Marker For Inflammatory Bowel Disease Research Articles

The Role of Vitamin D Levels in Optimizing Treatment for Pediatric Inflammatory Bowel Disease (IBD) Patients and an Examination Into Different Factors That Influence IBD Treatment Outcomes.

Background Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), presents significant challenges, particularly in pediatric patients. Vitamin D deficiency has been associated with IBD, but its role in disease activity and remission remains unclear. This study investigates the relationship between serum vitamin D levels and IBD markers, including Pediatric Crohn's Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), fecal calprotectin levels, and endoscopy findings. It also explores racial and ethnic disparities in these relationships. Methodology A retrospective study was conducted involving 51 pediatric patients with IBD from the Nemours Children's Health EMR system. Inclusion criteria required documented serum vitamin D levels at diagnosis and post-treatment, and at least one post-treatment assessment of PUCAI/PCDAI, calprotectin, or endoscopy. The study employed Spearman and Pearson correlation tests to analyze the associations between vitamin D levels and IBD markers. Ethnicity and race were analyzed using t-tests and chi-square tests. Results No statistically significant correlations were found between changes in serum vitamin D levels and IBD markers (endoscopy results, calprotectin levels, PUCAI/PCDAI scores) for both UC and CD. Analysis of racial and ethnic disparities revealed that Hispanic patients had significantly higher post-treatment calprotectin levels compared to non-Hispanics, although other markers showed no significant differences. Vitamin D levels did not significantly differ between racial or ethnic groups. Conclusions This study found no significant correlation between serum vitamin D levels and IBD activity markers in pediatric patients. Despite initial hypotheses, vitamin D levels do not appear to be useful in assessing IBD remission or disease state. Racial and ethnic disparities in IBD severity were observed, but further research with larger sample sizes and more consistent data collection is needed to draw more definitive conclusions.

The Effect of Renin-Angiotensin-Aldosterone System Blocking Agents on the Long-term Disease Course of Patients With Crohn's Disease.

The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn's disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.

Continuous Monitoring of CRP, IL-6, and Calprotectin in Inflammatory Bowel Disease Using a Perspiration-Based Wearable Device.

Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration. Participants with IBD were monitored for 40 to 130 minutes with a proprietary wearable sensor device used to measure C-reactive protein, interleukin-6, and calprotectin. Sensor response using electrochemical impedance spectroscopy and serum samples were measured on the same day. The Mann-Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed. A total of 33 subjects were enrolled. Expression of calprotectin was significantly elevated in the active cohort compared with the remission cohort in perspiration (P < .05; median = 906.69ng/mL; active 95% confidence interval [CI], 466.0-1833ng/mL; remission 95% CI, 328.4-950.8ng/mL), serum (median = 1860.82ng/mL; active 95% CI, 1705-2985ng/mL; remission 95% CI, 870.2-1786ng/mL), and stool (P < .05; median = 126.74 µg/g; active 95% CI, 77.08-347.1 µg/g; remission 95% CI, 5.038-190.4 µg/g). Expression of CRP in perspiration and serum was comparable between the active and remission cohorts (perspiration: P > .05; median = 970.83 pg/mL; active 95% CI, 908.7-992 pg/mL; remission 95% CI, 903.3-991.9 pg/mL; serum: median = 2.34 µg/mL; active 95% CI, 1.267-4.492 µg/mL; remission 95% CI, 1.648-4.287 µg/mL). Expression of interleukin-6 in perspiration was nonsignificant in the active cohort compared with the remission cohort and was significantly elevated in serum (perspiration: P < .05; median = 2.13 pg/mL; active 95% CI, 2.124-2.44 pg/mL; remission 95% CI, 1.661-2.451 pg/mL; serum: median = 1.15 pg/mL; active 95% CI, 1.549-3.964 pg/mL; remission 95% CI, 0.4301-1.257 pg/mL). Analysis of the linear relationship between perspiration and serum calprotectin (R2 = 0.7195), C-reactive protein (R2 = 0.615), and interleukin-6 (R2 = 0.5411) demonstrated a strong to moderate relationship across mediums. We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.

Pyodermatitis-pyostomatitis vegetans: a case report and systematic review focusing on oral involvement.

