Crohn's Colitis Research Articles

Isongifolene Improves Crohn's Disease-Like Colitis in Mice by Reducing Apoptosis of Intestinal Epithelial Cells

To investigate the effect and molecular mechanism of isolongifolene (ISO) on the apoptosis of intestinal epithelial cells and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD)-like colitis in mice. In the animal experiments, mice were randomly assigned to the wild type (WT) group, TNBS group and TNBS+ISO group, with 8 mice in each group. Colitis models of mice were established in the TNBS group and the TNBS+ISO group by rectal injection of TNBS. After modeling, the mice in the TNBS+ISO group were given ISO intervention via intragastric gavage (10 mg/kg), and the other two groups were given the same amount of normal saline via intragastric gavage. The mice were sacrificed on the 7th day. The changes in body mass, disease activity scores (DAI), and the colon length of mice were measured, and transepithelial electrical resistance (TEER) of the colon tissues was determined. The score of colon inflammation was calculated according to HE staining. The levels of intestinal mucosal inflammatory factors, including tumor necrosis factor alpha (TNF-α), interferon (IFN)-γ, interleukin (IL)-1β, and IL-6, were measured by RT-PCR and ELISA. The apoptosis of colon tissue cells was determined by TUNEL assay. The expressions of apoptotic proteins (cleaved caspase-3/caspase-3 and Bax), an anti-apoptotic protein (Bcl-2), and tight junction proteins (ZO-1 and claudin-1) were detected by Western blot and immunofluorescence. In the cell experiment, TNF-α was used to induce intestinal epithelial cell Caco-2 apoptosis model, which was treated with ISO. Then, intervention with the AMPK inhibitor Compound C was given. TUNEL assay, Western blot assay, and immunofluorescence assay were performed to measure apoptosis and the expression of apoptosis proteins in the Caco-2 cells. Gene Ontology (GO) enrichment analysis was performed to predict the biological function of ISO. Then, the mechanism involved was verified by examination of the mice and Caco-2 cells. Western blot was performed to determine the expression levels of p-AMPK/AMPK and p-PGC1α in the colon tissues from the mice of different groups and Caco-2 cells. The apoptosis of the cells was determined by TUNEL assay. According to the results of the animal experiment, ISO could alleviate experimental colitis and intestinal barrier dysfunction, leading to improvements in body mass loss, colon length shortening, DAI score, inflammatory rating, and TEER values (all P<0.05) in mice. Furthermore, ISO decreased the expression of pro-inflammatory factors TNF-α, IFN-γ, IL-1β, and IL-6 and increased the expression of the tight junction proteins ZO-1 and claudin-1 (all P<0.05). In the cell experiment, in a TNF-α-induced intestinal epithelial cell model, ISO was also found to protect intestinal barrier against damage. ISO reduced the proportion of apoptotic intestinal epithelial cells, reduced the expression of cleaved-caspase-3/caspase-3 and Bax, and upregulated the level of Bcl-2 (all P<0.05). GO enrichment predictive analysis showed that the role of ISO in improving CD-like enteritis might be associated with the negative regulation of apoptosis. Verification of the mechanism showed that the expression of p-AMPK and p-PGC1α in the mice colon tissue was significantly upregulated after ISO intervention (P<0.05). In contrast, the AMPK inhibitor Compound C increased the apoptosis rate of ISO-treated Caco-2 cells and decreased the relative expression levels of ZO-1 and claudin-1 (P<0.05). ISO reduces intestinal epithelial cell apoptosis at least in part by activating AMPK/PGC1α signaling pathway, thereby alleviating TNBS-induced intestinal barrier dysfunction and CD-like colitis in mice.

Targeting TNF/TNFR superfamilies in immune-mediated inflammatory diseases.

Dysregulated signaling from TNF and TNFR proteins is implicated in several immune-mediated inflammatory diseases (IMIDs). This review centers around seven IMIDs (rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, psoriasis, atopic dermatitis, and asthma) with substantial unmet medical needs and sheds light on the signaling mechanisms, disease relevance, and evolving drug development activities for five TNF/TNFR signaling axes that garner substantial drug development interest in these focus conditions. The review also explores the current landscape of therapeutics, emphasizing the limitations of the approved biologics, and the opportunities presented by small-molecule inhibitors and combination antagonists of TNF/TNFR signaling.

