Inflammatory bowel disease (IBD) represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients' quality of life. Effective diagnostic strategies involve clinical assessments, endoscopic evaluations, imaging studies, and biomarker testing, where early diagnosis is essential for effective management and prevention of long-term complications, highlighting the need for continual advancements in diagnostic methods. The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance. Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics. Through an in-depth examination of current literature, this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD. Understanding these genetic actors paves the way for personalized approaches, informing clinicians on predicting, tailoring, and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.

Pregnancy-onset inflammatory bowel disease (POIBD) is a rare diagnosis that has been associated with diagnostic delay and increased risk of hospitalization compared with inflammatory bowel disease diagnosed outside of pregnancy. There is a paucity of data on the clinical presentation and risk factors associated with maternal and fetal outcomes of POIBD. We present a 29-year-old patient who presented with acute severe ulcerative colitis at 24 weeks gestational age whose course was complicated by delayed diagnosis and therapy, colonic perforation, colectomy, prolonged hospitalization, and neonatal prematurity. The case illustrates the high index for suspicion required for making this diagnosis and the prevention of maternal and neonatal morbidity, together with a growing need to advocate for timely investigations and in-patient management in unwell pregnant patients.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), lacks a known etiology. Although clinical symptoms, imaging, and colonoscopy are common diagnostic tools, fecal calprotectin (FC) serves as a widely used biomarker to track disease activity. Metabolomics, within the omics sciences, holds promise for identifying disease progression biomarkers. This approach involves studying metabolites in biological media to uncover pathological factors.

The purpose of this study was to explore fecal metabolomics in IBD patients, evaluate its potential in differentiating subtypes, and assess disease activity using FC.

Cross-sectional study including IBD patients, clinical data, and FC measurements (=200 μg/g as an indicator of active disease).

Fecal metabolomics utilized chromatography mass spectrometry/solid phase microextraction with MetaboAnalyst 5.0 software for analysis. Of 52 patients (29 UC, 23 CD), 36 (69.2%) exhibited inflammatory activity. We identified 56 fecal metabolites, with hexadecanoic acid, squalene, and octadecanoic acid notably distinguishing CD from UC. For UC, octadecanoic and hexadecanoic acids correlated with disease activity, whereas octadecanoic acid was most relevant in CD.

These findings highlight the potential of metabolomics as a noninvasive complement for evaluating IBD, aiding diagnosis, and assessing disease activity.

Inflammatory bowel disease (IBD) is a condition of unknown origin. It does not have a definite cure and its response to various treatments can be evaluated based on symptom-based measures, invasive procedures, or biomarker levels, highlighting the need for an accurate biomarker. Since C-reactive protein (CRP) and fecal calprotectin have their shortcomings, the need for a novel biomarker remains critical. Systematic searches of PubMed, Scopus, Web of Science, and Embase were performed In January 2024. PROSPERO number is CRD42024507383. We assessed the accuracy of leucine-rich alpha-2 glycoprotein (LRG) in identifying disease activity among patients with IBD using a bivariate diagnostic random-effects model. Fourteen studies involving 1794 individuals conducted in Japan were selected for our systematic review. The sensitivity and specificity of LRG levels for detecting disease activity were analyzed in patients with IBD and in two subgroups (ulcerative colitis and Crohn's disease). The synthesized sensitivity and specificity were 75.4% [95% confidence interval (CI), 68.9-80.9%] and 77.3% (95% CI, 69.9-83.2%), respectively, in patients with IBD, 73.1% (95% CI, 62.7-81.5%) and 81.9% (95% CI, 73.9-87.8%), respectively, in patients with CD, and the secondary analysis of the ulcerative colitis subgroup showed a pooled sensitivity and specificity of 72.8 and 59.7%, respectively. Our systematic review and meta-analysis demonstrated that LRG could be useful in detecting IBD activity. It is superior for detecting disease activity, especially in patients with normal CRP levels. The LRG was more accurate in monitoring disease activity in patients with CD than in patients with IBD.

Small bowel (SB) lesions in Crohn's disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB.

This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%.

Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67-0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65-0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1).

LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility.

Serum free thiols (SFTs) reflecting oxidative stress appear to correlate with inflammatory bowel disease (IBD) activity. We aimed to evaluate the performance of SFTs concentrations vs endoscopic and histological activity, compare SFTs with established biomarkers, and identify clinical and laboratory parameters independently associated with SFT levels in IBD patients.

Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited, with serum samples obtained concurrently for SFTs and routine bloods, plus fecal calprotectin and immunochemical tests were collected ±30 days from ileocolonoscopy. Endoscopic activity was assessed via established indices and histological activity graded as inactive/mild/moderate. Receiver-operating characteristic curve analyses were utilized to assess performance of SFTs vs endoscopic activity, and multiple regression analysis was used to identify factors associated with SFT levels.

A total of 141 (80 Crohn's disease, 61 ulcerative colitis) patients were recruited. Median SFTs were significantly lower in moderate vs inactive/mild endoscopic activity (309 µM vs 433/471 µM, respectively; P < .01). There was no significant difference in median SFTs across inactive/mild/moderate histological activity. SFTs achieved higher sensitivity than C-reactive protein in predicting moderate, endoscopically active disease (89% vs 78%; area under the curve, 0.80 each) yet was outperformed by fecal calprotectin (100%; area under the curve, 0.93). Advancing age and increasing albumin levels were independently associated with SFT levels, and thus are possible confounders.

This prospective study has demonstrated the potential of SFTs as a serum biomarker in IBD. It was more sensitive than C-reactive protein, yet less sensitive than fecal biomarkers for prediction of endoscopically active IBD.

Over the past decades, an increased importance has been given to gastrointestinal (GI) endoscopy in the management of children with inflammatory bowel diseases (IBD), considering that mucosal healing has been recognized as the optimal endpoint in the treat-to-target paradigm. The recent advances in technology and anesthesia have facilitated the comprehensive evaluation of the GI tract. In this review, we will discuss the role of ileocolonoscopy, upper GI endoscopy, and device-assisted enteroscopy in the work-up and management of pediatric Crohn's disease (CD) and ulcerative colitis, with particular attention on non-invasive endoscopic techniques, such as wireless capsule endoscopy. We will also analyze the most commonly used endoscopic scoring systems, including small bowel scoring systems and endoscopic recurrence grading of neo-terminal ileum CD. Moreover, we will focus on the endoscopic management of complications, such as strictures, that commonly require surgery. Lastly, we will discuss cancer surveillance in children with IBD, with particular consideration of the role of high-definition endoscopic equipment and chromoendoscopy in dysplasia detection rates.

Inflammatory bowel disease (IBD) displays an increased venous and arterial thrombotic risk despite the common occurrence of intestinal bleeding. While some of the mechanisms leading to these thrombotic complications have been studied, other specific changes in the hemostasis profile of IBD patients have been less explored. One such example relates to von Willebrand factor (VWF) whose plasma levels have been reported to be modulated in IBD. Von Willebrand factor is a plasma glycoprotein crucial for hemostatic functions via roles both in platelet function and coagulation. High plasma VWF is a known risk factor for venous thromboembolism. In addition to its canonical roles in hemostasis, VWF is known to be directly or indirectly involved in other vascular processes such as maintenance of endothelial barrier integrity or proliferation of vascular smooth muscle cells. The purpose of this review is to recapitulate and update the existing data about VWF biology in IBD and to highlight its role both in the existing procoagulant phenotype and in vascular alterations that may occur in IBD.

