Trends in precision diagnosis and monitoring of inflammatory bowel diseases: the potential of proteomic and metabolomic biomarkers

Omics technologies, including proteomics and metabolomics approaches, provide promising opportunities to improve the accuracy of diagnosis and monitoring of the course of inflammatory bowel disease (IBD). Integration of these advanced research areas into clinical medicine not only allows for a more in-depth assessment of the pathogenesis of IBD, but also opens avenues for innovative therapeutic strategies adapted to individual patient profiles and patient cohorts.
The lecture analyzes trends in the identification of biomarkers with high sensitivity and specificity that can be used both for diagnosis and prognosis of the course of IBD subtypes, and for predicting the response to therapy, which, ultimately, will contribute not only to improved treatment outcomes, but also to an increase in the quality of life of patients.
The authors conducted a non-systematic, descriptive review of the literature with a search depth of 10 years, aimed at systematizing data on the achievements of proteomics and metabolomics approaches for the diagnosis, monitoring of the IBD course, and personalization of therapeutic strategies. The search for literary references was carried out using Scopus, Web of Science, MedLine, the Cochrane Library, EMBASE, Global Health, CyberLeninka, and RSCI databases.
The analysis of the results of experimental and clinical studies allowed to identify a number of biomarkers – candidates for testing and potential implementation in routine clinical practice. Convincing data were obtained on the potential benefits of integrating proteomics and metabolomics studies with other omics approaches. The importance of an interdisciplinary approach combining the results of clinical studies with modern approaches in bioinformatics and molecular biology for the development of more effective diagnostic tools and strategies is obvious.

1. Liu C., Yu R., Zhang J., Wei S., Xue F., Guo Y. et al. Research hotspot and trend analysis in the diagnosis of inflammatory bowel disease: A machine learning bibliometric analysis from 2012 to 2021. Front. Immunol. 2022;13:972079. DOI: 10.3389/fimmu.2022.972079.

2. Fabian O., Bajer L., Drastich P., Harant K., Sticova E., Ďásková N. et al. A Current State of Proteomics in Adult and Pediatric Inflammatory Bowel Diseases: A Systematic Search and Review. International Journal of Molecular Sciences. 2023;24(11):9386–9386. DOI: 10.3390/ijms24119386.

3. Clough J., Colwill M., Poullis A., Pollok R., Patel K., Honap S. Biomarkers in inflammatory bowel disease: a practical guide. Ther. Adv. Gastroenterol. 2024;17:1–19. DOI: 10.1177/17562848241251600.

4. Mestrovic A., Perkovic N., Bozic D., Kumric M., Vilovic M., Bozic J. Precision medicine in inflammatory bowel disease: a spotlight on emerging molecular biomarkers. Advances in Cardiovascular Diseases. 2024;12(7):1520–1520. DOI: 10.3390/biomedicines12071520.

5. D’Incà R., Sturniolo G. Biomarkers in IBD: what to utilize for the diagnosis? Diagnostic. 2023;13(18):2931. DOI: 10.3390/diagnostics13182931.

6. Kim J., Suh D.H., Park Y., Jae S., Kang Oh.H., Ji. Y. et al. P140 Serum metabolomic biomarkers can identify and characterize associated subtypes and phenotypes in inflammatory bowel disease. Journal of Crohn’s and Colitis. 2024;18:i437–i438. DOI: 10.1093/ecco-jcc/jjad212.0270.

7. Ning L., Zhou Y.L., Sun H., Zhang Y., Shen Ch., Wang Z. et al. Microbiome and metabolome features in inflammatory bowel disease via multi-omics integration analyses across cohorts. Nat. Commun. 2023;14:7135. DOI: 10.1038/s41467-023-42788-0.

8. Chen L., Zhang C., Niu R., Mao R., Qiu Yun, Feng R. P915 multi-omics biomarkers for the prediction of response to biologics in patients with inflammatory bowel disease. Journal of Crohn’s and Colitis. 2024;18(1):i1670–i1671. DOI: 10.1093/ecco-jcc/jjad212.1045.

9. Bourgonje A.R., Goor H., Faber K.N., Dijkstra G. Clinical value of multi-omics-based biomarker signatures in inflammatory bowel diseases: challenges and opportunities. Clinical and translational gastroenterology. Clin. Transl. Gastroenterol. 2023;14(7):e00579. DOI: 10.14309/ctg.0000000000000579.

10. Wright I., Van Eyk J.E. A Roadmap to successful clinical proteomics. Clin. Chem. 2017;63:245–247. DOI: 10.1373/clinchem.2016.254664.

