Targeting of microbe-derived metabolites to improve human health: The next frontier for drug discovery

被引：88

作者：

Brown, J. Mark ^{[1
,2
]}

Hazen, Stanley L. ^{[1
,2
,3
]}

机构：

[1] Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44195 USA

[2] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44195 USA

[3] Cleveland Clin, Ctr Microbiome & Human Hlth, Cleveland, OH 44195 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2017年 / 292卷 / 21期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1074/jbc.R116.765388

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：

Recent advances in metabolomic and genome mining approaches have uncovered a poorly understood metabolome that originates solely or in part from bacterial enzyme sources. Whether living on exposed surfaces or within our intestinal tract, our microbial inhabitants produce a remarkably diverse set of natural products and small molecule metabolites that can impact human health and disease. Highlighted here, the gut microbe-derived metabolite trimethylamine N-oxide has been causally linked to the development of cardiovascular diseases. Recent studies reveal drugging this pathway can inhibit atherosclerosis development in mice. Building on this example, we discuss challenges and untapped potential of targeting bacterial enzymology for improvements in human health.

引用

页码：8560 / 8568

页数：9

共 101 条

[21] Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension [J].

Durgan, David J. ;

Ganesh, Bhanu P. ;

Cope, Julia L. ;

Ajami, Nadim J. ;

Phillips, Sharon C. ;

Petrosino, Joseph F. ;

Hollister, Emily B. ;

Bryan, Robert M., Jr. .

HYPERTENSION, 2016, 67 (02) :469-474

[22] Microbiology Meets Big Data: The Case of Gut Microbiota-Derived Trimethylamine [J].

Falony, Gwen ;

Vieira-Silva, Sara ;

Raes, Jeroen .

ANNUAL REVIEW OF MICROBIOLOGY, VOL 69, 2015, 69 :305-321

[23] HIGH-FIBER DIETS - INFLUENCE ON CHARACTERISTICS OF CECAL DIGESTA INCLUDING SHORT-CHAIN FATTY-ACID CONCENTRATIONS AND PH [J].

FLEMING, SE ;

FITCH, MD ;

CHANSLER, MW .

AMERICAN JOURNAL OF CLINICAL NUTRITION, 1989, 50 (01) :93-99

[24] Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet [J].

Gao, Xiang ;

Liu, Xiaofang ;

Xu, Jie ;

Xue, Changhu ;

Xue, Yong ;

Wang, Yuming .

JOURNAL OF BIOSCIENCE AND BIOENGINEERING, 2014, 118 (04) :476-481

[25] The discovery of microorganisms by Robert Hooke and Antoni Van Leeuwenhoek, fellows of the Royal Society [J].

Gest, H .

NOTES AND RECORDS OF THE ROYAL SOCIETY OF LONDON, 2004, 58 (02) :187-201

[26] Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation [J].

Gregory, Jill C. ;

Buffa, Jennifer A. ;

Org, Elin ;

Wang, Zeneng ;

Levison, Bruce S. ;

Zhu, Weifei ;

Wagner, Matthew A. ;

Bennett, Brian J. ;

Li, Lin ;

DiDonato, Joseph A. ;

Lusis, Aldons J. ;

Hazen, Stanley L. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (09) :5647-5660

[27] The Human Microbiome: Our Second Genome [J].

Grice, Elizabeth A. ;

Segre, Julia A. .

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 13, 2012, 13 :151-170

[28] Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity [J].

Henao-Mejia, Jorge ;

Elinav, Eran ;

Jin, Chengcheng ;

Hao, Liming ;

Mehal, Wajahat Z. ;

Strowig, Till ;

Thaiss, Christoph A. ;

Kau, Andrew L. ;

Eisenbarth, Stephanie C. ;

Jurczak, Michael J. ;

Camporez, Joao-Paulo ;

Shulman, Gerald I. ;

Gordon, Jeffrey I. ;

Hoffman, Hal M. ;

Flavell, Richard A. .

NATURE, 2012, 482 (7384) :179-U67

[29] Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders [J].

Hsiao, Elaine Y. ;

McBride, Sara W. ;

Hsien, Sophia ;

Sharon, Gil ;

Hyde, Embriette R. ;

McCue, Tyler ;

Codelli, Julian A. ;

Chow, Janet ;

Reisman, Sarah E. ;

Petrosino, Joseph F. ;

Patterson, Paul H. ;

Mazmanian, Sarkis K. .

CELL, 2013, 155 (07) :1451-1463

[30] Structure, function and diversity of the healthy human microbiome [J].

Huttenhower, Curtis ;

Gevers, Dirk ;

Knight, Rob ;

Abubucker, Sahar ;

Badger, Jonathan H. ;

Chinwalla, Asif T. ;

Creasy, Heather H. ;

Earl, Ashlee M. ;

FitzGerald, Michael G. ;

Fulton, Robert S. ;

Giglio, Michelle G. ;

Hallsworth-Pepin, Kymberlie ;

Lobos, Elizabeth A. ;

Madupu, Ramana ;

Magrini, Vincent ;

Martin, John C. ;

Mitreva, Makedonka ;

Muzny, Donna M. ;

Sodergren, Erica J. ;

Versalovic, James ;

Wollam, Aye M. ;

Worley, Kim C. ;

Wortman, Jennifer R. ;

Young, Sarah K. ;

Zeng, Qiandong ;

Aagaard, Kjersti M. ;

Abolude, Olukemi O. ;

Allen-Vercoe, Emma ;

Alm, Eric J. ;

Alvarado, Lucia ;

Andersen, Gary L. ;

Anderson, Scott ;

Appelbaum, Elizabeth ;

Arachchi, Harindra M. ;

Armitage, Gary ;

Arze, Cesar A. ;

Ayvaz, Tulin ;

Baker, Carl C. ;

Begg, Lisa ;

Belachew, Tsegahiwot ;

Bhonagiri, Veena ;

Bihan, Monika ;

Blaser, Martin J. ;

Bloom, Toby ;

Bonazzi, Vivien ;

Brooks, J. Paul ;

Buck, Gregory A. ;

Buhay, Christian J. ;

Busam, Dana A. ;

Campbell, Joseph L. .

NATURE, 2012, 486 (7402) :207-214

← 1 2 3 4 5 6 7 8 9 10 →