Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Fecal calprotectin (FC) is a marker commonly used in the diagnosis and follow-up of inflammatory bowel diseases (IBD). However, other gastrointestinal conditions, like H. pylori (HP) infection, can result in increased neutrophil activity as well. We set out to assess the impact of HP infection on FC and downstream gastrointestinal care via a retrospective study.

In this study, we collected data from two institutions in Brooklyn, NY, in a high immigrant density community. We reviewed data from patients who underwent esophagogastroduodenoscopy (EGD) between January 2017 and October 2022. Patients aged 6-18 years old with an FC level 6 months prior to EGD and HP testing were included.

Of 129 patients, 37 (28.7%) tested positive for HP infection. The mean FC level was significantly elevated in HP-positive patients (241.2, confidence interval [CI]: 161.0-321.3) as compared with HP-negative patients (88.1, CI: 59.1-117.0) (p < 0.001). Patients with higher FC levels were also more likely to undergo colonoscopies (p = 0.003).

HP infection is associated with increased calprotectin, and calprotectin increases in HP patients are associated with an increased risk of colonoscopy.

Previous literature suggests that faecal calprotectin (FC) discriminates Crohn's disease perianal fistulas from cryptoglandular fistulas, irrespective of luminal disease. This study aims to prospectively validate this and analyse if increased local fistula calprotectin levels are associated with fistula characteristics.

In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anaesthesia were included. Faecal and fistula tract scraping calprotectin levels were determined. The primary objective was to analyse whether FC levels could be used to differentiate between Crohn's disease and cryptoglandular perianal fistulas. Secondary outcome parameters were the levels of local calprotectin in fistula scrapings and their correlation with fistula characteristics.

Sixty-three patients were included in this study (perianal Crohn's disease; 45, cryptoglandular; 18). Faecal calprotectin levels were significantly higher in Crohn's disease patients compared with cryptoglandular fistula (354.3 [58.8-1076.3] vs. 47.3 [14.6-233.6] μg/g, p = 0.003). Faecal calprotectin could accurately discriminate Crohn's disease patients with active luminal disease from patients without luminal disease (median [interquartile range]) (1167.0 [557.0-2806.3] vs. 93.0 [47.5-571.6] μg/g, p = 0.001). Faecal calprotectin was not related to calprotectin levels in fistula scrapings. No fistula characteristic was found to be correlated to scraping calprotectin, but a correlation was found with the TOpCLASS classification system, which stratifies fistulas according to disease severity and outcome: class 2a (amenable for repair), class 2b (symptom control) and class 2c (gradually debilitating disease): 140[31.0-149.0]) μg/g versus 706[198.5-1936] μg/g versus 4000[1337-5894] μg/g, p < 0.001). Scraping calprotectin was also related to pronounced hyperintensity of the fistula tract on MRI in Crohn's disease patients: (69.0[30.0-821.0] vs. 1284.0[204.3-4185.5]; p = 0.01)) and cryptoglandular patients: (30.0[13.5-80.5] vs. 3012.0 [923.8-5021.0]; p = 0.002).

Crohn's disease and cryptoglandular perianal fistulas differ in FC levels. Local fistula calprotectin production did not explain this difference, implying FC reflects the luminal condition. A correlation exists between scraping calprotectin levels and Crohn's disease fistula severity, which could be clinically relevant for prognostic cohorts and tailored treatment.

The genetic contribution to inflammatory bowel disease (IBD), encompassing both Crohn's disease (CD) and ulcerative colitis (UC), accounts for around 20% of disease variance, highlighting the need to characterize environmental and epigenetic influences. Recently, considerable progress has been made in characterizing the adult methylome in epigenome-wide association studies.

We report detailed analysis of the circulating methylome in 86 patients with childhood-onset CD and UC and 30 controls using the Illumina Infinium Human MethylationEPIC platform.

We derived and validated a 4-probe methylation biomarker (RPS6KA2, VMP1, CFI, and ARHGEF3), with specificity and high diagnostic accuracy for pediatric IBD in UK and North American cohorts (area under the curve: 0.90-0.94). Significant epigenetic age acceleration is present at diagnosis, with the greatest observed in CD patients. Cis-methylation quantitative trait loci (meQTL) analysis identifies genetic determinants underlying epigenetic alterations notably within the HLA 6p22.1-p21.33 region. Passive smoking exposure is associated with the development of UC rather than CD, contrary to previous findings.