Fecal calprotectin (FC) is a promising biomarker for assessing ulcerative colitis (UC) endoscopic activity. However, the optimal FC cutoff to identify each Mayo endoscopic subscore (MES) remains inconclusive.

The electronic medical records of 177 adult UC patients evaluated at Mayo Clinic Rochester from January 2017 to March 2023 were retrospectively reviewed, obtaining clinical data and US-based Werfen Diagnostics FC levels collected within 30 days before colonoscopy or flexible sigmoidoscopy. Three independent inflammatory bowel disease specialist endoscopists blindly reviewed the most severe endoscopic images for grading MES.

The median interval between FC collection and endoscopy was 2 days. Fecal calprotectin showed strong positive correlations with MES (Spearman's r = 0.709; P < .01) and other clinical parameters. Fecal calprotectin cutoff of 60 mcg/g effectively distinguished MES 0 from MES 1-3 (sensitivity, 0.78; specificity, 0.97; area under the receiver operating characteristic curve [AUC], 0.901) and predicted clinical remission (Total Mayo Score ≤2 and no subscore >1; sensitivity, 0.83; specificity, 0.98; AUC, 0.921). Fecal calprotectin cutoff of 110 mcg/g effectively differentiated MES 0-1 from MES 2-3 (sensitivity, 0.86; specificity, 0.87; AUC, 0.915), while a cutoff of 310 mcg/g distinguished MES 0-2 from MES 3 (sensitivity, 0.80; specificity, 0.76; AUC, 0.820).

This study supports the reliability and applicability of FC as a valuable marker of endoscopic inflammation, particularly in distinguishing MES 0 from MES 1-3 using the FC cutoff of 60 mcg/g. Sensitivity analysis demonstrated robust results.

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) characterised by endoscopic inflammation, progressive bowel damage and gastrointestinal lesions. Although treatment strategies for CD have traditionally focused on a stepwise pharmacological approach to achieve clinical remission or symptom resolution, these treatment goals correlate poorly with disease activity. Thus, achieving full clinical remission and full endoscopic healing alone may be insufficient, as patients may remain at risk of inflammatory complications. Individualised 'treat-to-target' (T2T) pharmacological and treatment approaches represent a promising strategy for improving endoscopic remission and symptom resolution among patients with CD. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) and STRIDE-II guidelines, launched in 2013 and later renewed, identified individualised targets for a T2T therapeutic approach for patients with IBD. These guidelines facilitate the individualisation of target treatment goals through evidence-based, long-term (health-related quality of life, absence of disability, endoscopic healing) and intermediate/short-term (abdominal pain, stool frequency, normalisation of biomarker levels) treatment targets, allowing patients and clinicians to consider the risk-to-benefit balance of goals and selected therapeutic strategies. This article aims to summarise the STRIDE-II guidelines and provide intellectual guidance for healthcare professionals to apply the STRIDE-II principles to current clinical practice in the United Kingdom (UK). Management recommendations for primary and secondary first-line non-responders are provided, along with suggestions for utilising the endoscopic outcomes scoring system in UK clinical practice.

Minimally invasive modalities may replace ileocolonoscopy (IC) in the follow-up of Crohn's disease (CD). The aim of this study was to evaluate intestinal ultrasound (IUS), magnetic resonance enterocolonography (MREC), panenteric capsule endoscopy (PCE), and fecal calprotectin (FC) for determining response to medical treatment in patients with ileocolonic CD.

This prospective, blinded, multicenter study included patients with endoscopically active CD. Patients were scheduled for IC, MREC, IUS, PCE, and FC before and 12 weeks after treatment with corticosteroids or biological therapy. A ≥50% reduction of the Simple Endoscopic Score for Crohn's Disease (SES-CD) with IC defined treatment response.

Fifty patients completed the pre- and posttreatment evaluation with IC, and endoscopic response was achieved in 25 (50.0%). PCE was omitted in 12 (24.0%) patients because of stricturing CD. All activity scores decreased in patients achieving endoscopic response: The Simple Ultrasound Score for Crohn's Disease 2.2 vs 6.1 (P < .001), Magnetic Resonance Index of Activity 29.0 vs 37.1 (P = .05), SES-CD with PCE 3.1 vs 12.8 (P < .001), and FC 115.3 vs 1339.9 mg/kg (P < .001). The sensitivity and specificity of IUS, MREC, PCE, and FC were 80.0% (95% CI, 56.3-94.3)/77.8% (95% CI, 52.4-93.6), 65.2% (95% CI, 42.7-83.6)/87.0% (95% CI, 66.4-97.2), 87.5% (95% CI, 61.7-98.4)/86.7% (95% CI, 59.5-98.3), and 90.0% (95% CI, 68.3-98.8)/86.4% (95% CI, 65.1-97.1), respectively.

IUS and FC are equally effective for determining treatment response in patients with active CD. PCE is limited by the occurrence of strictures in this group of patients.

We aimed to (1) analyze the applicability of the updated Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations in real-world clinical practice, (2) identify barriers to their implementation, and (3) propose practical measures to overcome these obstacles.

This qualitative study was based on a survey, a literature review, and expert opinions. Nine inflammatory bowel disease (IBD) experts identified 7 areas likely to be controversial or potential implementation barriers in daily clinical practice: endoscopy, histology, ultrasound, quality of life, biomarkers, symptom control, and patient-reported outcomes (PROs). Based on this, a survey was carried out among educational course participants. The experts discussed the literature review and survey results and proposed several statements and practical actions.

A total of 55 gastroenterologists answered the survey. The reported difficulty level in reaching STRIDE-II treatment goals in clinical practice was high. Only 22% of participants performed clinical remission assessments using clinical indexes and PROs. Seventy percent of responders did not use fecal calprotectin cutoffs and considered changes from the previous levels instead. Mucosal healing as a long-term therapeutic goal was considered necessary to be individualized in specific patient subgroups (eg, elderly/fragile patients, multiple treatment failures, and last-line therapies). Other barriers, like the lack of access to imaging techniques or insufficient knowledge and skills among healthcare professionals, were detected. The experts suggested adding less stringent treatment goals and measurements, patient stratification, local adaptations, educational activities, and research.

STRIDE-II recommendations face various implementation barriers needing careful evaluation in order to enhance their adoption in clinical practice, and ultimately improve outcomes in IBD patients.

