Incidence Of Inflammatory Bowel Disease Research Articles

The relationship between weight change and inflammatory bowel disease. Apopulation-based cohort study, the HUNT study.

The incidence of inflammatory bowel disease (IBD) is increasing. The prevalence of overweight and obesity is increasing in parallel with IBD and could contribute to IBD development. The aim of this study was to assess the relationship between weight change and the risk for IBD. Data gathered from 55,896 adult participants in the three first population-based Trøndelag Health Studies (HUNT1-3), Norway, performed in 1984-2008 was used. The exposure was change in body mass index between two HUNT studies. The outcome was a new IBD diagnosis recorded during a ten-year follow-up period after the exposure assessment. The risk of IBD by weight change was assessed by Cox regression analyses reporting hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for sex, age, and smoking status. There were 334 new cases of ulcerative colitis (UC) and 54 of Crohn's disease (CD). Weight loss decreased the risk of a new UC diagnosis by 38% (adjusted HR 0.62, 95% CI 0.39-0.97) and seemed to double the risk of getting a new CD diagnosis (adjusted HR 2.01, 95% CI 0.91-4.46). Weight gain was not associated with a new diagnosis of neither UC (adjusted HR 1.00, 95% CI 0.78-1.26) nor CD (adjusted HR 1.08, 95% CI 0.56-2.08). In this study, weight loss was associated with decreased risk of UC. However, no associations were seen between weight gain and the risk of UC or CD, suggesting that the increasing weight in the general population cannot explain the increasing incidence of IBD.

Therapeutic Prospects of Mesenchymal Stem Cell and Their Derived Exosomes in the Regulation of the Gut Microbiota in Inflammatory Bowel Disease

Mesenchymal stem cells (MSCs) have shown great potential in the treatment of several inflammatory diseases due to their immunomodulatory ability, which is mediated by exosomes secreted by MSCs (MSC-Exs). The incidence of inflammatory bowel disease (IBD) is increasing globally, but there is currently no long-term effective treatment. As an emerging therapy, MSC-Exs have proven to be effective in alleviating IBD experimentally, and the specific mechanism continues to be explored. The gut microbiota plays an important role in the occurrence and development of IBD, and MSCs and MSC-Exs can effectively regulate gut microbiota in animal models of IBD, but the mechanism involved and whether the outcome can relieve the characteristic dysbiosis necessary to alleviate IBD still needs to be studied. This review provides current evidence on the effective modulation of the gut microbiota by MSC-Exs, offering a basis for further research on the pathogenic mechanism of IBD and MSC-Ex treatments through the improvement of gut microbiota.

Inflammatory Bowel Diseases in the Elderly: A Focus on Disease Characteristics and Biological Therapy Patterns

Background: The incidence of inflammatory bowel diseases (IBDs) in elderly patients is constantly increasing. It results from the combination of an aging population with compounding prevalence of IBD, as well as the growing burden of elderly-onset IBD. The clinical characteristics of elderly patients differ from young subjects with IBD due to the multimorbidity or polypharmacy, affecting the choice of adequate therapeutic options. The aim of this study was to determine the clinical aspects and biological therapy safety in elderly Polish IBD patients. Methods: We conducted a retrospective study aimed at describing the demographic, clinical, and management characteristics of IBD patients treated with a biological therapy in two referral centers within the National Drug Program in Poland. Results: Out of the entire group of 366 studied patients, 51 (13.9%) were aged over 60—32 with ulcerative colitis (UC) and 19 with Crohn’s disease (CD). The disease location was predominantly ileocolonic (57.89%) in patients with CD and pancolitis for patients with UC (56.25%). Most of the elderly IBD subjects were characterized by significant comorbidities, with Charlson Comorbidity Index (CCI) ≥ 1 in 66.67% patients. The probability of stopping biological therapy due to adverse events had the tendency to be higher in the CCI ≥ 1 group (20.58% vs. 5.88% in CCI = 0; p = 0.087). The main reasons for the therapy discontinuation included hypersensitivity reactions and liver enzyme abnormalities. Conclusions: In conclusion, our results underline the importance of assessing the comorbidity status instead of the age prior to initiating biological therapy, analyzing additional safety risks, and close monitoring in IBD patients with multiple comorbidities.

