Trichosanthes cucumerina L. (TC), Momordica charantia var. muricata (Willd.) Chakrav. (MCM), and Luffa acutangula (L) Roxb. (LA) are common vegetables widely used in traditional and folk systems of medicine for various ailments including diabetes.

This work evaluated the antidiabetic potential of 95% ethanolic extract (EE) obtained from Trichosanthes cucumerina, Momordica charantia var. muricata, and Luffa acutangula whole plant. Their antidiabetic activity was screened in fasted, fed, glucose-loaded, and diabetic rats treated for up to 4 h.

The tested herbal extracts possess potent therapeutic applications; more specifically Momordica charantia var. muricata whole plant extract possessed the most significant blood glucose lowering in fasted (19.68%; p<0.001), fed (8.1%; p<0.001), glucose loaded (18.78%; p<0.001), and diabetic (30.99%; p<0.001) models.

Our method of testing the glucose-lowering in four experimental models offers a time-saving approach to screen the hypoglycemic potential of candidate drugs. These findings validate the traditional claims and provide novel insights into the quest for antidiabetic cure.

Given the evolving literature regarding the optimal surgical approach to mitigate post-operative recurrence of Crohn's disease (CD), this survey study aimed to elucidate the practices and preferences of colorectal surgeons in Australia and New Zealand (ANZ) in their surgical management of CD.

Colorectal surgical consultants and fellows (n = 337) registered with the Colorectal Surgical Society of Australia and New Zealand (CSSANZ) were invited by email in April 2022 to participate in a cross-sectional survey consisting of basic demographics and 12 questions relating to their usual surgical practice and preferred operative strategy.

A total of 135 responses were received (39.9%). Regarding anastomotic configuration, 47% (n = 68) preferred the side-to-side anastomosis (STSA), 19% (n = 28) the end-to-end anastomosis (ETEA), and 15% (n = 21) the Kono S anastomosis. Most respondents preferred to resect at the proximal junction of the abnormal mesentery (75%, n = 97), while radical resection of the mesentery was preferred in 10% (n = 13) and close intestinal resection through abnormal mesentery in 15% (n = 20). The preferred surgical approach was by far laparoscopic (93%, n = 125) with extraction from the midline peri-umbilical port (80%, n = 108).

Amongst participating colorectal surgeons, there was a clear consensus on the approach, where the dominant practice was laparoscopy with a midline peri-umbilical extraction. Similarly, most respondents preferred some degree of mesenteric resection. However, anastomotic configuration and technique were domains of resection in CD lacking unanimity despite clear guidelines, highlighting an area requiring further attention.

Limited epidemiological evidence exists regarding the role of healthy eating patterns in reducing the risk of Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to investigate the association between adherence to four established healthy eating patterns and subsequent CD or UC risk, and further examined whether these associations are linked to anti-inflammatory mechanisms.

We conducted a prospective cohort study of 197,391 participants from the UK Biobank who completed at least one dietary questionnaire and were free from inflammatory bowel disease or cancer at baseline. Four dietary patterns were assessed, including Alternate Mediterranean Diet (AMED), Healthy Eating Index 2015 (HEI-2015), Healthful Plant-based Diet Index (HPDI), and EAT-Lancet. Cox proportional models with restricted cubic splines were applied to explore the associations. The potential role of low-grade inflammation in these associations was examined through mediation analysis.

During 2,193,436 person-years follow-up, 260 CD and 601 UC cases were identified. Higher AMED and HEI-2015 scores were associated with a reduced risk of CD but no UC, with no evidence against nonlinearity. These associations remained consistent across multiple sensitive and subgroup analyses. For dietary components, the fruits and monounsaturated fatty acids: saturated fatty acids ratio in AMED, and total fruits, total protein foods and fatty acid in HEI-2015 were linked to a decreased CD risk. Both diets were also associated with lower plasma inflammation biomarkers. Mediation analysis indicated that 7.66% and 13.40% of the reductions in CD risk attributed to AMED and HEI-2015 diets, respectively, were mediated by low-grade inflammation scores.

Higher adherence to AMED and HEI-2015 might significantly reduce CD risk, partly due to their anti-inflammatory properties.

Patients with inflammatory bowel disease (IBD) have an increased risk of developing immune-mediated diseases. However, the genetic basis of IBD is complex, and an integrated approach should be used to elucidate the complex genetic relationship between IBD and immune-mediated diseases.

The genetic relationship between IBD and 16 immune-mediated diseases was examined using linkage disequilibrium score regression. GWAS data were synthesized from two IBD databases using the METAL, and multi-trait analysis of genome-wide association studies was performed to enhance statistical robustness and identify novel genetic associations. Independent risk loci were meticulously examined using conditional and joint genome-wide multi-trait analysis, multi-marker analysis of genomic annotation, and functional mapping and annotation of significant genetic loci, integrating the information of quantitative trait loci and different methodologies to identify risk-related genes and proteins.

