, Hui AU - Chun, Eunyoung AU - Michaud, Monia AU - Lang, Jessica K AU - Gallini Comeau, Carey Ann AU - Dreyfuss, Jonathan M AU - Glickman, Jonathan N AU - Vlamakis, Hera AU - Ananthakrishnan, Ashwin AU - Kostic, Aleksander AU - Garrett, Wendy S AU - Xavier, Ramnik J A2 - Cadwell, Ken H A2 - Taniguchi, Tadatsugu VL - 8 PY - 2019 DA - 2019/01/22 SP - e39982 C1 - eLife 2019;8:e39982 DO - 10.7554/eLife.39982 UR - https://doi.org/10.7554/eLife.39982 AB - Inflammatory bowel disease (IBD) is driven by dysfunction between host genetics, the microbiota, and immune system. Knowledge gaps remain regarding how IBD genetic risk loci drive gut microbiota changes. The Crohn’s disease risk allele ATG16L1 T300A results in abnormal Paneth cells due to decreased selective autophagy, increased cytokine release, and decreased intracellular bacterial clearance. To unravel the effects of ATG16L1 T300A on the microbiota and immune system, we employed a gnotobiotic model using human fecal transfers into ATG16L1 T300A knock-in mice. We observed increases in Bacteroides ovatus and Th1 and Th17 cells in ATG16L1 T300A mice. Association of altered Schaedler flora mice with B. ovatus specifically increased Th17 cells selectively in ATG16L1 T300A knock-in mice. Changes occur before disease onset, suggesting that ATG16L1 T300A contributes to dysbiosis and immune infiltration prior to disease symptoms. Our work provides insight for future studies on IBD subtypes, IBD patient treatment and diagnostics. KW - Bacteroides KW - Bacteroides ovatus KW - Crohn's Disease KW - gut KW - T cell KW - ATG16L1T300A JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -