miRNA-Gene Regulatory Network in Gnotobiotic Mice Stimulated by Dysbiotic Gut Microbiota Transplanted From a Genetically Obese Child
被引:10
作者:
Deng, Liman
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Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Deng, Liman
[1
,2
]
Wang, Ruirui
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Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Wang, Ruirui
[1
,2
]
Li, Hui
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Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Li, Hui
[1
,2
]
Zhang, Chenhong
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Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Zhang, Chenhong
[1
,2
]
Zhao, Liping
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Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai, Peoples R China
Rutgers Univ New Brunswick, Rutgers New Jersey Inst Food Nutr, Sch Environm & Biol Sci, Dept Biochem & Microbiol, New Brunswick, NJ USAShanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Zhao, Liping
[1
,2
,3
]
Zhang, Menghui
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Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
Zhang, Menghui
[1
,2
]
机构:
[1] Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai, Peoples R China
[3] Rutgers Univ New Brunswick, Rutgers New Jersey Inst Food Nutr, Sch Environm & Biol Sci, Dept Biochem & Microbiol, New Brunswick, NJ USA
Gut microbiota (GM) dysbiosis has been considered a pathogenic origin of many chronic diseases. In our previous trial, a shift in GM structure caused by a complex fiber-rich diet was associated with the health improvement of obese Prader-Willi syndrome (PWS) children. The pre- and post-intervention GMs (pre- and post-group, respectively) from one child were then transplanted into gnotobiotic mice, which resulted in significantly different physiological phenotypes, each of which was similar to the phenotype of the corresponding GM donor. This study was designed to investigate the miRNAgene regulatory networks involved in causing these phenotypic differences. Using the post-group as a reference, we systematically identified and annotated the differentially expressed (DE) miRNAs and genes in the colon and liver of the pre-group in the second and fourth weeks after GM inoculation. Most of the significantly enriched GO terms and KEGG pathways were observed in the liver and were in the second week after GM transplantation. We screened 23 key genes along with their 73 miRNA regulators relevant to the host phenotype changes and constructed a network. The network contained 92 miRNA-gene regulation relationships, 51 of which were positive, and 41 of which were negative. Both the colon and liver had upregulated pro-inflammatory genes, and genes involved in fatty acid oxidation, lipolysis, and plasma cholesterol clearance were downregulated in only the liver. These changes were consistent with lipid and cholesterol accumulation in the host and with a high inflammation level. In addition, the colon showed an impacted glucagon-like peptide 1 (GLP-1) signaling pathway, while the liver displayed decreased insulin receptor signaling pathway activity. These molecular changes were mainly found in the second week, 2 weeks before changes in body fat occurred. This time lag indicated that GM dysbiosis might initially induce cholesterol and lipid metabolism-related miRNA and gene expression disorder and then lead to lipid accumulation and obesity development, which implicates a causative role of GM dysbiosis in obesity development rather than a result of obesity. This study provides fundamental molecular information that elucidates how dysbiotic GM increases host inflammation and disturbs host lipid and glucose metabolism.
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Kim D, 2015, NAT METHODS, V12, P357, DOI [10.1038/nmeth.3317, 10.1038/NMETH.3317]
机构:Univ Alberta, Fac Med, Dept Pediat, Cardiovasc Res Grp,Heritage Med Res Ctr 474, Edmonton, AB T6G 2S2, Canada
Kovacic, S
Soltys, CLM
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Soltys, CLM
Barr, AJ
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Barr, AJ
Shiojima, I
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Shiojima, I
Walsh, K
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Walsh, K
Dyck, JRB
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Univ Alberta, Fac Med, Dept Pediat, Cardiovasc Res Grp,Heritage Med Res Ctr 474, Edmonton, AB T6G 2S2, CanadaUniv Alberta, Fac Med, Dept Pediat, Cardiovasc Res Grp,Heritage Med Res Ctr 474, Edmonton, AB T6G 2S2, Canada
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St Vincents Inst Med Res, Melbourne, Vic, Australia
INSERM, UMR S957, Lab Physiopathol Resorpt Osseuse, Nantes, FranceSt Vincents Inst Med Res, Melbourne, Vic, Australia
Le Goff, Benoit
Singbrant, Sofie
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St Vincents Inst Med Res, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
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Tonkin, Brett A.
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Martin, T. John
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St Vincents Inst Med Res, Melbourne, Vic, Australia
Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
Martin, T. John
Romas, Evange
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Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, Australia
St Vincents Hosp, Dept Rheumatol, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
Romas, Evange
Sims, Natalie A.
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St Vincents Inst Med Res, Melbourne, Vic, Australia
Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
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Walsh, Nicole C.
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St Vincents Inst Med Res, Melbourne, Vic, Australia
Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
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Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Li, Lei O.
Ellis, Jessica M.
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Altshuller, George
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Watkins, Steven M.
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Lip Technol Inc, W Sacramento, CA 95691 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Watkins, Steven M.
Muoio, Deborah M.
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Duke Univ, Dept Med, Durham, NC 27710 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
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Cline, Gary W.
