title: Dual-specificity phosphatase 6 deficiency regulates gut microbiome and transcriptome response against diet-induced obesity in mice.
abstract: The gut microbiota plays profound roles in host metabolism and the inflammatory response associated with the development of obesity. Dusp6-deficient mice have been shown to be resistant to diet-induced obesity, but the mechanism behind this remains unclear. 16S ribosomal RNA gene analysis demonstrated that dusp6-deficient mice harbour unique gut microbiota with resistance to diet-induced-obesity-mediated alteration of the gut microbiome. Using a germ-free mouse model, we found that faecal/gut microbiota derived from dusp6-deficient mice significantly increased energy expenditure and reduced weight gain in recipient wild-type mice fed on a high-fat diet. On analysis of the intestinal transcriptome of dusp6-deficient mice, we found that dusp6 deficiency mainly induced biological processes involved in metabolism and the extracellular matrix, particularly the peroxisome proliferator-activated receptor gamma (Pparγ) pathway and tight-junction genes. Furthermore, dusp6-deficient mice have a high-fat-diet-specific transcriptomic response to reverse the expression of genes associated with intestinal barrier functions and mucosal immunity involved in microbiome homeostasis. This study demonstrates that dusp6 deficiency is a strong genetic factor shaping gut microbiota, and that it confers obesity protection by ameliorating the gut microbiota response to diet-mediated stress.
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Jhen-Wei
authors.identifier: http://orcid.org/0000-0002-0636-1937
authors.initials: JW
authors.lastname: Ruan
authors.affiliation: Asuragen, Inc., Austin, Texas 78744, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Statt
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Chih-Ting
authors.initials: CT
authors.lastname: Huang
authors.affiliation: Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Tsai
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Cheng-Chin
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Chan
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Liao
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.|Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Tse-Hua
authors.initials: TH
authors.lastname: Tan
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Cheng-Yuan
authors.identifier: http://orcid.org/0000-0003-0946-9270
authors.initials: CY
authors.lastname: Kao
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D004032:Diet; D054642:Dual Specificity Phosphatase 6 / Q000172:deficiency*; D004734:Energy Metabolism; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D020869:Gene Expression Profiling; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S; D054642:Dual Specificity Phosphatase 6; C517036:Dusp6 protein, mouse