The results revealed four immune-mediated diseases (AS, psoriasis, iridocyclitis, and PsA) with a significant relationship with IBD. The multi-trait analysis revealed 909 gene loci of statistical significance. Of these loci, 28 genetic variants were closely related to IBD, and 7 single-nucleotide polymorphisms represented novel independent risk loci. In addition, 14 genes and 514 proteins were found to be associated with susceptibility to immune-mediated diseases. Notably, IL1RL1 emerged as a key player, present within pleiotropic genes across multiple protein databases, highlighting its potential as a therapeutic target.

This study suggests that the common polygenic determinants between IBD and immune-mediated diseases are widely distributed across the genome. The findings not only support a shared genetic relationship between IBD and immune-mediated diseases but also provide novel therapeutic targets for these diseases.

Inflammatory bowel disease (IBD) is a kind of chronic inflammatory disorders of the gastrointestinal tract with diverse prevalence rates and patterns globally. Accurate comprehension of the disease's epidemiological characteristics is imperative for disease control and prevention all over the world.

To provide the most updated estimates on the global burden of IBD using the 2019 Global Burden of Disease (GBD) study data, to systematically analyze the IBD epidemiological characteristics at the global, regional, and national levels including the prevalence, incidence, and disability-adjusted life years (DALY) rates, and to analyze the correlations of the socioeconomic development level with IBD epidemiological characteristics.

We conducted an overall analysis of the global, regional, and national burden of IBD from 1990 to 2019, data from the 2019 GBD study. The GBD's classification of the world into 21 regions and 204 countries and territories facilitated a thorough examination. Age-standardized estimated annual percentage changes (EAPCs) were computed to assess the temporal trends in IBD age-standardized rates (ASRs), with age standardization employed to mitigate potential confounding effects from age structure. The sociodemographic Index (SDI) was used to correlate the socioeconomic development level with the epidemiological characteristics of IBD.

From 1990 to 2019, the global age-standardized prevalence, incidence, and DALY rates of IBD remained high. There was a slight downward trend in the global age-standardized incidence and DALY rates of IBD and men exhibited higher DALY rates than women. In 2019, high-income North America recorded the highest age-standardized prevalence, incidence, and DALY rates, while Oceania had the lowest age-standardized prevalence and incidence rates. South Asia had the lowest age-standardized DALY rates. The age-standardized mortality and DALY rates decreased as SDI values increased and remained higher than the expected levels over the past three decades. A negative correlation was observed between age-standardized DALY rates and SDI at the national level.

This analysis of the GBD 2019 database demonstrates that the overall global burden of IBD is still high. Meanwhile, an increasing disease burden is observed in the middle and low SDI locations.

The incidence of inflammatory bowel diseases [IBD] has risen over the past decade to become a global issue. The objectives of this review were to describe the incidence and/or prevalence of IBD in the era of advanced therapies, and to describe the association between environmental risk factors and both pathogenesis and disease course across the ages.

We performed a search of English language publications listed in PubMed regarding the epidemiology of IBD and key environmental factors implicated in IBD from January 2000 to December 2023.

Annual incidence rates varied by geographical region with IBD estimates ranging from 10.5 to 46.14 per 100 000 in Europe, 1.37 to 1.5 per 100 000 in Asia and the Middle East, 23.67 to 39.8 per 100 000 in Oceania, 0.21 to 3.67 per 100 000 in South America, and 7.3 to 30.2 per 100 000 in North America. The burden of IBD among children and adolescents, and older people is rising globally. Key environmental factors implicated in IBD pathogenesis include exposure to tobacco smoking, antibiotics, non-steroidal anti-inflammatory drugs, oral contraceptives, infections, and ultra-high processed foods. Breastfeeding and a high-quality diet rich in fruit, vegetables, fish, and other fibre sources are important protective factors. Smoking has consistently been shown to negatively impact disease outcomes for Crohn's disease.

The epidemiology of IBD has undergone considerable change in recent decades, with an increase in the burden of disease worldwide. Optimally studying and targeting environmental triggers in IBD may offer future opportunities for disease modification.

Paediatric-onset and elderly-onset inflammatory bowel disease (IBD) present unique treatment challenges.

We investigated treatment patterns following a first and second course of systemic steroids in paediatric- and elderly-onset IBD and compared them to adult-onset IBD.

All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2000 and 2018 were identified through the Danish healthcare registries. Patients were divided into groups based on their age at diagnosis. Kaplan-Meier plots were prepared for medications and surgeries after diagnosis and after the first and second courses of systemic steroids. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox regression analysis for steroid-sparing medications.