Pediatric to Adult Transition in Inflammatory Bowel Disease: Consensus Guidelines for Australia and New Zealand.

The incidence of pediatric inflammatory bowel disease (IBD) is rising, and there is an increasing need to support adolescents when they transition to adult care. Evidence supports the use of a structured transition process but there is great variation across Australasia. The study aim was to develop evidence and expert opinion-based consensus statements to guide transitional care services in IBD. A modified UCLA-RAND methodology was employed to develop consensus statements. An IBD expert steering committee was formed and a systematic literature review was conducted to guide the drafting of consensus statements. A multidisciplinary group was formed comprising 16 participants (clinicians, nurses, surgeons, psychologists), who anonymously voted on the appropriateness and necessity of the consensus statements using Likert scales (1 = lowest, 9 = highest) with a median ≥7 required for inclusion. Patient support groups, including direct input from young people with IBD, informed the final recommendations. Fourteen consensus statements were devised with key recommendations including use of a structured transition program and transition coordinator, mental health and transition readiness assessment, key adolescent discussion topics, allied health involvement, age for transition, and recommendations for clinical communication and handover, with individualized patient considerations. Each statement reached median ≥8 for appropriateness, and ≥7 for necessity, in the first voting round, and the results were discussed in an online meeting to refine statements. A multidisciplinary group devised consensus statements to optimize pediatric to adult transitional care for adolescents with IBD. These guidelines should support improved and standardized delivery of IBD transitional care within Australasia.

Global Epidemiology and Geographic Variations of Pediatric-Onset Inflammatory Bowel Disease: A Comprehensive Analysis of the Global Burden of Disease Study 1990 to 2019.

An increasing incidence of pediatric-onset inflammatory bowel disease (PIBD) has been reported in many countries. However, the global burden and distribution of this disease remain less understood. We aimed to examine the global epidemiology and trends of PIBD from 1990 to 2019. Data from the 2019 Global Burden of Disease Study, covering 204 countries, were analyzed. We assessed key measures like incidence, prevalence, mortality, and disability-adjusted life years (DALYs) using linear regression to calculate annual percentage changes and assess trends. Between 1990 and 2019, the PIBD incidence rate increased and the DALY rate and mortality rate declined. The incidence rate was notably elevated in the high Socio-demographic Index (SDI) quintile, reaching 6.3 per 100 000 person-years, corresponding to 13 914 new cases in 2019. Incidence and prevalence of PIBD positively correlated with the SDI, while higher death and DALY burdens were observed in lower-SDI countries. In 2019, the top 5 countries with the highest PIBD incidence rates were Canada (19.9 per 100 000 population), Denmark (12.4 per 100 000 population), Hungary (8.5 per 100 000 population), Austria (8.1 per 100 000 population), and the United States (7.4 per 100 000 population). Several countries experienced significant increases in incidence rates from 1990 to 2019, led by Taiwan (annual percent change 4.2%), followed by China (2.8%), Japan (2.1%), Australia (1.8%), and Hungary (1.6%). PIBD incidence has significantly increased since 1990. High-SDI countries face higher incidence, while lower-SDI countries experience higher mortality and DALY burdens. The study underscores the need for ongoing monitoring and research to address this emerging public health issue.

Effects of p-coumaric acid on probiotic properties of Lactobacillus acidophilus LA-5 and lacticaseibacillus rhamnosus GG.

