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Journal of Crohn's & Colitis Jun 2023
Topics: Humans; Inflammatory Bowel Diseases; Crohn Disease; Neoplasms
PubMed: 36528797
DOI: 10.1093/ecco-jcc/jjac187 -
Archives of Disease in Childhood Apr 2024Paediatric-onset inflammatory bowel disease (IBD) is a complex and heterogenous condition. Incidence of disease in those aged <18 years has doubled over the last 25... (Review)
Review
Paediatric-onset inflammatory bowel disease (IBD) is a complex and heterogenous condition. Incidence of disease in those aged <18 years has doubled over the last 25 years, with concurrent increased prevalence and no decrease in disease severity. The tools available at diagnosis for investigation have developed over the last 10 years, including better utilisation of faecal calprotectin, improved small bowel imaging and video capsule endoscopy. Alongside this, management options have increased and include biological and small molecule therapies targeting alternative pathways (such as interleukin 12/23, integrins and Janus kinase/signal transducers and activators of transcription, JAK-STAT pathways) and better understanding of therapeutic drug monitoring for more established agents, such as infliximab. Dietary manipulation remains an interesting but contentious topic.This review summarises some of the recent developments in the diagnosis, investigation and management of IBD in children and young people. IBD is increasingly recognised as a continuum of disease, with a proportion of patients presenting with classical Crohn's disease or ulcerative colitis phenotypes. Future implementation of personalisation and stratification strategies, including clinical and molecular biomarkers, implementation of predictors of response and outcome and use of additional therapies, will continue to require working within clinical networks and multiprofessional teams.
Topics: Child; Humans; Adolescent; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Intestine, Small; Biomarkers
PubMed: 37468139
DOI: 10.1136/archdischild-2023-325668 -
Cells Jun 2023Biologicals have dominated the therapeutic scenery in inflammatory bowel diseases (IBDs), namely ulcerative colitis (UC) and Crohn's disease (CD), for the past 20 years.... (Review)
Review
Biologicals have dominated the therapeutic scenery in inflammatory bowel diseases (IBDs), namely ulcerative colitis (UC) and Crohn's disease (CD), for the past 20 years. The development of tofacitinib was the starting point for an era of small molecules after the era of biologicals. These new agents may challenge the use of biological agents in the future. They share properties that appeal to both patients and physicians. Low production costs, a lack of immunogenicity, and ease of use are only some of their benefits. On the other hand, patients and their physicians must manage the potential side effects of small molecules such as JAK inhibitors or S1P1R modulators. Here, we present agents that have already entered the clinical routine and those that are still being investigated in clinical trials.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases; Biological Products
PubMed: 37443765
DOI: 10.3390/cells12131730 -
Gut Jul 2023The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp...
OBJECTIVE
The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp metabolism end-products are essential to intestinal homeostasis. Here, we investigated the role of metabolites from the kynurenine pathway.
DESIGN
Targeted quantitative metabolomics was performed in two large human IBD cohorts (1069 patients with IBD). Dextran sodium sulphate-induced colitis experiments in mice were used to evaluate effects of identified metabolites. In vitro, ex vivo and in vivo experiments were used to decipher mechanisms involved. Effects on energy metabolism were evaluated by different methods including Single Cell mEtabolism by profiling Translation inHibition.
RESULTS
In mice and humans, intestinal inflammation severity negatively correlates with the amount of xanthurenic (XANA) and kynurenic (KYNA) acids. Supplementation with XANA or KYNA decreases colitis severity through effects on intestinal epithelial cells and T cells, involving Aryl hydrocarbon Receptor (AhR) activation and the rewiring of cellular energy metabolism. Furthermore, direct modulation of the endogenous tryptophan metabolism, using the recombinant enzyme aminoadipate aminotransferase (AADAT), responsible for the generation of XANA and KYNA, was protective in rodent colitis models.
CONCLUSION
Our study identified a new mechanism linking Trp metabolism to intestinal inflammation and IBD. Bringing back XANA and KYNA has protective effects involving AhR and the rewiring of the energy metabolism in intestinal epithelial cells and CD4 T cells. This study paves the way for new therapeutic strategies aiming at pharmacologically correcting its alterations in IBD by manipulating the endogenous metabolic pathway with AADAT.
