The Gut Microbial Endocrine Organ: Bacterially Derived Signals Driving Cardiometabolic Diseases

被引:318
作者
Brown, J. Mark [1 ]
Hazen, Stanley L. [1 ]
机构
[1] Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44195 USA
来源
ANNUAL REVIEW OF MEDICINE, VOL 66 | 2015年 / 66卷
关键词
atherosclerosis; cardiovascular disease; microbiota; trimethylamine-N-oxide; TRIMETHYLAMINE-N-OXIDE; GENOME-WIDE ASSOCIATION; ENERGY-EXPENDITURE; PROGNOSTIC VALUE; L-CARNITINE; RED MEAT; METABOLISM; ACID; OBESITY; CHOLINE;
D O I
10.1146/annurev-med-060513-093205
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The human gastrointestinal tract is home to trillions of bacteria, which vastly outnumber host cells in the body. Although generally overlooked in the field of endocrinology, gut microbial symbionts organize to form a key endocrine organ that converts nutritional cues from the environment into hormone-like signals that impact both normal physiology and chronic disease in the human host. Recent evidence suggests that several gut microbial-derived products are sensed by dedicated host receptor systems to alter cardiovascular disease (CVD) progression. In fact, gut microbial metabolism of dietary components results in the production of proatherogenic circulating factors that act through a meta-organismal endocrine axis to impact CVD risk. Whether pharmacological interventions at the level of the gut microbial endocrine organ will reduce CVD risk is a key new question in the field of cardiovascular medicine. Here we discuss the opportunities and challenges that lie ahead in targeting meta-organismal endocrinology for CVD prevention.
引用
收藏
页码:343 / 359
页数:17
相关论文
共 99 条
[11]   Clinical trials update from the European Society of Cardiology: SENIORS, ACES, PROVE-IT, ACTION, and the HF-ACTION trial [J].
Cleland, JGF ;
Loh, PH ;
Freemantle, N ;
Clark, AL ;
Coletta, AP .
EUROPEAN JOURNAL OF HEART FAILURE, 2004, 6 (06) :787-791
[12]   Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme [J].
Craciun, Smaranda ;
Balskus, Emily P. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (52) :21307-21312
[13]   Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour [J].
Cryan, John F. ;
Dinan, Timothy G. .
NATURE REVIEWS NEUROSCIENCE, 2012, 13 (10) :701-712
[14]   Emerging role of Toll-like receptors in atherosclerosis [J].
Curtiss, Linda K. ;
Tobias, Peter S. .
JOURNAL OF LIPID RESEARCH, 2009, 50 :S340-S345
[15]   Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits [J].
De Vadder, Filipe ;
Kovatcheva-Datchary, Petia ;
Goncalves, Daisy ;
Vinera, Jennifer ;
Zitoun, Carine ;
Duchampt, Adeline ;
Backhed, Fredrik ;
Mithieux, Gilles .
CELL, 2014, 156 (1-2) :84-96
[16]   Microbiota Modification with Probiotics Induces Hepatic Bile Acid Synthesis via Downregulation of the Fxr-Fgf15 Axis in Mice [J].
Degirolamo, Chiara ;
Rainaldi, Stefania ;
Bovenga, Fabiola ;
Murzilli, Stefania ;
Moschetta, Antonio .
CELL REPORTS, 2014, 7 (01) :12-18
[17]   Large-scale association analysis identifies new risk loci for coronary artery disease [J].
Deloukas, Panos ;
Kanoni, Stavroula ;
Willenborg, Christina ;
Farrall, Martin ;
Assimes, Themistocles L. ;
Thompson, John R. ;
Ingelsson, Erik ;
Saleheen, Danish ;
Erdmann, Jeanette ;
Goldstein, Benjamin A. ;
Stirrups, Kathleen ;
Koenig, Inke R. ;
Cazier, Jean-Baptiste ;
Johansson, Asa ;
Hall, Alistair S. ;
Lee, Jong-Young ;
Willer, Cristen J. ;
Chambers, John C. ;
Esko, Tonu ;
Folkersen, Lasse ;
Goel, Anuj ;
Grundberg, Elin ;
Havulinna, Aki S. ;
Ho, Weang K. ;
Hopewell, Jemma C. ;
Eriksson, Niclas ;
Kleber, Marcus E. ;
Kristiansson, Kati ;
Lundmark, Per ;
Lyytikainen, Leo-Pekka ;
Rafelt, Suzanne ;
Shungin, Dmitry ;
Strawbridge, Rona J. ;
Thorleifsson, Gudmar ;
Tikkanen, Emmi ;
Van Zuydam, Natalie ;
Voight, Benjamin F. ;
Waite, Lindsay L. ;
Zhang, Weihua ;
Ziegler, Andreas ;
Absher, Devin ;
Altshuler, David ;
Balmforth, Anthony J. ;
Barroso, Ines ;
Braund, Peter S. ;
Burgdorf, Christof ;
Claudi-Boehm, Simone ;
Cox, David ;
Dimitriou, Maria ;
Do, Ron .
NATURE GENETICS, 2013, 45 (01) :25-U52
[18]   Targeting gut microbiota in obesity: effects of prebiotics and probiotics [J].
Delzenne, Nathalie M. ;
Neyrinck, Audrey M. ;
Baeckhed, Fredrik ;
Cani, Patrice D. .
NATURE REVIEWS ENDOCRINOLOGY, 2011, 7 (11) :639-646
[19]   Gut Microbiota and the Pathogenesis of Insulin Resistance [J].
Delzenne, Nathalie M. ;
Cani, Patrice D. .
CURRENT DIABETES REPORTS, 2011, 11 (03) :154-159
[20]   Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids [J].
den Besten, Gijs ;
Lange, Katja ;
Havinga, Rick ;
van Dijk, Theo H. ;
Gerding, Albert ;
van Eunen, Karen ;
Muller, Michael ;
Groen, Albert K. ;
Hooiveld, Guido J. ;
Bakker, Barbara M. ;
Reijngoud, Dirk-Jan .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2013, 305 (12) :G900-G910