Probiotics are defined as "live microorganisms that provide health benefits to the host when administered in adequate amounts." Probiotics have beneficial effects on human health, including antibacterial activity against intestinal pathogens, regulation of blood cholesterol levels, reduction of colitis and inflammation incidence, regulation of the immune system, and prevention of colon cancer. In addition to probiotic bacteria, some phenolic compounds found in foods we consume (both food and beverages) have positive effects on human health. p-coumaric acid (p-CA) is one of the most abundant phenolic compounds in nature and human diet. The interactions between these two different food components (phenolics and probiotics), resulting in more beneficial combinations called synbiotics, are not well understood in terms of how they will affect the gut microbiota by promoting the probiotic properties and growth of probiotic bacteria. Thus, this study aimed to investigate synbiotic relationship between p-CA and Lactobacillus acidophilus LA-5 (LA-5), Lacticaseibacillus rhamnosus GG (LGG). Probiotic bacteria were grown in the presence of p-CA at different concentrations, and the effects of p-CA on probiotic properties, as well as its in vitro effects on AChE and BChE activities, were investigated. Additionally, Surface analysis was conducted using FTIR. The results showed that treatment with p-CA at different concentrations did not exhibit any inhibitory effect on the growth kinetics of LA-5 and LGG probiotic bacteria. Additionally, both probiotic bacteria demonstrated high levels of antibacterial properties. It showed that it increased the auto-aggregation of both probiotics. While p-CA increased co-aggregation of LA-5 and LGG against Escherichia coli, it decreased co-aggregation against Staphylococcus aureus. Probiotics grown with p-CA were more resistant to pepsin. While p-CA increased the resistance of LA-5 to bile salt, it decreased the resistance of LGG. The combinations of bacteria and p-CA efficiently suppressed AChE and BChE with inhibition (%) 11.04-68.43 and 13.20-65.72, respectively. Furthermore, surface analysis was conducted using FTIR to investigate the interaction of p-coumaric acid with LA-5 and LGG, and changes in cell components on the bacterial surface were analyzed. The results, recorded in range of 4000 -600cm-1 with resolution of 4cm-1, demonstrated that p-CA significantly affected only the phosphate/CH ratio for both bacteria. These results indicate the addition of p-CA to the probiotic growth may enhance the probiotic properties of bacteria.

Anti–Tumor Necrosis Factor Therapy and Risk of Kidney Function Decline and Mortality in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is associated with adverse clinical outcomes, including chronic kidney disease and mortality, due in part to chronic inflammation. Little is known about the effects of anti-tumor necrosis factor (TNF) therapy on kidney disease progression and mortality among patients with new-onset IBD. To examine the association of incident use of TNF inhibitors with subsequent decline in kidney function and risk of all-cause mortality. This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants were US veterans with new-onset IBD enrolled from October 1, 2004, through September 30, 2019. Data were analyzed from December 2022 to February 2024. Incident use of TNF inhibitors. The main outcomes were at least 30% decline in estimated glomerular filtration rate (eGFR) and all-cause mortality. Among 10 689 patients (mean [SD] age, 67.4 [12.3] years; 9999 [93.5%] male) with incident IBD, 3353 (31.4%) had diabetes, the mean (SD) baseline eGFR was 77.2 (19.2) mL/min/1.73 m2, and 1515 (14.2%) were newly initiated on anti-TNF therapy. During a median (IQR) follow-up of 4.1 (1.9-7.0) years, 3367 patients experienced at least 30% decline in eGFR, and over a median (IQR) follow-up of 5.0 (2.5-8.0) years, 2502 patients died. After multivariable adjustments, incident use (vs nonuse) of TNF inhibitors was significantly associated with higher risk of decline in eGFR (adjusted hazard ratio [HR], 1.34 [95% CI, 1.18-1.52]) but was not associated with risk of all-cause mortality (adjusted HR, 1.02 [95% CI, 0.86-1.21]). Similar results were observed in sensitivity analyses. In this cohort study of US veterans with incident IBD, incident use (vs nonuse) of TNF inhibitors was independently associated with higher risk of progressive eGFR decline but was not associated with risk of all-cause mortality. Further studies are needed to elucidate potentially distinct pathophysiologic contributions of TNF inhibitor use to kidney and nonkidney outcomes in patients with IBD.

Immunotherapy-induced colitis in metastatic colorectal cancer: a systematic review and meta-analysis

Colorectal cancer (CRC) presents significant mortality risks, underscoring the urgency of timely diagnosis and intervention. Advanced stages of CRC are managed through chemotherapy, targeted therapy, immunotherapy, radiotherapy, and surgery. Immunotherapy, while effective in bolstering the immune system against cancer cells, often carries toxic side effects, including colitis. This study aimed to evaluate the incidence of colitis in patients with metastatic CRC (mCRC) undergoing various immunotherapy treatments. Through a systematic search of Google Scholar and PubMed databases from inception until November 2023, nine relevant studies were identified. Subgroup analyses revealed a higher incidence of colitis, particularly in patients treated with anti-cytotoxic T-lymphocyte-associated molecule-4 (anti-CTLA-4) and combination therapies compared to monotherapy with programmed cell death receptor-1 (PD-1) or programmed cell death ligand receptor-1 (PDL-1) inhibitors. Notably, naive-treated metastatic CRC patients exhibited elevated colitis incidences compared to those previously treated. In conclusion, anti-CTLA-4 and combination therapies, such as nivolumab plus ipilimumab, were associated with increased colitis occurrences in metastatic CRC patients, highlighting the need for vigilant monitoring and management strategies, especially in immunotherapy-naive individuals.