11. Deeke S.A., Starr A.E., Ning Z., Ahmadi S., Zhang X., Mayne J. et al. Open: Mucosal-luminal interface proteomics reveals biomarkers of pediatric inflammatory bowel disease-associated colitis. Am. J. Gastroenterol. 2018;113:713–724. DOI: 10.1038/s41395-018-0024-9.

12. Berndt U., Bartsch S., Philipsen L., Danese S., Wiedenmann B., Dignass A.U. et al. Proteomic analysis of the inflamed intestinal mucosa reveals distinctive immune response profiles in Crohn’s disease and ulcerative colitis. J. Immunol. 2007;179:295–304. DOI: 10.4049/jimmunol.179.1.295.

13. Kalla R., Adams A.T., Bergemalm D., Vatn S., Kennedy N.A., Ricanek P. et al. Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease. BioRxiv. 2020;15(5):699–708. DOI: 10.1093/ecco-jcc/jjaa230.

14. Livanos A.E., Dunn A., Fischer J., Ungaro R.C., Turpin W., Lee S.H. et al. Anti-Integrin αvβ6 autoantibodies are a novel biomarker that antedate ulcerative colitis. Gastroenterology. 2023;164:619–629. DOI: 10.1053/j.gastro.2022.12.042.

15. Arai Y., Matsuura T., Matsuura M., Fujiwara M., Okayasu I., Ito S. et al. Prostaglandin E-major urinary metabolite as a biomarker for inflammation in ulcerative colitis: prostaglandins revisited. Digestion. 2016;93:32–39. DOI: 10.1159/000441665.

16. Meuwis M.-A., Fillet M., Geurts P., de Seny D., Lutteri L., Chapelle J.-P. et al. Biomarker discovery for inflammatory bowel disease, using proteomic serum profiling. Biochem. Pharmacol. 2007;73:1422–1433. DOI: 10.1016/j.bcp.2006.12.019.

17. Starr A.E., Deeke S.A., Ning Z., Chiang C.-K., Zhang X., Mottawea W. et al. Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn’s disease from UC. Gut. 2017;66:1573–1583. DOI: 10.1136/gutjnl-2015-310705.

18. Han N.Y., Choi W., Park J.M., Kim E.H., Lee H., Hahm K.B. Label-free quantification for discovering novel biomarkers in the diagnosis and assessment of disease activity in inflammatory bowel disease. J. Dig. Dis. 2013;14(4):166–174. DOI: 10.1111/1751-2980.12035.

19. Hsieh S.Y., Shih T..C, Yeh C.Y., Lin C.J., Chou Y.Y., Lee Y.S. Comparative proteomic studies on the pathogenesis of human ulcerative colitis. Proteomics. 2006;6(19):5322–5331. DOI:10.1002/pmic.200500541.

20. Sun M., He C., Cong Y., Liu Z. Regulatory immune cells in regulation of intestinal inflammatory response to microbiota. Mucosal. Immunol. 2015;8:969–978. DOI: 10.1038/mi.2015.49.

21. Kumric M., Zivkovic P.M., Ticinovic Kurir T., Vrdoljak J., Vilovic M., Martinovic D. et al. Role of B-cell activating factor (BAFF) in inflammatory bowel disease. Diagnostics. 2021;12:45. DOI: 10.3390/diagnostics12010045.

22. Uzzan M., Colombel J.F., Cerutti A., Treton X., Mehandru S. B Cell-activating factor (BAFF)-targeted b cell therapies in inflammatory bowel diseases. Dig. Dis. Sci. 2016;61:3407–3424. DOI: 10.1007/s10620-016-4317-9.

23. Timmermans W.M., van Laar J.A., van der Houwen T.B., Kamphuis L.S., Bartol S.J., Lam K.H. et al. B-Cell Dysregulation in Crohn’s disease is partially restored with infliximab therapy. PLoS One. 2016;11(7):e0160103. DOI: 10.1371/journal.pone.0160103.

24. Andreou N.P., Legaki E., Dovrolis N., Boyanov N., Georgiou K., Gkouskou K. et al. B-cell activating factor (BAFF) expression is associated with Crohn’s disease and can serve as a potential prognostic indicator of disease response to Infliximab treatment. Dig. Liver Dis. 2021;53:574–580. DOI: 10.1016/j.dld.2020.11.030.

25. Quan R., Chen C., Yan W., Zhang Y., Zhao X., Fu Y. BAFF blockade attenuates inflammatory responses and intestinal barrier dysfunction in a murine endotoxemia model. Front. Immunol. 2020;11:570920. DOI: 10.3389/fimmu.2020.570920.