These data provide new insights into epigenetic alterations in IBD and illustrate the reproducibility and translational potential of epigenome-wide association studies in complex diseases.

Inflammatory bowel disease (IBD) is an immune-mediated, chronic, remitting, and relapsing disease. Calprotectin, used in monitoring the disease activity, is expressed from neutrophilic granulocytes during inflammation. Neutrophil gelatinase-associated lipocalin (NGAL) is strongly expressed in both granulocytes and the intestinal epithelial cell layer. The aim of the study was to compare fecal NGAL (FNGAL) with fecal calprotectin (FCAL) in children with IBD.

Forty-four children with IBD and 22 healthy children were included in the study. The patients were divided into two groups, patients with active disease and remission group. Clinical and demographic characteristics, disease activity scores, and serum and fecal markers of the patients were recorded.

The mean age of the patients was 13.2 ± 3.4 years (range 6-17 years) and male/female: 0.62. FNGAL levels of patients with active disease were higher than those in the remission group (p < 0.001). A statistically significant positive correlation was observed between Pediatric Ulcerative Colitis Activity Index scores and white blood cell count, platelets, neutrophil-to-albumin ratio (NAR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and FNGAL. There was a positive correlation between Pediatric Crohn's Disease Activity Index scores and platelets, NAR, ESR, CRP, and FNGAL, whereas there was a statistically significantly negative correlation with activity scores and albumin. While FNGAL had 95.5% sensitivity and 81.8% specificity, FCAL had 86.7% sensitivity and 85.7% specificity.

FNGAL levels were found to be high and sensitive in determining disease activity in our patients with IBD, suggesting that it may be a valuable biomarker.

Leucine-rich alpha 2 glycoprotein (LRG) is one of the serum biomarkers for disease activity of ulcerative colitis (UC). We focused on the correlation between the changes of LRG and the changes of endoscopic and histologic activity of UC, in comparison to the changes of fecal calprotectin (Fcal), fecal immunochemical test (FIT), and C-reactive protein (CRP). Seventy-nine patients with two or more colonoscopies were enrolled, and 123 paired colonoscopies and 121 paired biopsies were examined. With regard to the change of endoscopic/histologic activity between the preceding and subsequent colonoscopy, there was improvement (n = 29/45), unchanging (n = 63/36), and worsening (n = 31/40). The correlations between the changes of marker levels and endoscopic/histologic activity were Fcal; r = 0.50/0.39 and FIT; r = 0.41/0.40, LRG; r = 0.42/0.40 and CRP; r = 0.22/0.17. Furthermore, when the correlation between the changes of LRG levels and the changes of endoscopic/histological activity was compared with those of other markers, the correlation of LRG tended to be superior to those of CRP (CRP vs. LRG; p = 0.08/0.01). LRG is equivalent to fecal markers and superior to CRP, when inferring changes in disease activity of UC based on changes in its level.

We aimed to evaluate the diagnostic accuracy of fecal calprotectin (FC) and intestinal ultrasound (IUS), independently and in combination, as screening tools for adults with suspected IBD to reduce the number of unnecessary endoscopic procedures.

We conducted a retrospective monocentric study that included consecutive adult patients with (i) ileocolonoscopy for suspected IBD between January 2021 and June 2023 who had either (ii) IUS and/or (iii) a FC test within 6 weeks. Bowel wall thickness (BWT) and the color Doppler signal (CDS) were evaluated for all segments. The presence of lymphadenopathy, loss of stratification, stricture, and fistula were also recorded.