Crohn’s disease in patients with Hirschsprung disease and Hirschsprung-associated enterocolitis: A review

In the last decade, the incidence of inflammatory bowel disease in children has been increasing. Some studies have reported the development of Crohn’s disease in patients with Hirschsprung disease and Hirschsprung-associated enterocolitis. Suggestions have been made about the possible causes of the development of Crohn’s-like lesions after intestinal resection in early childhood. This study aimed to summarize information about Hirschsprung-associated Crohn’s disease and Crohn’s-like lesions after surgical treatment of Hirschsprung disease. The search was carried out in scientific databases of eLibrary, PubMed, ScienceDirect, and Google Scholar. The search time interval was 2000–2023. Fourteen articles dedicated to Hirschsprung-associated Crohn’s disease were identified. Common pathogenesis factors in inflammatory bowel diseases and Hirschsprung-associated enterocolitis were identified, such as microbiota disturbance and chronic inflammation. Predisposing factors for pathological immune response to dysbiosis and incidence of enterocolitis included enteric nervous system dysfunction, impaired neuroimmune regulatory mechanisms, general immunological disturbance, and “immaturity” and abnormality of the barrier function of the intestinal mucosa. The “classic form” of Crohn’s disease may not develop in patients with Hirschsprung disease and recurrent attacks of enterocolitis but Crohn’s-like lesions. Persistent functional or organic obstruction after surgical treatment of Hirschsprung disease enhances the negative effect of predisposing factors, leading to chronic inflammation of the intestinal mucosa. Delayed occurrence of Hirschsprung-associated enterocolitis is a predisposing factor for the development of chronic inflammation. When Hirschsprung-associated enterocolitis occurs repeatedly, endoscopic assessment should be performed for the exclusion of Crohn’s disease and chronic inflammatory changes in the anastomosis area for treatment selection.

Physical Activity Is Associated With A Decreased Risk Of Developing Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis.

Modifiable risk factors in Inflammatory Bowel Disease (IBD), such as physical activity, may be utilised as prevention strategies. However, the findings of previous studies on the association between physical activity and IBD risk have been inconsistent. We aimed to perform a systematic review and meta-analysis to estimate the effect of physical activity on IBD risk. A search was conducted for relevant studies published before April 2023 that assessed the effect of pre-IBD diagnosis levels of physical activity on IBD incidence. Individual summary statistics (relative risks; RR), and confidence intervals (CI) were extracted with forest plots generated. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. 10 observational studies were included. For cohort studies, there were 1,182 Crohn's disease (CD) and 2,361 ulcerative colitis (UC) patients, with 860,992 participants without IBD. For case-control studies, there were 781 CD to 2,636 controls, and 1,127 UC to 3,752 controls. Compared to individuals with low physical activity levels, the RRs of CD in individuals with high physical activity levels for cohort and case-control studies were 0.78 (95% CI 0.68-0.88, P = 0.0001) and 0.87 (95% CI 0.79-0.95, P = 0.003), respectively. For UC, the RRs were 0.62 (95% CI 0.43-0.88, P = 0.008) and 0.74 (95% CI 0.51-1.07, P = 0.11). This meta-analysis suggests that physical activity is inversely associated with the risk of developing IBD, more so in CD than in UC.

Clinical effectiveness and safety of ustekinumab in youth with refractory inflammatory bowel disease: A retrospective cohort study.