1851 CD (13%) and 1687 (6%) UC patients were paediatric-onset, while 2952 (20%) CD and 5812 (23%) UC patients were elderly-onset. Paediatric-onset more frequently received immunomodulators [CD: HR: 1.64, CI: 1.52-1.77, UC: HR: 2.29, CI: 2.02-2.61] and biologics [CD: HR: 1.43, CI: 1.25-1.65, UC: HR: 1.27, CI: 0.99-1.64], while elderly-onset less frequently received immunomodulators [CD: HR: 0.39, CI: 0.35-0.44, UC: HR: 0.58, CI: 0.50-0.67] and biologics [CD: HR: 0.19, CI: 0.14-0.25, UC: HR: 0.36, CI: 0.27-0.48] compared to adult-onset age groups. After two courses of systemic steroids, elderly-onset still received less steroid-sparing medications. High frailty was associated with lower usage of medications for elderly-onset.

There are significant differences in the use of steroid-sparing medication between age of onset, even after two courses with systemic steroids. High frailty could account for some of these differences in elderly-onset IBD.

Inflammatory bowel disease (IBD) is a recurrent chronic intestinal disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Its pathogenesis involves intricate interactions between pathogenic microorganisms, native intestinal microorganisms, and the intestinal immune system via the oral-gut axis. The strong correlation observed between oral diseases and IBD indicates the potential involvement of oral pathogenic microorganisms in IBD development. Consequently, therapeutic strategies targeting the proliferation, translocation, intestinal colonization and exacerbated intestinal inflammation of oral microorganisms within the oral-gut axis may partially alleviate IBD. Tea consumption has been identified as a contributing factor in reducing IBD, with epigallocatechin gallate (EGCG) being the primary bioactive compound used for IBD treatment. However, the precise mechanism by which EGCG mediates microbial crosstalk within the oral-gut axis remains unclear. In this review, we provide a comprehensive overview of the diverse oral microorganisms implicated in the pathogenesis of IBD and elucidate their colonization pathways and mechanisms. Subsequently, we investigated the antibacterial properties of EGCG and its potential to attenuate microbial translocation and colonization in the gut, emphasizing its role in attenuating exacerbations of IBD. We also elucidated the toxic and side effects of EGCG. Finally, we discuss current strategies for enhancing EGCG bioavailability and propose novel multi-targeted nano-delivery systems for the more efficacious management of IBD. This review elucidates the role and feasibility of EGCG-mediated modulation of the oral-gut axis microbiota in the management of IBD, contributing to a better understanding of the mechanism of action of EGCG in the treatment of IBD and the development of prospective treatment strategies.

Inflammatory bowel disease (IBD), mainly including ulcerative colitis and Crohn's disease, imposes a huge medical and economic burden worldwide. Recently, the diagnosis, treatment, and surveillance of IBD have advanced rapidly, which has changed the epidemiology, cancer risk, and surgery risk of IBD. Here, we reviewed the recent literature on the epidemiology, IBD-related cancer, and IBD-related surgery. We created a choropleth map to show the worldwide incidence trend for Crohn's disease and ulcerative colitis. We also found that the cancer risk and surgery risk of IBD are declining and discussed some risk factors associated with them. Based on the recent trend, we proposed several suggestions and hoped to reduce the global burden of IBD as far as possible.

Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency.

The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants.

Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines.

Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.

There is limited data on the long-term clinical outcomes of bio-naïve ulcerative colitis (UC) patients who are initiated on adalimumab (ADA). Our study aims to evaluate the clinical course of a nationwide cohort of bio naïve UC patients who were started on ADA, and then followed for 5 years after initiation of the drug.

We conducted a retrospective cohort study using the US Veteran Affairs Healthcare System (VAHS). Bio naïve UC patients were followed for 5 years after initiation of ADA. The primary outcome was to determine the time to discontinuation of ADA and if patients achieved endoscopic remission by the end of follow-up.

A total of 387 patients were included among whom 193 (49.87%) had pancolitis. The highest rate of ADA discontinuation was within the first year, with the elderly having a higher rate of discontinuation (HR 1.67, 95% CI: 1.14-2.45) and those on concomitant immunomodulators having a lower rate of discontinuation (HR 0.70, 95% CI: 0.48-1.03). In total, 125 (32.30%) patients remained on ADA at the end of their maximum follow-up. 54 (43.90%) achieved endoscopic remission.

Among bio-naive UC patients who were started on ADA, a third were still on the drug at the end of 5 years and half had endoscopic remission. The rate of discontinuation was highest within the first year of initiation, but patients continued to stop the drug over the course of follow-up.

There is limited evidence on the associations of dietary factors and patterns with risk of later-onset ulcerative colitis (UC) in Chinese adults.

To investigate the associations of dietary factors and patterns with risk of later-onset UC in Chinese.

