Identification of a gut microbiota member that ameliorates DSS-induced colitis in intestinal barrier enhanced Dusp6-deficient mice
Journal
Cell Reports
Journal Volume
37
Journal Issue
8
Pages
110016
Date Issued
2021-11-23
Author(s)
Chang, Cherng Shyang
Liao, Yi Chu
Huang, Chih Ting
Lin, Chiao Mei
Cheung, Chantal Hoi Yin
Ruan, Jhen Wei
Yu, Wen Hsuan
Tsai, Yi Ting
Lin, I. Jung
Huang, Chien Hsun
Liou, Jong Shian
Chou, Ya Hsien
Chien, Hung Jen
Chuang, Hsiao Li
Huang, Hsuan Cheng
Chan, Hong Lin
Liao, Yu Chieh
Tang, Shiue Cheng
Su, Yu Wen
Tan, Tse Hua
Bäumler, Andreas J.
Kao, Cheng Yuan
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.
Subjects
barrier integrity | DUSP6 | experimental colitis | gut microbiota | leaky gut
SDGs
Other Subjects
dual specificity phosphatase 6; transcriptome; aged; animal cell; Article; bacterium identification; Caco-2 cell line; clinical article; colitis; colon epithelium; controlled study; dextran sulfate sodium-induced colitis; Dusp6 gene; dysbiosis; fecal microbiota transplantation; gene identification; gene knockout; gene mutation; glucose metabolism; glycolysis; histology; human; human cell; intestine flora; male; microvillus; mitochondrion; mouse; nonhuman; oxygen consumption; protein phosphorylation; real time polymerase chain reaction; RNA sequencing; tight junction; Western blotting
Publisher
Elsevier B.V.
Type
journal article