Advertisement

Metabolomics

, 12:70 | Cite as

Characterization of ankylosing spondylitis and rheumatoid arthritis using 1H NMR-based metabolomics of human fecal extracts

  • Tie-juan Shao
  • Zhi-xing He
  • Zhi-jun Xie
  • Hai-chang Li
  • Mei-jiao Wang
  • Cheng-ping Wen
Original Article

Abstract

Introduction

The differences in fecal metabolome between ankylosing spondylitis (AS)/rheumatoid arthritis (RA) patients and healthy individuals could be the reason for an autoimmune disorder.

Objectives

The study explored the fecal metabolome difference between AS/RA patients and healthy controls to clarify human immune disturbance.

Methods

Fecal samples from 109 individuals (healthy controls 34, AS 40, and RA 35) were analyzed by 1H NMR spectroscopy. Data were analyzed with principal component analysis (PCA) and orthogonal projection to latent structure discriminant (OPLS-DA) analysis.

Results

Significant differences in the fecal metabolic profiles could distinguish AS/RA patients from healthy controls but could not distinguish between AS and RA patients. The significantly decreased metabolites in AS/RA patients were butyrate, propionate, methionine, and hypoxanthine. Significantly increased metabolites in AS/RA patients were taurine, methanol, fumarate, and tryptophan.

Conclusion

The metabolome variations in feces indicated AS and RA were two homologous diseases that could not be distinguished by 1H NMR metabolomics.

Keywords

Metabolomics Faces Ankylosing spondylitis Rheumatoid arthritis NMR Autoimmune disorder 

Notes

Acknowledgments

This study was financially supported by the National Natural Science Foundation of China (No. 81302936) and the Natural Science Foundation of Zhejiang Province (No. Q13H270006).

Compliance with Ethical Standards

Research involving human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional, national research committee and with the 1964 Helsinki Declaration and its later amendments.

Conflict of interest

The authors declare no conflicts of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11306_2016_1000_MOESM1_ESM.docx (458 kb)
Supplementary material 1 (DOCX 457 kb)

