1887

Abstract

Existing metagenome datasets from many different environments contain untapped potential for understanding metabolic pathways and their biological impact. Our interest lies in the formation of trimethylamine (TMA), a key metabolite in both human health and climate change. Here, we focus on bacterial degradation pathways for choline, carnitine, glycine betaine and trimethylamine N-oxide (TMAO) to TMA in human gut and marine metagenomes. We found the TMAO reductase pathway was the most prevalent pathway in both environments. Proteobacteria were found to contribute the majority of the TMAO reductase pathway sequences, except in the stressed gut, where Actinobacteria dominated. Interestingly, in the human gut metagenomes, a high proportion of the Proteobacteria hits were accounted for by the genera Klebsiella and Escherichia. Furthermore Klebsiella and Escherichia harboured three of the four potential TMA-production pathways (choline, carnitine and TMAO), suggesting they have a key role in TMA cycling in the human gut. In addition to the intensive TMAO–TMA cycling in the marine environment, our data suggest that carnitine-to-TMA transformation plays an overlooked role in aerobic marine surface waters, whereas choline-to-TMA transformation is important in anaerobic marine sediments. Our study provides new insights into the potential key microbes and metabolic pathways for TMA formation in two contrasting environments.

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2016-09-01
2019-12-06
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References

  1. Andreesen J. R.. 1994; Glycine metabolism in anaerobes. Antonie Van Leeuwenhoek66:223–237 [CrossRef][PubMed]
    [Google Scholar]
  2. Andreesen J. R., Wagner M., Sonntag D., Kohlstock M., Harms C., Gursinsky T., Jäger J., Parther T., Kabisch U. et al. 1999; Various functions of selenols and thiols in anaerobic Gram-positive, amino acids-utilizing bacteria. Biofactors10:263–270 [CrossRef][PubMed]
    [Google Scholar]
  3. Ansaldi M., Théraulaz L., Baraquet C., Panis G., Méjean V.. 2007; Aerobic TMAO respiration in Escherichia coli. Mol Microbiol66:484–494 [CrossRef][PubMed]
    [Google Scholar]
  4. Beumer R. R., Te Giffel M. C., Cox L. J., Rombouts F. M., Abee T.. 1994; Effect of exogenous proline, betaine, and carnitine on growth of Listeria monocytogenes in a minimal medium. Appl Environ Microbiol60:1359–1363[PubMed]
    [Google Scholar]
  5. Chen Y., Patel N. A., Crombie A., Scrivens J. H., Murrell J. C.. 2011; Bacterial flavin-containing monooxygenase is trimethylamine monooxygenase. Proc Natl Acad Sci108:17791–17796 [CrossRef]
    [Google Scholar]
  6. Craciun S., Balskus E. P.. 2012; Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc Natl Acad Sci109:21307–21312 [CrossRef]
    [Google Scholar]
  7. Dos Santos J. P., Iobbi-Nivol C., Couillault C., Giordano G., Méjean V.. 1998; Molecular analysis of the trimethylamine N-oxide (TMAO) reductase respiratory system from a Shewanella species. J Mol Biol284:421–433 [CrossRef][PubMed]
    [Google Scholar]
  8. Eddy S. R.. 2011; Accelerated profile HMM searches. PLoS Comput Biol7:e1002195 [CrossRef][PubMed]
    [Google Scholar]
  9. Edgar R. C.. 2004; MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res32:1792–1797 [CrossRef][PubMed]
    [Google Scholar]
  10. Edgar R. C.. 2010; Search and clustering orders of magnitude faster than blast. Bioinformatics26:2460–2461 [CrossRef][PubMed]
    [Google Scholar]
  11. Fairweather-Tait S. J., Bao Y., Broadley M. R., Collings R., Ford D., Hesketh J. E., Hurst R.. 2011; Selenium in human health and disease. Antioxid Redox Signal14:1337–1383 [CrossRef][PubMed]