The Diagnostic Accuracy of Colon Capsule Endoscopy in Inflammatory Bowel Disease-A Systematic Review and Meta-Analysis.

Colon capsule endoscopy (CCE) has regained popularity for lower gastrointestinal investigations since the COVID-19 pandemic. While there have been systematic reviews and meta-analyses on colonic polyp detection using CCE, there is a lack of comprehensive evidence concerning colonic inflammation. Therefore, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of CCE for colonic inflammation, predominantly ulcerative colitis (UC) and Crohn's disease (CD). Methods: We systematically searched electronic databases (EMBASE, MEDLINE, PubMed Central, and Cochrane Library) for studies comparing the diagnostic accuracy between CCE and optical endoscopy as the standard reference. A bivariate random effect model was used for the meta-analysis. Results: From 3797 publications, 23 studies involving 1353 patients were included. Nine studies focused on UC, and ten focused on CD. For UC, CCE showed a pooled sensitivity of 92% (95% CI, 88-95%), a specificity of 71% (95% CI, 35-92%), and an AUC of 0.93 (95% CI, 0.89-0.97). For CD, the pooled sensitivity was 92% (95% CI, 89-95%), and the specificity was 88% (95% CI, 84-92%), with an AUC of 0.87 (95% CI, 0.76-0.98). Overall, for inflammatory bowel disease, the pooled sensitivity, specificity, and AUC were 90% (95% CI, 85-93%), 76% (95% CI, 56-90%), and 0.92 (95% CI, 0.94-0.97), respectively. Conclusions: Despite the challenges around standardised disease scoring and the lack of histological confirmation, CCE performs well in diagnosing inflammatory bowel disease. It demonstrates high sensitivity in both UC and Crohn's terminal ileitis and colitis and high specificity in Crohn's disease. Further studies are needed to evaluate the diagnostic accuracy of other colonic inflammatory conditions.

Unique sterol metabolite shifts in inflammatory bowel disease and primary sclerosing cholangitis

Inflammatory bowel disease (IBD) triggers chronic intestinal inflammation and is linked to primary sclerosing cholangitis (PSC). Cholesterol homeostasis, tightly regulated under normal conditions, becomes disrupted in both inflammation and chronic liver disease. We analyzed fecal and serum levels of cholesterol synthesis precursors, oxysterols, and phytosterols in 87 patients with IBD (81 for serum analysis) including patients with Crohn's disease (CD) and ulcerative colitis (UC), 11 patients with PSC, 21 patients with PSC-IBD (18 for serum analysis), and 16 healthy controls (17 for serum analysis). Cholesterol was analysed by flow injection analysis on a high-resolution hybrid quadrupole-Orbitrap mass spectrometer and further serum sterols and all fecal sterols were analysed by a gas chromatograph mass spectrometer. Serum levels of lanosterol, 7-dehydrocholesterol, 7-beta-hydroxycholesterol, 27-hydroxycholesterol, and the plant sterols campesterol, stigmasterol, and sitosterol were similar across control and patient groups. Notably, serum lathosterol was elevated in CD patients compared to those with UC, PSC, PSC-IBD, and healthy controls. All other serum and fecal sterols showed no differences between CD and UC. Cholesterol synthesis precursors in serum, serum cholesterol levels, and both serum and fecal plant sterol levels decreased with increasing IBD severity. Consequently, serum cholesterol, campesterol, sitosterol, and fecal 5-beta sitostanol and 5-alpha sitostanol were negatively correlated with C-reactive protein and fecal calprotectin. The conversion of cholesterol to coprostanol in feces was impaired in IBD, PSC, and PSC-IBD, independent of bowel inflammation severity or liver disease extent. Patients with PSC, and to a lesser extent PSC-IBD, had elevated serum plant sterol levels, positively correlating with liver disease markers. In conclusion, in patients with IBD, cholesterol biosynthetic precursors, serum cholesterol levels, and fecal plant sterols decrease with intestinal inflammation. An inverse association of serum plant sterols with intestinal inflammation was observed in patients with IBD and a direct association of serum phytosterols with liver injury in patients with PSC. The conversion of fecal cholesterol to coprostanol was impaired in all patient cohorts. IBD and PSC alter serum sterol levels differently, whereas changes in fecal sterols are not disease specific and are moderate.

