Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Enterobacter aerogenes ZDY01 Attenuates Choline-Induced Trimethylamine N-Oxide Levels by Remodeling Gut Microbiota in Mice

  • Qiu, Liang (State Key Laboratory of Food Science and Technology, Nanchang University) ;
  • Yang, Dong (State Key Laboratory of Food Science and Technology, Nanchang University) ;
  • Tao, Xueying (State Key Laboratory of Food Science and Technology, Nanchang University) ;
  • Yu, Jun (Jiangxi University of Traditional Chinese Medicine) ;
  • Xiong, Hua (State Key Laboratory of Food Science and Technology, Nanchang University) ;
  • Wei, Hua (State Key Laboratory of Food Science and Technology, Nanchang University)
  • Received : 2017.03.20
  • Accepted : 2017.05.16
  • Published : 2017.08.28
Download PDF
⟨ Previous Next ⟩

Abstract

Trimethylamine N-oxide (TMAO), which is transformed from trimethylamine (TMA) through hepatic flavin-containing monooxygenases, can promote atherosclerosis. TMA is produced from dietary carnitine, phosphatidylcholine, and choline via the gut microbes. Previous works have shown that some small molecules, such as allicin, resveratrol, and 3,3-dimethyl-1-butanol, are used to reduce circulating TMAO levels. However, the use of bacteria as an effective therapy to reduce TMAO levels has not been reported. In the present study, 82 isolates were screened from healthy Chinese fecal samples on a basal salt medium supplemented with TMA as the sole carbon source. The isolates belonged to the family Enterobacteriaceae, particularly to genera Klebsiella, Escherichia, Cronobacter, and Enterobacter. Serum TMAO and cecal TMA levels were significantly decreased in choline-fed mice treated with Enterobacter aerogenes ZDY01 compared with those in choline-fed mice treated with phosphate-buffered saline. The proportions of Bacteroidales family S24-7 were significantly increased, whereas the proportions of Helicobacteraceae and Prevotellaceae were significantly decreased through the administration of E. aerogenes ZDY01. Results indicated that the use of probiotics to act directly on the TMA in the gut might be an alternative approach to reduce serum TMAO levels and to prevent the development of atherosclerosis and "fish odor syndrome" through the effect of TMA on the gut microbiota.