References

  1. Amiot, A., Dona, A. C., Wijeyesekera, A., Tournigand, C., Baumgaertner, I., Lebaleur, Y., et al. (2015). 1H NMR spectroscopy of fecal extracts enables detection of advanced colorectal neoplasia. Journal of Proteome Research, 14(9), 3871–3881. doi: 10.1021/acs.jproteome.5b00277.CrossRefPubMedGoogle Scholar
  2. Arase, T., Uchida, H., Kajitani, T., Ono, M., Tamaki, K., Oda, H., et al. (2009). The UDP-glucose receptor P2RY14 triggers innate mucosal immunity in the female reproductive tract by inducing IL-8. Journal of Immunology, 182(11), 7074–7084. doi: 10.4049/jimmunol.0900001.CrossRefGoogle Scholar
  3. Azzam, M., Zou, X., Dong, X., & Xie, P. (2011). Effect of supplemental l-threonine on mucin 2 gene expression and intestine mucosal immune and digestive enzymes activities of laying hens in environments with high temperature and humidity. Poultry Science, 90(10), 2251–2256. doi: 10.3382/ps.2011-01574.CrossRefPubMedGoogle Scholar
  4. Bjerrum, J. T., Wang, Y., Hao, F., Coskun, M., Ludwig, C., Gunther, U., & Nielsen, O. H. (2015). Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn’s disease and healthy individuals. Metabolomics, 11, 122–133. doi: 10.1007/s11306-014-0677-3.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Cani, P. D., & Delzenne, N. M. (2007). Gut microflora as a target for energy and metabolic homeostasis. Current Opinion in Clinical Nutrition & Metabolic Care, 10(6), 729–734. doi: 10.1097/MCO.0b013e3282efdebb.CrossRefGoogle Scholar
  6. Chen, R., Han, S., Dong, D., Wang, Y., Liu, Q., Xie, W., et al. (2015). Serum fatty acid profiles and potential biomarkers of ankylosing spondylitis determined by gas chromatography-mass spectrometry and multivariate statistical analysis. Biomedical Chromatography, 29(4), 604–611. doi: 10.1002/bmc.3321.CrossRefPubMedGoogle Scholar
  7. Conterno, L., Fava, F., Viola, R., & Tuohy, K. M. (2011). Obesity and the gut microbiota: Does up-regulating colonic fermentation protect against obesity and metabolic disease? Genes and Nutrition, 6(3), 241–260. doi: 10.1007/s12263-011-0230-1.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Costello, M. E., Ciccia, F., Willner, D., Warrington, N., Robinson, P. C., Gardiner, B., et al. (2015). Brief Report: Intestinal dysbiosis in ankylosing spondylitis. Arthritis & Rheumatology, 67(3), 686–691. doi: 10.1002/art.38967.CrossRefGoogle Scholar
  9. Fan, W. M. T. (1996). Metabolite profiling by one- and two-dimensional NMR analysis of complex mixtures. Progress in Nuclear Magnetic Resonance Spectroscopy, 28(2), 161–219. doi: 10.1016/0079-6565(95)01017-3.CrossRefGoogle Scholar
  10. Fan, T. W. M., & Lane, A. N. (2008). Structure-based profiling of metabolites and isotopomers by NMR. Progress in Nuclear Magnetic Resonance Spectroscopy, 52(2), 69–117. doi: 10.1016/j.pnmrs.2007.03.002.CrossRefGoogle Scholar
  11. Fischer, R., Trudgian, D.C., Wright, C., Thomas, G., Bradbury, L.A., Brown, M.A., Bowness, P., Kessler, B.M. (2012). Discovery of candidate serum proteomic and metabolomic biomarkers in ankylosing spondylitis. Molecular & Cellular Proteomics, 11 (2), M111. 013904. doi:  10.1074/mcp.M111.013904.
  12. Fukuda, S., Toh, H., Hase, K., Oshima, K., Nakanishi, Y., Yoshimura, K., et al. (2011). Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature, 469(7331), 543–547. doi: 10.1038/nature09646.CrossRefPubMedGoogle Scholar
  13. Gold, R., Linker, R. A., & Stangel, M. (2012). Fumaric acid and its esters: An emerging treatment for multiple sclerosis with antioxidative mechanism of action. Clinical Immunology, 142(1), 44–48. doi: 10.1016/j.clim.2011.02.017.CrossRefPubMedGoogle Scholar
  14. Gregory, K. E., Bird, S. S., Gross, V. S., Marur, V. R., Lazarev, A. V., Walker, W. A., & Kristal, B. S. (2012). Method development for fecal lipidomics profiling. Analytical Chemistry, 85(2), 1114–1123. doi: 10.1021/ac303011k.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Hamard, A., Mazurais, D., Boudry, G., Le Huërou-Luron, I., Sève, B., & Le Floc’h, N. (2010). A moderate threonine deficiency affects gene expression profile, paracellular permeability and glucose absorption capacity in the ileum of piglets. Journal of Nutritional Biochemistry, 21(10), 914–921. doi: 10.1016/j.jnutbio.2009.07.004.CrossRefPubMedGoogle Scholar
  16. Hamer, H. M., Jonkers, D., Venema, K., Vanhoutvin, S., Troost, F., & Brummer, R. J. (2008). Review article: The role of butyrate on colonic function. Alimentary Pharmacology & Therapeutics, 27(2), 104–119. doi: 10.1111/j.1365-2036.2007.03562.x.CrossRefGoogle Scholar
  17. Huda-Faujan, N., Abdulamir, A. S., Fatimah, A. B., Anas, O. M., Shuhaimi, M., Yazid, A. M., & Loong, Y. Y. (2010). The impact of the level of the intestinal short chain Fatty acids in inflammatory bowel disease patients versus healthy subjects. The Open Biochemistry Journal, 4, 53–58. doi: 10.2174/1874091X01004010053.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Jacobs, S. R., Herman, C. E., MacIver, N. J., Wofford, J. A., Wieman, H. L., Hammen, J. J., & Rathmell, J. C. (2008). Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. The Journal of Immunology, 180(7), 4476–4486. doi: 10.4049/jimmunol.180.7.4476.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Lamichhane, S., Yde, C. C., Schmedes, M. S., Jensen, H. M., Meier, S., & Bertram, H. C. (2015). Strategy for nuclear-magnetic-resonance-based metabolomics of human feces. Analytical Chemistry, 87(12), 5930–5937. doi: 10.1021/acs.analchem.5b00977.CrossRefPubMedGoogle Scholar