Microbiome- and Host Inflammasome-Targeting Inhibitor Nanoligomers Are Therapeutic in the Murine Colitis Model.

Autoimmune and autoinflammatory diseases account for more than 80 chronic conditions affecting more than 24 million people in the US. Among these autoinflammatory diseases, noninfectious chronic inflammation of the gastrointestinal (GI) tract causes inflammatory bowel diseases (IBDs), primarily Crohn's and ulcerative colitis (UC). IBD is a complex disease, and one hypothesis is that these are either caused or worsened by compounds produced by bacteria in the gut. While traditional approaches have focused on pan immunosuppressive techniques (e.g., steroids), low remission rates, prolonged illnesses, and an increased frequency of surgical procedures have prompted the search for more targeted and precision therapeutic approaches. IBD is a complex disease resulting from both genetic and environmental factors, but several recent studies have highlighted the potential pivotal contribution of gut microbiota dysbiosis. Gut microbiota are known to modulate the immune status of the gut by producing metabolites that are encoded in biosynthetic gene clusters (BGCs) of the bacterial genome. Here, we show a targeted and high-throughput screening of more than 90 biosynthetic genes in 41 gut anaerobes, through downselection using available bioinformatics tools, targeted gene manipulation in these genetically intractable organisms using the Nanoligomer platform, and identification and synthesis of top microbiome targets as a Nanoligomer BGC cocktail (SB_BGC_CK1, abbreviated as CK1) as a feasible precision therapeutic approach. Further, we used a host-directed immune target screening to identify the NF-κB and NLRP3 cocktail SB_NI_112 (or NI112 for short) as a targeted inflammasome inhibitor. We used these top two microbe- and host-targeted Nanoligomer cocktails in acute and chronic dextran sulfate sodium (DSS) mouse colitis and in TNFΔARE/+ transgenic mice that develop spontaneous Crohn's like ileitis. The mouse microbiome was humanized to replicate that in human IBD through antibiotic treatment, followed by mixed fecal gavage from 10 human donors and spiked with IBD-inducing microbial species. Following colonization, colitis was induced in mice using 1 week of 3% DSS (acute) or 6 weeks of 3 rounds of 2.5% DSS induction for a week followed by 1 week of no DSS (chronic colitis model). Both Nanoligomer cocktails (CK1 and NI112) showed a strong reduction in disease severity, significant improvement in disease histopathology, and profound downregulation of disease biomarkers in colon tissue, as assessed by multiplexed ELISA. Further, we used two different formulations of intraperitoneal injections (IP) and Nanoligomer pills in the chronic DSS colitis model. Although both formulations were highly effective, the oral pill formulation demonstrated a greater reduction in biochemical markers compared to IP. A similar therapeutic effect was observed in the TNFΔARE/+ model. Overall, these results point to the potential for further development and testing of this inflammasome-targeting host-directed therapy (NI112) and more personalized microbiome cocktails (CK1) for patients with recalcitrant IBD.

Mortality Trends in Inflammatory Bowel Disease by Age, Sex, and Race in the United States from 1999 to 2020.