The prospective China Kadoorie Biobank cohort study recruited 512,726 participants aged 30-79. Dietary habits were assessed using food frequency questionnaires. Dietary patterns were derived by factor analysis with a principal component method. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

During a median follow-up of 12.1 years, 312 cases of newly diagnosed UC were documented (median age of diagnosis 60.1 years). Egg consumption was associated with higher risk of UC (HR for daily vs. never or rarely: 2.29 [95% CI: 1.26-4.16]), while spicy food consumption was inversely associated with risk of UC (HR: 0.63 [0.45-0.88]). The traditional northern dietary pattern, characterised by high intake of wheat and low intake of rice, was associated with higher risk of UC (HR for highest vs. lowest quartile of score: 2.79 [1.93-4.05]). The modern dietary pattern, characterised by high intake of animal-origin foods and fruits, was associated with higher risk of UC (HR: 2.48 [1.63-3.78]). Population attributable fraction was 13.04% (7.71%-19.11%) for daily/almost daily consumption of eggs and 9.87% (1.94%-18.22%) for never/rarely consumption of spicy food.

The findings highlight the importance of evaluating dietary factors and patterns in the primary prevention of later-onset UC in Chinese adults.

There is paucity of data on the effectiveness and safety of tofacitinib among elderly patients with ulcerative colitis (UC).

Through a retrospective cohort study among the US National Veterans Affairs Healthcare System, we evaluated effectiveness among the elderly (≥65) and young (<65) patients with UC initiated on tofacitinib.

Among 158 patients (53 elderly, 105 young), effectiveness at 12 months was 50.94% in the elderly and 33.33% in the young ( P = 0.032).

In a nationwide cohort of patients with UC initiating tofacitinib, effectiveness was seen in half of the elderly patients.

Although surgical management of the ileocolic segment in pediatric Crohn's disease is not curative, the main goal of therapy is to allow for growth, adequate nutrition, and age-appropriate development. Recurrent disease at the site of anastomosis presents as a major morbidity. Several factors have been implicated in the development of surgical recurrence though data in the literature is scarce. This review explores the epidemiology of recurrent ileocolic disease following primary surgery, indications for surgical intervention, and techniques reported in the literature. Pediatric data is scarce, and therefore, much of it is extrapolated from adult literature.

This study aims to characterize pediatric inflammatory bowel disease (IBD) patients who change diagnosis and describe the characteristics of that change.

A retrospective study was conducted on pediatric IBD patients from the ImproveCareNow (ICN) multicenter international cohort from 2007 to January 2019. Primary outcome was change in diagnosis after the first four visits. Other variables included demographics, diagnostics, disease characteristics, and timing.

6.1% of 18,055 patients aged 1-20 years changed diagnosis. Median time between the baseline visit and first diagnosis change was 0.9 years. Change in diagnosis occurred in 257/12,178 (2.1%) patients with Crohn's disease (CD), 347/4758 (7.3%) patients with ulcerative colitis (UC), and 495/1119 (44.2%) patients with IBD-Unclassified (IBD-U). In multivariable analysis, initial diagnosis of IBD-U and longer follow-up times were associated with greater odds of a diagnosis change.

IBD-U initial diagnosis and longer follow-up were associated with increased diagnosis change risk. The most common change was reclassification to CD. Disease activity, moderate malnutrition, and presence of EIMs were not associated with change in diagnosis.

With the increasing age of the general population in developed countries, the management of several chronic diseases becomes more and more complex due to comorbidities. Some, especially inflammatory bowel diseases, formerly believed to belong to the young adult population, have now been recognized as being present at disease onset also in the ageing population, representing medical challenges different from those in the younger population. In the past few years, knowledge on this special older population has increased, changing initial beliefs concerning epidemiology and course of disease. In the present review, we addressed the most recent evidence concerning their current incidence compared with other age groups, their clinical course, potential risk factors for the development of late-onset IBDs, associated diseases, and cancer risk beyond therapy-related neoplasias.

Numerous pathogenic processes are mediated by short noncoding RNAs (sncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether sncRNAs can predict CD or UC among IBDU patients. 35 IBDU patients who were initially diagnosed with IBDU were included in this retrospective investigation; of them, 12, 15, and 8 were reclassified into CD (IBDU-CD), UC (IBDU-UC), or remained as IBDU (IBDU-IBDU), respectively. Eight IBD patients, were included as references. SncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95% CI: 60-97) in discriminating IBDU-CD from IBDU-UC. Based on the three sncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.

Nutri-score is now widely available in food packages in Europe.

To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort METHODS: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake.

We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24-3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69-1.21; p-trend: 0.76).

A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.

Inflammatory bowel disease (IBD) comprises a group of relapsing, chronic diseases of the gastrointestinal tract that, in addition to adults, can affect children and adolescents. To detect relapses of inflammation, these patients require close observation, frequent follow-up, and therapeutic adjustments. While reference standard diagnostics include anamnestic factors, laboratory and stool sample assessment, performing specific imaging in children and adolescents is much more challenging than in adults. Endoscopic and classic cross-sectional imaging modalities may be invasive and often require sedation for younger patients. For this reason, intestinal ultrasound (IUS) is becoming increasingly important for the non-invasive assessment of the intestine and its inflammatory affection. In this review, we would like to shed light on the current state of the art and provide an outlook on developments in this field that could potentially spare these patients more invasive follow-up procedures.