    [Google Scholar]
  12. Flores-Mateo G., Navas-Acien A., Pastor-Barriuso R., Guallar E.. 2006; Selenium and coronary heart disease: a meta-analysis. Am J Clin Nutr84:762–773[PubMed]
    [Google Scholar]
  13. Freudenberg W., Hormann K., Rieth M., Andreesen J.. 1989; Involvement of a selenoprotein in glycine, sarcosine, and betaine reduction by Eubacterium acidaminophilum. In Selenium in Biology and Medicine25–28 Edited by Wendel A.. Berlin Heidelberg: Springer;
    [Google Scholar]
  14. Gibb S. W., Hatton A. D.. 2004; The occurrence and distribution of trimethylamine-N-oxide in Antarctic coastal waters. Marine Chemistry91:65–75 [CrossRef]
    [Google Scholar]
  15. Guindon S., Dufayard J.-F., Lefort V., Anisimova M., Hordijk W., Gascuel O.. 2010; New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Systematic biology.. 59307–321
  16. Ierardi E., Sorrentino C., Principi M., Giorgio F., Losurdo G., Di leo A.. 2015; Intestinal microbial metabolism of phosphatidylcholine: a novel insight in the cardiovascular risk scenario. Hepatobiliary Surg Nutr4:289–92
    [Google Scholar]
  17. Jameson E., Fu T., Brown I. R., Paszkiewicz K., Purdy K. J., Frank S., Chen Y.. 2015; Anaerobic choline metabolism in microcompartments promotes growth and swarming of Proteus mirabilis. Environ Microbiol [CrossRef][PubMed]
    [Google Scholar]
  18. King G. M.. 1984; Metabolism of trimethylamine, choline, and glycine betaine by sulfate-reducing and methanogenic bacteria in marine sediments. Appl Environ Microbiol48:719–725[PubMed]
    [Google Scholar]
  19. King G. M.. 1988; Distribution and metabolism of quaternary amines in marine sediments. Nitrogen Cycling in Coastal Marine Environments143–173
    [Google Scholar]
  20. Koeth R. A., Wang Z., Levison B. S., Buffa J. A., Org E., Sheehy B. T., Britt E. B., Fu X., Wu Y. et al. 2013; Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med19:576–585 [CrossRef][PubMed]
    [Google Scholar]
  21. Lidbury I. D., Murrell J. C., Chen Y.. 2015; Trimethylamine and trimethylamine N-oxide are supplementary energy sources for a marine heterotrophic bacterium: implications for marine carbon and nitrogen cycling. ISME J9:760–769 [CrossRef][PubMed]
    [Google Scholar]
  22. Mackay R. J., McEntyre C. J., Henderson C., Lever M., George P. M.. 2011; Trimethylaminuria: causes and diagnosis of a socially distressing condition. Clin Biochem Rev32:33–43[PubMed]
    [Google Scholar]
  23. Martínez-del Campo A., Bodea S., Hamer H. A., Marks J. A., Haiser H. J., Turnbaugh P. J., Balskus E. P.. 2015; Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria. MBio6:e0004215 [CrossRef][PubMed]
    [Google Scholar]
  24. Mccrindle S. L., Kappler U., McEwan A. G.. 2005; Microbial dimethylsulfoxide and trimethylamine-N-oxide respiration. Adv Microb Physiol50:147–201 [CrossRef][PubMed]
    [Google Scholar]
  25. Méjean V., Iobbi-Nivol C., Lepelletier M., Giordano G., Chippaux M., Pascal M. C.. 1994; TMAO anaerobic respiration in Escherichia coli: involvement of the tor operon. Mol Microbiol11:1169–1179 [CrossRef][PubMed]
    [Google Scholar]
  26. Petrenko P., Lobb B., Kurtz D. A., Neufeld J. D., Doxey A. C.. 2015; MetAnnotate: function-specific taxonomic profiling and comparison of metagenomes. BMC Biol13:92 [CrossRef][PubMed]
    [Google Scholar]
  27. Ravcheev D. A., Thiele I.. 2014; Systematic genomic analysis reveals the complementary aerobic and anaerobic respiration capacities of the human gut microbiota. Front Microbiol5:674 [CrossRef][PubMed]
