1932

Abstract

During the past decade, meta-omics approaches have revolutionized microbiology, allowing for a cultivation-free assessment of the composition and functional properties of entire microbial ecosystems. On the one hand, a phylogenetic and functional interpretation of such data relies on accumulated genetic, biochemical, metabolic, and phenotypic characterization of microbial variation. On the other hand, the increasing availability of extensive microbiome data sets and corresponding metadata provides a vast, underused resource for the microbiology field as a whole. To demonstrate the potential for integrating big data into a functional microbiology workflow, we review literature on trimethylamine (TMA), a microbiota-generated metabolite linked to atherosclerosis development. Translating recently elucidated microbial pathways resulting in TMA production into genomic orthologs, we demonstrate how to mine for their presence in public (meta-) genomic databases and link findings to associated metadata. Reviewing pathway abundance in public data sets shows that TMA production potential is associated with symptomatic atherosclerosis and allows identification of currently uncharacterized TMA-producing bacteria.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-micro-091014-104422
2015-10-15
2024-06-21
Loading full text...

Full text loading...

/deliver/fulltext/micro/69/1/annurev-micro-091014-104422.html?itemId=/content/journals/10.1146/annurev-micro-091014-104422&mimeType=html&fmt=ahah

Literature Cited

  1. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1.  1990. Basic local alignment search tool. J. Mol. Biol. 215:3403–10 [Google Scholar]
  2. al-Waiz M, Mikov M, Mitchell SC, Smith RL. 2.  1992. The exogenous origin of trimethylamine in the mouse. Metabolism 41:2135–36 [Google Scholar]
  3. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T. 3.  et al. 2011. Enterotypes of the human gut microbiome. Nature 473:7346174–80 [Google Scholar]
  4. Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y. 4.  et al. 2013. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 17:149–60 [Google Scholar]
  5. Borrel G, Harris HMB, Tottey W, Mihajlovski A, Parisot N. 5.  et al. 2012. Genome sequence of “Candidatus Methanomethylophilus alvus” Mx1201, a methanogenic archaeon from the human gut belonging to a seventh order of methanogens. J. Bacteriol. 194:246944–45 [Google Scholar]
  6. Brugère JF, Borrel G, Gaci N, Tottey W, O'Toole PW, Malpuech-Brugère C. 6.  2014. Archaebiotics: proposed therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease. Gut Microbes 5:15–10 [Google Scholar]
  7. Caspi R, Altman T, Billington R, Dreher K, Foerster H. 7.  et al. 2014. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res. 42:D459–71 [Google Scholar]
  8. Clemente JC, Ursell LK, Parfrey LW, Knight R. 8.  2012. The impact of the gut microbiota on human health: an integrative view. Cell 148:61258–70 [Google Scholar]
  9. Craciun S, Balskus EP. 9.  2012. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. PNAS 109:5221307–12 [Google Scholar]
  10. Cryan JF, Dinan TG. 10.  2012. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 13:10701–12 [Google Scholar]
  11. De Filippi F. 11.  1906. Das Trimethylamin als normales Produkt des Stoffwechsels, nebst einer Methode für dessen Bestimmung im Harn und Kot. Z. Physiol. Chem. 49:433–56 [Google Scholar]
  12. Dridi B, Fardeau ML, Ollivier B, Raoult D, Drancourt M. 12.  2012. Methanomassiliicoccus luminyensis gen. nov., sp. nov., a methanogenic archaeon isolated from human faeces. Int. J. Syst. Evol. Microbiol. 62:81902–7 [Google Scholar]
  13. Erickson AR, Cantarel BL, Lamendella R, Darzi Y, Mongodin EF. 13.  et al. 2012. Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease. PLOS ONE 7:11e49138 [Google Scholar]
  14. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C. 14.  et al. 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. PNAS 110:229066–71 [Google Scholar]
  15. Faust K, Raes J. 15.  2012. Microbial interactions: from networks to models. Nat. Rev. Microbiol. 10:8538–50 [Google Scholar]
  16. Fiebig K, Gottschalk G. 16.  1983. Methanogenesis from choline by a coculture of Desulfovibrio sp. and Methanosarcina barkeri. Appl. Environ. Microbiol. 45:1161–68 [Google Scholar]
  17. Gorlas A, Robert C, Gimenez G, Drancourt M, Raoult D. 17.  2012. Complete genome sequence of Methanomassiliicoccus luminyensis, the largest genome of a human-associated archaea species. J. Bacteriol. 194:174745 [Google Scholar]