The inflammatory bowel disease (IBD) is associated with gut microbiota dysbiosis; however, studies on methanogens-especially those focused on children-are extremely limited. The aim of this study was to determine the abundance of total methanogenic archaea and their three subgroups: Methanobrevibacter (Mb.) smithii, Methanosphaera (Ms.) stadtmanae, and Methanomassiliicoccales, in the feces of children with both active and inactive Crohn's disease (CD) and ulcerative colitis (UC). The results of a quantitative real-time PCR were cross-referenced with the disease type (CD vs. UC) and activity assessed with the use of Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) indices, and fecal calprotectin (FCP) concentration, and compared with controls. There was a significant decrease in the number of total methanogens in CD and UC compared to controls. The prevalence of total methanogens was also lower in UC compared to controls. Furthermore, patients from the inactive UC group were colonized by a lower number of Mb. smithii, and demonstrated the most pronounced positive correlation between the number of Ms. stadtmanae and the FCP concentration. Our results demonstrate that gut methanogens are related to the type and activity of pediatric IBD.

Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies.

Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD.

In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data.

Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

Our aims were to better understand the interplay of diet and gut microbiota in Crohn's disease [CD], taking advantage of a new-onset treatment-naïve CD cohort. We focus on phenylacetylglutamine [PAGln], a diet-derived meta-organismal prothrombotic metabolite.

We collected faecal and serum samples from a CD cohort [n = 136] and healthy controls [n = 126] prior to treatment, and quantified serum PAGln using LC-MS/MS. Diet was assessed using food-frequency questionnaires. Mice [C57BL/6] were fed high/low-protein diets and administered dextran sodium sulphate [DSS] to examine plasma PAGly, thrombosis potential, and colitis severity. PAGly or saline was administered to DSS-induced colitis mice, and colitis severity and colonic tissue gene expression were examined. P-selectin and CD40L expression were determined in human platelet-rich plasma [n = 5-6] after exposure to platelet agonists following PAGln priming. Bioinformatic analysis and bacterial culturing identified the main contributor of PAGln in CD.

PAGln, a meta-organismal prothrombotic metabolite, is associated with CD. Administration of PAGly exacerbated colitis in a mouse model and upregulated coagulation-related biological processes. Antiplatelet medicine, dipyridamole, attenuated PAGly-enhanced colitis susceptibility. PAGln enhanced platelet activation and CD40L expression in platelet-rich plasma ex vivo. Further study revealed that high dietary protein intake and increased abundance of phenylacetic acid [PAA]-producing Proteobacteria mediated by phenylpyruvate decarboxylase act in concert to cause the elevated PAGln levels in CD patients.

Taken together, ppdc-carrying Proteobacteria-generated PAGln from dietary protein is associated with CD and exacerbates colitis possibly via platelet-induced coagulation and inflammation These results suggest that PAGln is a potential early diagnostic marker and therapeutic target of CD.

Defective neutrophil regulation in inflammatory bowel disease (IBD) is thought to play an important role in the onset or manifestation of IBD, as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens. Like neutrophils in the context of innate immune responses, immunoglobulin A (IgA) as an acquired immune response partakes in the defense of the intestinal epithelium. Under normal conditions, IgA contributes to the elimination of microbes, but in connection with the loss of tolerance to chitinase 3-like 1 (CHI3L1) in IBD, IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms. The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target, the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.

To determine the predictive potential of Ig subtypes of a novel serological marker, anti-CHI3L1 autoantibodies (aCHI3L1) in determining the disease phenotype, therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.

Sera of 257 Crohn's disease (CD) and 180 ulcerative colitis (UC) patients from a tertiary IBD referral center of Hungary (Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen) were assayed for IgG, IgA, and secretory IgA (sIgA) type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1, along with 86 healthy controls (HCONT).

The IgA type was more prevalent in CD than in UC (29.2% vs 11.1%) or HCONT (2.83%; P < 0.0001 for both). However, sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT (39.3% and 32.8% vs 4.65%, respectively; P < 0.0001). The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement (P < 0.0001 and P = 0.038, respectively) in patients with CD. Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity (57.1% vs 36.0%, P = 0.009). IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group (46.9% vs 25.7%, P = 0.005). In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis, positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models. This association disappeared after merging subgroups of different disease locations.

CHI3L1 is a novel neutrophil autoantigenic target in IBD. The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.