Pyodermatitis-pyostomatitis vegetans (PPV) is a rare mucocutaneous disease characterized by multiple pustules and it is considered a marker for inflammatory bowel disease (IBD). The oral manifestations of this condition are referred to as pyostomatitis vegetans (PSV). To investigate which features could help in establishing the diagnosis of PSV, with or without cutaneous lesions, based on information retrieved from all cases of PSV described in the literature. A case of PV from the authors was also included in the analysis. An electronic search was undertaken, last updated in August 2022. Inclusion criteria included publications reporting cases of PSV, with the diagnosis confirmed by the pathological examination of oral or skin lesions, and presence of IBD. Sixty-two publications with 77 cases of PSV and an associated IBD were included. Features that are helpful in establishing the diagnosis of PSV are snail track appearance of oral lesions, an associated IBD (which is not always symptomatic), evidence of intraepithelial clefting on microscopic examination of oral lesions, and peripheral blood eosinophilia. A gold standard for the management of PSV does not exist and high-level evidence is limited. There is no established therapeutic protocol for PSV and management primarily consists of topical and/or systemic corticosteroids, antirheumatic drugs (sulfasalazine, mesalazine), monoclonal antibody (infliximab, adalimumab) immunosuppressives (azathioprine, methotrexate), antibiotics (dapsone), or a combination of these. The risk of recurrence of oral lesions is considerable when the medication dose is decreased or fully interrupted.

Longitudinal assessment of sweat-based TNF-alpha in inflammatory bowel disease using a wearable device

Wearable devices can non-invasively monitor patients with chronic diseases. Sweat is an easily accessible biofluid for continuous sampling of analytes, including inflammatory markers and cytokines. We evaluated a sweat sensing wearable device in subjects with and without inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract. Participants with an IBD related hospital admission and a C-reactive protein level above 5 mg/L wore a sweat sensing wearable device for up to 5 days. Tumor necrosis factor-alpha (TNF-α) levels were continually assessed in the sweat via the sensor, and daily in the blood. A second cohort of healthy subjects without chronic diseases wore the device for up to 48 h. Twenty-eight subjects were enrolled. In the 16 subjects with IBD, a moderate linear relationship between serum and sweat TNF-α levels was observed (R2 = 0.72). Subjects with IBD were found to have a mean sweat TNF-α level of 2.11 pg/mL, compared to a mean value of 0.19 pg/mL in 12 healthy controls (p < 0.0001). Sweat TNF-α measurements differentiated subjects with active IBD from healthy subjects with an AUC of 0.962 (95% CI 0.894–1.000). A sweat sensing wearable device can longitudinally measure key sweat-based markers of IBD. TNF-α levels in the sweat of subjects with IBD correlate with serum values, suggesting feasibility in non-invasive disease monitoring.

CONTINUOUS MONITORING OF CRP, IL-6, AND CALPROTECTIN IN INFLAMMATORY BOWEL DISEASE USING A PERSPIRATION BASED WEARABLE

Abstract BACKGROUND Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration. METHODS Participants with IBD were monitored for 40-130 minutes with a proprietary wearable sensor device used to measure C-reactive protein (CRP), interleukin-6 (IL-6), and calprotectin. Sensor response using Electrochemical Impedance Spectroscopy (EIS) and serum samples were measured on the same day. Mann Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed. RESULTS A total of 33 subjects were enrolled. Expression of CRP in perspiration and serum were comparable between Active and Remission cohorts (p&amp;gt;0.05). Median expression of IL-6 in perspiration was elevated in the Active cohort compared to Remission cohort, and significantly elevated in serum (p&amp;lt;0.05). Expression of calprotectin in perspiration, serum, and stool were significantly elevated in the Active cohort compared to Remission cohort (p&amp;lt;0.05). Temporal data for three ulcerative colitis and Crohn’s disease patients provided insight into the basal levels of the markers across different disease states. CONCLUSIONS We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity. Positive linear relationship between serum and sweat of all markers. Serum and sweat levels of both Calprotectin and CRP demonstrate strong linear relationship between mediums. Serum and sweat levels of IL6 demonstrate moderate linear relationship and high homoscedasticity.

Clinical Validity of Anti-Proteinase 3 Antibodies in Patients with Inflammatory Bowel Disease: A Short Meta-Analysis.

