VIOLATION OF MICROBIAL AND ENDOGENOUS METABOLISM IN CELIAC DISEASE

Ludmila Oreshko, Elena Semenova, Alexander Shomin, Stanislav Sitkin

Abstract


Aim: to investigate a fecal microbiota composition and to identify candidate biomarkers of celiac disease (CD) by serum metabolomics analysis.

Methods: the quantitative real-time polymerase chain reaction was used for fecal microbiota assessment. Serum metabolomic assays were conducted using the GC–MS.

Results: serum of CD patients showed significant increases in stearic acid, 2-HIVA, succinate, fumarate and benzoate compared to HC. A decrease in the level of eicosadiene and an increase in AA in blood were determined. The ratio of AA to EDA was statistically significant (4.84 vs. 3.28, p=0.033). The elongase activity index in patients with celiac disease tended to increase (p=0.067). The colon microbiome in CD was characterized by decreasing in the level of butyrate-producing Faecalibacterium prausnitzii (F.p.) and Bifidobacterium spp.. Significant negative correlations were observed; between the levels of Bifidobacterium spp. and F.p. and the concentration of succinic acid (rs=–0.343 [p=0.026] and rs=–0.430 [p=0.005], respectively); the F.p. and the fumaric acid (r=–0.429, p=0.005); the benzoic acid and the amount of Bifidobacterium spp. (r=–0.341, p=0.025).

Conclusion: significant changes in serum levels of microbial and endogenous metabolites, reflecting some metabolic pathways disturbances were observed in CD. Metabolites and metabolomic index reflecting the balance between pro-inflammatory and anti-inflammatory components, may be considered as candidate biomarkers of chronic inflammation and metabolic dysbiosis in CD. An increased B. fragilis/F.p. ratio can serve as available biomarker for intestinal pro-inflammatory dysbiosis in CD.


Keywords


butyrate; butyric acid; celiac disease; dysbiosis; Faecalibacterium prausnitzii; gut microbiota; serum metabolome; biomarkers; metabolomics

Full Text:

PDF

References


Thursby, E., Juge, N. (2017). Introduction to the human gut microbiota. Biochemical Journal, 474 (11), 1823–1836. doi: http://doi.org/10.1042/bcj20160510

Verdu, E. F., Galipeau, H. J., Jabri, B. (2015). Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nature Reviews Gastroenterology & Hepatology, 12 (9), 497–506. doi: http://doi.org/10.1038/nrgastro.2015.90

Marasco, G., Di Biase, A. R., Schiumerini, R., Eusebi, L. H., Iughetti, L., Ravaioli, F. et. al. (2016). Gut Microbiota and Celiac Disease. Digestive Diseases and Sciences, 61 (6), 1461–1472. doi: http://doi.org/10.1007/s10620-015-4020-2

Lazebnik, L. B., Tkachenko, E. I., Oreshko, L. S., Sitkin, S. I., Karpov, A. A., Nemtsov, V. I. et. al. (2015). Guidelines for diagnosis and treatment of celiac disease. Experimental and clinical gastroenterology, 5 (117), 3–12.

Wapenaar, M. C., Monsuur, A. J., van Bodegraven, A. A., Weersma, R. K., Bevova, M. R., Linskens, R. K. et. al. (2007). Associations with tight junction genes PARD3 and MAGI2 in Dutch patients point to a common barrier defect for coeliac disease and ulcerative colitisAn unusual case of ascites. Gut, 57 (4), 463–467. doi: http://doi.org/10.1136/gut.2007.133132

Miner-Williams, W. M., Moughan, P. J. (2016). Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel. Nutrition Research Reviews, 29 (1), 40–59. doi: http://doi.org/10.1017/s0954422416000019

Pastorelli, L., De Salvo, C., Mercado, J. R., Vecchi, M., Pizarro, T. T. (2013). Central Role of the Gut Epithelial Barrier in the Pathogenesis of Chronic Intestinal Inflammation: Lessons Learned from Animal Models and Human Genetics. Frontiers in Immunology, 4, 280. doi: http://doi.org/10.3389/fimmu.2013.00280