Inflammatory bowel disease (IBD) incidence and prevalence has been increasing worldwide. Limited data exists on the effectiveness of ustekinumab (UST) in children. We aimed to describe the effectiveness and safety of UST in pediatric patients with IBD. A single-center retrospective study was conducted between January 2017 and February 2022. The study included patients ≤16 years of age who were treated with UST and followed up for ≥1 year. Clinical remission was defined as a score of the Pediatric Crohn's Disease (CD) and Pediatric Ulcerative Colitis (UC) Activity Indices ≤10 at week 52. Thirteen patients who had failed anti-tumor necrosis factor-α (anti-TNFα) therapy were included, eight (61.5%) with CD and five (38.5%) with UC. The median age was 13 years (interquartile range [IQR]: 11.5 to 14). UST treatment was initiated at a median age of 3 years (IQR: 2.3 to 7) after diagnosis. Ten patients (76.9%) achieved clinical remission. There were no statistically significant differences in characteristics between patients who achieved and did not achieve clinical remission. Biochemical remission (BioR) was achieved in six patients (46.2%). Body mass index (BMI) significantly improved, C-reactive protein (CRP) significantly decreased, and the need for corticosteroids significantly decreased in the remission group. Endoscopy conducted post-treatment in seven patients confirmed remission in six patients. Adverse events included two cases of infection and one of headache. UST was effective as a secondary biologic therapy for the induction and maintenance of remission in patients with anti-TNFα refractory IBD. At one year, 84% of patients remained on UST with no severe adverse reactions reported.

Sishen Pill and its active phytochemicals in treating inflammatory bowel disease and colon cancer: an overview.

The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects. Common mechanisms in treating IBD and colon cancer mainly include regulating inflammation-related signaling pathways such as nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, NOD-like receptor heat protein domain-related protein 3, and wingless-type MMTV integration site family; NF-E2-related factor 2 and hypoxia-inducible factor 1α to inhibit oxidative stress; mitochondrial autophagy and endoplasmic reticulum stress; intestinal immune cell differentiation and function through the Janus kinase/signal transducer and activator of transcription pathway; and improving the gut microbiota and intestinal barrier. Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required.

Higher incidence of paediatric inflammatory bowel disease by increasing latitude in Norway, but stable incidence by age.

To examine possible geographical and temporal differences in the incidence of childhood-onset inflammatory bowel disease (IBD) in Norway, motivated by previous research indicating relevant environmental factors explaining changing epidemiology. We analysed data from children born in Norway from 2004 to 2012 (n = 541 036) in a registry-based nationwide study. After validating registry diagnoses against medical records, we defined IBD as ≥2 entries of International Classification of Diseases, 10th revision (ICD-10) codes K50, K51 and K52.3 in the Norwegian Patient registry. We estimated hazard ratios (HR) for IBD across four geographical regions with a south-to-north gradient and the incidence by period of birth. By the end of follow-up on 31 December 2020, 799 IBD diagnoses were identified (Crohn's disease: n = 465; ulcerative colitis, n = 293, IBD: unclassified, n = 41). Compared to children in the southernmost region, there was almost a two-fold HR for IBD in children in the most Northern region (HR = 1.94, 95% Cl = 1.47-2.57; Mid region: HR = 1.68, 95% CI = 1.29-2.19, ptrend <0.001). These estimates remained largely unchanged after adjustment for potential confounding factors. The cohorts born in 2004-2006 and 2010-2012 had comparable cumulative incidences, with a slightly higher incidence for those born in 2007-2009. We observed an increase in the risk of IBD by increasing latitude which may suggest that environmental factors influence the development of IBD, although non-causal explanations cannot be ruled out.

Multicenter registry of pediatric inflammatory bowel disease from a developing country

BackgroundDespite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry.MethodsFour teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up.ResultsWe included 35 Crohn’s disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up.ConclusionsA high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

De Novo Inflammatory Bowel Disease after Liver Transplantation: Eleven Years' Experience in Shiraz, Iran