Topics: Humans; Animals; Mice; Tryptophan; Inflammatory Bowel Diseases; Colitis; Intestines; Inflammation
PubMed: 36270778
DOI: 10.1136/gutjnl-2022-327337 -
Clinical Gastroenterology and... Aug 2023The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century.
METHODS
We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries.
RESULTS
Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence).
CONCLUSIONS
Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases; Hospitalization; Asia; Incidence
PubMed: 35863682
DOI: 10.1016/j.cgh.2022.06.030 -
International Journal of Molecular... Oct 2023Eosinophilic gastrointestinal diseases (EGIDs) are an emerging group of pathological entities characterized by an eosinophil-predominant infiltration of different tracts... (Review)
Review
Eosinophilic gastrointestinal diseases (EGIDs) are an emerging group of pathological entities characterized by an eosinophil-predominant infiltration of different tracts of the gut in the absence of secondary causes of eosinophilia. According to the specific tract of the gut involved, EGIDs can be classified into eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The epidemiology of EGIDs is evolving rapidly. EoE, once considered a rare disease, now has an incidence and prevalence of 7.7 new cases per 100,000 inhabitants per years and 34.4 cases per 100,000 inhabitants per year, respectively. Fewer data are available regarding non-EoE EGIDs, whose prevalence are estimated to range between 2.1 and 17.6 in 100,000 individuals, depending on age, sex, and ethnicity. Diagnosis requires the presence of suggestive symptoms, endoscopic biopsies showing abnormal values of eosinophils infiltrating the gut, and exclusion of secondary causes of eosinophilia. EoE typically presents with dysphagia and episodes of food bolus impactions, while EoG, EoN, and EoC may all present with abdominal pain and diarrhea, with or without other non-specific symptoms. In addition, although different EGIDs are currently classified as different entities, there may be overlap between different diseases in the same patient. Despite EGIDs being relatively novel pathological entities, the research on possible treatments is rapidly growing. In this regard, several randomized controlled trials are currently ongoing to investigate novel molecules, including ad-hoc steroid formulations, immunosuppressants, and mostly monoclonal antibodies that target the specific molecular mediators of EGIDs. This narrative review provides an up-to-date overview of available and investigational drugs for different EGIDs.
Topics: Humans; Gastritis; Enteritis; Eosinophilic Esophagitis; Eosinophils
PubMed: 37894846
DOI: 10.3390/ijms242015165 -
Gastroenterology Jan 2024The gut microbiota plays a significant role in the pathogenesis of both forms of inflammatory bowel disease (IBD), namely, Crohn's disease (CD) and ulcerative colitis... (Review)
Review
The gut microbiota plays a significant role in the pathogenesis of both forms of inflammatory bowel disease (IBD), namely, Crohn's disease (CD) and ulcerative colitis (UC). Although evidence suggests dysbiosis and loss of beneficial microbial species can exacerbate IBD, many new studies have identified microbes with pathogenic qualities, termed "pathobionts," within the intestines of patients with IBD. The concept of pathobionts initiating or driving the chronicity of IBD has largely focused on the putative aggravating role that adherent invasive Escherichia coli may play in CD. However, recent studies have identified additional bacterial and fungal pathobionts in patients with CD and UC. This review will highlight the characteristics of these pathobionts and their implications for IBD treatment. Beyond exploring the origins of pathobionts, we discuss those associated with specific clinical features and the potential mechanisms involved, such as creeping fat (Clostridium innocuum) and impaired wound healing (Debaryomyces hansenii) in patients with CD as well as the increased fecal proteolytic activity (Bacteroides vulgatus) seen as a biomarker for UC severity. Finally, we examine the potential impact of pathobionts on current IBD therapies, and several new approaches to target pathobionts currently in the early stages of development. Despite recognizing that pathobionts likely contribute to the pathogenesis of IBD, more work is needed to define their modes of action. Determining whether causal relationships exist between pathobionts and specific disease characteristics could pave the way for improved care for patients, particularly for those not responding to current IBD therapies.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Intestines; Feces
PubMed: 37734419
DOI: 10.1053/j.gastro.2023.09.019 -
Gut Sep 2023Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for...