26. Zhang Y., Tao M., Chen C., Zhao X., Feng Q., Chen G. et al. BAFF blockade attenuates DSS-induced chronic colitis via inhibiting NLRP3 inflammasome and NF-κB activation. Front. Immunol. 2022;13:783254. DOI: 10.3389/fimmu.2022.783254.

27. Magnusson M.K., Strid H., Isaksson S., Bajor A., Lasson A., Ung K.-A. et al. Response to infliximab therapy in ulcerative colitis is associated with decreased monocyte activation, reduced CCL2 expression and downregulation of tenascin C. J. Crohn’s Colitis. 2014;9:56–65. DOI: 10.1093/ecco-jcc/jju008.

28. Heier C.R., Fiorillo A.A., Chaisson E., Gordish-Dressman H., Hathout Y., Damsker J.M. et al. Identification of pathway-specific serum biomarkers of response to glucocorticoid and infliximab treatment in children with inflammatory bowel disease. Clin. Transl. Gastroenterol. 2016;7:e192. DOI: 10.1038/ctg.2016.49.

29. Ma R., Zhu Y., Li X., Hu S., Zheng D., Xiong S. et al. A novel serum metabolomic panel for the diagnosis of Crohn’s disease. Inflammatory Bowel Diseases. 2023;29(10):1524–1535. DOI: 10.1093/ibd/izad080.

30. Vakhitov T., Kononova S., Demyanova E., Morugina A.S., Utsal V.A., Skalinskaya M.I. et al. Identification of candidate biomarkers for inflammatory bowel disease using non-targeted serum metabolomics. Voprosy Detskoj Dietologii. 2022;20(6):21–32. DOI: 10.20953/1727-5784-2022-6-21-32.

31. Wu X.P., Liu K., Wu Q., Wang M., Chen X., Li Y. et al. Biomarkers of Metabolomics in Inflammatory Bowel Disease and Damp-Heat Syndrome: A Preliminary Study. Evidence-based Complementary and Alternative Medicine. 2022;3319646. DOI: 10.1155/2022/3319646.

32. Gallaghe K., Catesson A., Griffin J.L., Holmes E., Williams H.R.T. Metabolomic Analysis in Inflammatory Bowel Disease: A Systematic Review. J. Crohns Colitis. 2021;15:813–826. DOI: 10.1093/ecco-jcc/jjaa227.

33. Vich Vila A., Zhang J., Liu M., Faber K.N., Weersma R.K. Untargeted faecal metabolomics for the discovery of biomarkers and treatment targets for inflammatory bowel diseases. Gut. 2024;73(11):1909–1920. DOI: 10.1136/gutjnl-2023-329969.

34. Zheng X., Zhu Y., Zhao Z., Chu Y., Yang W. The role of amino acid metabolism in inflammatory bowel disease and other inflammatory diseases. Frontiers in Immunology. 2023.14:1284133. DOI: 10.3389/fimmu.2023.1284133.

35. He F., Wu C., Li P., Li N., Zhang D., Zhu Q. et al. Functions and signaling pathways of amino acids in intestinal inflammation. BioMed Research International. 2018:9171905. DOI: 10.1155/2018/9171905.

36. 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. Frontiers in Immunology. 2023;14:1286667. DOI: 10.3389/fimmu.2023.1286667.

37. Wang C., Gu Y., Chu Q., Wang X., Ding Y., Qin X. et al. Gut microbiota and metabolites as predictors of biologics response in inflammatory bowel disease: A comprehensive systematic review. Microbiology Research. 2024;282:127660–127660. DOI: 10.1016/j.micres.2024.127660.

38. Reider S., Watschinger C., Koch R., Tilg H., Moschen A. P206 Metabolomic predictors of response to vedolizumab in inflammatory bowel disease. Journal of Crohn’s and Colitis. 2024;18(1):i527. DOI: 10.1093/ecco-jcc/jjad212.0336.

39. Garg M., Karpinski M., Matelska D. Disease prediction with multi-omics and biomarkers empowers case–control genetic discoveries in the UK Biobank. Nat. Genet. 2024;56:1821–1831. DOI: 10.1038/s41588-024-01898-1.

40. Smelik M., Zhao Y., Li X., Loscalzo J., Sysoev O., Mahmud F. et al. An interactive atlas of genomic, proteomic, and metabolomic biomarkers promotes the potential of proteins to predict complex diseases. Sci. Rep. 2024;14(1):12710. DOI: 10.1038/s41598-024-63399-9.