In total, 119 patients with a median age of 32 years (IQR, 24.0-41.0) were included. The most common symptoms were abdominal pain (n = 88, 75 %) and chronic diarrhea (n = 89, 75 %). Among the 119 patients, 74 (62 %) had IUS, 101 (82 %) had a FC test, and 56 (47 %) had both. Forty patients (34 %) had a diagnosis of IBD, including 31 (26 %) with CD and 9 (8 %) with UC. By ROC curve analysis, the best threshold of FC to diagnose IBD was 117 ug/g (Se 97 %, Sp 73 %, PPV 67 %, NPV 98 %, AUC 0.88, 95 %CI [0.81; 0.94], p = 0.006). Using this threshold, only 3 % of patients were misclassified as non-IBD. Screening by measuring FC levels would result in a 48 % reduction in the number of adults requiring endoscopy. Abnomal IUS was significantly associated with a diagnosis of IBD (OR 5.6, 95 %IC [2.1;16.2], P = 0.0008). The association of a BWT>3 mm and a positive CDS was associated with a Se, Sp, PPV, and NPV of 48 %, 100 %, 100 %, and 75 %, respectively, but 52 % of patients were misclassified as non-IBD. The combination of a BWT>3 mm, CDS, and FC>117 ug/g had a Se, Sp, PPV, and NPV of 44 %, 100 %, 100 %, and 69 %, respectively. For patients with a normal IUS and FC<117 ug/g, 4 % were misclassified as non-IBD.

The combination of FC and IUS is a useful screening strategy to identify patients who truly require endoscopy for suspected IBD. Calprotectin is a highly effective test for ruling out IBD. Conversely, relying solely on IUS lacks the discriminative power to safely rule out IBD. However, it shows a high PPV and is a potent tool for diagnosing IBD.

Wearables are electronic devices worn on the body to collect health data. These devices, like smartwatches and patches, use sensors to gather information on various health parameters. This review highlights the current use and the potential benefit of wearable technology in patients with inflammatory bowel disease (IBD).

In this review, we explore the current use of wearable technology in healthcare and the studies applying this technology in patients with IBD. We also discuss the limitations of using digital health data in general and wearable technology in particular in the current clinical paradigm and predict a path forward in how to rationally and effectively apply this technology to improve the care of patients with IBD. A comprehensive search of all suitable studies was conducted using the databases of PubMed, MEDLINE, Embase, and Scopus from inception to August 2024.

Currently, wearable technology is applied to the monitoring of IBD and prediction of flares using devices and sensors. Future applications include early disease detection using biosensors, advanced data collection through ingestible devices, gut microbiome monitoring, and integration with machine learning. These advancements promise to revolutionize disease management, including IBD, by enabling early diagnosis, personalized treatment, and improved patient outcomes.

The development of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, involves various factors and is characterized by persistent inflammation of the mucosal lining. However, the role of neutrophils in this process remains controversial. Neutrophil extracellular traps (NETs), which consist of chromatin, antimicrobial proteins, and oxidative enzymes, are released by neutrophils to trap pathogens. They are also involved in various immune-mediated and vascular diseases. NETs act as a vital defense mechanisms at the gut-mucosal interface and are frequently exposed to bacterial, viral, and fungal threats. However, they can also contribute to inflammation and worsen imbalances in the gut bacteria. Recent studies have suggested that NETs have a significant impact on IBD development. Previous studies have shown increased levels of NETs in tissue and blood samples from patients with IBD, as well as in experimental colitis mouse models. Therefore, this review discusses how NETs are formed and their role in the pathophysiology of IBD. It discusses how NETs may lead to tissue damage and contribute to IBD-associated complications. Moreover, non-invasive biomarkers are needed to replace invasive procedures such as endoscopy to better evaluate the disease status. Given the crucial role of NETs in IBD progression, this review focuses on potential NET biomarkers that can help predict the evolution of IBD. Furthermore, this review identifies potential therapeutic targets for regulating NET production, which could expand the range of available treatment options for IBD.

In this article, we comment on the article by Blüthner et al published recently. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic relapsing and remitting condition primarily as a consequence of intestinal inflammation. It is important about adopting early and effective treatment to control clinical symptoms of IBD patients. Diagnostic delay can lead to adverse clinical outcomes and increase disease burden. Diagnostic delay is multifactorial. There are some factors related to diagnostic delay, such as patient factors and healthcare factors. We focus on the diagnostic tools for IBD, the outcomes and factors of diagnostic delay of IBD.

A randomised, double-blind, placebo-controlled pilot trial was conducted to assess the effect of heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in healthy adults with mild to moderate digestive symptoms. A total of 60 participants were recruited and received either HT-ES1 or an identical placebo for 8 weeks with a further follow-up at week 10.