  18. Haft DH, Selengut JD, Richter RA, Harkins D, Basu MK, Beck E. 18.  2013. TIGRFAMS and genome properties in 2013. Nucleic Acids Res. 41:D387–95 [Google Scholar]
  19. Hildebrand F, Nguyen TLA, Brinkman B, Yunta RG, Cauwe B. 19.  et al. 2013. Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice. Genome Biol. 14:1R4 [Google Scholar]
  20. Joossens M, Huys G, Cnockaert M, De Preter V, Verbeke K. 20.  et al. 2011. Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives. Gut 60:5631–37 [Google Scholar]
  21. Kanehisa M, Goto S, Sato Y, Kawashima M, Furumichi M, Tanabe M. 21.  2014. Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res. 42:D199–205 [Google Scholar]
  22. Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B. 22.  et al. 2012. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat. Commun. 3:1245 [Google Scholar]
  23. King GM. 23.  1984. Metabolism of trimethylamine, choline, and glycine betaine by sulfate-reducing and methanogenic bacteria in marine sediments. Appl. Environ. Microbiol. 48:4719–25 [Google Scholar]
  24. Koeth RA, Levison BS, Culley MK, Buffa JA, Wang Z. 24.  et al. 2014. γ-Butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of l-carnitine to TMAO. Cell Metab. 20:5799–812 [Google Scholar]
  25. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E. 25.  et al. 2013. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19:5576–85 [Google Scholar]
  26. Krych L, Hansen CHF, Hansen AK, van den Berg FWJ, Nielsen DS. 26.  2013. Quantitatively different, yet qualitatively alike: a meta-analysis of the mouse core gut microbiome with a view towards the human gut microbiome. PLOS ONE 8:5e62578 [Google Scholar]
  27. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F. 27.  et al. 2013. Richness of human gut microbiome correlates with metabolic markers. Nature 500:7464541–46 [Google Scholar]
  28. Li J, Jia H, Cai X, Zhong H, Feng Q. 28.  et al. 2014. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 32:8834–41 [Google Scholar]
  29. Markowitz VM, Chen IM, Palaniappan K, Chu K, Szeto E. 29.  et al. 2012. IMG: the integrated microbial genomes database and comparative analysis system. Nucleic Acids Res. 40:D115–22 [Google Scholar]
  30. Mihajlovski A, Alric M, Brugère JF. 30.  2008. A putative new order of methanogenic archaea inhabiting the human gut, as revealed by molecular analyses of the mcrA gene. Res. Microbiol. 159:7–8516–21 [Google Scholar]
  31. Mihajlovski A, Doré J, Levenez F, Alric M, Brugère JF. 31.  2010. Molecular evaluation of the human gut methanogenic archaeal microbiota reveals an age-associated increase of the diversity. Environ. Microbiol. Rep. 2:2272–80 [Google Scholar]
  32. Monk JM, Charusanti P, Aziz RK, Lerman JA, Premyodhin N, Orth JD. 32.  2013. Genome-scale metabolic reconstructions of multiple Escherichia coli strains highlight strain-specific adaptations to nutritional environments. PNAS 110:5020338–43 [Google Scholar]
  33. Neill AR, Grime DW, Dawson RM. 33.  1978. Conversion of choline methyl groups through trimethylamine into methane in the rumen. Biochem. J. 170:3529–35 [Google Scholar]
  34. Nguyen TLA, Vieira-Silva S, Liston A, Raes J. 34.  2015. How informative is the mouse for human gut microbiota research?. Dis. Model. Mech. 8:11–16 [Google Scholar]
  35. Paul K, Nonoh JO, Mikulski L, Brune A. 35.  2012. “Methanoplasmatales”: Thermoplasmatales-related archaea in termite guts and other environments are the seventh order of methanogens. Appl. Environ. Microbiol. 78:238245–53 [Google Scholar]
  36. Powell S, Szklarczyk D, Trachana K, Roth A, Kuhn M. 36.  et al. 2012. eggNOG v3.0: orthologous groups covering 1133 organisms at 41 different taxonomic ranges. Nucleic Acids Res. 40:D284–89 [Google Scholar]
  37. Qin J, Li Y, Cai Z, Li S, Zhu J. 37.  et al. 2012. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490:741855–60 [Google Scholar]
  38. Raes J. 38.  2011. Why meta-omics should be mega-omics: on experimental design and multiple testing hell. Environ. Microbiol. Rep. 3:119–20 [Google Scholar]
  39. Raes J, Bork P. 39.  2008. Molecular eco-systems biology: towards an understanding of community function. Nat. Rev. Microbiol. 6:9693–99 [Google Scholar]
  40. Rajilić-Stojanović M, Jonkers DM, Salonen A, Hanevik K, Raes J. 40.  et al. 2015. Intestinal microbiota and diet in IBS: causes, consequences or epiphenomena. Am. J. Gastroenterol. 110:2278–87 [Google Scholar]
  41. Reddy BS. 41.  1981. Diet and excretion of bile acids. Cancer Res. 41:3766–68 [Google Scholar]
  42. Romano KA, Vivas EI, Amador-Noguez D, Rey FE. 42.  2015. Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. mBio 6:2e02481–14 [Google Scholar]