Inflammatory bowel disease (IBD) is a multifactorial intractable intestinal disease. Focusing on only one facet of the pathogenesis of IBD is insufficient to fully capture the complexity of the disease, and results in limited advance in clinical management. Therefore, it is critical to dissect the interactions amongst the multifarious contributors to the pathogenesis to comprehensively understand its pathology and subsequently improve clinical outcomes. In this context, the systemic interactions between organs, particularly the oral-gut axis mediated by host immune cells and resident microorganisms, have garnered significant attention in IBD research. More specifically, periodontal disease such as periodontitis has been implicated in augmenting intestinal inflammation beyond the confines of the oral cavity. There is mounting evidence suggesting that potentially harmful oral resident bacteria, termed pathobionts, and pro-inflammatory immune cells from the oral mucosa can migrate to the gastrointestinal tract, thereby potentiating intestinal inflammation. This article aims to provide a holistic overview of the causal relationship between periodontal disease and intestinal inflammation. Furthermore, we will discuss potential determinants that facilitate the translocation of oral pathobionts into the gut, a key event underpinning the oral-gut axis. Unraveling the complex dynamics of microbiota and immunity in the oral-gut continuum will lead to a better understanding of the pathophysiology inherent in both oral and intestinal diseases and the development of prospective therapeutic strategies.

The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals who mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. Whereas IBD clinical presentation is well described, how interactions between microbiota and host genotype impact early subclinical stages of the disease remains unclear. The transcription factor hepatocyte nuclear factor 4 alpha (HNF4A) has been associated with human IBD, and deletion of Hnf4a in intestinal epithelial cells (IECs) in mice (Hnf4aΔIEC) leads to spontaneous colonic inflammation by 6-12 mo of age. Here, we tested if pathology in Hnf4aΔIEC mice begins earlier in life and if microbiota contribute to that process. Longitudinal analysis revealed that Hnf4aΔIEC mice reared in specific pathogen-free (SPF) conditions develop episodic elevated fecal lipocalin 2 (Lcn2) and loose stools beginning by 4-5 wk of age. Lifetime cumulative Lcn2 levels correlated with histopathological features of colitis at 12 mo. Antibiotic and gnotobiotic tests showed that these phenotypes in Hnf4aΔIEC mice were dependent on microbiota. Fecal 16S rRNA gene sequencing in SPF Hnf4aΔIEC and control mice disclosed that genotype significantly contributed to differences in microbiota composition by 12 mo, and longitudinal analysis of the Hnf4aΔIEC mice with the highest lifetime cumulative Lcn2 revealed that microbial community differences emerged early in life when elevated fecal Lcn2 was first detected. These microbiota differences included enrichment of a novel phylogroup of Akkermansia muciniphila in Hnf4aΔIEC mice. We conclude that HNF4A functions in IEC to shape composition of the gut microbiota and protect against episodic inflammation induced by microbiota throughout the lifespan. IMPORTANCE The inflammatory bowel diseases (IBD), characterized by chronic inflammation of the intestine, affect millions of people around the world. Although significant advances have been made in the clinical management of IBD, the early subclinical stages of IBD are not well defined and are difficult to study in humans. This work explores the subclinical stages of disease in mice lacking the IBD-associated transcription factor HNF4A in the intestinal epithelium. Whereas these mice do not develop overt disease until late in adulthood, we find that they display episodic intestinal inflammation, loose stools, and microbiota changes beginning in very early life stages. Using germ-free and antibiotic-treatment experiments, we reveal that intestinal inflammation in these mice was dependent on the presence of microbiota. These results suggest that interactions between host genotype and microbiota can drive early subclinical pathologies that precede the overt onset of IBD and describe a mouse model to explore those important processes.

Elderly-onset inflammatory bowel disease [IBD] patients exhibit a distinct natural history compared to younger IBD patients, with unique disease phenotypes, differential responses to therapy, and increased surgical morbidity and mortality. Despite the foreseeable high demand for personalized medicine and specialized IBD care in the elderly, current paradigms of IBD management fail to capture the required nuances of care for elderly-onset IBD patients. Our review postulates the roles of systemic and mucosal immunosenescence, inflammageing and a dysbiotic microbial ecosystem in the pathophysiology of elderly-onset IBD. Ultimately, a better understanding of elderly-onset IBD can lead to improved patient outcomes and the tailoring of future preventative and treatment strategies.

Tumour necrosis factor-α (TNF) antagonists have improved the management of inflammatory bowel disease (IBD), however, their usage and administration persist to be suboptimal. Here, we examined the relationship between tissue-specific TNF mRNA expression in mucosal biopsies from IBD patients and anti-TNF treatment response.

Archived tissue samples from patients with luminal IBD that had all been or were in treatment with anti-TNF were included (18 adults and 24 paediatric patients). Patients were stratified into three groups according to anti-TNF response: responders, primary non-responders (PNR) and secondary loss of response (SLOR). TNF mRNA was detected using RNAscope in situ hybridisation (ISH) and the expression was quantified using image analysis.