BACKGROUND
Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery, type of placebo and evaluated endpoints. Although the overall outcomes appear to be promising, they are highly dependent on both donor and recipient factors.
OBJECTIVE
To develop concensus-based statements and recommendations for the evaluation, management and potential treatment of IBD using FMT in order to move towards standardised practices.
DESIGN
An international panel of experts convened several times to generate evidence-based guidelines by performing a deep evaluation of currently available and/or published data. Twenty-five experts in IBD, immunology and microbiology collaborated in different working groups to provide statements on the following key issues related to FMT in IBD: (A) pathogenesis and rationale, (B) donor selection and biobanking, (C) FMT practices and (D) consideration of future studies and perspectives. Statements were evaluated and voted on by all members using an electronic Delphi process, culminating in a plenary consensus conference and generation of proposed guidelines.
RESULTS AND CONCLUSIONS
Our group has provided specific statements and recommendations, based on best available evidence, with the end goal of providing guidance and general criteria required to promote FMT as a recognised strategy for the treatment of IBD.
Topics: Humans; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Rome; Inflammatory Bowel Diseases; Colitis, Ulcerative; Treatment Outcome
PubMed: 37339849
DOI: 10.1136/gutjnl-2023-329948 -
BMC Medicine Oct 2023The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it is not clear whether there is a causal relationship. We aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between IBD and extracolonic cancers.
METHODS
Independent genetic variants strongly associated with IBD were extracted as instrumental variables from genome-wide association study (GWAS) conducted by the International IBD Genetics Consortium including 12,882 IBD patients, 5956 Crohn's disease (CD) patients, and 6968 ulcerative colitis (UC) patients. Three sources of cancer GWAS were selected as outcome data. Two-sample Mendelian randomization (MR) analysis was conducted to assess the causal effects of IBD on 32 extracolonic cancers. The meta-analysis was applied to assess the combined causal effect with multiple MR results.
RESULTS
IBD, CD, and UC have potential causal associations with oral cavity cancer (IBD: OR = 1.180, 95% CI: 1.059 to 1.316, P = 0.003; CD: OR = 1.112, 95% CI: 1.008 to 1.227, P = 0.034; UC: OR = 1.158, 95% CI: 1.041 to 1.288, P = 0.007). Meta-analysis showed a significant positive causal relationship between IBD and breast cancer (OR = 1.059; 95% CI: 1.033 to 1.086; P < 0.0001) as well as a potential causal relationship between CD and breast cancer (OR = 1.029; 95% CI: 1.002 to 1.055; P = 0.032) based on combining multiple MR results.
CONCLUSIONS
This comprehensive MR analysis suggested that genetically predicted IBD, as well as its subtypes, may be a risk factor in the development of oral cavity and breast cancer.
Topics: Humans; Female; Genome-Wide Association Study; Mendelian Randomization Analysis; Inflammatory Bowel Diseases; Breast Neoplasms; Crohn Disease; Colitis, Ulcerative
PubMed: 37817217
DOI: 10.1186/s12916-023-03096-y -
Ugeskrift For Laeger Nov 2023In this case report, a previously healthy six-year-old presented with fever and altered mental status, and was found to have bacteremia with Listeria monocytogenes,...
In this case report, a previously healthy six-year-old presented with fever and altered mental status, and was found to have bacteremia with Listeria monocytogenes, acquired from premade fish balls. Invasive L. monocytogenes infection usually occurs in immunocompromised or newborns but may occasionally occur in healthy children with food-borne gastroenteritis. L. monocytogenes should be considered in patients with severe infection and symptoms of gastroenteritis, particularly since ceftriaxone, the Danish standard treatment for meningitis in children, does not cover L. monocytogenes.
Topics: Child; Humans; Bacteremia; Ceftriaxone; Gastroenteritis; Listeria monocytogenes; Meningitis, Listeria
PubMed: 37987449
DOI: No ID Found