  43. Savage DC. 43.  1977. Microbial ecology of the gastrointestinal tract. Annu. Rev. Microbiol. 31:107–33 [Google Scholar]
  44. Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C. 44.  et al. 2013. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2:e01202 [Google Scholar]
  45. Seim H, Löster H, Claus R, Kleber HP, Strack E. 45.  1982. Splitting of the C–N bond in carnitine by an enzyme (trimethylamine forming) from membranes of Acinetobacter calcoaceticus. FEMS Microbiol. Lett. 15:3165–67 [Google Scholar]
  46. Serino M, Blasco-Baque V, Nicolas S, Burcelin R. 46.  2014. Far from the eyes, close to the heart: dysbiosis of gut microbiota and cardiovascular consequences. Curr. Cardiol. Rep. 16:11540 [Google Scholar]
  47. Shimizu M, Cashman JR, Yamazaki H. 47.  2007. Transient trimethylaminuria related to menstruation. BMC Med. Genet. 8:2 [Google Scholar]
  48. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB. 48.  et al. 2013. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368:171575–84 [Google Scholar]
  49. Tang WH, Hazen SL. 49.  2014. The contributory role of gut microbiota in cardiovascular disease. J. Clin. Investig. 124:104204–11 [Google Scholar]
  50. Tang WH, Wang Z, Fan Y, Levison B, Hazen JE. 50.  et al. 2014. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J. Am. Coll. Cardiol. 64:181908–14 [Google Scholar]
  51. Tatusov RL, Koonin EV, Lipman DJ. 51.  1997. A genomic perspective on protein families. Science 278:5338631–37 [Google Scholar]
  52. Tatusova T, Ciufo S, Fedorov B, O'Neill K, Tolstoy I. 52.  2014. RefSeq microbial genomes database: new representation and annotation strategy. Nucleic Acids Res. 42:D553–59 [Google Scholar]
  53. 53. The Human Microbiome Project Consortium 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:7402207–14 [Google Scholar]
  54. Thibodeaux CJ, van der Donk WA. 54.  2012. Converging on a mechanism for choline degradation. PNAS 109:5221184–85 [Google Scholar]
  55. Touchon M, Hoede C, Tenaillon O, Barbe V, Baeriswyl S. 55.  et al. 2009. Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths. PLOS Genet. 5:1e1000344 [Google Scholar]
  56. Treacy EP, Akerman BR, Chow LML, Youil R, Bibeau C. 56.  et al. 1998. Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication. Hum. Mol. Genet. 7:5839–45 [Google Scholar]
  57. Tremaroli V, Bäckhed F. 57.  2012. Functional interactions between the gut microbiota and host metabolism. Nature 489:7415242–49 [Google Scholar]
  58. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A. 58.  et al. 2009. A core gut microbiome in obese and lean twins. Nature 457:7228480–84 [Google Scholar]
  59. Unemoto T, Hayashi M, Miyaki K, Hayashi M. 59.  1966. Formation of trimethylamine from dl-carnitine by Serratia marcescens. Biochim. Biophys. Acta 121:220–22 [Google Scholar]
  60. Ussher JR, Lopaschuk GD, Arduini A. 60.  2013. Gut microbiota metabolism of l-carnitine and cardiovascular risk. Atherosclerosis 231:2456–61 [Google Scholar]
  61. Vinjé S, Stroes E, Nieuwdorp M, Hazen SL. 61.  2014. The gut microbiome as novel cardio-metabolic target: The time has come!. Eur. Heart J. 35:14883–87 [Google Scholar]
  62. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS. 62.  et al. 2011. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:734157–63 [Google Scholar]
  63. Wang Z, Tang WH, Buffa JA, Fu X, Britt EB. 63.  et al. 2014. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur. Heart J. 35:14904–10 [Google Scholar]
  64. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY. 64.  et al. 2011. Linking long-term dietary patterns with gut microbial enterotypes. Science 334:6052105–8 [Google Scholar]
  65. Zeisel SH, Mar M, Howe JC, Holden JM. 65.  2003. Concentrations of choline-containing compounds and betaine in common foods. J. Nutr. 133:51302–7 [Google Scholar]
  66. Zeller G, Tap J, Voigt AY, Sunagawa S, Kultima JR. 66.  et al. 2014. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol. Syst. Biol. 10:766 [Google Scholar]
  67. Zhang AQ, Mitchell S, Smith R. 67.  1995. Fish odour syndrome: verification of carrier detection test. J. Inherit. Metab. Dis. 18:6669–74 [Google Scholar]
  68. Zhu Y, Jameson E, Crosatti M, Schäfer H, Rajakumar K. 68.  et al. 2014. Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota. PNAS 111:114268–73 [Google Scholar]
/content/journals/10.1146/annurev-micro-091014-104422
Loading
/content/journals/10.1146/annurev-micro-091014-104422
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error