A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites

Nature

Volumn 551, Issue 7682, 2017, Pages 648-652

  Dodd, Dylan ^a   Spitzer, Matthew H ^a   Van Treuren, William ^a   Merrill, Bryan D ^a   Hryckowian, Andrew J ^a   Higginbottom, Steven K ^a   Le, Anthony ^a   Cowan, Tina M ^a   Nolan, Garry P ^a   Fischbach, Michael A ^b   Sonnenburg, Justin L ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; AROMATIC AMINO ACID; PHENYLALANINE; TRYPTOPHAN; TYROSINE; INDOLE DERIVATIVE; INDOLEPROPIONIC ACID;

AMINO ACID; BACTERIUM; BLOOD; CONCENTRATION (COMPOSITION); DIGESTIVE SYSTEM; DRUG; ENZYME; ENZYME ACTIVITY; GENETICS; METABOLISM; METABOLITE; MICROBIAL ACTIVITY; MICROBIAL COMMUNITY; SERUM;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CLOSTRIDIUM SPOROGENES; GENE CLUSTER; GNOTOBIOTICS; HUMAN; IMMUNITY; INTESTINE FLORA; METABOLISM; MICROBIAL COMMUNITY; MOUSE; NONHUMAN; PRIORITY JOURNAL; ANIMAL; BLOOD; BLOOD ANALYSIS; CHEMISTRY; CLOSTERIUM; GENETICS; GERMFREE ANIMAL; INTESTINE; MALE; METABOLOME; METABOLOMICS; MULTIGENE FAMILY; PERMEABILITY; PHYSIOLOGY; SERUM;

BACTERIA (MICROORGANISMS); CLOSTRIDIUM SPOROGENES; MUS;

AMINO ACIDS, AROMATIC; ANIMALS; BLOOD CHEMICAL ANALYSIS; CLOSTERIUM; GASTROINTESTINAL MICROBIOME; GERM-FREE LIFE; HUMANS; IMMUNITY; INDOLES; INTESTINES; MALE; METABOLIC NETWORKS AND PATHWAYS; METABOLOME; METABOLOMICS; MICE; MULTIGENE FAMILY; PERMEABILITY; PHENYLALANINE; SERUM; TRYPTOPHAN; TYROSINE;

EID: 85036500288     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature24661     Document Type: Article

References (26)

1. Nicholson, J. K. et al. Host-gut microbiota metabolic interactions. Science 336, 1262-1267 (2012).
2. Wikoff, W. R. et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl Acad. Sci. USA 106, 3698-3703 (2009).
3. Danaceau, J. P., Anderson, G. M., McMahon, W. M. & Crouch, D. J. A liquid chromatographic-tandem mass spectrometric method for the analysis of serotonin and related indoles in human whole blood. J. Anal. Toxicol. 27, 440-444 (2003).
4. Venkatesh, M. et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity 41, 296-310 (2014).
5. Chyan, Y. J. et al. Potent neuroprotective properties against the Alzheimer-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid. J. Biol. Chem. 274, 21937-21942 (1999).
6. Elsden, S. R., Hilton, M. G. & Waller, J. M. The end products of the metabolism of aromatic amino acids by clostridia. Arch. Microbiol. 107, 283-288 (1976).
7. Dickert, S., Pierik, A. J., Linder, D. & Buckel, W. The involvement of coenzyme A esters in the dehydration of (R)-phenyllactate to (E)-cinnamate by Clostridium sporogenes. FEBS J. 267, 3874-3884 (2000).
8. Dickert, S., Pierik, A. J. & Buckel, W. Molecular characterization of phenyllactate dehydratase and its initiator from Clostridium sporogenes. Mol. Microbiol. 44, 49-60 (2002).
9. Heap, J. T. et al. The ClosTron: mutagenesis in Clostridium refined and streamlined. J. Microbiol. Methods 80, 49-55 (2010).
10. Lovitt, R. W., Morris, J. G. & Kell, D. B. The growth and nutrition of Clostridium sporogenes NCIB 8053 in defined media. J. Appl. Bacteriol. 62, 71-80 (1987).
11. Su, L. et al. Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis. Gastroenterology 136, 551-563 (2009).
12. Bendall, S. C. et al. Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332, 687-696 (2011).
13. Theys, J. et al. Repeated cycles of Clostridium-directed enzyme prodrug therapy result in sustained antitumour effects in vivo. Br. J. Cancer 95, 1212-1219 (2006).
14. Bader, J. & Simon, H. ATP formation is coupled to the hydrogenation of 2-enoates in Clostridium sporogenes. FEMS Microbiol. Lett. 20, 171-175 (1983).
15. Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114-2120 (2014).
16. Nurk, S. et al. Assembling single-cell genomes and mini-metagenomes from chimeric MDA products. J. Comput. Biol. 20, 714-737 (2013).
17. Aziz, R. K. et al. The RAST Server: rapid annotations using subsystems technology. BMC Genomics 9, 75 (2008).
18. Medema, M. H., Takano, E. & Breitling, R. Detecting sequence homology at the gene cluster level with MultiGeneBlast. Mol. Biol. Evol. 30, 1218-1223 (2013).
19. Case, R. J. et al. Use of 16S rRNA and rpoB genes as molecular markers for microbial ecology studies. Appl. Environ. Microbiol. 73, 278-288 (2007).
20. Sonnenburg, E. D. et al. Specificity of polysaccharide use in intestinal bacteroides species determines diet-induced microbiota alterations. Cell 141, 1241-1252 (2010).
21. Martens, E. C., Chiang, H. C. & Gordon, J. I. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 4, 447-457 (2008).
22. Spitzer, M. H. et al. An interactive reference framework for modeling a dynamic immune system. Science 349, 1259425 (2015).
23. Finck, R. et al. Normalization of mass cytometry data with bead standards. Cytometry A 83A, 483-494 (2013).
24. Elder, B. L., Boraker, D. K. & Fives-Taylor, P. M. Whole-bacterial cell enzymelinked immunosorbent assay for Streptococcus sanguis fimbrial antigens. J. Clin. Microbiol. 16, 141-144 (1982).
25. Bader, J., Rauschenbach, P. & Simon, H. On a hitherto unknown fermentation path of several amino acids by proteolytic clostridia. FEBS Lett. 140, 67-72 (1982).
26. Bühler, M., Giesel, H., Tischer, W. & Simon, H. Occurrence and the possible physiological role of 2-enoate reductases. FEBS Lett. 109, 244-246 (1980).