The prevalence and disease course of inflammatory bowel disease (IBD) have evolved over the years. It is unknown how these factors have impacted all-cause mortality. Our study assesses IBD mortality trends in the United States over 20 years by age, sex, and race. We used the Centers for Disease Control Wide-Ranging OnLine Data for Epidemiologic Research database for multiple causes of death in Crohn's disease (CD) and ulcerative colitis (UC) from 1999 to 2020. Age-adjusted mortality rates (AAMR) and crude mortality rates per 100 000 population were obtained. Joinpoint Analysis Software was used for annual percentage change (APC) overall and by age, sex, and race (White and Black). Overall AAMR in CD and UC were 0.79 and 0.53, respectively. All-cause mortality was stable from 1999 to 2018. There was a significant rise in APC from 2018 to 2020 (CD vs. UC, +11.28 vs. +9.29). This rise was observed across both races, sexes, and ages ≥45 years in the last 2-4 years of the study. AAMR in females compared with males varied in CD (0.81 vs. 0.79) and UC (0.45 vs. 0.62). White adults had higher AAMR than Black adults in both CD (0.94 vs. 0.50) and UC (0.58 vs. 0.28). The crude mortality rate increased with age and was highest in those ≥85 years (CD vs. UC, 5.07 vs. 5.23). All-cause mortality trends in IBD were stable until 2018 and rose between 2018 and 2020. Mortality rates were higher amongst the elderly and White adults. Females with CD and males with UC had higher mortality rates.

Development of dual GPBAR1 agonist and RORγt inverse agonist for the treatment of inflammatory bowel diseases

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic disorders characterized by dysregulated immune response and persistent inflammation. Recent studies suggest that bile acid receptors, particularly GPBAR1, and the transcription factor RORγt play critical roles in modulating intestinal inflammation. This study evaluates the therapeutic potential of PBT002, a dual GPBAR1 agonist and RORγt inverse agonist, in IBD models. The effects of PBT002 were assessed through in vitro and in vivo experiments. Macrophages and T lymphocytes obtained from the buffy coat were exposed to PBT002 to evaluate its immunomodulatory activity. The beneficial effects in vivo were evaluated in mouse models of colitis induced by TNBS, DSS or DSS + IL-23 using also a Gpbar1 knock-out male mice. PBT002 exhibited an EC50 of 1.2 µM for GPBAR1 and an IC50 of 2.8 µM for RORγt. In in vitro, PBT002 modulated macrophage polarization towards an anti-inflammatory M2 phenotype and reduced Th17 cell markers while increasing Treg markers. In the TNBS-induced colitis model, PBT002 reduced weight loss, CDAI, and colon damage, while it modulated cytokine gene expression towards an anti-inflammatory profile. In GPBAR1-/-, the anti-inflammatory effects of PBT002 were attenuated, indicating partial GPBAR1 dependence. RNA sequencing revealed significant modulation of inflammatory pathways by PBT002. In DSS+IL-23 induced colitis, PBT002 mitigated disease exacerbation, reducing pro-inflammatory cytokine levels and immune cell infiltration. In conclusion, PBT002, a GPBAR1 agonist and RORγt inverse agonist, modulates both the innate and adaptive immune responses to reduce inflammation and disease severity in models of IBD.

A PhD completed. Oral manifestations in inflammatory bowel diseases

Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. In addition to bowel symptoms, patients may also have oral manifestations. This thesis investigated potential associations between disease activity in the gut, oral health, salivary gland function, and saliva composition. Patients with Crohn's disease had a significantly higher DMFT index, but showed no difference in periodontal diseases compared to a healthy control group. The saliva composition in patients with active bowel disease differed from that in patients with inactive bowel disease, suggesting that saliva analysis could potentially be used in the future to determine the degree and severity of bowel disease. The knowledge of gastroenterologists and dentists regarding oral manifestations of bowel diseases was found to be limited. Gastroenterologists and dentists valued interdisciplinary patient consultation as very useful, but the frequency of consultation was considered insufficient.

Gastrointestinal adverse effects associated with the use of isotretinoin in the management of acne vulgaris