  20. Law, G. K., Bertolo, R. F., Adjiri-Awere, A., Pencharz, P. B., & Ball, R. O. (2007). Adequate oral threonine is critical for mucin production and gut function in neonatal piglets. American Journal of Physiology-Gastrointestinal and Liver Physiology, 292(5), 1293–1301. doi: 10.1152/ajpgi.00221.2006.CrossRefGoogle Scholar
  21. Le Gall, G., Noor, S. O., Ridgway, K., Scovell, L., Jamieson, C., Johnson, I. T., et al. (2011). Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome. Journal of Proteome Research, 10(9), 4208–4218. doi: 10.1021/pr2003598.CrossRefPubMedGoogle Scholar
  22. Marcinkiewicz, J., & Kontny, E. (2014). Taurine and inflammatory diseases. Amino Acids, 46(1), 7–20. doi: 10.1007/s00726-012-1361-4.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Maslowski, K. M., & Mackay, C. R. (2011). Diet, gut microbiota and immune responses. Nature Immunology, 12(1), 5–9. doi: 10.1038/ni0111-5.CrossRefPubMedGoogle Scholar
  24. Munn D, Mellor A. (2012) Regulation of T cell-mediated immunity by tryptophan: U.S. Patent 8, 198, 265. 2012-6-12.Google Scholar
  25. Natarajan, N., & Pluznick, J. L. (2014). From microbe to man: The role of microbial short chain fatty acid metabolites in host cell biology. American Journal of Physiology-Cell Physiology, 307(11), 979–985. doi: 10.1152/ajpcell.00228.2014.CrossRefGoogle Scholar
  26. Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012). Host-gut microbiota metabolic interactions. Science, 336(6086), 1262–1267. doi: 10.1126/science.1223813.CrossRefPubMedGoogle Scholar
  27. Nuenen, M. H., Ligt, R. A., Doornbos, R. P., Woude, J. C., Kuipers, E. J., & Venema, K. (2005). The influence of microbial metabolites on human intestinal epithelial cells and macrophages in vitro. FEMS Immunology and Medical Microbiology, 45(2), 183–189. doi: 10.1016/j.femsim.2005.03.010.CrossRefPubMedGoogle Scholar
  28. Ohno, H. (2015). Gut microbial short-chain fatty acids in host defense and immune regulation. Inflammation and Regeneration, 35(3), 114–121. doi: 10.2492/inflammregen.35.114.CrossRefGoogle Scholar
  29. Peng, L., Li, Z.-R., Green, R. S., Holzman, I. R., & Lin, J. (2009). Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. The Journal of Nutrition, 139(9), 1619–1625. doi: 10.3945/jn.109.104638.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Round, J. L., & Mazmanian, S. K. (2009). The gut microbiota shapes intestinal immune responses during health and disease. Nature Reviews Immunology, 9(5), 313–323. doi: 10.1038/nri2515.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Ruth, M. R., & Field, C. J. (2013). The immune modifying effects of amino acids on gut-associated lymphoid tissue. Journal of Animal Science and Biotechnology, 4(1), 27. doi: 10.1186/2049-1891-4-27.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Salazar, N., Dewulf, E. M., Neyrinck, A. M., Bindels, L. B., Cani, P. D., Mahillon, J., et al. (2015). Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women. Clinical Nutrition, 34(3), 501–507. doi: 10.1016/j.clnu.2014.06.001.CrossRefPubMedGoogle Scholar
  33. Samuel, B. S., Shaito, A., Motoike, T., Rey, F. E., Backhed, F., Manchester, J. K., et al. (2008). Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proceedings of the National Academy of Sciences, 105(43), 16767–16772. doi: 10.1073/pnas.0808567105.CrossRefGoogle Scholar
  34. Segain, J., De La Blétiere, D. R., Bourreille, A., Leray, V., Gervois, N., Rosales, C., et al. (2000). Butyrate inhibits inflammatory responses through NFκB inhibition: Implications for Crohn’s disease. Gut, 47(3), 397–403. doi: 10.1136/gut.47.3.397.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., et al. (2013). The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 341(6145), 569–573. doi: 10.1126/science.1241165.CrossRefPubMedGoogle Scholar
  36. Tjellstrom, B., Stenhammar, L., Hogberg, L., Falth-Magnusson, K., Magnusson, K. E., Midtvedt, T., et al. (2007). Gut microflora associated characteristics in first-degree relatives of children with celiac disease. Scandinavian Journal of Gastroenterology, 42(10), 1204–1208. doi: 10.1080/00365520701320687.CrossRefPubMedGoogle Scholar
  37. Wang, Z., Chen, Z., Yang, S., Wang, Y., Yu, L., Zhang, B., et al. (2012). 1H NMR-based metabolomic analysis for identifying serum biomarkers to evaluate methotrexate treatment in patients with early rheumatoid arthritis. Experimental & Therapeutic Medicine, 4(1), 165–171. doi: 10.3892/etm.2012.567.Google Scholar
  38. Weisbart, R. H., Min, Y., Wong, A. L., Kang, J., Kwunyeun, S., & Lin, A. (2005). Selective IgA immune unresponsiveness to Proteus mirabilis fumarate reductase A-chain in rheumatoid arthritis. The Journal of Rheumatology, 32(7), 1208–1212.PubMedGoogle Scholar
  39. Ye, Y., Wang, X., Zhang, L., Lu, Z., & Yan, X. (2012). Unraveling the concentration-dependent metabolic response of Pseudomonas sp. HF-1 to nicotine stress by 1H NMR-based metabolomics. Ecotoxicology, 21(5), 1314–1324. doi: 10.1007/s10646-012-0885-4.CrossRefPubMedGoogle Scholar
  40. Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., et al. (2013). Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity, 39(2), 372–385. doi: 10.1016/j.immuni.2013.08.003.CrossRefPubMedGoogle Scholar
  41. Zhang, X., Zhang, D., Jia, H., Feng, Q., Wang, D., Liang, D., et al. (2015). The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nature Medicine, 21, 895–905. doi: 10.1038/nm.3914.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Tie-juan Shao
    • 1
  • Zhi-xing He
    • 1
  • Zhi-jun Xie
    • 1
  • Hai-chang Li
    • 1
  • Mei-jiao Wang
    • 1
  • Cheng-ping Wen
    • 1
  1. 1.College of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhouChina

Personalised recommendations