Discovery and Validation of Potential Serum Biomarkers with Pro-Inflammatory and DNA Damage Activities in Ulcerative Colitis: A Comprehensive Untargeted Metabolomic Study

Abstract

Ulcerative colitis is a type of non-specific inflammatory bowel disease with unclear etiology. It is considered a progressive disease with risks of bowel motility disorders, anorectal dysfunction, and even colorectal cancer. Commonly used diagnostic markers have poor specificity and cannot predict the development of ulcerative colitis. In this study, 77 serum samples (31 patients, 46 healthy controls) were analyzed using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry and 31 metabolites with significant level changes were found, revealing the relationship of ulcerative colitis to disturbed glutathione metabolism and caffeine metabolism. In addition, pyroglutamic acid, a biomarker of cervical cancer and gastric cancer, was identified with elevated levels in the serum of ulcerative colitis patients. The role of pyroglutamic acid was further analyzed, and the results indicated its positive correlation with the upregulation of inflammatory factors and increased levels of phosphorylated histone H2AX (γH2AX) in IEC-6 cells, which are related to DNA damage. All these results suggest that pyroglutamic acid is not only a biomarker for distinguishing ulcerative colitis status, but that it is also a potential effective metabolite that promotes the transformation of ulcerative colitis to colorectal cancer.

Effects of medwakh smoking on salivary metabolomics and its association with altered oral redox homeostasis among youth

“…The findings here reported revealed among the medwakh smoker group an increased level of metabolites linked with inflammatory mechanism, such as pyroglutamic acid 23 , 24 , deoxyguanosine 25 and anserine 26 . In order to investigate futher an eventual association of metwakh smoking and inflammation, we decided to measure CRP, a widely known clinical indicator of inflammatory conditions 27 , 28 .…”

Patient Subtyping Analysis of Baseline Multi-omic Data Reveals Distinct Pre-immune States Predictive of Vaccination Responses

“…Mangiferin, a natural flavonoid compound with anti-inflammatory and anti-oxidant properties, and Evodiamine, a supplement with anti-tumor and anti-inflammatory pharmacological effects, were both up-regulated in the S-LoAI/HiII (low adaptive/high innate immunity) subtype. Pyroglutamic acid, a cancer biomarker and previously shown as being elevated in the serum of ulcerative colitis patients, was found up-regulated in the S-LoII (low innate immunity) subtype [53]. Further, the up-regulated metabolite Pyroglutamic acid was found to be significantly altered in influenza high-risk groups in a recent study [10].…”

Does caffeine have a double-edged sword role in inflammation and carcinogenesis in the colon?

“…80 Relationship between coffee/CAF consumption and colonic inflammation has been summarized in Table 1. [81][82][83][84][85][86] An association between coffee/CAF consumption and colonic tumorigenesis has been summarized in Table 2. [87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102] Within this table, about 84% of studies showed the beneficial effects of coffee/CAF intake for CRC development among the various type of studies.…”

“…Although coffee/CAF intake seems to reduce the inflammatory responses in the colon [ 9 , 74 , 79 ], recent 2 reports suggest that CAF consumption is positively associated with the prevalence of CD or UC [ 75 ] as well as irritable bowel syndrome [ 80 ]. Relationship between coffee/CAF consumption and colonic inflammation has been summarized in Table 1 [ 81 - 86 ].…”