This study monitored changes in the total Gastrointestinal Symptom Rating Scale for IBS score (GSRS-IBS), Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS), IBS Quality of Life index (IBS-QoL), gut microbiome using 16S rRNA sequencing, and the Visceral Sensitivity Index, as well as a range of biochemical markers, anthropometric parameters, and adverse events.

While minimal changes were observed in gastrointestinal (GI) symptoms, the HT-ES1 group showed a significant decrease in total and non-HDL cholesterol compared to the placebo. The intervention group also exhibited a significant increase in the abundance of the genera Faecalibacterium and Anaerobutyricum, both of which were positively correlated with butyrate concentrations. Faecal calprotectin significantly increased over time in the placebo group but remained stable in the HT-ES1 group.

Overall, these findings suggest that HT-ES1 may promote gut health by increasing butyrate-producing bacteria in the gut, maintaining normal levels of faecal calprotectin and reducing serum cholesterol.

Chronic urticaria is one of the most common diseases in allergology and dermatology practice with unclear causes of occurrence. Background: Some studies emphasize the correlation between inflammation in chronic urticaria and disturbed intestinal microbiota. It raises the question about the role of some intestine-related substances in the pathogenesis of urticaria as well as their potential role as disease predictors. Calprotectin is an acute-phase protein with a well-established diagnostic position in the field of gastroenterology. There are some data on the relationship between this parameter and gut microbiota. The major aim of this preliminary study is to investigate whether calprotectin can be potentially taken into account as a disease course predictor in urticaria. Methods: We included in our study 54 chronic spontaneous urticaria (CSU) patients (of whom 26 manifested the symptoms of recurrent angioedema) and 29 patients allergic to Hymenoptera venom for the reference group (in these patients, before venom immunotherapy induction, full diagnostics is performed including intestinal problems). Disease activity in the CSU patients was assessed using the Urticaria Activity Score (UAS) and the disease control in this group was assessed with the Urticaria Control Test (UCT). Moreover, we analyzed fecal and serum calprotectin concentrations. Results: Positive correlation was found only between the values of serum calprotectin concentration and the control level of CSU symptoms with the lack of other relations. Conclusions: Our results do not supply unequivocal evidence for calprotectin as a potential marker of CSU course, though this concept, in the light of growing evidence for microbiota's role in urticaria, requires further research.

In this editorial, we discuss a recently published manuscript by Blüthner et al in the World Journal of Gastroenterology, with a specific focus on the delayed diagnosis of inflammatory bowel disease (IBD). IBD, which includes Crohn's disease and ulcerative colitis, is a chronic intestinal disorder. A time lag may exist between the onset of inflammation and the appearance of signs and symptoms, potentially leading to an incorrect or delayed diagnosis, a situation referred to as the delayed diagnosis of IBD. Early diagnosis is crucial for effective patient treatment and prognosis, yet delayed diagnosis remains common. The reasons for delayed diagnosis of IBD are numerous and not yet fully understood. One key factor is the nonspecific nature of IBD symptoms, which can easily be mistaken for other conditions. Additionally, the lack of specific diagnostic methods for IBD contributes to these delays. Delayed diagnosis of IBD can result in numerous adverse consequences, including increased intestinal damage, fibrosis, a higher risk of colorectal cancer, and a decrease in the quality of life of the patient. Therefore, it is essential to diagnose IBD promptly by raising physician awareness, enhancing patient education, and developing new diagnostic methods.

Ulcerative colitis (UC) is an incurable, relapsing-remitting inflammatory disease that increases steadily. Mucosal healing has become the primary therapeutic objective for UC. Nevertheless, endoscopic assessments are invasive, expensive, time-consuming, and inconvenient. Therefore, it is crucial to develop a noninvasive predictive model to monitor endoscopic activity in patients with UC.

Clinical data of 198 adult patients with UC were collected from January 2016 to August 2022 at Huadong Hospital, China.

Patients with UC were randomly divided into the training cohort (70%, n=138) and the validation cohort (30%, n=60). The receiver operating characteristic curve value for the training group was 0.858 (95% confidence interval [CI], 0.781 to 0.936), whereas it was 0.845 (95% CI, 0.731 to 0.960) for the validation group. The calibration curve employed the Hosmer-Lemeshow test (p>0.05) to demonstrate the consistency between the predicted and the actual probabilities in the nomogram of these two groups. The decision curve analysis validated that the nomogram had clinical usefulness.