McCole, D. F. (2014). IBD Candidate Genes and Intestinal Barrier Regulation. Inflammatory Bowel Diseases, 20 (10), 1829–1849. doi: http://doi.org/10.1097/mib.0000000000000090

Sitkin, S. I., Tkachenko, E. I., Vakhitov, T. Ya., Oreshko, L. S., Zhigalova, T. N., Avalueva, E. B. (2014). Serum metabolome and gut microbiota in ulcerative colitis and celiac disease. Newsletter of North-Western State Medical University named after I. I. Mechnikov, 6 (3), 12–22.

De Palma, G., Nadal, I., Collado, M. C., Sanz, Y. (2009). Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects. British Journal of Nutrition, 102 (8), 1154–1160. doi: http://doi.org/10.1017/s0007114509371767

Brown, K., DeCoffe, D., Molcan, E., Gibson, D. L. (2012). Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease. Nutrients, 4 (8), 1095–1119. doi: http://doi.org/10.3390/nu4081095

Verbeke, K. A., Boobis, A. R., Chiodini, A., Edwards, C. A., Franck, A., Kleerebezem, M. et. al. (2015). Towards microbial fermentation metabolites as markers for health benefits of prebiotics. Nutrition Research Reviews, 28 (1), 42–66. doi: http://doi.org/10.1017/s0954422415000037

Osipov, G. A., Zybina, N. N., Rodionov, G. G. (2013). Experience in the use of mass spectrometry of microbial markers in laboratory diagnostics. Medical Alphabet, 1 (3), 64–67.

Al-Toma, A., Volta, U., Auricchio, R., Castillejo, G., Sanders, D. S., Cellier, C. et. al. (2019). European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterology Journal, 7 (5), 583–613. doi: http://doi.org/10.1177/2050640619844125

Smith, B., Li, N., Andersen, A. S., Slotved, H. C., Krogfelt, K. A. (2011). Optimising Bacterial DNA Extraction from Faecal Samples: Comparison of Three Methods. The Open Microbiology Journal, 5 (1), 14–17. doi: http://doi.org/10.2174/1874285801105010014

Psychogios, N., Hau, D. D., Peng, J., Guo, A. C., Mandal, R., Bouatra, S. et. al. (2011). The Human Serum Metabolome. PLoS ONE, 6 (2), e16957. doi: http://doi.org/10.1371/journal.pone.0016957

Wishart, D. S., Jewison, T., Guo, A. C., Wilson, M., Knox, C., Liu, Y. et. al. (2012). HMDB 3.0 – The Human Metabolome Database in 2013. Nucleic Acids Research, 41 (D1), D801–D807. doi: http://doi.org/10.1093/nar/gks1065

Russell, W. R., Duncan, S. H., Scobbie, L., Duncan, G., Cantlay, L., Calder, A. G. et. al. (2013) Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Molecular Nutrition & Food Research, 57 (3), 523–535. doi: http://doi.org/10.1002/mnfr.201200594

Gonthier, M. P., Remesy, C., Scalbert, A., Cheynier, V., Souquet, J. M., Poutanen, K., Aura, A. M. (2006). Microbial metabolism of caff eic acid and its esters chlorogenic and caft aric acids by human faecal microbiota in vitro. Biomedicine & Pharmacotherapy, 60 (9), 536–540. doi: http://doi.org/10.1016/j.biopha.2006.07.084

Quehenberger, O., Armando, A. M., Brown, A. H., Milne, S. B., Myers, D. S., Merrill, A. H. et. al. (2010). Lipidomics reveals a remarkable diversity of lipids in human plasma. Journal of Lipid Research, 51 (11), 3299–3305. doi: http://doi.org/10.1194/jlr.M009449




DOI: http://dx.doi.org/10.21303/2585-663.2019.001089

Refbacks

  • There are currently no refbacks.


Copyright (c) 2019 Ludmila Oreshko, Elena Semenova, Alexander Shomi, Stanislav Sitkin

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2585-6634 (Online), ISSN 2585-6626 (Print)