The Veterans Health Administration (VHA) listed the infliximab (IFX) biosimilar, IFX-dyyb (Inflectra), on the Veterans Affairs National Formulary (VANF) in May 2017. In September 2018, biosimilar IFX-abda (Renflexis) became the VANF IFX product. The recommended formulary changes from one IFX biosimilar to another provided a unique opportunity to study IFX utilization patterns in IFX-naïve Veterans with Inflammatory Bowel Disease (IBD). This study aimed to describe IFX and healthcare utilization during the 365 days after initiation with IFX reference product (RP) or biosimilars IFX-dyyb and IFX-adba. This descriptive study was performed using the VHA Corporate Data Warehouse. All Veterans initiated on IFX-RP (Remicade) or biosimilars IFX-dyyb and IFX-adba between September 1, 2016 and December 30, 2019 were included and followed for 365 days. Veterans enrolled in the VHA for at least 365 days with no evidence of IFX before their index date were considered IFX-naïve. Continuous data on IFX use, laboratory measurements, and healthcare utilization were reported with means, 95% confidence interval (CI), medians, and interquartile ranges. Frequency, proportions, and 95% CIs were presented for categorical variables. Statistical tests included ANOVA and Kruskal-Wallis for continuous outcomes, Poisson regression for count-based outcomes (i.e., healthcare utilization visits), and Chi-square for dichotomous outcomes. The study identified 1763 IFX-naïve patients with IBD, and 785, 441, and 537 was indexed to RP, IFX-dyyb, and IFX-adba, respectively. Statistical differences were observed in IFX utilization measures related to dosing, adherence, and persistence. The proportion of days covered (PDC) during the 365-day follow-up period varied among the IFX groups: IFX-RP at 66%, IFX-dyyb at 60%, and IFX-abda at 69% (P value < .001). Persistence with the index IFX product during the 365-day follow-up period also varied: IFX-RP at 43%, IFX-dyyb at 32%, and IFX-abda at 51% (P value < .001). Healthcare utilization and laboratory findings were similar among the IFX groups. IFX utilization and laboratory patterns were clinically similar among the IFX biosimilars and RP groups, suggesting that providers did not modify their practice with biosimilars. Statistically significant differences in IFX utilization patterns are explained by formulary dynamics when the VANF product switched from IFX-dyyb to IFX-abda.

Inflammatory indices are promising indicators that can be used to evaluate inflammation in inflammatory bowel diseases (IBDs). The present study aimed to investigate the test accuracy of several inflammatory indices to identify endoscopic, and histological activity in a cohort of IBD patients.

All IBD patients who underwent colonoscopy and blood examination (within 4 weeks and without therapeutic change) were included. For these patients, 10 different inflammatory biomarkers were collected. Our primary outcome was the assessment of accuracy [evaluated with a receiver operating characteristics (ROC) analysis] of each inflammatory biomarker and indices. Furthermore, we tried to establish the optimal cutoff to identify patients with endoscopic and histologic activity among the inflammatory biomarkers and indices with higher performance.

Regarding endoscopic activity, at the ROC analysis, the systemic inflammation response index (SIRI) showed the best accuracy [area under the curve (AUC), 0.627; confidence interval (CI), 0.552-0.698]. Whereas the ROC analysis showed a suboptimal AUC for the neutrophil-to-lymphocytes ratio (NLR) and platelets-to-lymphocytes ratio; (AUC, 0.620; CI, 0.545-0.691 and AUC, 0.607; CI, 0.532-0.679, respectively). Concerning histological activity, the C-reactive protein albumin ratio (CAR) presented a higher accuracy among the calculated inflammatory biomarkers (AUC, 0.682; CI, 0.569-0.781) while SIRI and NLR presented a subdued diagnostic performance.

SIRI and CAR presented the best test accuracy in an IBD outpatient setting to identify endoscopic and histological activity. However, the test accuracy of all the evaluated Inflammatory indices appeared suboptimal. Fecal calprotectin has still the highest accuracy in predicting endoscopic and histological activity in patients with IBD.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic conditions marked by persistent inflammation, impacting patients' quality of life. This study assessed differences in coffee consumption between CD and UC patients and its potential effects on the subjective perception and objective changes in inflammation markers in these two categories of patients. Using questionnaires, coffee consumption patterns, and perceived symptom effects were evaluated. Biological samples were collected to measure the following inflammatory markers: leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and fecal calprotectin (FC). Among 148 patients, 60% reported regular coffee consumption, with no significant difference between CD and UC patients. While 45.93% perceived no impact on symptoms, 48% of those reporting exacerbation continued their regular coffee consumption. FC values were significantly lower in coffee consumers than in non-consumers (p < 0.05), particularly in those consuming natural coffee (p < 0.001), and the case was observed for UC patients (p < 0.05). No significant differences were observed in other inflammatory markers, regardless of coffee type, frequency, or milk addition. This study highlights the commonality of coffee consumption among IBD patients and the association of lower FC levels with coffee consumption, especially in UC patients, suggesting that coffee may influence intestinal inflammatory responses.

Close monitoring of disease activity in IBD patients is essential to avoid long term complications. Although endoscopic assessment is the ideal monitoring tool, the usage of noninvasive biomarkers is more practical and patient friendly. We aimed to study the performance of Interleukin-6(IL-6) and Serum Amyloid A(SAA) as serum biomarkers in assessment of the disease activity of IBD patients in correlation to C-reactive protein (CRP), Fecal Calprotectin (FC) and endoscopic indices.

83 IBD (26 CD and 57 UC) patients on stable treatment regimen were recruited. Serum markers included CRP, CBC, IL-6, SAA were analyzed, together with FC. These markers were compared with the endoscopic and clinical disease parameters. Harvey-Bradshaw Index (HBI) and the Simple Clinical Colitis Activity Index (SCCAI) were used to assess clinical activity in CD and UC patients, respectively. Endoscopic activity was recorded using the Simple Endoscopic Score (SES) for Crohn's disease or the Mayo Endoscopic Score (MES) for ulcerative colitis.

In prediction of disease activity, IL-6, SAA and CRP demonstrated good area under receiver operating characteristics (AUC) (>0.7), with FC being the best (0.94) for endoscopically active disease (P < 0.01). Combining FC and IL-6 or SAA improved its discriminative accuracy with an AUC (∼0.96).

FC most accurately predicts endoscopic disease activity in IBD patients, in comparison to other studied serological biomarkers. The serum IL-6 and SAA are potential predictors of endoscopic disease activity, and they might be valuable for assessment of disease activity. Finally, a composite score of FC and SAA or IL-6 can increased its diagnostic accuracy.

Transmural healing (TH) has emerged as a potential treatment goal for Crohn's disease (CD). However, further research is needed to confirm its benefits and risk factors associated with TH remain unclear.

We aimed to assess the value of TH based on magnetic resonance enterography (MRE) in Chinese CD patients regarding the long-term outcomes and its associated factors.

Retrospective, observational cohort study.

Patients with CD diagnosed by colonoscopy and MRE examination between 2015 and 2022 were included. All patients were evaluated with endoscopy together with MRE within 6-12 months after baseline and followed up for at least 6 months after evaluation. The primary endpoint was the occurrence of major outcomes during the follow-up, including drug escalation, hospitalization, and surgery. The cumulative probabilities of major outcomes were calculated using Kaplan-Meier survival curves. Logistic regression analyses were used to predict TH within 6-12 months after baseline.