The nomogram, which incorporated activated partial thromboplastin time, fecal occult blood test, β2-globulin level, and fibrinogen degradation products, served as a prospective tool for evaluating UC activity in clinical practices.

Faecal biomarkers can be used to assess inflammatory bowel disease (IBD).

To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD.

We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression.

All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006).

This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.

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.

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.

Managing inflammatory bowel disease (IBD) is becoming increasingly complex and personalized, considering the advent of new advanced therapies with distinct mechanisms of action. Achieving mucosal healing (MH) is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares, hospitalization, surgery, intestinal damage, and colorectal cancer. Employing proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation, even if subclinical, to alter the natural course of IBD. Periodic monitoring of fecal calprotectin (FC) levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD, assessing MH, and detecting subclinical recurrence. Here, we comment on the article by Ishida et al Moreover, this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with IBD. Furthermore, we intend to present some evidence on the role of these markers in future targets, such as histological and transmural healing. Additional prospective multicenter studies with a stricter MH criterion, standardized endoscopic and histopathological analyses, and virtual chromoscopy, potentially including artificial intelligence and other biomarkers, are desired.

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.

Inflammatory bowel disease (IBD) is a chronic and relapsing immune-mediated disease of the gastrointestinal tract with a gradually increasing global incidence and prevalence. A prolonged course of IBD leads to a decline in patient quality of life and the creation of a substantial economic burden on society. Owing to the lack of specific diagnostic markers, the diagnosis of IBD still needs a gold standard based on a combination of clinical manifestations, imaging, laboratory, and endoscopic results. Accordingly, the current goals of IBD treatment are to alleviate clinical symptoms and reduce recurrence rates. Therefore, it is imperative to develop a standard set of procedures to diagnose and treat IBD. In this review, we summarize prominent and emerging studies, outline classical and contemporary approaches to diagnosing and managing IBD, and integrate multiple guidelines. Furthermore, we propose the possibility of establishing an early and comprehensive diagnostic workflow and personalized management strategy in the future. We aim to enhance the quality and standardization of diagnostic and treatment procedures for IBD.

The value of lower gastrointestinal endoscopy (LGIE; colonoscopy or sigmoidoscopy) relates to its ability to detect clinically relevant findings, predominantly cancers, preneoplastic polyps or inflammatory bowel disease. There are concerns that many LGIEs are performed on low-risk patients with limited benefit.

To determine the diagnostic outcomes of LGIE for common symptoms.

We performed a cross-sectional study of diagnostic LGIE between March 2019 and February 2020 using the UK National Endoscopy Database. We used mixed-effects logistic regression models, incorporating random (endoscopist) and fixed (symptoms, patient age, and sex) effects upon two dependent variables (large polyp [≥10 mm] and cancer diagnosis). Adjusted positive predictive values (aPPVs) were calculated.

We analysed 384,510 LGIEs; 33.2% were performed on patients aged under 50 and 53.6% on women. Regarding colonoscopies, the unadjusted PPV for cancer was 1.5% (95% CI: 1.4-1.5); higher for men than women (1.9% vs. 1.1%, p < 0.01). The PPV for large polyps was 3.2% (95% CI: 3.1-3.2). The highest colonoscopy cancer aPPVs were in the over 50s (1.9%) and in those with rectal bleeding (2.5%) or anaemia (2.1%). Cancer aPPVs for other symptoms were <1% despite representing 54.3% of activity. In patients under 50, aPPVs were 0.4% for cancer and 1.6% for large polyps. Results were similar for sigmoidoscopy.

Most colonoscopies were performed on patients with low-risk symptoms, where cancer risk was similar to the general population. Cancer and large polyp yield was highest in elderly patients with rectal bleeding or anaemia, although still fell short of FIT-based screening yields.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.

We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.

This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.

NCT05414578; Pre-results.

