Precise diagnostic biomarker in inflammatory bowel diseases (IBD) is still missing. We conducted a comprehensive overview of oxidative stress markers (OSMs) as potential diagnostic, differential, progression, and prognostic markers in IBD. A Pubmed, Web of Knowledge, and Scopus search of original articles on OSMs in IBD, published between January 2000 and April 2020, was conducted. Out of 874 articles, 79 eligible studies were identified and used to prepare the interpretative synthesis. Antioxidants followed by lipid peroxidation markers were the most popular and markers of oxidative DNA damage the least popular. There was a disparity in the number of retrieved papers evaluating biomarkers in the adult and pediatric population (n = 6). Of the reviewed OSMs, a promising performance has been reported for serum total antioxidant status as a mucosal healing marker, mucosal 8-OHdG as a progression marker, and for multi-analyte panels of lipid peroxidation products assessed non-invasively in breath as diagnostic and differential markers in the pediatric population. Bilirubin, in turn, was the only validated marker. There is a desperate need for non-invasive biomarkers in IBD which, however, will not be met in the near future by oxidative stress markers as they are promising but mostly at the early research phase of discovery.

Mucosal healing (MH) is the key therapeutic target of inflammatory bowel disease (IBD). The evaluation of MH remains challenging, with endoscopy being the golden standard. We performed a comprehensive overview of the performance of fecal-, serum-, and urine-based biochemical markers in colonic IBD to find out whether we are ready to replace endoscopy with a non-invasive but equally accurate instrument. A Pubmed, Web of Knowledge, and Scopus search of original articles as potential MH markers in adults, published between January 2009 and March 2020, was conducted. Finally, 84 eligible studies were identified. The most frequently studied fecal marker was calprotectin (44 studies), with areas under the curves (AUCs) ranging from 0.70 to 0.99 in ulcerative colitis (UC) and from 0.70 to 0.94 in Crohn`s disease (CD), followed by lactoferrin (4 studies), matrix metalloproteinase-9 (3 studies), and lipocalin-2 (3 studies). The most frequently studied serum marker was C-reactive protein (30 studies), with AUCs ranging from 0.60 to 0.96 in UC and from 0.64 to 0.93 in CD. Fecal calprotectin is an accurate MH marker in IBD in adults; however, it cannot replace endoscopy and the application of calprotectin is hampered by the lack of standardization concerning the cut-off value. Other markers are either not sufficiently accurate or have not been studied extensively enough.

L-arginine/nitric oxide pathway metabolites are altered in colorectal cancer (CRC). We evaluated underlying changes in pathway enzymes in 55 paired tumor/tumor-adjacent samples and 20 normal mucosa using quantitative-PCR and assessed the impact of classic and novel oxicam analogues on enzyme expression and intracellular metabolite concentration (LC-MS/MS) in Caco-2, HCT116, and HT-29 cells. Compared to normal mucosa, ARG1, PRMT1, and PRMT5 were overexpressed in both tumor and tumor-adjacent tissue and DDAH2 solely in tumor-adjacent tissue. Tumor-adjacent tissue had higher expression of ARG1, DDAH1, and DDAH2 and lower NOS2 than patients-matched tumors. The ARG1 expression in tumors increased along with tumor grade and reflected lymph node involvement. Novel oxicam analogues with arylpiperazine moiety at the thiazine ring were more effective in downregulating DDAHs and PRMTs and upregulating ARG2 than piroxicam and meloxicam. An analogue distinguished by propylene linker between thiazine’s and piperazine’s nitrogen atoms and containing two fluorine substituents was the strongest inhibitor of DDAHs and PRMTs expression, while an analogue containing propylene linker but no fluorine substituents was the strongest inhibitor of ARG2 expression. Metabolic reprogramming in CRC includes overexpression of DDAHs and PRMTs in addition to ARG1 and NOS2 and is not restricted to tumor tissue but can be modulated by novel oxicam analogues.