Anti-neutrophil cytoplasmic antibodies (ANCA) directed to proteinase 3 (PR3) represent highly established markers for patients with ANCA-associated vasculitis (AAV). PR3-ANCA have also demonstrated utility in the management of inflammatory bowel disease (IBD). More specifically, PR3-ANCA discriminate individuals with ulcerative colitis (UC) from Crohn's disease (CD) patients and are associated with disease severity, activity, and treatment non-response. Here, we aim to summarize the current data on the diagnostic utility of PR3-ANCA in IBD. A structured, systematic literature review, including three electronic databases, was conducted on June 6th, 2023, to identify studies assessing the diagnostic accuracy of the QUANTA Flash® PR3 assay in UC vs. CD patients. Electronic searches were supplemented by hand searching. A hierarchical, bivariate, mixed-effect meta-analysis was conducted using the metandi function, as per the Cochrane collaboration recommendations. Study quality was assessed using the QUADAS-2 tool, which considers the risk of bias and applicability. Six out of a hundred and eleven citations met the inclusion criteria and reported QUANTA Flash® PR3 diagnostic accuracy in UC vs. CD (UC, n = 667, CD, n = 682 patients). The sensitivity/specificity point estimate for UC was 34.9%/95.9%. This resulted in a Diagnostic Odds Ratio (DOR) of 12.6. The risk of bias was low in the index test and reference standard domains. Four of the six studies (67%) showed an unclear risk of bias in patient selection and in flow and timing domains. All studies had low concerns about applicability in all the domains. PR3-ANCA measured with the QUANTA Flash® PR3 assay represent novel diagnostic markers in IBD and enables discrimination between UC and CD.

Disentangling the age-related manner in the associations between gut microbiome and women’s health: a multi-cohort microbiome study

ABSTRACT Women’s health encompasses life-course healthcare, and mounting evidence emphasizes the pivotal contribution of gut microbiota. Therefore, understanding the temporal dynamics of gut microbiota and how age influences disease-gut microbiota associations is essential for improving women’s health. By analyzing metagenomic data from 3625 healthy women, we revealed significant effects of age on gut microbiota and age-dependent patterns in microbial features, such as relative abundance, Shannon index, and microbial network properties. Additionally, declining trends in the predictive accuracy of gut microbiota for age groups were shown using iterative sub-sampling based random forest (ISSRF) model. Age-specific species markers were also identified, many of which were shared across age groups. To investigate the influence of age on disease-gut microbiota associations, metagenomic data from 681 women with various disease conditions and 491 matched healthy controls were collected. A substantial proportion of species markers for inflammatory bowel disease (IBD), type 2 diabetes (T2D), atherosclerotic cardiovascular disease (ACVD), and impaired glucose tolerance (IGT) differed in relative abundance across age groups, and were also age-specific species markers. Besides, the microbiota-based probabilities of IBD and ACVD were positively correlated with age. Furthermore, the age specificity of disease-gut microbiota associations was explored using the ISSRF model. Associations between IBD and gut microbiota were age-specific, with reduced stability of disease species markers in childhood and adolescence, possibly due to decrease in the effect size between patients and controls. Our findings provided valuable insights into promoting healthy aging and developing personalized healthcare strategies for women.

Amplification of an Electrochemiluminescence-Emissive Aptamer into DNA Nanotags for Sensitive Fecal Calprotectin Determination.

The precision additive manufacturing and tessellated multitasking out of the structural DNA nanotechnology enable a configurable expression of densified electrochemiluminescent (ECL) complexes, which would streamline the bioconjugation while multiplying signals. Herein, a completely DNA-scaffold ECL "polyploid" was replicated out via the living course of rolling circle amplification. The amplicon carried the aptameric sequences of ZnPPIX/TSPP porphyrin as photoreactive centers that rallied at periodical intervals of the persistent extension into a close-packed nanoflower, ZnPDFI/II. Both microscopies and electrophoresis proved the robust nesting of guests at their deployed gene loci, while multispectral comparisons among cofactor substituents pinpointed the pivotal roles of singlet seclusion and Zn2+-chelation for the sake of intensive ECL irradiation. The adversity-resilient hydrogel texture made lipoidal filmogens as porphyrinic ECL prerequisites to be of no need at all, thus not only simplifying assay flows but also inspiring an in situ labeling plan. Upon bioprocessing optimization, an enriched probe ZnPDFIII was further derived that interpolated the binding motif related to calprotectin as validated by molecular docking and affinity titration. With it being a strongly indicative marker of inflammatory bowel disease (IBD), a competitive ECL aptasensing strategy was contrived, managing a signal-on and sensitive detection in mild conditions with a subnanogram-per-milliliter limit of detection by 2 orders of magnitude lower than the standard method as well as a comparable accuracy in clinical stool sample testing. Distinct from those conventional chemophysical rebuilding routes, this de novo biosynthetic fusion demonstrated a promising alternative toward ECL-source bioengineering, which may intrigue vibrant explorations of other ECL-shedding fabrics and, accordingly, a new bioanalytic mode downstream.

