Fatty Acids of Erythrocyte Membranes and Blood Serum as Possible Predictors of Exacerbation in Patients with Inflammatory Bowel Diseases
https://doi.org/10.22416/1382-4376-2024-34-6-28-41
Abstract
Aim: to study the levels of fatty acids in the membranes of erythrocytes and blood serum in patients with inflammatory bowel diseases (IBD) examined over time, as possible predictors of exacerbation of the disease.
Materials and methods. Over a period of 6–12 months, 24 patients (mean age — 38.2 ± 4.4 years) with IBD with of moderate and mild severity of the disease were examined, of which 10 patients had ulcerative colitis, 10 — Crohn’s disease, 4 — unclassified colitis: the first examination was in the acute stage, the second was in the remission stage. In 48 additionally examined patients with IBD in remission (25 patients with ulcerative colitis, 15 — with Crohn’s disease, 8 — with unclassified colitis), the course of the disease was monitored over the next 12 months. The comparison group included 53 people comparable to the main groups in age. The study of the composition of fatty acids (FAs) in the membranes of erythrocytes and blood serum was carried out using a gas chromatograph mass spectrometry system based on three quadrupoles Agilent 7000B (Agilent Technologies Inc., USA).
Results. In the acute stage, patients with IBD have a higher total content of saturated fatty acids (SFAs) in erythrocyte membranes compared to the control group (p = 0.006), and, on the contrary, lower levels of unsaturated fatty acids (UFAs) (p = 0.005), mainly due to polyunsaturated FAs (PUFAs) (p = 0.026), namely omega-6 PUFAs (p = 0.011).
Remission of IBD is associated with an increase in the level of a number of SFAs in the blood serum — margaric C17:0 (p = 0.024), arachidic acid (C20:0) — in erythrocyte membranes and serum (p = 0.0001 and p = 0.019, respectively), with a decrease in the total content of monounsaturated FAs in erythrocyte membranes (p = 0.022), an increase in the total concentration of PUFAs due to both omega-3 PUFAs (p = 0.0008) and omega-6 PUFAs (p = 0.033) in erythrocyte membranes compared with a group of healthy individuals.
The exacerbation stage in patients with IBD examined over time is associated with higher levels of stearic FA C18:0 (p = 0.005), SFA/UFA (p = 0.034) and SFA/PUFA (p = 0.039) ratios in erythrocyte membranes, serum level of arachidic FA C20:0 (p = 0.008), and, on the contrary, lower content of UFAs in erythrocyte membranes — eicosapentaenoic C20:5n-3 (p = 0.0023), eicosadienoic C20:2n-6 (p = 0.0027), hexadecadienoic C16:2n-6 (p = 0.006), docosatetraenoic C22:4n-6 (p = 0.008) and alpha-linolenic C18:3n-3 (p = 0.039).
A combined “panel” of fatty acids, including the levels of C20:2n-6, C18:0 in erythrocyte membranes and the content of C20:0 in blood serum, provided an AUC of 0.683 (95 % CI: 0.500–0.844), sensitivity 91.4 %, specificity 68.3 %.
Levels of C20:5n-3, C20:2n-6, C18:0, C16:2n-6, C22:4n-6, C18:3n-3 fatty acids, SFA/UFA and SFA/PUFA ratios in erythrocyte membranes and content C20:0 in blood serum, used as biomarkers — predictors of the development of exacerbation in patients with IBD who were in remission, predicted the development of exacerbation of IBD after 2–4 months in the case of maximally changed levels of FAs, after 6–8 months — with moderately changed levels FAs, maintaining remission for 12 months — with minimally changed FAs levels.
Conclusion. Fatty acids of erythrocyte membranes and blood serum should be considered as promising markers for further studies related to the diagnosis and prediction of exacerbation in IBD.