L-arginine/nitric oxide pathway in Crohn’s disease (CD) and ulcerative colitis (UC) is poorly investigated. The aim of current study is to quantify pathway serum metabolites in 52 CD (40 active), 48 UC (33 active), and 18 irritable bowel syndrome patients and 40 controls using mass spectrometry and at determining mRNA expression of pathway-associated enzymes in 91 bowel samples. Arginine and symmetric dimethylarginine decreased (p < 0.05) in active-CD (129 and 0.437 µM) compared to controls (157 and 0.494 µM) and active-UC (164 and 0.52 µM). Citrulline and dimethylamine increased (p < 0.05) in active-CD (68.7 and 70.9 µM) and active-UC (65.9 and 73.9 µM) compared to controls (42.7 and 50.4 µM). Compared to normal, CD-inflamed small bowel had downregulated (p < 0.05) arginase-2 by 2.4-fold and upregulated dimethylarginine dimethylaminohydrolase (DDAH)-2 (1.5-fold) and arginine N-methyltransferase (PRMT)-2 (1.6-fold). Quiescent-CD small bowel had upregulated (p < 0.05) arginase-2 (1.8-fold), DDAH1 (2.9-fold), DDAH2 (1.5-fold), PRMT1 (1.5-fold), PRMT2 (1.7-fold), and PRMT5 (1.4-fold). Pathway enzymes were upregulated in CD-inflamed/quiescent and UC-inflamed colon as compared to normal. Compared to inflamed, quiescent CD-colon had upregulated DDAH1 (5.7-fold) and ornithine decarboxylase (1.6-fold). Concluding, the pathway is deregulated in CD and UC, also in quiescent bowel, reflecting inflammation severity and angiogenic potential. Functional analysis of PRMTs and DDAHs as potential targets for therapy is warranted.

Achieving mucosal healing in patients with inflammatory bowel disease is related to a higher incidence of sustained clinical remission and it translates to lower rates of hospitalisation and surgery. The assessment methods of disease activity and response to therapy are limited and mainly rely on colonoscopy. This meta-analysis reviews the effectiveness of using faecal calprotectin as a marker for mucosal healing in inflammatory bowel disease. Two meta-analyses were conducted in parallel. The analysis on the use of faecal calprotectin in monitoring mucosal healing in colonic Crohn’s disease is based on 16 publications (17 studies). The data set for diagnostic values of faecal calprotectin in ulcerative colitis is composed of 35 original publications (total 49 studies). The DOR for the use of faecal calprotectin in Crohn’s disease is estimated to be 11.20 and the area under the sROCis 0.829. In cases of ulcerative colitis, the DOR is 14.48, while the AUC sROC is 0.858. Heterogeneity of the studies was moderatetosubstantial. Collected data show overall good sensitivity and specificity of the faecal calprotectin test, as well as a good DOR. Thus, monitoring of mucosal healing with a non-invasive faecal calprotectin test may represent an attractive option for physicians and patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic condition affecting primarily the gastrointestinal tract and characterized by growing incidence worldwide. Complex diagnostic process of IBD as well as evaluation of disease activity and intestinal complications that are crucial for the therapeutic decisions, require repetitive, invasive, expensive, time-consuming and poorly tolerated tests. In contrast to endoscopy and computed tomography, ultrasound elastography (UE) is non-invasive, non-radiating and non-contrasting dependent tool which might be utilized in IBD patients for the assessment of the intestinal changes. Therefore, we performed the systematic review to evaluate the possible application of the ultrasound elastography for assessment of the intestinal changes in IBD. After the search of three databases: PubMed, World of Knowledge and Scopus, we identified 12 papers which were included in the final analysis. The majority of the studies were focused on the evaluation of the symptomatic ileal/ileocolonic strictures in Crohn’s disease patients that required surgical resection. Only one study concerned ulcerative colitis. The authors evaluated different UE techniques: strain elastography (SE), acoustic radiation force impulse (ARFI) and shear wave elastography (SWE). Results were expressed with semi-quantitative color mapping and strain measurement. Histological scores of inflammation and fibrosis in Crohn’s disease were used as a reference test in the majority of studies. Ultrasound elastography seems to be a promising novel imaging technique supporting evaluation of the intestinal strictures in Crohn’s disease patients in respect to fibrosis detection as well as differentiation between fibrosis and inflammation. However, further research is needed to establish the position of ultrasound elastography in IBD management.