Introduction: Isotretinoin is widely used in the treatment of moderate to severe acne vulgaris due to its proven efficacy. However, the use of this medication is associated with several adverse effects, including gastrointestinal symptoms. The possible association with inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis remains a subject of debate. Methods: A systematic review of the literature was performed in the PubMed, Embase and Cochrane Library databases, covering studies published from 2000 to 2024. The inclusion criteria considered randomized clinical trials, cohort studies, case-control studies and systematic reviews that reported gastrointestinal adverse effects related to the use of isotretinoin. The assessment of methodological quality was performed using the GRADE system, and the data were extracted independently by two reviewers. Results: The review found that mild gastrointestinal side effects, such as abdominal pain, nausea, and dyspepsia, are relatively common during isotretinoin treatment and tend to be transient and manageable. The association with inflammatory bowel disease remains unclear, with some studies indicating an increased risk, while others found no significant correlation. Risk factors such as high dose, prolonged duration of treatment, and history of previous gastrointestinal disease were associated with an increased likelihood of adverse effects. Conclusion: Although isotretinoin remains an effective treatment for acne vulgaris, its use should be accompanied by close monitoring, especially in patients with identified risk factors. A personalized approach is essential to maximize benefits and minimize risks. Future research should focus on identifying predictive risk factors to optimize treatment safety.

Improving access to inflammatory bowel disease care in Canada: The patient experience.

Canada has one of the highest age-adjusted incidence and prevalence rates of inflammatory bowel disease (IBD). Large patient volumes and limited resources have created challenges concerning the quality of IBD care, but little is known about patients' experiences. This paper aimed to better understand patient-perceived barriers to IBD care. An exploratory qualitative approach was used for this study. Fourteen focus groups (with 63 total participants) were co-facilitated by a researcher and patient research partner across eight Canadian provinces in 2018. Patients diagnosed with IBD (>18 years of age) and their caregivers were purposefully recruited through Crohn's and Colitis Canada, gastroenterology clinics and communities, and national social media campaigns. Focus group sessions were recorded, transcribed, and analyzed using thematic analysis. Most participants self-identified as being white and women. The analysis generated four key themes regarding patient-perceived barriers and gaps in access to IBD care: (1) gatekeepers and their lack of IBD knowledge, (2) expenses and time, (3) lack of holistic care, and (4) care that is not patient-centered. An additional four themes were generated on the topic of patient-perceived areas of health system improvement for IBD care: (1) direct access to care, (2) good care providers, (3) electronic records and passports, and (4) multidisciplinary care or an 'IBD dream team'. This research contributes to the limited global knowledge on patients' experiences accessing IBD care. It is valuable for the development of care plans and policies to target gaps in care. Patients have identified system-level barriers and ideas for improvement, which should be taken into consideration when implementing system redesign and policy change.

Maximizing Treatment Options for IBD through Drug Repurposing.

Chronic inflammation characterizes Inflammatory Bowel Disease (IBD), encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC). Despite modest activity of disease in most UC patients, exacerbations occur, especially in those with severe symptoms, necessitating interventions, like colectomy. Current treatments for IBD, predominantly small molecule therapies, impose significant economic burdens. Drug repurposing offers a cost-effective alternative, leveraging existing drugs for novel therapeutic applications. This approach capitalizes on shared molecular pathways across diseases, accelerating therapeutic discovery while minimizing costs and risks. This article provides an overview of IBD and explores drug repurposing as a promising avenue for more effective and affordable treatments. Through computational and animal studies, potential drug candidates are categorized, offering insights into IBD pathogenesis and treatment strategies.

Intestinal flora and inflammatory bowel disease: Causal relationships and predictive models

BackgroundInflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is significantly influenced by intestinal flora. Understanding the genetic and microbiotic interplay is crucial for IBD prediction and treatment. MethodsWe used Mendelian randomization (MR), transcriptomic analysis, and machine learning techniques, integrating data from the MiBioGen Consortium and various GWAS datasets. SNPs associated with intestinal flora were mapped to genes, with LASSO regression refining gene selection. Differentially expressed genes (DEGs) and immune infiltration patterns were identified through transcriptomic analysis. Six machine learning models were used for predictive modeling. FindingsMR analysis identified 25 gut microbiota classifications causally related to IBD. SNP mapping and gene expression analysis highlighted 24 significant genes. Drug target MR and colocalization validated these genes' causal relationships with IBD. Key pathways identified included the PI3K-Akt signaling pathway and epithelial-mesenchymal transition. Immune infiltration analysis revealed distinct patterns between high and low LASSO score groups. Machine learning models demonstrated high predictive value, with soft voting enhancing reliability. InterpretationBy integrating MR, transcriptomic analysis, and sophisticated machine learning approaches, this study elucidates the causal relationships between intestinal flora and IBD. The application of machine learning not only enhanced predictive modeling but also offered new insights into IBD pathogenesis, highlighted potential therapeutic targets, and established a robust framework for predicting IBD onset.

