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 SuTse Hua Tan, Andreas J. Bäumler, Cheng Yuan Kao

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number110016
JournalCell Reports
Volume37
Issue number8
DOIs
StatePublished - Nov 23 2021

Keywords

  • barrier integrity
  • DUSP6
  • experimental colitis
  • gut microbiota
  • leaky gut

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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