Abstract
Abstract Background Clinically heterogeneous spectrum and molecular phenotypes of inflammatory bowel disease (IBD) remain to be comprehensively elucidated. Methods This study set out to explore the serum molecular profiles (I) underlying the disease subtypes, in association with (II) elevated fecal calprotectin and (III) disease activity states, (IV) upon treatment escalation, and (V) in patients who needed treatment escalation. The serum proteome, metabolome, and lipidome of 75 IBD patients were profiled. Single- and multi-omic data analysis was performed to determine differential analytes and integrative biosignatures. Results In (I), chronic inflammation along with tight junction disturbances promoting impaired barrier function might underly the differences between IBD subtypes. Compared to Crohn’s disease, ulcerative colitis showed a lower abundance of hypoxanthine correlating negatively with cell adhesion-related proteins of ITGB2, CD200, PRELP, and positively with lysophosphatidylcholines [LPC(16:0-SN1), LPC(O-18:1)]; and up-regulation of bile acids and FGF19. For (II), while proteins related to inflammatory-promoting signaling pathways, sphingomyelins (SMs), and LPC were increased; bile acids, amino acids, and triacylglycerols (TGs) were decreased. Not only in (II), TGs were a major class change in (III), whose abundance was consistently higher in the active state. This, along with decreased SMs levels, correlated strongly with the up-regulation of inflammatory-inducing proteins (CXCL9, CXCL1, ITGB2, IL17A). In (IV), treatment escalation promoted augmentations of signaling pathways-related proteins and triggered significant metabolome responses, especially decreased amino acids. Noticeably, the levels of TGs were consistently increased in the post-treatment escalation group, thereby suggesting treatment response with relation to (III). For (V), down-regulation of signaling pathways-related proteins and higher levels of SMs and PCs was observed. A consistent decrease of TGs in patients who needed treatment escalation along with lower level of TGs in elevated calprotectin group could imply for the inflammatory level. Conclusion This study provided the multi-ome profiles of IBD patients in five clinical scenarios and laid a foundation for opening new doors for disease management and treatment. References M. Agrawal, K.H. Allin, F. Petralia, J.-F. Colombel, T. Jess, Multiomics to elucidate inflammatory bowel disease risk factors and pathways, Nature Reviews Gastroenterology & Hepatology 19(6) (2022) 399-409.
Published Version
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