Scribble deficiency mediates colon inflammation by inhibiting autophagy-dependent oxidative stress elimination

Scribble is a master scaffold protein in apical-basal polarity. Current knowledge about the biological function of Scribble in colonic epithelial plasticity/regeneration during intestinal inflammation is limited. Here, we showed that the level of Scribble is decreased in inflammatory bowel disease (IBD) patients and mice with DSS-induced colitis. ScribΔIEC mice develops severe acute colitis with disrupted epithelial barrier integrity and impaired crypt stem cell’s function. Mechanistically, Scribble suppressed the process of autophagy by modulating the stability of caspase-dependent degradation of Atg16L1 by directly interacting with Atg16L1 in a LRR domain-dependent manner in IECs and led to an accumulation of ROS both in intestinal stem cells and epithelial cells. In addition, further study indicates that dietary sphingomyelin alleviates DSS-induced colitis by increase the expression of Scribble, which suggests that Scribble may be the critical marker of IBD. Our study shows that Scribble deficiency is associated with the dysregulated autophagy and impaired maintenance of colonic stemness, and it may be a target for diagnosis and treatment of IBD.

B-028 Clinical Performance of a Fully-Automated Fecal Calprotectin Chemiluminescence Immunoassay (CLIA)

Abstract Background Fecal calprotectin is a noninvasive marker for inflammatory bowel disease (IBD). Traditionally, calprotectin is measured by the well-established enzyme linked immunosorbent assay (ELISA) method. More recently, advances in fully automated platforms allow for comparable performance and diagnostic accuracy whilst improving laboratory efficiency. In this study, we assessed the diagnostic performance of the fully automated ALPCO calprotectin chemiluminescence immunoassay (CLIA), and compared it to the predicate, ALPCO’s 510(k) cleared manual calprotectin chemiluminescence ELISA. Methods Fecal calprotectin levels were measured with the ALPCO Calprotectin Chemiluminescence ELISA and the recently developed ALPCO Calprotectin CLIA, utilizing glow and flash chemiluminescence, respectively. An IRB approved study included over 400 individuals with clinical suspicion of IBD. The estimates of clinical sensitivity, and clinical specificity of the ALPCO Calprotectin Chemiluminescence ELISA and the ALPCO Calprotectin CLIA were determined by comparing analytical test results of the prospectively collected stool specimens against the clinical diagnosis made by the clinical investigator/gastroenterologist with ileocolonoscopic and histopathological sampling (reference standard). Results When distinguishing IBD from irritable bowel syndrome (IBS) and healthy persons, the sensitivity (70/76) and specificity (322/348), at a fecal calprotectin cut-off level of 50 µg/g, were 92.1% and 92.5%, respectively for the ALPCO Calprotectin Chemiluminescence ELISA. Sensitivity (73/78) and specificity (319/342), at a fecal calprotectin cut-off level of 50 µg/g, were 93.6% and 93.3%, respectively for the ALPCO Calprotectin CLIA. Conclusion The ALPCO Calprotectin CLIA showed comparable clinical performance for detection of IBD compared to the predicate 510(k) cleared ALPCO Calprotectin Chemiluminescence ELISA. The automation of the ALPCO calprotectin immunoassay allows for increased laboratory efficiency without sacrificing diagnostic accuracy.