Keywords

References

  1. Sekirov I, Russell SL, Antunes LC, Finlay BB. 2010. Gut microbiota in health and disease. Physiol. Rev. 90: 859-904. https://doi.org/10.1152/physrev.00045.2009
  2. Lee WJ, Hase K. 2014. Gut microbiota-generated metabolites in animal health and disease. Nat. Chem. Biol. 10: 416-424. https://doi.org/10.1038/nchembio.1535
  3. Tremaroli V, Backhed F. 2012. Functional interactions between the gut microbiota and host metabolism. Nature 489: 242-249. https://doi.org/10.1038/nature11552
  4. Bennett BJ, Vallim TQDA, Wang Z, Shih DM, Meng Y, Gregory J, et al. 2013. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 17: 49-60. https://doi.org/10.1016/j.cmet.2012.12.011
  5. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. 2011. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472: 57-65. https://doi.org/10.1038/nature09922
  6. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. 2013. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19: 576-585. https://doi.org/10.1038/nm.3145
  7. Tang WHW, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. 2013. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368: 1575-1584. https://doi.org/10.1056/NEJMoa1109400
  8. Ulman CA, Trevino JJ, Miller M, Gandhi RK. 2014. Fish odor syndrome: a case report of trimethylaminuria. Dermatol. Online J. 20: 21260.
  9. Brugere JF, Borrel G, Gaci N, Tottey W, O'Toole PW, Malpuech-Brugere C. 2014. Archaebiotics: proposed therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease. Gut Microbes 5: 5-10. https://doi.org/10.4161/gmic.26749
  10. Kuka J, Liepinsh E, Makrecka-Kuka M, Liepins J, Cirule H, Gustina D, et al. 2014. Suppression of intestinal microbiotadependent production of pro-atherogenic trimethylamine Noxide by shifting L-carnitine microbial degradation. Life Sci. 117: 84-92. https://doi.org/10.1016/j.lfs.2014.09.028
  11. Wu W-K, Panyod S, Ho C-T, Kuo C-H, Wu M-S, Sheen L-Y. 2015. Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota. J. Funct. Foods 15: 408-417. https://doi.org/10.1016/j.jff.2015.04.001
  12. Wang Z, Roberts AB, Buffa JA, Levison BS, Zhu W, Org E, et al. 2015. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163: 1585-1595. https://doi.org/10.1016/j.cell.2015.11.055
  13. Chen ML, Yi L, Zhang Y, Zhou X, Ran L, Yang J, et al. 2016. Resveratrol attenuates trimethylamine-N-oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota. mBio 7: e02210-e02215.
  14. Miao J, Ling AV, Manthena PV, Gearing ME, Graham MJ, Crooke RM, et al. 2015. Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis. Nat. Commun. 6: 6498. https://doi.org/10.1038/ncomms7498
  15. Shih DM, Wang Z, Lee R, Meng Y, Che N, Charugundla S, et al. 2015. Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis. J. Lipid Res. 56: 22-37. https://doi.org/10.1194/jlr.M051680
  16. Gregory JC, Buffa JA, Org E, Wang Z, Levison BS, Zhu W, et al. 2015. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J. Biol. Chem. 290: 5647-5660. https://doi.org/10.1074/jbc.M114.618249
  17. Mejean V, Iobbi-Nivol C, Lepelletier M, Giordano G, Chippaux M, Pascal MC. 1994. TMAO anaerobic respiration in Escherichia coli: involvement of the tor operon. Mol. Microbiol. 11: 1169-1179. https://doi.org/10.1111/j.1365-2958.1994.tb00393.x
  18. Ocque AJ, Stubbs JR, Nolin TD. 2015. Development and validation of a simple UHPLC-MS/MS method for the simultaneous determination of trimethylamine N-oxide, choline, and betaine in human plasma and urine. J. Pharm. Biomed. Anal. 109: 128-135. https://doi.org/10.1016/j.jpba.2015.02.040
  19. Romano KA, Vivas EI, Amador-Noguez D, Rey FE. 2015. Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. mBio 6: e02481.
  20. Magoc T, Salzberg SL. 2011. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27: 2957-2963. https://doi.org/10.1093/bioinformatics/btr507
  21. Bokulich NA, Subramanian S, Faith JJ, Gevers D, Gordon JI, Knight R, et al. 2013. Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing. Nat. Methods 10: 57-59. https://doi.org/10.1038/nmeth.2276
  22. Edgar RC. 2013. UPARSE: highly accurate OTUs equences from microbial amplicon reads. Nat. Methods 10: 996-998. https://doi.org/10.1038/nmeth.2604
  23. Wang Q, Garrity GM, Tiedje JM, Cole JR. 2007. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 73: 5261-5267. https://doi.org/10.1128/AEM.00062-07
  24. Suchodolski JS, Foster ML, Sohail MU, Leutenegger C, Queen EV, Steiner JM, Marks SL. 2015. The fecal microbiome in cats with diarrhea. PLoS One 10: e0127378. https://doi.org/10.1371/journal.pone.0127378
  25. Randrianarisoa E, Lehn-Stefan A, Wang X, Hoene M, Peter A, Heinzmann SS, et al. 2016. Relationship of serum trimethylamine N-oxide (TMAO) levels with early atherosclerosis in humans. Sci. Rep. 6: 26745. https://doi.org/10.1038/srep26745
  26. Kim SG, Bae HS, Oh HM, Lee ST. 2003. Isolation and characterization of novel halotolerant and/or halophilic denitrifying bacteria with versatile metabolic pathways for the degradation of trimethylamine. FEMS Microbiol. Lett. 225: 263-269. https://doi.org/10.1016/S0378-1097(03)00530-5
  27. Mewies M, Packman LC, Mathews FS, Scrutton NS. 1996. Flavinylation in wild-type trimethylamine dehydrogenase and differentially charged mutant enzymes: a study of the protein environment around the N1 of the flavin isoalloxazine. Biochem. J. 317: 267-272. https://doi.org/10.1042/bj3170267
  28. Liffourrena AS, Lucchesi GI. 2014. Identification, cloning and biochemical characterization of Pseudomonas putida A (ATCC 12633) monooxygenase enzyme necessary for the metabolism of tetradecyltrimethylammonium bromide. Appl. Biochem. Biotechnol. 173: 552-561. https://doi.org/10.1007/s12010-014-0862-x
  29. Kasprzak AA, Papas EJ, Steenkamp DJ. 1983. Identity of the subunits and the stoichiometry of prosthetic groups in trimethylamine dehydrogenase and dimethylamine dehydrogenase. Biochem. J. 211: 535-541. https://doi.org/10.1042/bj2110535
  30. Koeth RA, Levison BS, Culley MK, Buffa JA, Wang Z, Gregory JC, et al. 2014. ${\gamma}$-Butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO. Cell Metab. 20: 799-812. https://doi.org/10.1016/j.cmet.2014.10.006
  31. Denby KJ, Rolfe MD, Crick E, Sanguinetti G, Poole RK, Green J. 2015. Adaptation of anaerobic cultures of Escherichia coli K-12 in response to environmental trimethylamine-Noxide. Environ. Microbiol. 17: 2477-2491. https://doi.org/10.1111/1462-2920.12726
  32. Hoyles L, Jimenez-Pranteda ML, Chilloux J, Myridakis A, Gauguier D, Nicholson JK, et al. 2015. Reduction of trimethylamine N-oxide to trimethylamine by the human gut microbiota: supporting evidence for 'metabolic retroversion'. Poster in Conference on Exploring Human Host-Microbiome Interactions in Health and Disease. Imperial College of London.
  33. Chen Y, Patel NA, Crombie A, Scrivens JH, Murrell JC. 2011. Bacterial flavin-containing monooxygenase is trimethylamine monooxygenase. Proc. Natl. Acad. Sci. USA 108: 17791-17796. https://doi.org/10.1073/pnas.1112928108
  34. Ussher JR, Lopaschuk GD, Arduini A. 2013. Gut microbiota metabolism of L-carnitine and cardiovascular risk. Atherosclerosis 231: 456-461. https://doi.org/10.1016/j.atherosclerosis.2013.10.013
  35. Moller B, Hippe H, Gottschalk G. 1986. Degradation of various amine compounds by mesophilic clostridia. Arch. Microbiol. 145: 85-90. https://doi.org/10.1007/BF00413032
  36. Zhu Y, Jameson E, Crosatti M, Schafer H, Rajakumar K, Bugg TD, Chen Y. 2014. Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota. Proc. Natl. Acad. Sci. USA 111: 4268-4273. https://doi.org/10.1073/pnas.1316569111