A total of 175 patients were included in the study. Of these, 69 (39.4%) patients achieved mucosal healing (MH), but only 34 (19.4%) of them achieved TH. The median follow-up duration was 17.4 months (interquartile range, 11.6-25.5), and major outcomes occurred in 58.3% of patients. A lower occurrence rate of major outcomes was noted in patients who achieved TH than in those who achieved MH only (p = 0.012). The baseline lymphocyte/C-reactive protein ratio (LCR) [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.50; p = 0.039] and bowel wall thickness (BWT) (OR, 0.72; 95% CI, 0.59-0.90; p = 0.003) were independent predictors associated with TH. According to multivariate Cox regression analysis, low LCR [hazard ratio (HR), 2.34; 95% CI, 1.51-3.64; p < 0.001], and no healing (HR, 5.45; 95% CI, 2.28-13.00; p < 0.001) were associated with an increased risk of major outcomes.

Patients with CD who achieved TH showed improved prognosis compared to those who achieved MH only. Baseline LCR and BWT might predict TH.

Ulcerative colitis (UC), a chronic inflammatory gastrointestinal disorder, is becoming increasingly prevalent worldwide. Ophiopogonin D, which is derived from Ophiopogon japonicus, exhibits anti-inflammatory and antioxidant properties, yet its therapeutic potential in UC remains unclear.

In this study, we employed a mouse model of DSS-induced colitis to assess the impact of Ophiopogonin D on various parameters, including weight loss, bloody stools, and inflammation in the colon.

Ophiopogonin-D treatment significantly mitigated these DSS-induced effects, improved colon permeability, and modulated inflammatory markers like ZO-1, MUC-2, TNF-α, and IL-1β in mice compared with the control. Furthermore, compared to the DSS-treatment group, Ophiopogonin-D treatment improved the α- and β-diversity indices of the mouse intestinal microbiota, along with an increase in the abundance of genera such as Akkermansia (AKK) and a decrease in the abundance of genera such as Enterobacter. Notably, propionic acid, a metabolite of AKK, demonstrated significant improvement in the symptoms of DSS-induced colitis in mice compared to the control. Moreover, propionic-acid administration also resulted in alterations in the levels of inflammatory factors and calreticulin within the intestinal tissues.

Overall, Ophiopogonin D significantly affects intestinal microbiota composition, thereby improving symptoms of DSS-induced colitis in mice. These findings present promising therapeutic strategies and potential pharmaceutical candidates for the treatment of ulcerative colitis.

Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.

The disease severity index (DSI) encapsulates the inflammatory bowel disease (IBD) burden but requires endoscopic investigations. This study developed a non-invasive DSI using faecal calprotectin (DSI-fCal) and faecal myeloperoxidase (DSI-fMPO) instead of colonoscopy.

Adults with IBD were recruited prospectively. Baseline biomarker concentrations were used to develop DSI-fCal and DSI-fMPO, and these were correlated with the original DSI, IBD-symptoms, endoscopic activity, and quality-of-life (QoL). Area under the receiver-operating-characteristics curves (AUROC) assessed DSI-fCal/DSI-fMPO as predictors of clinical and biochemical remission at six months (symptom remission and fCal <150 μg/g, respectively), and a complicated IBD-course at 24 months (disease relapse needing escalation of biologicals/immunomodulators/recurrent corticosteroids, IBD-hospitalisations/surgeries). Multivariable logistic regression assessed the utility of DSI-fCal/DSI-fMPO in predicting a complicated IBD-course at 24 months.

In total, 171 patients were included (Crohn's disease=99, female=90, median age=46y (IQR 36-59)). DSI-fCal and DSI-fMPO correlated with the original DSI (r>0.9, p<0.001), endoscopic indices (r=0.45-0.49, p<0.001), IBD-symptoms (r=0.53-0.58, p<0.001) and QoL (r=-0.57-0.58, p<0.001). Baseline DSI-fCal (AUROC=0.79, 95% CI 0.65-0.92) and DSI-fMPO (AUROC=0.80, 95% CI 0.67-0.93) were associated with 6-month clinical and biochemical remission. DSI-fCal (AUROC=0.83, 95% CI 0.77-0.89) and DSI-fMPO (AUROC=0.80, 95% CI 0.73-0.87) performed similarly in predicting a complicated IBD-course to the original DSI (pdifference>0.05). The non-invasive DSI was independently associated with a complicated IBD-course on multivariable analyses (DSI-fCal28, aOR=6.04, 95% CI 2.42-15.08; DSI-fMPO25, aOR=7.84, 95% CI 2.96-20.73).

The DSI-fCal and DSI-fMPO perform similarly in prognosticating the longitudinal disease course as the original DSI, whilst avoiding a need for an endoscopic assessment.

Pharmacokinetic non-inferiority of subcutaneous (SC) to intravenous (IV) CT-P13 maintenance therapy was demonstrated in a randomized trial (NCT02883452). This post hoc analysis evaluated longitudinal clinical outcomes with the two infliximab treatment strategies.

Patients with Crohn's disease or ulcerative colitis received CT‑P13 IV loading doses (5 mg/kg; Week [W] 0 and W2) before randomization (1:1) to receive CT-P13 SC (body weight-based dosing every 2 weeks [Q2W]; W6-54; 'SC maintenance group') or CT‑P13 IV (5 mg/kg Q8W; W6-22) then CT-P13 SC (Q2W; W30-54; 'IV-to-SC switch group'). Paired W30/W54 patient-level data were analyzed.

Fifty-three (IV-to-SC switch) and fifty-nine (SC maintenance) patients were analyzed. Median trough serum CT-P13 concentrations were significantly higher at W54 versus W30 in the IV-to-SC switch group (20.4 versus 2.3 µg/mL; p < 0.00001), while remaining consistent in the SC maintenance group. Statistically significant improvements in pharmacokinetics, efficacy, fecal calprotectin levels, and quality of life were seen following switch to SC administration at W30 in the IV-to-SC switch group; safety findings were similar pre- and post-switch.

Formulation switching from IV to SC infliximab maintenance therapy was well tolerated and may provide additional clinical improvements. Findings require confirmation in larger prospective studies.

The serum-based endoscopic healing index (EHI) test identifies endoscopic Crohn's disease (CD) activity. Data are lacking on the relationship between EHI with other endpoints. We assessed the relationship between EHI and the simplified Magnetic Resonance Index of Activity.

Data were prospectively collected on patients with CD with either an EHI or fecal calprotectin (FCAL) within 90 days of magnetic resonance enterography (MRE). Diagnostic accuracy was assessed using area under the receiver operator characteristics. Proportions with any, severe, and terminal ileum MR inflammation were compared above/below identified thresholds for both EHI and FCAL.

A total of 241 MREs paired to either EHI or FCAL from 155 patients were included. Both EHI and FCAL had similar accuracy to diagnose inflammation (area under the receiver operator characteristics: EHI: 0.635 to 0.651, FCAL: 0.680 to 0.708). Optimal EHI values were 42 and 26 for inflammation on MRE and endoscopy, respectively. Patients with EHI ≥42 (100% vs. 63%, P =0.002), FCAL >50 µg/g (87% vs. 64%, P <0.001) and FCAL >250 µg/g (90% vs. 75%, P =0.02) had higher rates of simplified Magnetic Resonance Index of Activity ≥1 compared with lower values. EHI differentiated ileitis numerically more than FCAL (delta: 24% to 25% vs. 11% to 21%). Patients with FCAL ≥50 µg/g had higher rates of severe inflammation compared with FCAL <50 µg/g (75% vs. 47%, P <0.001), whereas smaller differentiation existed for EHI threshold of 42 (63% vs. 49%, P =0.35).