Collagenous gastritis is a rare and chronic inflammatory condition of undetermined etiology characterized histologically by thickened subepithelial collagen bands and increased intraepithelial lymphocytes. Here, we present a collagenous gastritis case in a 16-year-old female with chronic abdominal pain, persistently elevated fecal calprotectin (507 and 796 mcg/g), and resolved iron deficiency anemia. The patient's history, laboratory tests, endoscopy, and magnetic resonance imaging ruled out common causes of elevated fecal calprotectin, including Helicobacter pylori and gastrointestinal infections, medications, celiac disease, and inflammatory bowel disease, as well as less common causes such as collagenous colitis. Esophagogastroduodenoscopy revealed significant antral nodularity. Gastric biopsies showed thickened subepithelial collagen band and surface epithelium damage with increased intraepithelial lymphocytes. The ileocolonoscopy was normal. This is among the first reported cases of collagenous gastritis with elevated fecal calprotectin levels that could solely be attributed to this condition.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract that might lead to progressive bowel damage and disability. The exact cause of Crohn's disease is unknown, but evidence points towards multifactorial events causing dysregulation of the innate immune system in genetically susceptible people. Commonly affecting the terminal ileum and proximal colon, Crohn's disease inflammation is often discontinuous and patchy, segmental, and transmural. Identification of characteristic findings on ileocolonoscopy and histology remains the diagnostic gold standard, but complete assessment involves laboratory abnormalities, including micronutrient deficiencies, cross-sectional imaging to identify transmural disease extent, severity and complications, and a psychosocial assessment. Treatment strategies for patients with Crohn's disease now go beyond achieving clinical remission to include deeper targets of endoscopic healing and consideration of adjunctive histological and transmural targets to alter disease progression potentially further. The use of early effective advanced therapies and development of therapies targeting alternative novel pathways with improved safety profiles have resulted in a new era of healing in Crohn's disease management. Future combination of advanced therapies with diet or other biological drugs and small molecules, together with improvements in tight control monitoring tools and predictive biomarkers might continue to improve outcomes for patients with Crohn's disease.

Ulcerative colitis (UC) is a serious inflammatory bowel disease (IBD) with high morbidity and mortality worldwide. As the traditional diagnostic techniques have various limitations in the practice and diagnosis of early ulcerative colitis, it is necessary to develop new diagnostic models from molecular biology to supplement the existing methods. In this study, we developed a machine learning-based synthesis to construct an artificial intelligence diagnostic model for ulcerative colitis, and the correctness of the model is verified using an external independent dataset. According to the significantly expressed genes related to the occurrence of UC in the model, an unsupervised quantitative ulcerative colitis related score (UCRScore) based on principal coordinate analysis was established. The UCRScore is not only highly generalizable across UC bulk cohorts at different stages, but also highly generalizable across single-cell datasets, with the same effect in terms of cell numbers, activation pathways and mechanisms. As an important role of screening genes in disease occurrence, based on connectivity map analysis, 5 potential targeting molecular compounds were identified, which can be used as an additional supplement to the therapeutic of UC. Overall, this study provides a potential tool for differential diagnosis and assessment of bio-pathological changes in UC at the macroscopic level, providing an opportunity to optimize the diagnosis and treatment of UC.

Fecal calprotectin (FC) is a promising biomarker for diagnosis and treatment of inflammatory bowel disease, ulcerative colitis (UC), and Crohn's disease. An enzyme immunoassay (EIA) is widely used for FC detection, though the considerable lag time, up to several days, causes clinical management delay. This study was performed to examine the new rapid kit fCAL-turbo, which is based on a particle-enhanced turbidimetric immunoassay (15 min), by comparing FC values with other EIAs (EliA, PhiCal, Bühlmann) and endoscopic scores. Using 94 samples, fCAL-turbo showed strong significant positive correlations with the other kits (Spearman's r = 0.9178-0.9886). Of 74 UC patients, 69 underwent an endoscopy and fCAL-turbo reflected endoscopic activity with a moderate correlation with Mayo endoscopic subscore (MES) (r = 0.6945, others r = 0.6682-0.7013). Receiver operating characteristic analyses based on MES 0 versus 1-3 showed a similar efficacy as compared to the other kits (cut-off and area under the curve: 89.70 µg/g and 0.8592, respectively, others 62.35-138.4 µg/g and 0.8280-0.8611, respectively). Furthermore, multiple regression analysis confirmed that fCAL-turbo results significantly contributed to prediction of MES 0 with a higher t-value as compared to the other biomarkers. fCAL-turbo showed strong correlations with the other kits and also demonstrated excellent performance for predicting endoscopic remission of UC.

Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract.

We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279).

There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]).

All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults.

There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.

Symptoms of inflammatory bowel disease (IBD) often overlap with those of irritable bowel syndrome (IBS).

To evaluate the diagnostic performance of faecal calprotectin in distinguishing patients with IBD from those with IBS METHODS: We searched MEDLINE, Embase, Scopus, and Cochrane Library databases up to 1 January 2023. Studies were included if they assessed the diagnostic performance of faecal calprotectin in distinguishing IBD from IBS (defined according to the Rome criteria) using colonoscopy with histology or radiology as reference standard in adults. We calculated summary sensitivity and specificity and their 95% confidence intervals (CI) using a random-effect bivariate model. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies II.

We included 17 studies with a total of 1956 patients. The summary sensitivity was 85.8% (95% CI: 78.3-91), and the specificity was 91.7% (95% CI: 84.5-95.7). At a prevalence of IBD of 1%, the negative predictive value was 99.8%, while the positive predictive value was only 9%. Subgroup analyses showed a higher sensitivity in Western than in Eastern countries (88% vs 73%) and at a cut-off of ≤50 μg/g than at >50 μg/g (87% vs. 79%), with similar estimates of specificity. All studies were at "high" or "unclear" risk of bias.

Faecal calprotectin is a reliable test in distinguishing patients with IBD from those with IBS. Faecal calprotectin seems to have a better sensitivity in Western countries and at a cut-off of ≤50 μg/g.

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been identified as potential inflammatory biomarkers. In this work we aimed to analyze whether the hematological composite scores differ between inflammatory bowel disease (IBD) patients and healthy controls, and if they are related to disease activity. A total of 197 IBD patients-130 Crohn's (CD) disease and 67 ulcerative colitis (UC)-and 208 age- and sex-matched healthy controls were enrolled. C-reactive protein and fecal calprotectin were assessed. Multivariable linear regression analysis was executed. After adjustment, NLR and PLR, but not SIRI and MLR, were significantly higher in IBD patients compared to controls. C-reactive protein and SIRI and NLR were correlated in IBD patients. However, fecal calprotectin was not related to any of these blood scores. Furthermore, disease activity parameters were not associated with any of the blood composite scores in both CD and UC patients. In conclusion, NLR and PLR, but not SIRI and MLR, are independently higher in IBD patients compared to controls. However, the four hematological scores are not related to disease activity in either CD or UC patients. Based on these results, blood-based inflammatory scores may not serve as subrogated biomarkers of disease activity in IBD.

Age-related disease may be mediated by low levels of chronic inflammation ("inflammaging"). Recent work suggests that gut microbes can contribute to inflammation via degradation of the intestinal barrier. While aging and age-related diseases including Alzheimer's disease (AD) are linked to altered microbiome composition and higher levels of gut microbial components in systemic circulation, the role of intestinal inflammation remains unclear. To investigate whether greater gut inflammation is associated with advanced age and AD pathology, we assessed fecal samples from older adults to measure calprotectin, an established marker of intestinal inflammation which is elevated in diseases of gut barrier integrity. Multiple regression with maximum likelihood estimation and Satorra-Bentler corrections were used to test relationships between fecal calprotectin and clinical diagnosis, participant age, cerebrospinal fluid biomarkers of AD pathology, amyloid burden measured using 11C-Pittsburgh compound B positron emission tomography (PiB PET) imaging, and performance on cognitive tests measuring executive function and verbal learning and recall. Calprotectin levels were elevated in advanced age and were higher in participants diagnosed with amyloid-confirmed AD dementia. Additionally, among individuals with AD dementia, higher calprotectin was associated with greater amyloid burden as measured with PiB PET. Exploratory analyses indicated that calprotectin levels were also associated with cerebrospinal fluid markers of AD, and with lower verbal memory function even among cognitively unimpaired participants. Taken together, these findings suggest that intestinal inflammation is linked with brain pathology even in the earliest disease stages. Moreover, intestinal inflammation may exacerbate the progression toward AD.