Keywords
About the Authors
M. V. KruchininaRussian Federation
Margarita V. Kruchinina — Dr. Sci. (Med.), Docent, Head of the Gastroenterology Laboratory, Leading Researcher of the Gastroenterology Laboratory; Professor of the Department of Propaedeutics of Internal Diseases
630089, Novosibirsk, Borisa Bogatkova str., 175/1
M. F. Osipenko
Russian Federation
Marina F. Osipenko — Dr. Sci. (Med.), Professor, Head of the Department of Propaedeutics of Internal Diseases
630091, Novosibirsk, Krasny Ave., 52
A. I. Valuyskikh
Russian Federation
Alexander I. Valuiskikh — Resident
630089, Novosibirsk, Borisa Bogatkova str., 175/1
E. Yu. Valuiskikh
Russian Federation
Ekaterina Yu. Valuyskikh — Cand. Sci. (Med.), Docent, Associate Professor at the Department of Therapy, Hematology and Transfusiology of the Faculty of Continuing Education and Retraining of Physicians
630091, Novosibirsk, Krasny Ave., 52
I. O. Svetlova
Russian Federation
Irina O. Svetlova — Cand. Sci. (Med.), Docent, Associate Professor at the Department of Therapy, Hematology and Transfusiology of the Faculty of Continuing Education and Retraining of Physicians; Gastroenterologist
630091, Novosibirsk, Krasny Ave., 52
References
1. Kniazev O.V., Shkurko T.V., Kagramanova A.V., Veselov A.V., Nikonov E.L. Epidemiology of inflammatory bowel disease. State of the problem (review). Russian Journal of EvidenceBased Gastroenterology. 2020;9(2):66–73. (In Russ.). DOI: 10.17116/dokgastro2020902166
2. Cushing K., Higgins P.D.R. Management of Crohn disease: A review. JAMA. 2021;325(1):69–80. DOI: 10.1001/jama.2020.18936
3. Liverani E., Scaioli E., Digby R.J., Bellanova M., Belluzzi A. How to predict clinical relapse in inflammatory bowel disease patients. World J Gastroenterol. 2016;22(3):1017–33. DOI: 10.3748/wjg.v22.i3.1017
4. Li M., Tao Y., Sun Y., Wu J., Zhang F., Wen Y., et al. Constructing a prediction model of inflammatory bowel disease recurrence based on factors affecting the quality of life. Front Med (Lausanne). 2023;10:1041505. DOI: 10.3389/fmed.2023.1041505
5. Chen P., Zhou G., Lin J., Li L., Zeng Z., Chen M., et al. Serum biomarkers for inflammatory bowel disease. Front Med (Lausanne). 2020;7:123. DOI: 10.3389/fmed.2020.00123
6. Yan D., Ye S., He Y., Wang S., Xiao Y., Xiang X., et al. Fatty acids and lipid mediators in inflammatory bowel disease: From mechanism to treatment. Front Immunol. 2023;14:1286667. DOI: 10.3389/fimmu.2023.1286667
7. Shelygin Yu.A., Ivashkin V.T., Achkasov S.I., Reshetov I.V., Maev I.V., Belousova E.A., et al. Clinical guidelines. Crohn’s Disease (K50), Adults. Koloproktologia. 2023;22(3):10–49. (In Russ.). DOI: 10.33878/2073-7556-2023-22-3-10-49
8. Russian Gastroenterological Association; Association of Coloproctologists of Russia. Ulcerative colitis. Clinical guidelines. Moscow, 2020. (In Russ.). URL: https://legalacts.ru/doc/klinicheskie-rekomendatsii-iazvennyi-kolit-utv-minzdravom-rossii/
9. Kruchinina M.V., Kruchinin V.N., Prudnikova Ya.I., Gromov A.A., Shashkov M.V., Sokolova A.S. Study of the level of fatty acids in erythrocyte membranes and blood serum in patients with colorectal cancer in Novosibirsk. Advances in Molecular Oncology. 2018;5(2):50–61. (In Russ.). DOI: 10.17650/2313-805X-2018-5-2-50-61
10. Breiman L. Random forests. Machine learning. 2001;45:5–32. DOI: 10.1023/A:1010933404324
