Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome

被引:346
作者
Knights, Dan [1 ,2 ,3 ]
Lassen, Kara G. [1 ,2 ]
Xavier, Ramnik J. [1 ,2 ,4 ,5 ]
机构
[1] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA
[2] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA
[3] Univ Minnesota, Dept Comp Sci & Engn, Minneapolis, MN USA
[4] Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA
[5] Harvard Univ, Sch Med, Boston, MA USA
关键词
INFLAMMATORY BOWEL DISEASE; GENETICS; INTESTINAL BACTERIA; CROHN'S DISEASE; ULCERATIVE COLITIS; GENOME-WIDE ASSOCIATION; INTESTINAL MICROBIOTA; SP NOV; SUSCEPTIBILITY; CELLS; NOD2; VARIANTS; PROMOTES; INDUCTION; BACTERIUM;
D O I
10.1136/gutjnl-2012-303954
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Studies of the genetics underlying inflammatory bowel diseases have increased our understanding of the pathways involved in both ulcerative colitis and Crohn's disease and focused attention on the role of the microbiome in these diseases. Full understanding of pathogenesis will require a comprehensive grasp of the delicate homeostasis between gut bacteria and the human host. In this review, we present current evidence of microbiome-gene interactions in the context of other known risk factors and mechanisms, and describe the next steps necessary to pair genetic variant and microbiome sequencing data from patient cohorts. We discuss the concept of dysbiosis, proposing that the functional composition of the gut microbiome may provide a more consistent definition of dysbiosis and may more readily provide evidence of genome-microbiome interactions in future exploratory studies.
引用
收藏
页码:1505 / 1510
页数:6
相关论文
共 52 条
[1]   An integrated map of genetic variation from 1,092 human genomes [J].
Altshuler, David M. ;
Durbin, Richard M. ;
Abecasis, Goncalo R. ;
Bentley, David R. ;
Chakravarti, Aravinda ;
Clark, Andrew G. ;
Donnelly, Peter ;
Eichler, Evan E. ;
Flicek, Paul ;
Gabriel, Stacey B. ;
Gibbs, Richard A. ;
Green, Eric D. ;
Hurles, Matthew E. ;
Knoppers, Bartha M. ;
Korbel, Jan O. ;
Lander, Eric S. ;
Lee, Charles ;
Lehrach, Hans ;
Mardis, Elaine R. ;
Marth, Gabor T. ;
McVean, Gil A. ;
Nickerson, Deborah A. ;
Schmidt, Jeanette P. ;
Sherry, Stephen T. ;
Wang, Jun ;
Wilson, Richard K. ;
Gibbs, Richard A. ;
Dinh, Huyen ;
Kovar, Christie ;
Lee, Sandra ;
Lewis, Lora ;
Muzny, Donna ;
Reid, Jeff ;
Wang, Min ;
Wang, Jun ;
Fang, Xiaodong ;
Guo, Xiaosen ;
Jian, Min ;
Jiang, Hui ;
Jin, Xin ;
Li, Guoqing ;
Li, Jingxiang ;
Li, Yingrui ;
Li, Zhuo ;
Liu, Xiao ;
Lu, Yao ;
Ma, Xuedi ;
Su, Zhe ;
Tai, Shuaishuai ;
Tang, Meifang .
NATURE, 2012, 491 (7422) :56-65
[2]   Enterotypes of the human gut microbiome [J].
Arumugam, Manimozhiyan ;
Raes, Jeroen ;
Pelletier, Eric ;
Le Paslier, Denis ;
Yamada, Takuji ;
Mende, Daniel R. ;
Fernandes, Gabriel R. ;
Tap, Julien ;
Bruls, Thomas ;
Batto, Jean-Michel ;
Bertalan, Marcelo ;
Borruel, Natalia ;
Casellas, Francesc ;
Fernandez, Leyden ;
Gautier, Laurent ;
Hansen, Torben ;
Hattori, Masahira ;
Hayashi, Tetsuya ;
Kleerebezem, Michiel ;
Kurokawa, Ken ;
Leclerc, Marion ;
Levenez, Florence ;
Manichanh, Chaysavanh ;
Nielsen, H. Bjorn ;
Nielsen, Trine ;
Pons, Nicolas ;
Poulain, Julie ;
Qin, Junjie ;
Sicheritz-Ponten, Thomas ;
Tims, Sebastian ;
Torrents, David ;
Ugarte, Edgardo ;
Zoetendal, Erwin G. ;
Wang, Jun ;
Guarner, Francisco ;
Pedersen, Oluf ;
de Vos, Willem M. ;
Brunak, Soren ;
Dore, Joel ;
Weissenbach, Jean ;
Ehrlich, S. Dusko ;
Bork, Peer .
