Identification of a gut microbiota member that ameliorates DSS-induced colitis in intestinal barrier enhanced Dusp6-deficient mice
Cherng–Shyang Chang, Yi-Chu Liao, Chih‐Ting Huang, Chiao-Mei Lin, Chantal Hoi Yin Cheung, Jhen‐Wei Ruan, Wen-Hsuan Yu, Yi‐Ting Tsai, I-Jung Lin, Chien‐Hsun Huang, Jong-Shian Liou, Ya-Hsien Chou, Hung‐Jen Chien, Hsiao-Li Chuang, Hsueh‐Fen Juan, Hsuan‐Cheng Huang, Hong‐Lin Chan, Yu-Chieh Liao, Shiue–Cheng Tang, Yu‐Wen Su, Tse‐Hua Tan, Andreas J. Bäumler, Cheng–Yuan Kao
Abstract
Strengthening the gut epithelial barrier is a potential strategy for management of gut microbiota-associated illnesses. Here, we demonstrate that dual-specificity phosphatase 6 (Dusp6) knockout enhances baseline colon barrier integrity and ameliorates dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 mutation in Caco-2 cells enhances the epithelial feature and increases mitochondrial oxygen consumption, accompanied by altered glucose metabolism and decreased glycolysis. We find that Dusp6-knockout mice are more resistant to DSS-induced dysbiosis, and the cohousing and fecal microbiota transplantation experiments show that the gut/fecal microbiota derived from Dusp6-knockout mice also confers protection against colitis. Further culturomics and mono-colonialization experiments show that one gut microbiota member in the genus Duncaniella confers host protection from DSS-induced injury. We identify Dusp6 deficiency as beneficial for shaping the gut microbiota eubiosis necessary to protect against gut barrier-related diseases.