11. Clarke E.D., Stanford J., Ferguson J.J.A., Wood L.G., Collins C.E. Red blood cell membrane fatty acid composition, dietary fatty acid intake and diet quality as predictors of inflammation in a group of Australian adults. Nutrients. 2023;15(10):2405. DOI: 10.3390/nu15102405
12. Lechner K., Bock M., von Schacky C., Scherr J., Lorenz E., Lechner B., et al. Trans-fatty acid blood levels of industrial but not natural origin are associated with cardiovascular risk factors in patients with HFpEF: A secondary analysis of the Aldo-DHF trial. Clin Res Cardiol. 2023;112(11):1541–54. DOI: 10.1007/s00392-022-02143-7
13. Kruchinina M.V., Svetlova I.O., Azgaldyan A.V., Osipenko M.F., Valuyskikh E.Yu., Shashkov M.V., et al. Fatty acid profile of erythrocyte membranes and blood serum in patients with inflammatory bowel diseases depending on the stage of the disease. Modern Science: Actual Problems of Theory And Practice. Series: Natural and Technical Sciences. 2021;5:161–84. (In Russ.). DOI: 10.37882/2223–2966.2021.05.18
14. Rosa Neto J.C., Calder P.C., Curi R., Newsholme P., Sethi J.K., Silveira L.S. The immunometabolic roles of various fatty acids in macrophages and lymphocytes. Int J Mol Sci. 2021;22(16):8460. DOI: 10.3390/ijms22168460
15. Korbecki J., Bajdak-Rusinek K. The effect of palmitic acid on inflammatory response in macrophages: An overview of molecular mechanisms. Inflamm Res. 2019;68(11):915–32. DOI: 10.1007/s00011-019-01273-5
16. Guan S., Jia B., Chao K., Zhu X. Tang J., Li M., et al. UPLC-QTOF-MS-based plasma lipidomic profiling reveals biomarkers for inflammatory bowel disease diagnosis. J Proteome Res. 2020;19(2):600–9. DOI: 10.1021/acs.jproteome.9b00440
17. Gori M., Altomare A., Cocca S., Solida E., Ribolsi M., Carotti S., et al. Palmitic acid affects intestinal epithelial barrier integrity and permeability in vitro. Antioxidants (Basel). 2020;9(5):417. DOI: 10.3390/antiox9050417
18. Bashllari R., Molonia M.S., Muscarà C., Speciale A., Wilde P.J., Saija A., et al. Cyanidin-3-O-glucoside protects intestinal epithelial cells from palmitate-induced lipotoxicity. Arch Physiol Biochem. 2023;129(2):379–86. DOI: 10.1080/13813455.2020.1828480
19. Escoula Q., Bellenger S., Narce M., Bellenger J. Docosahexaenoic and eicosapentaenoic acids prevent altered-Muc2 secretion induced by palmitic acid by alleviating endoplasmic reticulum stress in LS174T goblet cells. Nutrients. 2019;11(9):2179. DOI: 10.3390/nu11092179
20. Wiese D.M., Horst S.N., Brown C.T., Allaman M.M., Hodges M.E., Slaughter J.C., et al. Serum fatty acids are correlated with inflammatory cytokines in ulcerative colitis. PLoS One. 2016;11(5):e0156387. DOI: 10.1371/journal.pone.0156387
21. Matsuzaka T. Role of fatty acid elongase Elovl6 in the regulation of energy metabolism and pathophysiological significance in diabetes. Diabetol Int. 2020;12(1):68–73. DOI: 10.1007/s13340-020-00481-3
22. Valli A., Rodriguez M., Moutsianas L., Fischer R., Fedele V., Huang H.L., et al. Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways. Oncotarget. 2015;6(4):1920–41. DOI: 10.18632/oncotarget.3058
23. Jergens A.E., Parvinroo S., Kopper J., Wannemuehler M.J. Rules of engagement: Epithelial-microbe interactions and inflammatory bowel disease. Front Med (Lausanne). 2021;8:669913. DOI: 10.3389/fmed.2021.669913
24. Li S., Chen M., Wang Z., Abudourexiti W., Zhang L., Ding C., et al. Ant may well destroy a whole dam: Glycans of colonic mucus barrier disintegrated by gut bacteria. Microbiol Res. 2024;281:127599. DOI: 10.1016/j.micres.2023.127599