    [Google Scholar]
  28. Romano K. A., Vivas E. I., Amador-Noguez D., Rey F. E.. 2015; Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. MBio6:e0248114 [CrossRef][PubMed]
    [Google Scholar]
  29. Sleator R. D., Hill C.. 2002; Bacterial osmoadaptation: the role of osmolytes in bacterial stress and virulence. FEMS Microbiol Rev26:49–71 [CrossRef][PubMed]
    [Google Scholar]
  30. Sun J., Steindler L., Thrash J. C., Halsey K. H., Smith D. P., Carter A. E., Landry Z. C., Giovannoni S. J.. 2011; One carbon metabolism in SAR11 pelagic marine bacteria. PLoS One6:e23973 [CrossRef][PubMed]
    [Google Scholar]
  31. Svensson B.‐G., Akesson B., Nilsson A., Paulsson K.. 1994; Urinary excretion of methylamines in men with varying intake of fish from the Baltic Sea. J Toxicol Environ Health41:411–420 [CrossRef][PubMed]
    [Google Scholar]
  32. Tang W. H., Hazen S. L.. 2014; The contributory role of gut microbiota in cardiovascular disease. J Clin Invest124:4204–4211 [CrossRef][PubMed]
    [Google Scholar]
  33. Tang W. H., Wang Z., Levison B. S., Koeth R. A., Britt E. B., Fu X., Wu Y., Hazen S. L.. 2013; Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med368:1575–1584 [CrossRef][PubMed]
    [Google Scholar]
  34. Wang Z., Klipfell E., Bennett B. J., Koeth R., Levison B. S., Dugar B., Feldstein A. E., Britt E. B., Fu X. et al. 2011; Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature472:57–63 [CrossRef][PubMed]
    [Google Scholar]
  35. Winter S. E., Lopez C. A., Bäumler A. J.. 2013; The dynamics of gut-associated microbial communities during inflammation. EMBO Rep14:319–327 [CrossRef][PubMed]
    [Google Scholar]
  36. Zhu W., Gregory J. C., Org E., Buffa J. A., Gupta N., Wang Z., Li L., Fu X., Wu Y. et al. 2016; Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell165:111–124 [CrossRef][PubMed]
    [Google Scholar]
  37. Zhu Y., Jameson E., Crosatti M., Schafer H., Rajakumar K., Bugg T. D. H., Chen Y.. 2014; Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota. Proc Natl Acad Sci111:4268–4273 [CrossRef]
    [Google Scholar]
  38. Hayashi, T. & Hattori, M. iMicrobe http://data.imicrobe.us/project/view/33 2007
  39. Biddle, J. F., Fitz-Gibbon, S., Schuster, S. C., Brenchley, J. E. & House C. H. MG-RAST http://metagenomics.anl.gov/metagenomics.cgi?page=MetagenomeProject&project=105 2013
  40. Schunck, H., Lavik, G., Desai, D. K., Großkopf, T., Kalvelage, T., Löscher, C. R., Paulmier, A., Contreras, S., Siegel, H., Holtappels, M., Rosenstiel, P., Schilhabel, M. B., Graco, M., Schmitz, R. A., Kuypers, M. M. M. & LaRoche J. MG-RAST http://metagenomics.anl.gov/metagenomics.cgi?page=MetagenomeProject&project=6556 2013
  41. Thompson, C. E., Beys-da-Silva, W. O., Santi, L., Berger, M., Vainstein, M. H. & Vasconcelos, A. T. MG-RAST http://metagenomics.anl.gov/metagenomics.cgi?page=MetagenomeProject&project=6544 2013
  42. Mou, X., Sun, S., Edwards, R. A., Hodson, R. E. & Moran, M. A. MG-RAST http://metagenomics.anl.gov/metagenomics.cgi?page=MetagenomeProject&project=46 2007
  43. Mou, X., Sun, S., Edwards, R. A., Hodson, R. E. & Moran, M. A. MG-RAST http://metagenomics.anl.gov/metagenomics.cgi?page=MetagenomeProject&project=19 2007
  44. Yutin, N., Suzuki, M. T., Teeling, H., Weber, M., Venter, J. C., Rusch, D. B. & Béjà, O iMicrobe http://data.imicrobe.us/project/view/26 2008
  45. Lin, Y. C., Campbell, T., Chung, C. C., Gong, G. C., Chiang, K. P. & Worden, A. Z. CAMERA North Pacific metagenomes from Monterey Bay to Open Ocean (CalCOFI Line 67) 2007
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