Background: Inflammation may occur after solid and liquid liver transplantations at a rate higher than in the general population. Objectives: This study aimed to investigate the incidence of de novo inflammatory bowel disease (IBD) and assess some risk factors after Orthotopic liver transplantation (OLT) in liver transplant patients in Shiraz, Iran. Methods: The sample study comprised patients (n = 1702) who had received liver transplants between 2001 and 2012 at the Shiraz liver transplant center. The data were obtained from patient records, which included information on their medical history, colonoscopy reports, family history of IBD, and other risk factors. The study evaluated the status of inflammatory bowel disease (IBD) among patients who had undergone liver transplantations due to autoimmune hepatitis group (AIH), Primary Sclerosing Cholangitis (PSC), and other liver transplant patients. Additionally, case groups were formed, comprising AIH patients (n1 = 10) and other patients with IBD (n2 = 10), and were compared with transplant patients without IBD as the control group (n1 = 21, n2 = 21). Results: Out of the total 1702 patients, 254 (14.92%) had AIH, 211 (12.40%) had PSC, and 1237 (72.68%) had other outcomes. The mean of leukocyte counts (P-value = 0.73), types of immunosuppressant medications, and serum levels of cyclosporine (P-value = 0.77) and tacrolimus (P-value = 0.27) did not show any significant differences between the case and control groups. However, it was observed that IBD developed earlier in patients with AIH compared to other patients (20.1 ± 2.23 vs 53.9 ± 4.42 months). Conclusions: The incidence of IBD after liver transplantation was higher compared to the general population, and it occurred earlier in patients who underwent transplantation for AIH and other groups.

Colonic Dysregulation of Major Metabolic Pathways in Experimental Ulcerative Colitis.

Inflammatory bowel disease (IBD) is multifactorial chronic inflammatory disease in the gastrointestinal tract, affecting patients' quality of life profoundly. The incidence of IBD has been on the rise globally for the last two decades. Because the molecular mechanisms underlying the disease remain not well understood, therapeutic development is significantly impeded. Metabolism is a crucial cellular process to generate the energy needed for an inflammatory response and tissue repair. Comprehensive understanding of the metabolic pathways in IBD would help to unravel the disease pathogenesis/progression and facilitate therapeutic discoveries. Here, we investigated four metabolic pathways altered in experimental colitis. C57BL/6J mice were treated with dextran sulfate sodium (DSS) in drinking water for 7 days to induce experimental ulcerative colitis (UC). We conducted proteomics analysis for the colon samples using LC/MS, to profile key metabolic intermediates. Our findings revealed significant alterations in four major metabolic pathways: antioxidative defense, β-oxidation, glycolysis, and TCA cycle pathways. The energy metabolism by β-oxidation, glycolysis, and TCA cycle pathways were downregulated under UC, together with reduced antioxidative defense pathways. These results reveal metabolic re-programming in intestinal cells under UC, showing dysregulation in all four major metabolic pathways. Our study underscores the importance of metabolic drivers in the pathogenesis of IBD and suggests that the modification of metabolism may serve as a novel diagnostic/therapeutic approach for IBD.

Exploring the causal relationship between Takayasu arteritis and inflammatory bowel disease using Mendelian randomization.

Takayasu arteritis (TA) and inflammatory bowel disease (IBD) are two distinct diseases; however, previous studies have reported many cases of IBD-TA coexistence. Additionally, the incidence of IBD in patients with TA is estimated to be significantly higher than the incidence in the general population. Therefore, the two diseases are anticipated to be linked. Mendelian randomization (MR) analysis assesses whether an exposure might causally affect an outcome by using genetic variants inherited randomly at conception, thereby reducing the impact of confounding and reverse causality. The present study aimed to investigate the potential causal relationship between TA and IBD using MR analysis. Two-sample MR analysis, in which TA and IBD were regarded as the exposure and outcome, respectively, was conducted to investigate whether the two diseases are causally related using the R TwoSampleMR package. Summary GWAS data of TA consisted of 516 Turkish cohorts and 462 controls, and 119 patients and 993 controls of European ancestry. Summary data of IBD was from a sub-study of the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) that comprised 31,665 cases and 33,977 controls of European ancestry. Additionally, separate MR analyses stratified by the two major subtypes of IBD, Crohn's disease (CD) and ulcerative colitis (UC), were performed. Various statistical tests, including the intercept of MR-Egger regression, funnel plots, Cochran's Q tests, and leave-one-out sensitivity analyses, were employed to assess the presence of heterogeneity and horizontal pleiotropy among single nucleotide polymorphisms (SNPs). In the primary analysis using the inverse-variance weighted (IVW) method, the risk of developing IBD for a patient with TA compared to a non-TA control increased 1.053 times (Odds Ratio (OR) = 1.053, P = 0.065). The MR-Egger method (OR = 1.025, P = 0.470) yielded results consistent with this null finding. However, both the weighted median method (OR = 1.038, P = 0.002) and the weighted mode method (OR = 1.051, P = 0.009) identified a significant harmful causal effect. The MR outcomes from separate subgroup analyses slightly diverged from those of IBD and TA. Specifically, for CD, three methods indicated that TA is a risk factor: IVW estimated the OR as 1.045 (P = 0.032), MR-Egger as 0.997 (P = 0.957), weighed median as 1.028 (P = 0.021), and weighted mode as 1.031 (P = 0.022), respectively. This study represents one of the initial investigations into the potential causal association between TA and IBD. With three MR methods, including the primary IVW approach, indicating a notable effect on TA on CD, our analysis findings offer some indication that TA could be a contributing risk factor for CD.