The Role of Serum Calgranulin C as a Non-Invasive Marker for Inflammatory Bowel Disease

Abstract Background IBD has been recognized as a systemic inflammatory entity and as such, it is anticipated to induce changes exceeding the boundaries of bowel mucosa, being reflected in a broader spectrum of tissues, including blood. Calgranulin c is a calcium binding protein with proinflammatory properties. It has been associated with different diseases of inflammatory origin, including inflammatory bowel disease (IBD). In our present study, the utility of serum calgranulin c as marker for inflammatory bowel disease was tested. Objective is to evaluate the role of serum calgranulin c as a diagnostic and prognostic marker in IBD patients and to correlate it's level with different biochemical, endoscopic and clinical parameters. Patients and Methods Calgranulin c serum levels were determined in 50 patients with ulcerative colitis (UC), 20 patients with Crohn’s disease (CD) and 73 with functional bowel disorder (IBS). Calgranulin c serum concentrations were analysed using double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) to assay the level of Human S100 Calcium Binding Protein A12(S100A12) in samples. Results In the present study we found that the mean serum calgranulin c were 723.640±529.055 ng/ml (range: 63-2000) in UC, 759.233±797.963 ng/ml (range: 110-2000) in CD and 80.850±24.416 ng/mL (range: 52-135) in control group. UC and CD patients had significantly higher serum calgranulin c levels compared to IBS patients with p &amp;lt; 0.001 for both. the best cut-off for serum calgranulin c levels in prediction of IBD was &amp;gt;110 ng/Ml with sensitivity 96.67%, specificity 85.00%, and test accuracy was 97.8%. best cut-off for serum calgranulin c levels in prediction of UC was &amp;gt;135 ng/mL. the best cut-off for serum calgranulin c levels in prediction of CD was &amp;gt;110 ng/Ml. Moreover, the best cut-off for serum calgranulin c levels of &amp;gt; 435 ng/mL could predict activity in UC group depend on UCEIS, depend on ACGUCAI and Erosions and ulcers in endoscopy. another cut off level of Serum calgranulin c in prediction of luminal bleeding in endoscopy in UC patients was &amp;gt;625 ng/ml. the best cut off level of Serum calgranulin c in prediction of activity among CD patients depend on CDAI was &amp;gt;437 ng/ml. Conclusion Serum calgranulin c was found to be higher in patients with IBD than with functional bowel disorded (IBS). Levels of serum calgranulin c varied significantly with disease severity in patients with UC and CD. Serum calgranulin c was found to be higher among patients with active CD and UC than those in remission. Serum calgranulin c can be used as a non invasive marker of inflammatory bowel disease. It can distinguish IBD from IBS and can be considered as a maker of activity in IBD patients.

Identification and Validation of the Diagnostic Markers for Inflammatory Bowel Disease by Bioinformatics Analysis and Machine Learning.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract which is mediated by the inappropriate immune responses. This study was aimed to identify novel diagnostic biomarkers for diagnosis of IBD and explore the relationship between the diagnostic biomarkers and infiltrated immune cells. GSE38713, GSE53306, and GSE75214 downloaded from the Gene Expression Omnibus (GEO) database were split into training and testing sets. Differentially expressed genes (DEGs) were screened using the "limma" package. Gene Ontology (GO) and KEGG pathway enrichment analysis of DEGs were performed by clusterProfiler package. The LASSO regression and support vector machine recursive feature elimination (SVM-RFE) algorithms were conducted to identify novel diagnostic biomarkers. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic value of the candidate biomarkers. The relationship of the candidate biomarkers and infiltrating immune cells in IBD were evaluated by CIBERSOTR. Quantitative Real-Time PCR (qRT-PCR) was applied to measure the expression level of the biomarkers in IBD. A total of 289 dysregulated genes were identified as DEGs in IBD. These DEGs were significantly enriched in chemokine signaling pathway and cytokine-cytokine receptor interaction. RHOU was identified as a critical diagnostic gene in IBD, which was confirmed using ROC curve and qRT-PCR assays. Immune cell infiltration analysis showed that RHOU was correlated with macrophages M2, dendritic cells resting, mast cells resting, T cells CD4 memory resting, macrophages M0, and mast cells activated. Our results imply that RHOU may be a potential diagnostic biomarker for IBD.