Both EHI and FCAL were specific in their confirmation of inflammation and disease activity on MRE in patients with CD. However, MRE-detected inflammation was frequently present in the presence of low EHI and FCAL in similar proportions.

Faecal calprotectin (FC) shows an excellent correlation with endoscopic and histological activity of ulcerative colitis (UC) and it is the best predictor of clinical relapse. Our aim was to evaluate the usefulness of modifying the dose of mesalazine based on FC levels, in clinical practice.

Retrospective, single-centre study in UC patients in clinical remission while treated with mesalazine which dosage was decreased (DOWN) or increased (UP) according to FC levels. The main endpoint was the long-term maintenance of clinical remission.

A total of 56 patients were included (39 DOWN, 17 UP). In the DOWN group, the median baseline dose of mesalazine was 3.6g/day and the median baseline FC was 36μg/g. After a median follow-up of 22 months, 28% required rescue therapy. The cumulative relapse-free survival after tapering was 91% and 82% at 12 and 24 months, respectively. In the UP group, the median baseline dose of mesalazine was 2.4g/day, with a median baseline FC of 524μg/g. After a median follow-up of 12 months, 29% required rescue therapy. The cumulative relapse-free survival after dose increase was 86% and 72% at 12 and 24 months, respectively.

Mesalazine dose modification based on FC monitoring seems to be a safe strategy in patients with UC in clinical remission, with a probability of clinical relapse around 20% at two years.

The brain-gut axis represents a bidirectional communication network that integrates neural, hormonal, and immunological signaling between the central nervous system and the gastrointestinal tract. Adverse childhood experiences (ACEs) have increasingly been recognized for their profound impact on this axis, with implications for both mental and physical health outcomes. This mini-review explores the emerging field of epigenomics-specifically, how epigenetic modifications incurred by ACEs can influence the brain-gut axis and contribute to the pathophysiology of various disorders. We examine the evidence linking epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs to the modulation of gene expression involved in stress responses, neurodevelopment, and immune function-all of which intersect at the brain-gut axis. Additionally, we discuss the emerging potential of the gut microbiome as both a target and mediator of epigenetic changes, further influencing brain-gut communication in the context of ACEs. The methodological and therapeutic challenges posed by these insights are significant. The reversibility of epigenetic marks and the long-term consequences of early life stress require innovative and comprehensive approaches to intervention. This underscores the need for comprehensive strategies encompassing psychosocial, pharmacological, neuromodulation, and lifestyle interventions tailored to address ACEs' individualized and persistent effects. Future directions call for a multi-disciplinary approach and longitudinal studies to uncover the full extent of ACEs' impact on epigenetic regulation and the brain-gut axis, with the goal of developing targeted therapies to mitigate the long-lasting effects on health.

In an era of increasing paediatric obesity and inflammatory bowel disease (IBD), this study evaluates the disease phenotype and clinical course of Crohn's disease (CD) in paediatric patients who are obese or overweight.

This is a retrospective, single-center, descriptive observational study from January 2010 to May 2020. Participants were included if they were: aged 2 to 18 years at the time of diagnosis, had a confirmed diagnosis of CD, and met WHO criteria for overweight or obesity at the time of diagnosis or within one year before diagnosis.

A total of 345 patient charts with CD were screened during the study period, with 16 patients meeting inclusion criteria. Median age of patients was 15.5 years (IQR = 13.6, 16.1). Of the 15 patients over 10 years of age, median anthropometrics at diagnosis included body mass index (BMI) of 27.2 (IQR = 24.9, 29.4) and BMI for age z-score of 1.82 (IQR = 1.58, 2.19). Presenting symptoms included abdominal pain (80.0%), diarrhea (66.7%), hematochezia (66.7%), and weight loss (26.7%). Five patients (33.3%) had obesity-related complications. Median time from symptom onset to diagnosis was 146 days (IQR = 31, 367), and median time from diagnosis to remission was 229 days (IQR = 101.8, 496.3).

Patients with elevated BMI and CD present with typical symptoms of IBD, although weight loss was a less common presenting symptom. Time to disease remission is delayed, and obesity-related complications are common. Primary care providers must have a high degree of clinical suspicion in patients to prevent delays to gastroenterology referral and to improve time to disease remission.

Inflammatory bowel disease (IBD) is a complex gastrointestinal disease with 2 main subtypes of Crohn's disease (CD) and ulcerative colitis (UC), whose diagnosis mainly depends on the medical history, clinical symptoms, endoscopic, histologic, radiological, and serological findings. Extracellular vesicles (EVs) are now considered an additional mechanism for intercellular communication, allowing cells to exchange biomolecules. Long noncoding RNAs (lncRNAs) that are enriched in EVs have been defined as an ideal diagnostic biomarker for diseases. In this study, we investigated the expression differences of 5 lncRNAs in tissue and plasma EVs of active IBD patients compared with patients in the remission phase and healthy controls to introduce an EV-lncRNA as a noninvasive IBD diagnostic biomarker.

Twenty-two active IBD patients, 14 patients in the remission phase, 10 active rheumatoid arthritis (RA) patients, 14 irritable bowel syndrome (IBS) patients, and 22 healthy individuals were recruited in the discovery cohort. In addition, 16 patients with active IBD, 16 healthy controls, 10 inactive IBD patients, 12 active RA patients, and 14 IBS patients were also included in the validation cohort. The expression levels of 5 lncRNAs in tissue and EV-plasma were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) . Machine learning and receiver operating characteristic (ROC) curve analysis were performed to investigate the distinguishing ability of the candidate biomarkers.

While the expression levels of lncRNAs CDKN2B-AS1, GAS5, and TUG1 were significantly downregulated, lncRNAs H19 and CRNDE were overexpressed in active IBD lesions. Expression of H19 was detected in plasma EVs whose isolation had been confirmed via dynamic light scattering, microscopy images, and western blotting. The classification results demonstrated the excellent ability of H19 in distinguishing IBD/active from IBD/remission, healthy control, RA, and IBS (area under the ROC curve = 0.95, 0.97,1, and 0.97 respectively).

Our study suggests that circulating EV-lncRNA H19 exhibited promising potential for the diagnosis of active IBD.

Although fecal calprotectin is the most widely used biomarker for assessing Crohn's disease activity, serum leucine-rich alpha-2 glycoprotein has recently attracted attention, especially in Japan. Here we performed a systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein to obtain evidence for its accuracy in assessing Crohn's disease activity.

On February 1, 2023, we performed searches of PubMed, Web of Science, and CENTRAL. The Prospero number is CRD42023396034. The primary outcomes were the sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein for assessing Crohn's disease activity. We used a bivariate generalized linear mixed model, assuming a binomial distribution at the test level and a bivariate normal distribution at the between-test level.