Forecasting the Incidence and Prevalence of Inflammatory Bowel Disease: A Canadian Nationwide Analysis.

Canada has a high burden of inflammatory bowel disease (IBD). Historical trends of IBD incidence and prevalence were analyzed to forecast the Canadian burden over the next decade. Population-based surveillance cohorts in 8 provinces derived from health administrative data assessed the national incidence (2007-2014) and prevalence (2002-2014) of IBD. Autoregressive integrated moving average models were used to forecast incidence and prevalence, stratified by age, with 95% prediction intervals (PI), to 2035. The average annual percentage change (AAPC) with 95% confidence interval (CI) was calculated for the forecasted incidence and prevalence. The national incidence of IBD is estimated to be 29.9 per 100,000 (95% PI 28.3-31.5) in 2023. With a stable AAPC of 0.36% (95% CI -0.05 to 0.72), the incidence of IBD is forecasted to be 31.2 per 100,000 (95% PI 28.1-34.3) in 2035. The incidence in pediatric patients (younger than 18 years) is increasing (AAPC 1.27%; 95% CI 0.82-1.67), but it is stable in adults (AAPC 0.26%; 95% CI -0.42 to 0.82). The prevalence of IBD in Canada was 843 per 100,000 (95% PI 716-735) in 2023 and is expected to steadily climb (AAPC 2.43%; 95% CI 2.32-2.54) to 1,098 per 100,000 (95% PI 1,068-1,127) by 2035. The highest prevalence is in seniors with IBD (1,174 per 100,000 in 2023; AAPC 2.78%; 95% CI 2.75-2.81). Over the next decade, the Canadian health care systems will contend with the juxtaposition of rising incidence of pediatric IBD and a rising prevalence of overall IBD driven by the aging population.

Biologics, Small Molecules and More in Inflammatory Bowel Disease: The Present and the Future

Inflammatory bowel disease (IBD) is a group of heterogeneous chronic inflammatory diseases of the gut presenting with intestinal and extraintestinal manifestations. Most cases fit in predominantly two types, namely, ulcerative colitis and Crohn’s disease. The incidence of IBD has been increasing steadily in the past three decades. Focused research has resulted in many therapeutic options. Biologics (derived from humans or animals) and small molecules have emerged as the cornerstone in the management of IBD and have become widely available. Currently, monoclonal antibodies against tumor necrosis factor-alpha (infliximab, adalimumab, certolizumab, and golimumab), integrins (vedolizumab and natalizumab), and interleukin (IL)-12 and IL-23 antagonists (ustekinumab), along with small molecules (tofacitinib), are approved for use. This article summarizes various aspects of these drugs, like clinical pharmacology, indications for use in IBD, safety in pregnancy and lactation, and the adverse effects profile based on the studies leading to their approval. This review also focuses on the recent advances and future perspectives specific to biologics in IBD.

Pediatric inflammatory bowel disease: What’s new and what has changed?

Abstract The incidence and prevalence of inflammatory bowel disease (IBD) is on the rise in North America and worldwide, with young children being the fastest growing patient population. It is therefore essential for pediatricians and pediatric sub-specialists to be able to recognize signs and symptoms suspicious for a new diagnosis of IBD, as well as potential complications associated with IBD or its treatment. This article reviews the most recent literature regarding clinical presentation, helpful diagnostic clues, newer monitoring tools being used by pediatric gastroenterologists, and emerging new biologic and small molecule treatments.