Cited by

  1. Lactobacillus plantarumZDY04 exhibits a strain-specific property of lowering TMAOviathe modulation of gut microbiota in mice vol.9, pp.8, 2017, https://doi.org/10.1039/c8fo00349a
  2. Trimethylamine- N -Oxide (TMAO)-Induced Impairment of Cardiomyocyte Function and the Protective Role of Urolithin B-Glucuronide vol.23, pp.3, 2017, https://doi.org/10.3390/molecules23030549
  3. Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target vol.10, pp.None, 2017, https://doi.org/10.3389/fphar.2019.01360
  4. Gut Microbial Metabolism and Nonalcoholic Fatty Liver Disease vol.3, pp.1, 2019, https://doi.org/10.1002/hep4.1284
  5. Bacillus amyloliquefaciens SC06 Protects Mice Against High-Fat Diet-Induced Obesity and Liver Injury via Regulating Host Metabolism and Gut Microbiota vol.10, pp.None, 2019, https://doi.org/10.3389/fmicb.2019.01161
  6. Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in Hemodialysis Patients: a Pilot Study vol.11, pp.2, 2019, https://doi.org/10.1007/s12602-018-9411-1
  7. The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis vol.11, pp.8, 2019, https://doi.org/10.3390/nu11081821
  8. The Potential of Probiotics in the Prevention and Treatment of Atherosclerosis vol.64, pp.4, 2017, https://doi.org/10.1002/mnfr.201900797
  9. Gut microbiota in atherosclerosis: focus on trimethylamine N‐oxide vol.128, pp.5, 2020, https://doi.org/10.1111/apm.13038
  10. A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression vol.9, pp.5, 2017, https://doi.org/10.3390/jcm9051369
  11. The Role of Gut Microbiota in Host Lipid Metabolism: An Eye on Causation and Connection vol.4, pp.7, 2017, https://doi.org/10.1002/smtd.201900604
  12. The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases vol.12, pp.8, 2017, https://doi.org/10.3390/nu12082340
  13. Dietary bioactive ingredients to modulate the gut microbiota-derived metabolite TMAO. New opportunities for functional food development vol.11, pp.8, 2017, https://doi.org/10.1039/d0fo01237h
  14. Does intestinal dysbiosis contribute to an aberrant inflammatory response to severe acute respiratory syndrome coronavirus 2 in frail patients? vol.79, pp.None, 2017, https://doi.org/10.1016/j.nut.2020.110996
  15. Gut microbial composition in patients with atrial fibrillation: effects of diet and drugs vol.36, pp.1, 2017, https://doi.org/10.1007/s00380-020-01669-y
  16. Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets vol.13, pp.2, 2017, https://doi.org/10.3390/toxins13020142
  17. Trimethylamine-N-Oxide Pathway: A Potential Target for the Treatment of MAFLD vol.8, pp.None, 2017, https://doi.org/10.3389/fmolb.2021.733507
  18. Total volatile basic nitrogen and trimethylamine in muscle foods: Potential formation pathways and effects on human health vol.20, pp.4, 2017, https://doi.org/10.1111/1541-4337.12764
  19. Gut Microbiome-Derived Metabolite Trimethylamine N-Oxide Induces Aortic Stiffening and Increases Systolic Blood Pressure With Aging in Mice and Humans vol.78, pp.2, 2017, https://doi.org/10.1161/hypertensionaha.120.16895
  20. The Role of Gut Microbiota on Cholesterol Metabolism in Atherosclerosis vol.22, pp.15, 2021, https://doi.org/10.3390/ijms22158074
  21. Molecular Identification and Selection of Probiotic Strains Able to Reduce the Serum TMAO Level in Mice Challenged with Choline vol.10, pp.12, 2017, https://doi.org/10.3390/foods10122931