Evaluation of plasma Short chain fatty acid levels as markers for Inflammatory bowel disease

Background Specific variations of short chain fatty acids in fecal samples have been shown for patients with inflammatory bowel disease. The aim of this study was to assess if Crohn’s disease and ulcerative colitis are associated with altered concentrations of short chain fatty acids also in blood plasma. Method Between 2016-2019, Swedish adults referred to a tertiary center for colonoscopy were asked to participate in a cross-sectional study. Individuals with Crohn’s disease or ulcerative colitis as well as individuals with no findings on the colonoscopy (defined as clean colon) were included in the study. Data on colonoscopy findings, blood samples (including haemoglobin, C-reactive protein and short chain fatty acid analysis) as well as a validated lifestyle questionnaire including 277 questions were collected from all participants. Linear regression was used to compare mean concentrations of short chain fatty acids between Crohn’s disease, ulcerative colitis and clean colon. Results The cohort consisted of 132 individuals with Crohn’s disease, 119 with ulcerative colitis and 205 with clean colon. In the crude model, succinic acid was significantly lower (p < 0.05) among patients with Crohn’s disease (mean 3.00 µM SE 0.10) and ulcerative colitis (mean 3.13 µM SE 0.10) in comparison to clean colon (mean 3.41 µM SE 0.08), however when adjusting for sex, age and diet the results did not remain statistically significant. No differences in plasma concentration of the other measured short chain fatty acids were detected. Conclusion Crohn’s disease and ulcerative colitis are not associated with altered short chain fatty acid concentrations in plasma. Further research is needed to confirm or refute our findings.

Integration of semi-empirical MS/MS library with characteristic features for the annotation of novel amino acid-conjugated bile acids.

Recently, amino acids other than glycine and taurine were found to be conjugated with bile acids by the gut microbiome in mouse and human. As potential diagnostic markers for inflammatory bowel disease and farnesoid X receptor agonists, their physiological effects and mechanisms, however, remain to be elucidated. A tool for the rapid and comprehensive annotation of such new metabolites is required. Thus, we developed a semi-empirical MS/MS library for bile acids conjugated with 18 common amino acids, including alanine, arginine, asparagine, aspartate, glutamine, glutamate, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. To investigate their fragmentation rules, these amino acids were chemically conjugated with lithocholic acid, deoxycholic acid, and cholic acid, and their accurate-mass MS/MS spectra were acquired. The common fragmentation patterns from the amino acid moieties were combined with 10 general bile acid skeletons to generate a semi-empirical MS/MS library of 180 structures. Software named BAFinder 2.0 was developed to combine the semi-empirical library in negative mode and the characteristic fragments in positive mode for automatic unknown identification. As a proof of concept, this workflow was applied to the LC-MS/MS analysis of the feces of human, beagle dogs, and rats. In total, 171 common amino acid-conjugated bile acids were annotated and 105 of them were confirmed with the retention times of synthesized compounds. To explore other potential bile acid conjugates, user-defined small molecules were in-silico conjugated with bile acids and searched in the fecal dataset. Four novel bile acid conjugates were discovered, including D-Ala-D-Ala, Lys(iso)-Gly, L-2-aminobutyric acid, and ornithine.

OXIDATIVE STRESS AND INFLAMMATORY BOWEL DISEASE IN PEDIATRICS

Inflammatory bowel diseases (IBD) are chronic, idiopathic and complex diseases of the gastrointestinal tract. Their two most common forms are ulcerative colitis (UC) and Crohn’s disease, (CD). The incidence and prevalence of IBD increase, the age profile of IBD patients is also changing, in a direction that includes childhood. C-reactive protein (CRP) and calprotectin have been traditional inflammatory markers in IBD. The primary diagnostic tool in the hands of gastroenterologists remains endoscopy, which is an invasive, expensive, and patient-unwanted procedure. Furthermore, a wide range of diseases, from malignant and infectious to functional, can present with similar symptoms as IBD. This makes the diagnostic process even more complicated and requires a wide range of laboratory and instrumental studies, takes a lot of time and money. The oxidative imbalance presence in patients with IBD has been demonstrated. In addition, some markers of oxidative stress in IBD have the potential to become markers for the differential non-invasive diagnosis of inflammatory bowel diseases (IBD and CMA) and would shorten the time to diagnosis. Further, would become a suitable method for monitoring inflammation and the effect of treatment in these diseases.

ABX464 (Obefazimod) Upregulates miR-124 to Reduce Proinflammatory Markers in Inflammatory Bowel Diseases.