We selected 9 studies involving 797 individuals in our systematic review. Regarding the primary outcomes, the synthesized sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein were 77.0% (95% confidence interval, 67.8% to 84.2%) and 81.1% (95% confidence interval, 72.6% to 87.4%), respectively. The area under the curve was 0.86, and the partial area under the curve was 0.78. Regarding between-study heterogeneity, both the I2 value by Zhou and Dendukuri approach and the I2 value by Holling sample size-adjusted approaches were 0%.

Our systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein demonstrated its accuracy in assessing Crohn's disease activity. Further studies are needed to demonstrate its clinical utility and clinical validity.

Increasing evidence supports the use of transmural remission as a treatment target in Crohn's disease (CD), but it is seldom achieved in clinical practice. Tight monitoring of inflammation using fecal calprotectin with reactive treatment escalation may potentially improve these results.

To evaluate if treatment escalation based on fecal calprotectin can improve the rates of transmural remission in CD. The influence of the timing of intervention on this strategy was also evaluated.

Retrospective cohort study including 256 CD patients with 2 consecutive assessments by MRI-enterography and colonoscopy and with regular monitoring using fecal calprotectin. For each occurrence of an elevated fecal calprotectin (≥250 μg/g), we evaluated whether a reactive adjustment of medical treatment was performed. The ratio of treatment escalation/elevated fecal calprotectin was correlated with the chances of reaching transmural remission. Early disease was defined as disease duration <18 months without previous exposure to immunomodulators and biologics.

After a median follow-up of 2 years (IQR 1-4), 61 patients (23.8%) reached transmural remission. Ratios of escalation ≥50% resulted in higher rates of transmural remission (34.2% vs. 15.1%, p < 0.001). The effect was more pronounced in patients with early disease (50.0% vs. 12.0%, p = 0.003). In multivariate analysis, a treatment escalation ratio ≥50% (OR 3.46, 95% CI 1.67-7.17, p = 0.001) and early disease intervention (OR 3.24, 95% CI 1.12-9.34, p = 0.030) were independent predictors of achieving transmural remission.

Tight-monitoring and reactive treatment escalation increase the rates of transmural remission in CD. Intervention in early disease further improves these results.

Faecal biomarkers are increasingly utilized for disease assessment in inflammatory bowel disease (IBD).

To characterize the relative and combined accuracy of faecal calprotectin (FC) and faecal immunochemical testing (FIT) for detecting endoscopic and histologically active disease in Crohn's disease (CD) and ulcerative colitis (UC), subdivided by disease location.

A prospective cohort study.

Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited and performed both FC and FIT ±30 days of ileocolonoscopy. Endoscopic activity was assessed via the simplified endoscopic score for CD, Mayo endoscopic score for UC and histological activity graded as nil/mild/moderate. Receiver-operator curve analyses were utilized to assess the performance of FC and FIT per disease subtype and location.

In all, 137 (79 CD, 57 UC) patients were recruited. FC was more sensitive than FIT in detecting active endoscopic (CD: 91% versus 69%, UC: 94% versus 82%) and histological (CD: 86% versus 55%, UC 88% versus 56%) disease. However, FIT was more specific than FC in detecting active endoscopic (CD: 94% versus 56%, UC: 85% versus 69%) and histological (CD: 93% versus 55%, UC: 96% versus 70%) diseases. FIT was more sensitive and specific than FC in detecting active colonic CD (endoscopic activity: 94% versus 93%, histological activity: 92% versus 77%, respectively); however, it was poorly sensitive for active ileal CD (43% versus 89%).

FC demonstrated higher sensitivity and FIT higher specificity for active IBD. Hence, dual testing was synergistic, displaying excellent performance characteristics across most IBD locations and subtypes, holding promise for future clinical application.

Not applicable.

Inflammatory bowel diseases are a conglomerate of disorders causing inflammation of the gastrointestinal tract, which have gained a significant increase in prevalence in the 21st century. As they present a challenge in the terms of diagnosis as well as treatment, IBDs can present an overwhelming impact on the individual and can take a toll on healthcare costs. Thus, a quick and precise diagnosis is required in order to prevent the high number of complications that can arise from a late diagnosis as well as a misdiagnosis. Although endoscopy remains the primary method of evaluation for IBD, recent trends have highlighted various non-invasive methods of diagnosis as well as reevaluating previous ones. This review focused on the current non-invasive methods in the diagnosis of IBD, exploring their possible implementation in the near future, with the goal of achieving earlier, feasible, and cheap methods of diagnosis as well as prognosis in IBD.

Inflammatory bowel disease (IBD) flare-ups exhibit symptoms that are similar to other diseases and conditions, making diagnosis and treatment complicated. Currently, the gold standard for diagnosing and monitoring IBD is colonoscopy and biopsy, which are invasive and uncomfortable procedures, and the fecal calprotectin test, which is not sufficiently accurate. Therefore, it is necessary to develop an alternative method. In this study, our aim was to provide proof of concept for the application of Sequential Window Acquisition of All Theoretical Mass Spectra-Mass spectrometry (SWATH-MS) and machine learning to develop a non-invasive and accurate predictive model using the stool proteome to distinguish between active IBD patients and symptomatic non-IBD patients. Proteome profiles of 123 samples were obtained and data processing procedures were optimized to select an appropriate pipeline. The differentially abundant analysis identified 48 proteins. Utilizing correlation-based feature selection (Cfs), 7 proteins were selected for proceeding steps. To identify the most appropriate predictive machine learning model, five of the most popular methods, including support vector machines (SVMs), random forests, logistic regression, naive Bayes, and k-nearest neighbors (KNN), were assessed. The generated model was validated by implementing the algorithm on 45 prospective unseen datasets; the results showed a sensitivity of 96% and a specificity of 76%, indicating its performance. In conclusion, this study illustrates the effectiveness of utilizing the stool proteome obtained through SWATH-MS in accurately diagnosing active IBD via a machine learning model.

The landscape of ulcerative colitis has changed in the last two decades. Advancements in pharmacotherapeutics have heralded the introduction of new treatment options, with many agents in development. Better clinical outcomes are seen with tighter disease control, made possible with greater understanding of inflammatory pathways and their blockade with drugs. There has been a resultant shift in treatment targets, beyond symptoms to endoscopic and histological healing. Controlling the burden of disease activity also lowers the risk of developing colorectal cancer. Colorectal cancer screening now requires the use of dye-based agents and high-definition colonoscopy to improve the detection of colonic neoplasms.