25. Smyth M., Lunken G., Jacobson K. Insights into inflammatory bowel disease and effects of dietary fatty acid intake with a focus on polyunsaturated fatty acids using preclinical models. J Can Assoc Gastroenterol. 2023;7(1):104–14. DOI: 10.1093/jcag/gwad058
26. Diab J., Hansen T., Goll R., Stenlund H., Jensen E., Moritz T., et al. Mucosal metabolomic profiling and pathway analysis reveal the metabolic signature of ulcerative colitis. Metabolites. 2019;9(12):291. DOI: 10.3390/metabo9120291
27. Scaioli E., Liverani E., Belluzzi A. The imbalance between n-6/n-3 polyunsaturated fatty acids and inflammatory bowel disease: A comprehensive review and future therapeutic perspectives. Int J Mol Sci. 2017;18(12):2619. DOI: 10.3390/ijms18122619
28. Serhan C.N., Chiang N., Dalli J. New pro-resolving n-3 mediators bridge resolution of infectious inflammation to tissue regeneration. Mol Aspects Med. 2018;64:1–17. DOI: 10.1016/j.mam.2017.08.002
29. Rubbino F., Garlatti V., Garzarelli V., Massimino L., Spanò S., Iadarola P., et al. GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity. Sci Rep. 2022;12(1):381. DOI: 10.1038/s41598-021-03787-7
30. Hong S.W., Lee J., Moon S.J., Kwon H., Park S.E., Rhee E.J., et al. Docosahexanoic acid attenuates palmitate-induced apoptosis by autophagy upregulation via GPR120/mTOR axis in insulin-secreting cells. Endocrinol Metab (Seoul). 2024;39(2):353–63. DOI: 10.3803/EnM.2023.1809
31. Rohwer N., Chiu C.Y., Huang D., Smyl C., Rothe M., Rund K.M., et al. Omega-3 fatty acids protect from colitis via an Alox15-derived eicosanoid. FASEB J. 2021;35(4):e21491. DOI: 10.1096/fj.202002340RR
32. Yao J., Lu Y., Zhi M., Hu P., Wu W., Gao X. Dietary n-3 polyunsaturated fatty acids ameliorate Crohn’s disease in rats by modulating the expression of PPAR-γ/NFAT. Mol Med Rep. 2017;16(6):8315–22. DOI: 10.3892/mmr.2017.7673
33. Kim J., Ahn M., Choi Y., Kang T., Kim J., Lee N.H., et al. Alpha-linolenic acid alleviates dextran sulfate sodium-induced ulcerative colitis in mice. Inflammation. 2020;43(5):1876–83. DOI: 10.1007/s10753-020-01260-7
34. Wang X., Yue H., Zhang H., Wan L., Ji S., Geng C. Preventive effects of long-term intake of plant oils with different linoleic acid/alpha-linolenic acid ratios on acute colitis mouse model. Front Nutr. 2022;9:788775. DOI: 10.3389/fnut.2022.788775
35. El Mahdy R.N., Nader M.A., Helal M.G., Abu-Risha S.E., Abdelmageed M.E. Eicosapentaenoic acid mitigates ulcerative colitis-induced by acetic acid through modulation of NF-κB and TGF-β/EGFR signaling pathways. Life Sci. 2023;327:121820. DOI: 10.1016/j.lfs.2023.121820
36. Prossomariti A., Scaioli E., Piazzi G., Fazio C., Bellanova M., Biagi E., et al. Short-term treatment with eicosapentaenoic acid improves inflammation and affects colonic differentiation markers and microbiota in patients with ulcerative colitis. Sci Rep. 2017;7(1):7458. DOI: 10.1038/s41598-017-07992-1
37. Uchiyama K., Nakamura M., Odahara S., Koido S., Katahira K., Shiraishi H., et al. N-3 polyunsaturated fatty acid diet therapy for patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16(10):1696–707. DOI: 10.1002/ibd.21251
38. Diab J., Hansen T., Goll R., Stenlund H., Ahnlund M., Jensen E., et al. Lipidomics in ulcerative colitis reveal alteration in mucosal lipid composition associated with the disease state. Inflamm Bowel Dis. 2019;25(11):1780–7. DOI: 10.1093/ibd/izz098