The ISH analysis showed varying occurrence of TNF mRNA positive cells located in lamina propria and often with increased density in lymphoid follicles (LF). Consequently, expression estimates were obtained in whole tissue areas with and without LF. Significantly higher TNF mRNA expression levels were measured in adults compared to paediatric patients in both the analyses with and without LF (p = .015 and p = .016, respectively). Considering the relation to response, the adult and paediatric patients were evaluated separately. In adults, the TNF expression estimates were higher in PNRs compared to responders with and without LF (p = .017 and p = .024, respectively).

Our data indicate that adult PNR have significantly higher TNF mRNA levels than responders. This suggests that higher anti-TNF dose may be considered for IBD patients with high TNF mRNA expression estimates from the start of treatment.

High rates of inflammatory bowel disease (IBD) are reported in children of South Asian (SA) descent in some western countries. This population-based study describes the incidence and clinical course of IBD in SA children compared to non-South Asian (NSA) children in New Zealand (NZ).

Children (≤15 years) with new-onset IBD presenting to a centralized tertiary referral center in Auckland, NZ from 2010 to 2020 were identified. Disease phenotype, clinical characteristics, response to exclusive enteral nutrition, clinical remission rates at 3 and 12 months, biologic use, corticosteroid exposure, and disease complications were compared by ethnicity; IBD incidence was calculated.

There were 127 (26 SA; 101 NSA) children with Crohn disease, 41 (10 SA; 31 NSA) with ulcerative colitis, and 10 (3 SA; 7 NSA) with IBD-unclassified. IBD incidence in SA and NSA children was 14.1 per 100,000 and 4.3 per 100,000 respectively ( P < 0.001). IBD incidence increased by 5.6% per year ( P = 0.022), due to a greater rise in incidence in SA (SA 16.8% per year, P = 0.015; NSA 4.5% per year, P = 0.317). At presentation, SA children had worse biochemical parameters, severe colitis, and vitamin D deficiency. SA children had lower rates of remission following exclusive enteral nutrition (28.5% vs 65.0%, P < 0.001) or biologic induction (35.7% vs 70.8%, P = 0.020), at 3-month (35.3% vs 69.8%, P < 0.001) and 12-month follow-up (29.4% vs 55.0%, P = 0.005). No significant differences were found in disease location or corticosteroid burden.

Increasing incidence of IBD was disproportionately represented by SA children with more severe disease and lower remission rates following exclusive enteral nutrition or biologic therapy.

We aimed to identify pre- and perinatal risk factors for developing pediatric-onset immune-mediated inflammatory (pIMID).

This nation-wide, cohort study included all children born in Denmark from 1994 to 2014 identified from the Danish Medical Birth registry. Individuals were followed through 2014 and cross-linked to the continuously updated national socioeconomic and healthcare registers to obtain data on pre- and perinatal exposures (maternal age, educational level, smoking, maternal IMID, parity, mode of conception and delivery, plurality, child's sex, and birth season). The primary outcome was a pIMID diagnosis (inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, juvenile idiopathic arthritis, or systemic lupus erythematosus) before 18 years of age. Risk estimates were calculated using Cox proportional hazards model and presented by hazard ratios (HR) with 95% confidence intervals (95%CI).

We included 1,350,353 children with a follow-up time of 14,158,433 person-years. Among these, 2,728 were diagnosed with a pIMID. We found a higher risk of pIMID in children born to women with a preconception IMID diagnosis (HR: 3.5 [95%CI: 2.7-4.6]), children born by Caesarean section (HR: 1.2 [95%CI: 1.0-1.3]), and among females (1.5 [95%CI: 1.4-1.6]) than among children without these characteristics. Plural pregnancies were associated with a lower risk of pIMID than single pregnancies (HR: 0.7 [95%CI: 0.6-0.9]).

Our results indicate a high genetic burden in pIMID but also identifies intervenable risk factors, such as Cesarean section. Physicians should, keep this in mind when caring for high-risk populations and pregnant women previously diagnosed with an IMID.

There is an increasing incidence of inflammatory bowel disease (IBD) for which environmental factors are suspected. Antibiotics have been associated with development of IBD in earlier generations, but their influence on IBD risk in adults is uncertain.

To assess the impact of antibiotic exposure, including dose-response, timing and antibiotic class, on the risk of IBD in all individuals aged ≥10 years.

Using Denmark nationwide registries, a population-based cohort of residents aged ≥10 years was established between 2000 and 2018. Incidence rate ratios (IRRs) for IBD following antibiotic exposure were calculated using Poisson regression.

There were a total of 6 104 245 individuals, resulting in 87 112 328 person-years of follow-up, and 52 898 new cases of IBD. Antibiotic exposure was associated with an increased risk of IBD as compared with no antibiotic exposure for all age groups, although was greatest among individuals aged 40-60 years and ≥60 years (age 10-40 years, IRR 1.28, 95% CI 1.25 to 1.32; age 40-60 years, IRR 1.48, 95% CI 1.43 to 1.54; age ≥60 years, IRR 1.47, 95% CI 1.42 to 1.53). For all age groups a positive dose-response was observed, with similar results seen for both ulcerative colitis and Crohn's disease. The highest risk of developing IBD was seen 1-2 years after antibiotic exposure, and after use of antibiotic classes often prescribed to treat gastrointestinal pathogens.