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Yale Univ, Howard Hughes Med Inst, Dept Internal Med & Cellular & Mol Physiol, New Haven, CT 06510 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Cline, Gary W.
Shulman, Gerald I.
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Yale Univ, Howard Hughes Med Inst, Dept Internal Med & Cellular & Mol Physiol, New Haven, CT 06510 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Shulman, Gerald I.
Coleman, Rosalind A.
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Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South KoreaKyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
Lim, Su-Min
Jeong, Jin-Ju
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Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
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Jeong, Jin-Ju
Woo, Kyung Hee
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Han, Myung Joo
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Kyung Hee Univ, Dept Food & Nutr, Seoul 130701, South KoreaKyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
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Kim, Dong-Hyun
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Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
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Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R ChinaSecond Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
Liu, Xia
Zhang, Yongliang
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Beijing Inst Biotechnol, Beijing 100071, Peoples R ChinaSecond Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
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机构:Univ Alberta, Fac Med, Dept Pediat, Cardiovasc Res Grp,Heritage Med Res Ctr 474, Edmonton, AB T6G 2S2, Canada
Kovacic, S
Soltys, CLM
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机构:Univ Alberta, Fac Med, Dept Pediat, Cardiovasc Res Grp,Heritage Med Res Ctr 474, Edmonton, AB T6G 2S2, Canada
Soltys, CLM
Barr, AJ
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机构:Univ Alberta, Fac Med, Dept Pediat, Cardiovasc Res Grp,Heritage Med Res Ctr 474, Edmonton, AB T6G 2S2, Canada
Barr, AJ
Shiojima, I
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Walsh, K
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Dyck, JRB
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Univ Alberta, Fac Med, Dept Pediat, Cardiovasc Res Grp,Heritage Med Res Ctr 474, Edmonton, AB T6G 2S2, CanadaUniv Alberta, Fac Med, Dept Pediat, Cardiovasc Res Grp,Heritage Med Res Ctr 474, Edmonton, AB T6G 2S2, Canada
机构:
St Vincents Inst Med Res, Melbourne, Vic, Australia
INSERM, UMR S957, Lab Physiopathol Resorpt Osseuse, Nantes, FranceSt Vincents Inst Med Res, Melbourne, Vic, Australia
Le Goff, Benoit
Singbrant, Sofie
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St Vincents Inst Med Res, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
Singbrant, Sofie
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St Vincents Inst Med Res, Melbourne, Vic, Australia
Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
Martin, T. John
Romas, Evange
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Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, Australia
St Vincents Hosp, Dept Rheumatol, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
Romas, Evange
Sims, Natalie A.
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St Vincents Inst Med Res, Melbourne, Vic, Australia
Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
Sims, Natalie A.
Walsh, Nicole C.
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St Vincents Inst Med Res, Melbourne, Vic, Australia
Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic, Australia
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Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Li, Lei O.
Ellis, Jessica M.
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Gong, Nan
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Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
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Altshuller, George
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Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Altshuller, George
Thresher, Randy J.
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Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Thresher, Randy J.
Koves, Timothy R.
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Duke Univ, Dept Med, Durham, NC 27710 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Koves, Timothy R.
Watkins, Steven M.
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Lip Technol Inc, W Sacramento, CA 95691 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Watkins, Steven M.
Muoio, Deborah M.
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h-index: 0
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Duke Univ, Dept Med, Durham, NC 27710 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Muoio, Deborah M.
Cline, Gary W.
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h-index: 0
机构:
Yale Univ, Howard Hughes Med Inst, Dept Internal Med & Cellular & Mol Physiol, New Haven, CT 06510 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Cline, Gary W.
Shulman, Gerald I.
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h-index: 0
机构:
Yale Univ, Howard Hughes Med Inst, Dept Internal Med & Cellular & Mol Physiol, New Haven, CT 06510 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
Shulman, Gerald I.
Coleman, Rosalind A.
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Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USAUniv N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
机构:
Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South KoreaKyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
Lim, Su-Min
Jeong, Jin-Ju
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h-index: 0
机构:
Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
Kyung Hee Univ, Dept Pharm, Seoul 130701, South KoreaKyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
Jeong, Jin-Ju
Woo, Kyung Hee
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Kyung Hee Univ, Dept Pharm, Seoul 130701, South KoreaKyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
Woo, Kyung Hee
Han, Myung Joo
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机构:
Kyung Hee Univ, Dept Food & Nutr, Seoul 130701, South KoreaKyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
Han, Myung Joo
Kim, Dong-Hyun
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机构:
Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
Kyung Hee Univ, Dept Pharm, Seoul 130701, South KoreaKyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
机构:
Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R ChinaSecond Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
Liu, Xia
Zhang, Yongliang
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Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R ChinaSecond Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
Zhang, Yongliang
Yu, Yizhi
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Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R ChinaSecond Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
Yu, Yizhi
Yang, Xiao
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Beijing Inst Biotechnol, Beijing 100071, Peoples R ChinaSecond Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
Yang, Xiao
Cao, Xuetao
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Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R ChinaSecond Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China