Titanium dioxide (TiO2/E171) is used widely in foods, primarily as a food additive. Animal models have shown that chronic TiO2 exposure may disturb homeostasis of the gastrointestinal tract by increasing gut permeability, inducing gut inflammation, and increasing the likelihood of microbial infection. Adults have a wide range of ingested TiO2,which span two to three orders of magnitude, with a small portion of individuals consuming near gram quantities of TiO2/day. However, research on the health effects of chronic ingestion of TiO2/E171 in humans is limited. We hypothesized that regularly ingested TiO2/E171 is associated with increased gut inflammation and gut permeability in healthy adults. We tested this hypothesis in a cross-sectional design by measuring clinically established stool markers of gut inflammation (calprotectin, lactoferrin) and gut permeability (alpha-1 antitrypsin; A1AT) in 35 healthy adults, and comparing these markers between relatively high and low TiO2 exposure groups. Participants were stratified by TiO2 stool content (high dry stool TiO2 content: 0.95-9.92 μg/mg, n = 20; low content: 0.01-0.04 μg/mg; n = 15). Differences in gut health markers were tested between high and low exposure groups by independent samples t-test or Mann-Whitney U test. Multivariable linear regression was used to assess the association between TiO2 in dry stool and measured stool alpha-1 antitrypsin (A1AT). Participants in the high stool TiO2 group had greater stool A1AT (42.7 ± 21.6 mg/dL; median: 38.3; range: 1.0-49.2 mg/dL), compared to the low TiO2 group (22.8 ± 13.6 mg/dL; median: 20.9; range: 8.7-93.0 mg/dL), P = 0.003. There was also greater stool calprotectin in the high TiO2 group (51.4 ± 48.6 μg/g; median 29.2 μg/g; range: 15.3-199.0 μg/g) than in the low group (47.5 ± 63.3 μg/g; median 18.8 μg/g; range: 1.6-198.1 μg/g), P = 0.04. No clear difference was observed for lactoferrin (high TiO2 group 1.6 ± 2.1 μg/g; median: 0.68 μg/g; range: 0.01-7.7 μg/g, low TiO2 group: 1.3 ± 2.6 μg/g; median: 0.2; range: 0.01-7.6 μg/g) (P = 0.15). A1AT concentration was positively associated with stool TiO2, after adjusting for confounders (β ± SE: 19.6 ± 7.2; P = 0.01) R2 = 0.38). Community dwelling, healthy adults with the highest TiO2 stool content had higher stool A1AT and calprotectin, compared to those with the lowest TiO2 stool content. Ongoing research is needed to validate these observations in larger groups, and to determine the long-term effects of ingested TiO2 on human gut health, using these and additional health endpoints.

Fecal calprotectin (FCP) is used to monitor inflammatory bowel disease (IBD) activity and can also be elevated in gastrointestinal infections. Our study's objective was to quantify the relationship between FCP levels and lab-confirmed infections in people with and without IBD. We performed a cross-sectional study at a tertiary-care center of all encounters during which FCP and gastrointestinal pathogen polymerase-chain reaction (GI PCR) panel testings were conducted. Using non-parametric tests and quantile regression, we compared the FCP levels by IBD status and pathogen detection. There were 3,347 encounters with FCP and GI PCR testings from 2,780 unique individuals between 1 August 2016 and 17 February 2022. Overall, 54.4% had IBD (n = 1,819). Pathogens were detected in 744 encounters (22.2%), and the detection rate did not differ by IBD status. Median FCP without IBD was significantly elevated when a pathogen was detected (64 vs 41 mg/kg, P = 0.0003, normal ≤50.0 mg/kg), but FCP with IBD was not significantly elevated when a pathogen was detected (299 vs 255 mg/kg, P = 0.207). In quantile regression adjusted for age and IBD, pathogen detection was only significantly associated with higher FCP in the lower two quartiles, though IBD remained significantly associated with higher FCP at all levels (P > 0.001). Pathogen detection by GI PCR is associated with elevated FCP, though this relationship is nonlinear and varies by IBD status. Our findings indicate that FCP may be an adjunct to, but not a substitute for, stool pathogen testing.

The STRIDE consensus suggested to focus on mucosal healing, based on biomarkers and endoscopy, in addition to clinical endpoints as treatment target. This narrative review provides a critique of this concept in Crohn´s disease.

We analyze and discuss the limitations of endpoints as targets, their currently limited achievability, and the controversial evidence relating to 'treat to target.' The relevant publications in Pubmed were identified in a literature review with the key word 'Crohn´s disease.'

All targets and endpoints have their limitations, and, even if reached, not all have unequivocally been shown to improve prognosis. The major deficiency of STRIDE is not only the lack of validation and agreement upon endpoints but little evidence of their achievability in a sizable proportion of patients by dose or timing adjustments or switching the medication. Above all, the concept should be based on clear evidence that patients indeed benefit from appropriate escalation of treatment and relevant controlled studies in this regard have been controversial. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant and expect more convincing evidence before new targets are approved.

In this review, we have summarized the existing knowledge of ulcerative colitis (UC) markers based on current literature, specifically, the roles of potential new biomarkers, such as circulating, fecal, genetic, and epigenetic alterations, in UC onset, disease activity, and in therapy response. UC is a complex multifactorial inflammatory disease. There are many invasive and non-invasive diagnostic methods in UC, including several laboratory markers which are employed in diagnosis and disease assessment; however, colonoscopy remains the most widely used method. Common laboratory abnormalities currently used in the clinical practice include inflammation-induced alterations, serum autoantibodies, and antibodies against bacterial antigens. Other new serum and fecal biomarkers are supportive in diagnosis and monitoring disease activity and therapy response; and potential salivary markers are currently being evaluated as well. Several UC-related genetic and epigenetic alterations are implied in its pathogenesis and therapeutic response. Moreover, the use of artificial intelligence in the integration of laboratory biomarkers and big data could potentially be useful in clinical translation and precision medicine in UC management.

Background and Objectives: Calprotectin is a marker for intestinal inflammation. Recent research suggests a link between inflammation and depression. This study assessed the association between the levels of calprotectin in patients from South-Eastern Europe and the severity of depression, anxiety, and quality of life. Materials and Methods: This cross-sectional study included 30 confirmed patients with Crohn's disease (CD) and ulcerative colitis (UC) who were assessed using clinical interviews for determining the severities of mental disorders (i.e., depression severity-PHQ-9, anxiety-GAD-7) and the quality of life (EQ-5D). Stool samples were collected from all participants for measuring their levels of calprotectin. Results: The level of calprotectin is correlated with PHQ-9 (ρ = 0.416, p = 0.022) and EQ-5D (ρ = -0.304, p = 0.033) but not with GAD 7 (ρ = 0.059, p = 0.379). Calprotectin levels in patients with mild, moderate, and moderately severe depression were significantly higher than in patients with minimal depression (198 µg/g vs. 66,9 µg/g, p = 0.04). Calprotectin level was corelated with the following depressive symptoms: autolytic ideation (ρ = 0.557, p = 0.001), fatigue (ρ = 0.514, p = 0.002), slow movement (ρ = 0.490, p = 0.003), and sleep disorders (ρ = 0.403, p = 0.014). Calprotectin was an independent predictor of depression with an odds ratio of 1.01 (95%: 1.002-1.03, p < 0.01). An ROC analysis showed that a level of calprotectin of 131 µg/g or higher has a sensitivity of 82%, a specificity of 61%, and an accuracy of 70% for predicting depression. In this study, no significant correlations were found between calprotectin level and anxiety. Conclusions: Calprotectin levels are associated with the severity of depression, and checking for a calprotectin level of 131 µg/g or higher may be a potential accessible screening test for depression in patients with inflammatory bowel disease.