Outpatient use of antibiotics in uncomplicated diverticulitis decreases hospital admissions.

Recently, antibiotics use in uncomplicated acute diverticulitis (AD) has been controversial in Europe. The American Gastroenterological Association (AGA) in their 2015 guidelines recommend their selective use. Our study highlights their role in outpatient management. We queried the Diamond Network through TriNetX-Research Network including 92 healthcare organizations. We included large intestine diverticulitis without perforation, abscess or bleeding. Exclusion criteria included any of sepsis criteria, CRP > 15 mg/L, immunodeficiency or HIV, coronary artery disease, chronic kidney disease, history of Crohn's disease or ulcerative colitis, heart failure, hypertension, diabetes or any of the following in the 3 months before study date; clostridium difficile (C. diff) infection, diverticulitis or antibiotics. Patients with AD were divided into two cohorts; patients on antibiotics, and patients not on antibiotics. Cohorts were compared after propensity-score matching (PSM). 214,277 patients met inclusion criteria. 58.9% received antibiotics, and 41% did not. After PSM, both cohorts had 84,320. Rate of hospital admission was lower in the antibiotic group (3.3% vs 4.2%, p < .001). There was a statistical difference between ICU admission (0.1% vs 0.15%, p < .01) and the rate of bowel perforation, peritonitis, abscess formation or bleeding (1.3% vs 1.4%, p = .044). There was no difference in mortality (0.1% vs 0.1%, p = .11), C. diff (0.1% vs 0.1%, p = .9), colectomies (0.2% vs 0.2%, p = .33), or Acute Kidney Injury (AKI) (0.1% vs 0.1%, p = .28). Outpatient use of antibiotics in patients with uncomplicated AD is associated with lower rates of hospital admissions and complications without changing mortality rate or surgical intervention.

Incidence and risk factors for thromboembolic events in pediatric-onset inflammatory bowel disease: A French population-based study

IntroductionPatients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis. MethodsAll patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included. ResultsA total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002). ConclusionThe risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization.

Analysis of excessive corticosteroid use as an indicator of poor quality of care in patients with inflammatory bowel disease.

To evaluate the clinical impact of corticosteroids (CS) overuse in inflammatory bowel disease (IBD) patients. Excessive use of CS could delay more efficacious treatment and may indicate poor quality of care. This is a two-phase study that used Steroid Assessment Tool (SAT) to measure corticosteroid exposure in IBD patients. In the first phase, data from 211 consecutive ambulatory patients with IBD (91 with ulcerative colitis, 115 with Crohn's disease, and five with unclassified inflammatory bowel disease) were analysed by SAT. In the second phase, one year after data entry, clinical outcome of patients with corticosteroids overuse was analysed. Of the 211 IBD patients, 132 (62%) were not on corticosteroids, 45 (22%) were corticosteroid-dependent, and 34 (16%) used corticosteroids appropriately, according to the European Crohn's and Colitis Organization guidelines. In the group of patients with ulcerative colitis, 57 (63%) were not on corticosteroids, 18 (20%) were corticosteroid-dependent, and 16 (16%) used corticosteroids appropriately; in the group of patients with Crohn's disease 70 (61%), 27 (23%) and 18 (16%), respectively. Overall, 24 (out of 45; 53%) patients with IBD could avoid the overuse of corticosteroids if they had a timely change of the treatment, surgery, or entered a clinical trial. An excessive corticosteroid use can be recognized on time using the SAT. We have proven that excessive corticosteroid use could be avoided in almost half of cases and thus the overuse of CS may indicate poor quality of care in those patients.

Preventing Recurrence of Crohn's Disease Post-Ileocaecal Surgery in Paediatric Patients: A Therapy Guide Based on Systematic Review of the Evidence.