39. Edwards B.R. Lipid biogeochemistry and modern lipidomic techniques. Ann Rev Mar Sci. 2023;15:485–508. DOI: 10.1146/annurev-marine-040422-094104
40. Tanaka T., Uozumi S., Morito K., Osumi T., Tokumura A. Metabolic conversion of C20 polymethylene-interrupted polyunsaturated fatty acids to essential fatty acids. Lipids. 2014;49(5):423–9. DOI: 10.1007/s11745-014-3896-5
41. Liou Y.A., Innis S.M. Dietary linoleic acid has no effect on arachidonic acid, but increases n-6 eicosadienoic acid, and lowers dihomo-gamma-linolenic and eicosapentaenoic acid in plasma of adult men. Prostaglandins Leukot Essent Fatty Acids. 2009;80(4):201–6. DOI: 10.1016/j.plefa.2009.02.003
42. Prada M., Eichelmann F., Wittenbecher C., Kuxhaus O., Schulze M.B. Plasma lipidomic n-6 polyunsaturated fatty acids and type 2 diabetes risk in the EPIC-Potsdam prospective cohort study. Diabetes Care. 2023;46(4):836–44. DOI: 10.2337/dc22-1435
43. Duan J., Song Y., Zhang X., Wang C. Effect of ω-3 polyunsaturated fatty acids-derived bioactive lipids on metabolic disorders. Front Physiol. 2021;12:646491. DOI: 10.3389/fphys.2021.646491
44. Zhao Q., Hu Q., Meng S., Zhang Q., Wang T., Liu C., et al. Metabolic profiling of patients with different idiopathic inflammatory myopathy subtypes reveals potential biomarkers in plasma. Clin Exp Med. 2023;23(7):3417–29. DOI: 10.1007/s10238-023-01073-6
45. Payab M., Tayanloo-Beik A., Falahzadeh K., Mousavi M., Salehi S., Djalalinia S., et al. Metabolomics prospect of obesity and metabolic syndrome; a systematic review. J Diabetes Metab Disord. 2021;21(1):889–917. DOI: 10.1007/s40200-021-00917-w
46. Coltell O., Sorlí J.V., Asensio E.M., Barragán R., González J.I., Giménez-Alba I.M., et al. Genome-wide association study for serum omega-3 and omega-6 polyunsaturated fatty acids: Exploratory analysis of the sex-specific effects and dietary modulation in Mediterranean subjects with metabolic syndrome. Nutrients. 2020;12(2):310. DOI: 10.3390/nu12020310
47. Huang P.C., Cheng H., Su Y.T., Huang M.C., Hsu C.C., Hwang S.J., et al. Interaction among dietary n-3 and n-6 polyunsaturated fatty acid intake, fatty acid desaturase 2 genetic variants, and low-density lipoprotein cholesterol levels in type 2 diabetes patients. J Diabetes Investig. 2023;14(2):297–308. DOI: 10.1111/jdi.13944
48. Chaaba R., Bouaziz A., Ben Amor A., Mnif W., Hammami M., Mehri S. Fatty acid profile and genetic variants of proteins involved in fatty acid metabolism could be considered as disease predictor. Diagnostics (Basel). 2023;13(5):979. DOI: 10.3390/diagnostics13050979
49. Coniglio S., Shumskaya M., Vassiliou E. Unsaturated fatty acids and their immunomodulatory properties. Biology (Basel). 2023;12(2):279. DOI: 10.3390/biology12020279
50. Sitkin S., Pokrotnieks J. Alterations in polyunsaturated fatty acid metabolism and reduced serum eicosadienoic acid level in ulcerative colitis: Is there a place for metabolomic fatty acid biomarkers in IBD? Dig Dis Sci. 2018;63(9):2480–1. DOI: 10.1007/s10620-018-5182-5
Supplementary files
Review
For citations:
Kruchinina M.V., Osipenko M.F., Valuyskikh A.I., Valuiskikh E.Yu., Svetlova I.O. Fatty Acids of Erythrocyte Membranes and Blood Serum as Possible Predictors of Exacerbation in Patients with Inflammatory Bowel Diseases. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2024;34(6):28-41. https://doi.org/10.22416/1382-4376-2024-34-6-28-41