Advanced therapies have transformed the treatment of inflammatory bowel disease; however, many patients fail to respond, highlighting the need for therapies tailored to the underlying cell and molecular disease drivers. The first-in-class oral molecule ABX464 (obefazimod), which selectively upregulates miR-124, has demonstrated its ability to be a well-tolerated treatment with rapid and sustained efficacy in patients with ulcerative colitis (UC). Here, we provide evidence that ABX464 affects the immune system in vitro , in the murine model of inflammatory bowel disease, and in patients with UC. In vitro , ABX464 treatment upregulated miR-124 and led to decreases in proinflammatory cytokines including interleukin (IL) 17 and IL6, and in the chemokine CCL2. Consistently, miR-124 expression was upregulated in the rectal biopsies and blood samples of patients with UC, and a parallel reduction in Th17 cells and IL17a levels was observed in serum samples. In a mouse model of induced intestinal inflammation with dextran sulfate sodium, ABX464 reversed the increases in multiple proinflammatory cytokines in the colon and the upregulation of IL17a secretion in the mesenteric lymph nodes. By upregulating miR-124, ABX464 acts as "a physiological brake" of inflammation, which may explain the efficacy of ABX464 with a favorable tolerability and safety profile in patients with UC.

S936 Factors Associated With Fecal Calprotectin Sample Collection Compliance: An IBD Center Quality Improvement Project

Introduction: Regular assessment of objective markers of inflammatory bowel disease (IBD) activity is recommended. Fecal calprotectin (Fcal) is a non-invasive and inexpensive biomarker of disease activity, however, patient compliance with this test is variable and incompletely described. We assessed compliance rates with Fcal tests and identified factors associated with non-compliance. Methods: As a quality improvement project, we conducted a retrospective chart review of IBD patients who had a Fcal test ordered by us between August 2021 and December 2021. Demographic, clinical, disease-related, and test-related (location of lab relative to the patient’s visit in clinic or at home) information were recorded to determine predictors for non-compliance. Simple statistical analysis and multivariable logistic regression was performed. Results: Of 303 patients, 165 (54.4%) had an order for Fcal. Of the Fcal tests ordered, 55 (33.3%) were not completed. Between those with complete versus incomplete tests, IBD remission status (67.8% vs. 83.7%, p = 0.033), history of prior Fcal order completion (93.2% vs. 68.4%, p = 0.001), and test ordered to an external site (62.7% vs. 85.5%, p = 0.004) were significantly different. A multivariable logistic regression with these factors as well as age, gender, telehealth vs. in-person consultation, and patient residence revealed that history of a prior completed Fcal test is independently associated with subsequent test completion (odds ratio (OR) = 8.3, 95% CI 1.9-35.5, p = 0.004). Fcal testing location (institutional or third-party) was marginally significant (OR = 0.27, 95% CI 0.7-1.0, p = 0.051). A multivariable linear regression for days between test order and completion found that tests ordered for external locations are associated with delayed completion (95% CI 5.2-20.6, p = 0.002). Conclusion: In this single center analysis with Fcal testing in patients with IBD, we found that a history of incomplete testing is associated with subsequent non-compliance, and distant location of the lab is associated with delayed completion of the test. These findings suggest that ordering providers should identify additional methods to educate on the importance of disease monitoring with Fcal and when possible, simplify the lab used for testing. Future availability of at home Fcal tests may be helpful in this regard. Table 1. - Linear Regressions for Predictors of Fecal Calprotectin Compliance Logistic Regression for Test Compliance Regression for Delayed Testing Completion Estimate Effect Size (B) Standard Error P - Value 95% Confidence Interval Estimate Effect Size (B) Standard Error P - Value 95% Confidence Interval Age 0.017 0.015 0.248 0.998-1.048 0.148 0.104 0.163 -31.309-7.575 Gender -0.441 0.543 0.417 0.222-1.866 0.877 3.635 0.810 0.062-0.357 IBD Remission -0.949 0.624 0.128 0.114-1.316 -0.331 3.895 0.933 -6.421-8.176 Consultation Type -.0523 0.528 0.322 0.210-1.570 0.102 3.992 0.980 -8.151-7.490 History of Fecal Calprotectin Completion 2.116 0.741 0.004 1.942-35.493 6.628 2.625 0.357 -7.699-20.956 Fecal Calprotectin Testing Location -1.304 0.668 0.51 0.073-1.005 12.875 3.843 0.002 5.160-20.591