Antibiotic exposure is associated with an increased risk of IBD, and was highest among individuals aged 40 years and older. This risk increased with cumulative antibiotic exposure, with antibiotics targeting gastrointestinal pathogens and within 1-2 years after antibiotic exposure.

Maternal inflammatory bowel disease (IBD) during pregnancy may be associated with increased susceptibility to infection in offspring. We aimed to assess this association, taking into consideration the mediating role of anti-tumor necrosis factor α (anti-TNFα) agents and adverse birth outcomes.

This population-based cohort study included all live-born singletons born in Denmark during 1995-2016 (n = 1,343,960). The exposure was maternal IBD. Main outcome of interest was offspring infection younger than 5 years, defined by either infection-related hospitalization or systemic antibiotic prescription, whose corresponding risk estimates were hazard ratios (HRs) and incidence rate ratios (IRRs), respectively. We applied an inverse probability-weighted marginal structural model for mediation analysis.

Offspring born to mothers with Crohn's disease (CD) had an 18% increased risk of infection-related hospitalization (HR 1.18, 95% confidence interval 1.10-1.26) and a 16% increased frequency of prescribed antibiotics (IRR 1.16, 95% confidence interval 1.11-1.21). Anti-TNFα agents could explain 10% and 3% of the 2 estimated total associations, respectively, while a composite of preterm birth, low birth weight, and small for gestational age could explain 4% and 0%, respectively. The association between prenatal anti-TNFα and frequency of antibiotics attenuated after additional adjustment for maternal CD (IRR from 1.23 [0.98-1.55] to 1.10 [0.87-1.40]). Maternal ulcerative colitis, however, was not associated with offspring infection.

Maternal CD, but not ulcerative colitis, was associated with an increased risk of infection in offspring younger than 5 years, of which adverse birth outcomes and anti-TNFα had a minor role. The association between anti-TNFα agents and pediatric infection could be partially explained by maternal CD.

Vitamin D deficiency is very common among children with IBD. Since there are conflicting results regarding the association of vitamin D with IBD, we conducted this systematic review to confirm the association of vitamin D with IBD.

We conducted a systematic search in Scopus, Cochrane Library, Web of Science, PubMed, and Google Scholar to find relevant studies. Articles with cross-sectional and case-control designs that reported the association between vitamin D and IBD among children were included.

Eventually, 9 studies (with 16 effect sizes) reported the mean and SD or the median and the interquartile range of serum vitamin D levels in both subjects with IBD and control subjects. The random effects meta-analysis revealed that subjects with IBD had -1.159 ng/ml (95% CI: -2.783, 0.464) lower serum vitamin D concentrations compared with their healthy counterparts, but this difference was not significant. A total of 14 studies (with 18 effect sizes) with 2,602 participants provided information for the prevalence of vitamin D deficiency or insufficiency in patients with IBD as 44% (95% CI: 0.34-0.54) with significant heterogeneity noted among studies (p < 0.001; I² = 97.31%).

This systematic and meta-analysis study revealed that vitamin D deficiency was associated with IBD. Longitudinal studies should be conducted in the future to confirm our findings. Large randomized controlled trials assessing the doses of supplementation of vitamin D would provide a better understanding of the association between vitamin D and IBD.

Obesity is a potentially modifiable risk factor for inflammatory bowel disease (IBD). We aimed to evaluate the body mass index (BMI) of those diagnosed with IBD early versus late in life in the context of age-adjusted background population.

Patients with a new diagnosis of IBD from 2000 to 2021 were included. Early-onset IBD was classified as age <18 and late-onset IBD classified as age ≥65. Obesity was classified as BMI ≥30 kg/m2. Population data were obtained from community surveys.

Included were 1573 patients (56.0%) with Crohn's disease (CD) and 1234 (44.0%) with ulcerative colitis (UC). Overall, the median BMI at IBD diagnosis was 20 kg/m2 (IQR 18-24) among those diagnosed at age <18 vs 26.9 kg/m2 (IQR 23.1-30.0) among those diagnosed at age ≥65 (rank-sum p<0.01). In all age groups, BMI was stable during the 1-year preceding IBD diagnosis. At age <18, 11.5% of the background population was obese compared with 3.8% of those with newly diagnosed CD (p<0.01) and 4.8% of those with newly diagnosed UC (p=0.05). At age ≥65, 23.6% of the population was obese compared with 24.3% of those with newly diagnosed CD (p=0.78) and 29.5% of those with newly diagnosed UC (p=0.01).

Patients with IBD diagnosed at age <18 were less likely to be obese compared with the age-adjusted background population whereas those diagnosed at age ≥65 were more likely to be obese. Future prospective studies should investigate obesity as a modifiable risk factor for late-life IBD.