Ulcerative colitis (UC), a chronic inflammatory disease of gastrointestinal tract, can have initial presentation which is clinically difficult to differentiate from functional bowel disorders [irritable bowel syndrome (IBS) and irritable bowel disease (IBD)]. Conventional laboratory tests, such as erythrocyte sedimentation rate (ESR), C-reactive protein, and albumin express systemic patient responses instead of intestinal inflammation. In the last decade, fecal calprotectin, a calcium-binding protein, has been suggested as a sensitive marker of intestinal inflammation. However, only few studies have investigated its role in relation with the extent of the disease.

To evaluate the usefulness of fecal calprotectin as a biomarker for disease activity in UC, its correlation with disease extent and its utility in differentiating IBS from IBD.

A total of 75 patients (50 cases with colonoscopic evidence of inflammation and 25 cases with normal colonoscopic examination) were included in the study. Fecal calprotectin test was done on the day of colonoscopy. Severity of the disease was assessed by modified Mayo's endoscopy score (MMES).

Age and baseline parameters were comparable in both the groups (UC and IBS). Patients in the ulcerative group had tachycardia (95 vs 74), high ESR (26 vs 20), high leukocytes count (9198 vs 8852), high fecal calprotectin (594 vs 29), low albumin (3.00 vs 3.80) and low hemoglobin (11 vs 13.40). Minimum and maximum MMES were 2 and 13.2. A significant correlation was observed between fecal calprotectin and MMES (p-value < 0.001).

Fecal calprotectin is a simple, noninvasive, cost-effective marker that is strongly associated with colorectal inflammation; moreover, it has better role in the differentiation of IBD (UC) from IBS.

Acharya K, Bhardwaj V, Chuahan I, et al. Comparison of Fecal Calprotectin with Different Endoscopic Scores in the Assessment of Ulcerative Colitis (UC) Activity and Its Utility in Differentiating IBS from IBD. Euroasian J Hepato-Gastroenterol 2023;13(2):120-123.

Objective: To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn's disease (CD) and its relationship with disease location. Methods: Patients with CD were enrolled retrospectively, and clinical data, including FC levels, were collected. Clinical activity was assessed using the Crohn's disease activity index (CDAI). Endoscopic activity was assessed using a simple endoscopic score for Crohn's disease (SES-CD). The partial SES-CD (pSES-CD) was scored for the size of ulcers in each segment as defined by the SES-CD and was calculated as the sum of segmental ulcer scores. Results: This study included 273 CD patients. The FC level was significantly positively correlated with the CDAI and SES-CD, with correlation coefficients of 0.666 and 0.674, respectively. The median FC levels in patients with clinical remission and mildly active and moderately-severely active disease were 41.01, 164.20, and 444.45 μg/g. These values were 26.94, 66.77, and 327.22 μg/g during endoscopic remission and mildly and moderately-severely active stages, respectively. Compared with c-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and other biomarker parameters, FC was better at predicting disease activity for CD patients. For an FC <74.52 μg/g, the area under the curve (AUC) for predicting clinical remission was 0.86, with a sensitivity of 89.47% and a specificity of 71.70%. Moreover, endoscopic remission was predicted with a sensitivity of 68.02% and a specificity of 85.53%. The AUC was 0.83, and the cutoff value was 80.84 μg/g. In patients with ileal and (ileo) colonic CD, FC was significantly correlated with the CDAI, SES-CD, and pSES-CD. The correlation coefficients were 0.711 (CDAI), 0.473 (SES-CD), and 0.369 (pSES-CD) in patients with ileal CD and 0.687, 0.745, and 0.714 in patients with (ileo) colonic CD, respectively. For patients in remission, those in the active stage, and those with large or very large ulcers, differences in FC levels were not significant between patients with ileal and (ileo) colonic CD. Conclusion: FC is a reliable predictor of disease activity in patients with CD, including those with ileal CD. FC is thus recommended for the routine follow-up of patients with CD.

Inflammatory bowel disease (IBD) comprises a group of chronic conditions characterized by relapsing and remitting inflammation of the gastrointestinal tract. The incidence is increasing worldwide, and the therapeutic options for management are expanding. Endoscopy is the gold standard investigation for diagnosis of IBD and for assessing mucosal healing, which is increasingly being used as a measure of disease control. However, it is an invasive procedure that is unpleasant for patients and expensive and time-consuming for hospitals. Fecal calprotectin has been shown to be an accurate surrogate marker of gastrointestinal inflammation in IBD.

Fecal calprotectin was initially used for the diagnosis of IBD but is now recognized as having a role in assisting in assessment of disease activity, prediction of relapse, and informing decisions around therapy and may help to minimize requirement for endoscopy. However, there are various preanalytical and analytical factors that can affect interpretation of the results; these need to be understood to optimize clinical care.

Preanalytical and analytical factors that can potentially influence fecal calprotectin concentrations are examined, and an overview is provided of clinical situations in which fecal calprotectin is commonly measured.

Currently, faecal calprotectin (FC) is the predominate faecal biomarker utilised in clinical practice to monitor Crohn's disease (CD) activity. However, there are several potential faecal biomarkers described in the literature. We performed a meta-analysis to determine the accuracy of faecal biomarkers in discriminating endoscopic activity and mucosal healing in CD.

We searched the medical literature using MEDLINE, EMBASE, and PubMed from 1978 to 8 August 2022. Descriptive statistics, including sensitivity, specificity of the primary studies, their positive and negative likelihood ratios, and their diagnostic odds ratio (DOR), were calculated. The methodological quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS) criteria.

The search found 2382 studies, of which 33 were included for analysis after screening. FC was found to have a pooled sensitivity and specificity, DOR, and negative predictive value (NPV) in discriminating active endoscopic disease (versus inactive) of 81%, 74%, 13.93, and 0.27, respectively. Faecal lactoferrin (FL) had a pooled sensitivity and specificity, DOR, and NPV in discriminating active endoscopic disease of 75%, 80%, 13.41, and 0.34, respectively. FC demonstrated a pooled sensitivity and specificity, DOR, and NPV of 88%, 72%, 18.17, and 0.19 in predicting mucosal healing.

FC remains an accurate faecal biomarker. Further evaluation of the utility of novel faecal biomarkers is needed.

Despite the evolution in inflammatory bowel disease (IBD) management during the last 20 years owing to the advent of new advanced therapies, anti-TNF agents still remain the cornerstone of therapy for both Crohn's disease and ulcerative colitis. However, this does not only secure favorable outcomes for patients considering the progressive disease character and the high likelihood of primary or secondary loss of response. Therefore, trying to reach a better treatment approach and maximize the benefits anti-TNF agents offer, optimization strategies should be examined. It has been indicated that optimizing treatment with anti-TNF enhances drug efficacy and has been associated with improved disease outcomes and a complication-free disease course. From this perspective, we aim to provide an overview of currently available data and recent advances in the practices of anti-TNF treatment optimization. Special focus has been given to the role of therapeutic drug monitoring (TDM), as well as the utility of combining anti-TNF with an immunomodulator and the treat-to-target approach.