Ileocaecal resection (ICR) is frequent in paediatric patients with Crohn's disease (pCD). Despite rates of reoperation being low, the risk of clinical or endoscopic post-operative recurrence (POR) is high; effective medical strategies to prevent POR are thus needed. The aim of this systematic review(SR) was to identify and evaluate the published literature on post-operative medical prevention of POR in pCD to draft a possible therapy guide for pCD patients undergoing ICR. We performed an SR according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and registered it in the PROSPERO database (ID: CRD42024533855). The population, intervention, control, outcome (PICO) model was focussed on post-surgical medical prevention of POR in pCD with clearly expressed definition of recurrence (endoscopically using a standardized scoring system (e.g. Rutgeerts score) or by laboratory markers, for example, faecal calprotectin (F-CPT), C-reactive protein (CRP) or by histological findings or by clinical activity indexes [e.g. weighted paediatric Crohn's disease activity index - (w)PCDAI]. From inception until 29 February 2024, the following databases were searched: PubMed/MEDLINE, Scopus/Embase, Web of Sciences, Evidence-Based Medicine Reviews (including Cochrane), Cochrane Central Registrar of controlled Trials (CENTRAL), ClinicalTrials.gov and EudraCT. Retrieved articles were evaluated for eligibility and finally selected publications for risk of bias using ROBINS-I tool. Out of 811 publications identified by the search, only 5 fulfilled inclusion criteria of the SR. None of the studies fully answered our PICO question. The studies were overall of poor quality and the heterogeneity of the data did not allow us to perform meta-analysis, detailed statistical analysis or formal synthesis of data. Adverse events of post-operative medication were not described in any of the included studies. Existing guidelines of European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), North American Society for Paediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), European Crohn's and Colitis Organisation (ECCO) and American Gastroenterological Association (AGA) were reviewed and paediatric therapy guide for pCD undergoing ICR was drafted with respect to recent SRs and meta-analyses in adult population and including scarce paediatric data identified by our SR. As pCD patientsundergoing ICR are a high-risk population, they should not be left untreated post-operatively. Anti-tumour necrosis factor (anti-TNF) drugs should be considered as first-line therapy in the majority of patients. Non-anti-TNF biologics should be considered in case of anti-TNF failure. Regular endoscopic monitoring starting at 6 months after the surgery and supported by regular F-CPT evaluation should be used to identify early endoscopic recurrence and to escalate the treatment. Our SR revealed that there is wide variability in treatment strategies in children, and high-quality data are generally lacking. At the moment, paediatric prophylaxis of POR should be guided by available adult evidence with respect to the high-risk nature of pCD. Extensive research in pCD should be encouraged.

Gut bacterial type III secretion systems aggravate colitis in mice and serve as biomarkers of Crohn’s disease

Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat, is a pathologic characteristic of Crohn's disease (CD). In our previously reported cohort, we observed that Achromobacter pulmonis was the most abundant and prevalent bacteria cultivated from creeping fat. A whole genomic sequencing and identification of T3SS orthologs of mAT-derived A. pulmonis were used. A functional type III secretion system (T3SS) mediated the pathogenic potential of A. pulmonis invitro and in mouse colitis model. Furthermore, a T3SS Finder pipeline was introduced to evaluate gut bacterial T3SS orthologs in the feces of CD patients, ulcerative colitis and colorectal cancer patients. Here, we reveal that mAT-derived A. pulmonis possesses a functional T3SS, aggravates colitis in mice via T3SS, and exhibits T3SS-dependent cytotoxicity via a caspase-independent mechanism in macrophages and epithelial cells, which demonstrated the pathogenic potential of the T3SS-harboring A. pulmonis. Metagenomic analyses demonstrate an increased abundance of Achromobacter in the fecal of Crohn's disease patients compared to healthy controls. A comprehensive comparison of total microbial vT3SS abundance in various intestine diseases demonstrated that the specific enrichment of vT3SS genes was shown in fecal samples of CD, neither ulcerative colitis nor colorectal cancer patients, and ten T3SS gene-based biomarkers for CD were discovered and validated in a newly recruited CD cohort. Furthermore, treatment with exclusive enteral nutrition (EEN), an intervention that improves CD patient symptomatology, was found associated with a significant reduction in the prevalence of T3SS genes in fecal samples. These findings highlight the pathogenic significance of T3SSs in the context of CD and identify specific T3SS genes that could potentially function as biomarkers for diagnosing and monitoring the clinical status of CD patients. This work is supported by the National Key Research and Development Program of China (2020YFA0907800), the China Postdoctoral Science Foundation (2023M744089), the National Natural Science Foundation of China (32000096), the Shenzhen Science and Technology Programs (KQTD20200820145822023, RCIC20231211085944057, and ZDSYS20220606100803007), National Key Clinical Discipline, Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), Qingfeng Scientific Research Fund of the China Crohn's & Colitis Foundation (CCCF) (CCCF-QF-2022B71-1), and the Sixth Affiliated Hospital, Sun Yat-sen University Clinical Research 1010 Program 1010CG(2023)-08. These funding provided well support for this research work, which involved data collection, analysis, interpretation, patient recruitment and so on.