Biochemical markers of connective tissue in the pathogenesis of gastroenteritis in dogs and cats

The aim: to analyze and establish the pathogenetic role of biochemical markers of the state of connective tissue in diseases of the stomach and intestines in dogs and cats.&#x0D; Materials and methods. The research was carried out by the method of analysis of sources of scientific literature (PubMed, Elsevier, electronic resources of the V. I. Vernadskyi National Library), because of which a scheme of the pathogenesis of gastroenteritis in dogs and cats with the participation of connective tissue biopolymers was created.&#x0D; Results. In dogs and cats, the issue of the use of biochemical markers for the diagnosis of diseases of the stomach and intestines has not yet been fully clarified. It is known, that in dogs and cats, lymphocytic-plasmacytic enteritis is histologically determined by fibrosis of the intestinal wall, but biochemical tests for the diagnosis of this condition are not given. Among the biochemical markers of inflammatory bowel disease, tumor necrosis factor, C-reactive protein and microalbumin were identified. Although C-reactive protein was elevated in a greater number of diseased animals, this increase was insignificant. Other tests also did not show high diagnostic informativeness. Several stages can be identified in the pathogenesis of alimentary gastroenteritis in dogs and cats. First, the irritating components of food act on the mucous membrane of the stomach and disrupt its secretory and motor functions, which causes gastritis. Thus, the use of indicators of the state of connective tissue in the diagnosis of intestinal diseases in dogs can be used to assess the degree of the inflammatory process.&#x0D; Conclusions. According to the results of the analysis, it was established, that the development of the inflammatory process in the stomach and intestines causes an increase in the content of glycoproteins in the blood serum of cats and dogs, and a decrease in synthetic processes in the liver is accompanied by a decrease in the concentration of glycosaminoglycans (GAG) in the blood serum of sick animals. It should be noted, that this decrease has peculiarities: in dogs, the content of total chondroitin sulfates remained at the level of clinically healthy animals, while the concentration of total GAG decreased. In cats, on the contrary, the content of total chondroitin sulfates decreased, and the fractional composition of GAG remained unchanged. The level of excretion of oxyproline and uronic acids in the urine of animals with gastroenteritis did not change, which indicates the absence of catabolism of collagen and proteoglycans with gastroenteritis

Circulating Profile of ECM-Related Proteins as Diagnostic Markers in Inflammatory Bowel Diseases.

The aim of our research was to find new biomarkers that could be potentially used in the diagnosis, differentiation and monitoring of inflammatory bowel diseases (IBD). Since extracellular matrix (ECM) remodeling contributes to the pathological changes occurring in IBD, the serum profile of ECM-related proteins may reflect disease activity in the intestinal mucosa. Serum laminin (LM), fibronectin (FN) and gelatinase-associated lipocalin (NGAL) concentrations were determined in 51 patients with IBD before and after a year of treatment, as well as in 48 healthy individuals. A significant difference in serum concentration of FN (130,56 ± 52.87 vs. 287.93 ± 79.69, p < 0.001) and NGAL (133.34 ± 51.51 vs. 102.37.39, p < 0.05) between patients with ulcerative colitis (UC) and healthy individuals was found. In patients with Crohn’s disease (CD), serum concentrations of LM (1329.5 ± 389.36 vs. 1012.07 ± 260.85, p < 0.005) and NGAL (138.94 ± 51.31 vs. 102.65 ± 37.39, p < 0.05) were increased, while FN (89.26 ± 43.86 vs. 287.93 ± 79.69, p < 0.001) was decreased compared to healthy subjects. Moreover, a significant correlation was found between the Mayo score in patients with UC and the levels of NGAL (r = 0.49, p < 0.01) and LM (r = 0.035, p < 0.005), respectively. Another significant correlation was noted between the Crohn’s Disease Activity Index (CDAI) and LM (r = 0.49, p < 0.05) levels in CD group. The results presented in our studies indicate that ECM-related markers might be potential additional tools helpful in diagnosing IBD, differential diagnosis of UC and CD and monitoring the disease activity.