Therapeutic Opportunities in Inflammatory Bowel Disease: Mechanistic Dissection of Host-Microbiome Relationships

被引:188
|
作者
Plichta, Damian R. [1 ]
Graham, Daniel B. [1 ,2 ,3 ,4 ,5 ]
Subramanian, Sathish [6 ]
Xavier, Ramnik J. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
[2] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA
[3] Harvard Med Sch, Boston, MA 02115 USA
[4] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[5] MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[6] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA
关键词
REGULATORY T-CELLS; PROTEIN-COUPLED RECEPTOR; GUT MICROBIOME; ULCERATIVE-COLITIS; ANTIGEN DISCOVERY; CROHNS-DISEASE; E; COLI; INDUCTION; ACID; COLONIZATION;
D O I
10.1016/j.cell.2019.07.045
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The current understanding of inflammatory bowel disease (IBD) pathogenesis implicates a complex interaction between host genetics, host immunity, microbiome, and environmental exposures. Mechanisms gleaned from genetics and molecular pathogenesis offer clues to the critical triggers of mucosal inflammation and guide the development of therapeutic interventions. A complex network of interactions between host genetic factors, microbes, and microbial metabolites governs intestinal homeostasis, making classification and mechanistic dissection of involved pathways challenging. In this Review, we discuss these challenges, areas of active translation, and opportunities for development of next-generation therapies.
引用
收藏
页码:1041 / 1056
页数:16
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