Anti-DEFA5 Monoclonal Antibody Clones 1A8 and 4F5 Immunoreactive Bioassay for Diagnosing Inflammatory Bowel Disease.

Robust evidence suggests that the aberrant expression of α defensin 5 protein (DEFA5) in colon inflammatory bowel diseases (IBDs) underlies the distinct pathogenesis of Crohn's colitis, can be exploited as a reliable diagnostic biomarker to differential diagnosis of Crohn's colitis (CC) from Ulcerative colitis (UC) in otherwise indeterminate colitis (IC). We evaluated the specificity of the commercially available anti-DEFA5 antibodies and showed further validation of their appropriateness for a given application is required. We established two mouse monoclonal DEFA5 antibody clones 1A8 and 4F5 by immunizing the mice with purified recombinant protein and validated the specificity, selectivity and cross reactivity in recognizing the endogenous and recombinant DEFA5 protein, especially for Immunohistochemistry, Western blot, Immunoprecipitation, or enzyme-linked immunosorbent assay. Clones 1A8 and 4F5 recognized effectively the endogenous DEFA5 in active human diverticulitis (DV), UC, CC or IC disease samples, including transiently transfected HEK293T cells expressing DEFA5 with high degree of specificity and minimal non-confounding cross reactivity. 1A8 and 4F5 clones are worth studying in larger IBD cohorts to fully address whether DEFA5 expression may be used as a diagnostic biomarker to discrimination of the diagnosis of UC from CC or IC into authentic CC or UC or a colitis with different pathological characteristics.

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

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

Meta-analysis of the Therapeutic Impact of Cannabinoids in Inflammatory Bowel Disease.

With the increasing legalization of medical and recreational cannabis, patients and providers have growing interest in the role of cannabinoids in treating inflammatory bowel disease. Prior meta-analysis has shown inconclusive evidence for efficacy of cannabinoids. We sought to produce an up-to-date meta-analysis that pools new data to evaluate the therapeutic effects of cannabinoids in both Crohn's disease (CD) and ulcerative colitis (UC). PubMed, Embase, CENTRAL and CINAHL were queried for randomized-controlled trials evaluating the impact cannabinoids in CD or UC. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2. Eight studies, including 4 studies of CD, 3 studies of UC, and 1 study of both diseases met inclusion criteria. Among 5 studies of CD, a statistically significant decrease in clinical disease activity following intervention was observed (risk ratios [RR], -0.91; 95% CI, CI:1.54 to CI:0.28, I2 = 71.9%). Clinical disease activity in UC was not significantly lower in the pooled analysis (RR, -2.13; 95% CI, -4.80 to 0.55; I2 = 90.3%). Improvement in quality of life (QoL) was observed in both CD and UC combined (RR, 1.79; 95% CI, 0.92-0.2.66; I2 = 82.8%), as well as individually. No differences were observed in the analysis on endoscopic disease activity and inflammatory markers. This meta-analysis of clinical trials suggests that cannabinoids are associated with improved quality of life in both CD and UC, as well as improved disease activity but not inflammation.