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

doi:10.1016/j.celrep.2021.110016

Identification of a gut microbiota member that ameliorates DSS-induced colitis in intestinal barrier enhanced Dusp6-deficient mice

Cell Rep. 2021 Nov 23;37(8):110016. doi: 10.1016/j.celrep.2021.110016.

Authors

Cherng-Shyang Chang¹, Yi-Chu Liao², Chih-Ting Huang¹, Chiao-Mei Lin¹, Chantal Hoi Yin Cheung³, Jhen-Wei Ruan⁴, Wen-Hsuan Yu⁵, Yi-Ting Tsai¹, I-Jung Lin¹, Chien-Hsun Huang⁶, Jong-Shian Liou⁶, Ya-Hsien Chou⁷, Hung-Jen Chien⁷, Hsiao-Li Chuang⁸, Hsueh-Fen Juan⁹, Hsuan-Cheng Huang¹⁰, Hong-Lin Chan¹¹, Yu-Chieh Liao², Shiue-Cheng Tang¹², Yu-Wen Su¹, Tse-Hua Tan¹, Andreas J Bäumler¹³, Cheng-Yuan Kao¹⁴

Affiliations

¹ Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan.
² Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan.
³ Department of Life Science, National Taiwan University, Taipei, 10617, Taiwan.
⁴ Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, 70101, Taiwan.
⁵ Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 10617, Taiwan.
⁶ Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, 30062, Taiwan.
⁷ Institute of Biotechnology, National Tsing Hua University, Hsinchu, 30013, Taiwan.
⁸ National Laboratory Animal Center, National Applied Research Laboratories, Taipei, 11571, Taiwan.
⁹ Department of Life Science, National Taiwan University, Taipei, 10617, Taiwan; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 10617, Taiwan; Center for Computational and Systems Biology, National Taiwan University, Taipei 10617, Taiwan.
¹⁰ Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan.
¹¹ Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, 30013, Taiwan.
¹² Institute of Biotechnology, National Tsing Hua University, Hsinchu, 30013, Taiwan; Department of Medical Science, National Tsing Hua University, Hsinchu, 30013, Taiwan.
¹³ Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
¹⁴ Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan; Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, 40227, Taiwan. Electronic address: [email protected].

PMID: 34818535
DOI: 10.1016/j.celrep.2021.110016

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.

Keywords: DUSP6; barrier integrity; experimental colitis; gut microbiota; leaky gut.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caco-2 Cells
Colitis / microbiology*
Colitis / prevention & control
Colon / metabolism
Dextran Sulfate / pharmacology
Disease Models, Animal
Dual Specificity Phosphatase 6 / deficiency
Dual Specificity Phosphatase 6 / genetics
Dual Specificity Phosphatase 6 / metabolism*
Dysbiosis / metabolism
Epithelial Cells / metabolism
Feces
Female
Gastrointestinal Microbiome / physiology*
Humans
Intestinal Mucosa / microbiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
RNA, Ribosomal, 16S / metabolism

Substances

RNA, Ribosomal, 16S
Dextran Sulfate
Dual Specificity Phosphatase 6
Dusp6 protein, mouse