NATURE, 2011, 473 (7346) :174-180
[3]   Moving pictures of the human microbiome [J].
Caporaso, J. Gregory ;
Lauber, Christian L. ;
Costello, Elizabeth K. ;
Berg-Lyons, Donna ;
Gonzalez, Antonio ;
Stombaugh, Jesse ;
Knights, Dan ;
Gajer, Pawel ;
Ravel, Jacques ;
Fierer, Noah ;
Gordon, Jeffrey I. ;
Knight, Rob .
GENOME BIOLOGY, 2011, 12 (05)
[4]   IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+ Th17 cells [J].
Coccia, Margherita ;
Harrison, Oliver J. ;
Schiering, Chris ;
Asquith, Mark J. ;
Becher, Burkhard ;
Powrie, Fiona ;
Maloy, Kevin J. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2012, 209 (09) :1595-1609
[5]   NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation [J].
Cooney, Rachel ;
Baker, John ;
Brain, Oliver ;
Danis, Benedicte ;
Pichulik, Tica ;
Allan, Philip ;
Ferguson, David J. P. ;
Campbell, Barry J. ;
Jewell, Derek ;
Simmons, Alison .
NATURE MEDICINE, 2010, 16 (01) :90-U128
[6]   NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer [J].
Couturier-Maillard, Aurelie ;
Secher, Thomas ;
Rehman, Ateequr ;
Normand, Sylvain ;
De Arcangelis, Adele ;
Haesler, Robert ;
Huot, Ludovic ;
Grandjean, Teddy ;
Bressenot, Aude ;
Delanoye-Crespin, Anne ;
Gaillot, Olivier ;
Schreiber, Stefan ;
Lemoine, Yves ;
Ryffel, Bernhard ;
Hot, David ;
Nunez, Gabriel ;
Chen, Grace ;
Rosenstiel, Philip ;
Chamaillard, Mathias .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (02) :700-711
[7]   Mucin-bacterial interactions in the human oral cavity and digestive tract [J].
Derrien, Muriel ;
van Passel, Mark W. J. ;
van de Bovenkamp, Jeroen H. B. ;
Schipper, Raymond G. ;
de Vos, Willem M. ;
Dekker, Jan .
GUT MICROBES, 2010, 1 (04) :254-268
[8]   Critical Role of NOD2 in Regulating the Immune Response to Staphylococcus aureus [J].
Deshmukh, Hitesh S. ;
Hamburger, James B. ;
Ahn, Sun Hee ;
McCafferty, Dewey G. ;
Yang, Suxiao R. ;
Fowler, Vance G., Jr. .
INFECTION AND IMMUNITY, 2009, 77 (04) :1376-1382
[9]   Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice [J].
Devkota, Suzanne ;
Wang, Yunwei ;
Musch, Mark W. ;
Leone, Vanessa ;
Fehlner-Peach, Hannah ;
Nadimpalli, Anuradha ;
Antonopoulos, Dionysios A. ;
Jabri, Bana ;
Chang, Eugene B. .
NATURE, 2012, 487 (7405) :104-+
[10]   A Novel Role for Interleukin-27 (IL-27) as Mediator of Intestinal Epithelial Barrier Protection Mediated via Differential Signal Transducer and Activator of Transcription (STAT) Protein Signaling and Induction of Antibacterial and Anti-inflammatory Proteins [J].
Diegelmann, Julia ;
Olszak, Torsten ;
Goeke, Burkhard ;
Blumberg, Richard S. ;
Brand, Stephan .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (01) :286-298