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Early-life exposures and the microbiome: implications for IBD prevention. Gut The early-life period is one of microbiome establishment and immune maturation. Early-life exposures are increasingly being recognised to play an important role in IBD risk. The composition of functions of the gut microbiome in the prenatal, perinatal, and postnatal period may be crucial towards development of health or disease, including IBD, later in life. We herein present a comprehensive summary of the interplay between early-life factors and microbiome perturbations, and their association with risk of IBD. In addition, we provide an overview of host and external factors in early life that are known to impact gut microbiome maturation and exposures implicated in IBD risk. Considering the emerging concept of IBD prevention, we propose strategies to minimise maternal and offspring exposure to potentially harmful variables and recommend protective measures during pregnancy and the postpartum period. This holistic view of early-life factors and microbiome signatures among mothers and their offspring will help frame our current understanding of their importance towards IBD pathogenesis and frame the roadmap for preventive strategies. 10.1136/gutjnl-2023-330002
Clostridium difficile in inflammatory bowel disease. Current opinion in gastroenterology PURPOSE OF REVIEW:The chronic inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis, are associated with an increased risk of symptomatic Clostridium difficile infection (CDI). CDI may also masquerade as an IBD flare and complicate IBD management. This review provides a comprehensive overview of the epidemiology, diagnosis, and treatment of CDI in IBD patients. RECENT FINDINGS:CDI remains common in IBD with complications including flares in disease activity, recurrent CDI episodes, and prolonged hospital stays. Newer IBD therapeutics including vedolizumab, ustekinumab, and tofacitinib are less likely to cause severe CDI. A high index of suspicion, rapid testing via a two-step method, and prompt treatment with vancomycin or fidaxomicin are paramount to managing CDI in IBD patients. Strategies to prevent recurrent CDI (rCDI) include the monoclonal antibody bezlotoxumab as well as fecal microbiota transplantation (FMT). FMT has a robust profile of safety and effectiveness in preventing rCDI in adults and children. SUMMARY:Clinicians must remain vigilant in the prompt diagnosis and treatment of CDI in IBD patients. Corticosteroids, unnecessary antibiotics, and ongoing colonic inflammatory disease are modifiable risk factors. Improved infection control measures, newer IBD medications, and using effective CDI treatments will facilitate a reduced burden of severe CDI and complications for IBD patients. 10.1097/MOG.0000000000000949
Sarcopenia in Inflammatory Bowel Disease: A Narrative Overview. Dhaliwal Amritpal,Quinlan Jonathan I,Overthrow Kellie,Greig Carolyn,Lord Janet M,Armstrong Matthew J,Cooper Sheldon C Nutrients Malnutrition is a common condition encountered in patients with inflammatory bowel disease (IBD) and is often associated with sarcopenia (the reduction of muscle mass and strength) which is an ever-growing consideration in chronic diseases. Recent data suggest the prevalence of sarcopenia is 52% and 37% in Crohn's disease and ulcerative colitis, respectively, however it is challenging to fully appreciate the prevalence of sarcopenia in IBD. Sarcopenia is an important consideration in the management of IBD, including the impact on quality of life, prognostication, and treatment such as surgical interventions, biologics and immunomodulators. There is evolving research in many chronic inflammatory states, such as chronic liver disease and rheumatoid arthritis, whereby interventions have begun to be developed to counteract sarcopenia. The purpose of this review is to evaluate the current literature regarding the impact of sarcopenia in the management of IBD, from mechanistic drivers through to assessment and management. 10.3390/nu13020656
Macrophage immunometabolism in inflammatory bowel diseases: From pathogenesis to therapy. Pharmacology & therapeutics Inflammatory bowel disease (IBD), comprised of ulcerative colitis and Crohn's disease, is a chronic relapsing inflammatory disease of the gastrointestinal tract that closely related to immune dysfunction. Macrophages are the key gatekeeper of intestinal immune homeostasis and have vital influence on IBD. Hence, macrophages have been recognized as attractive targets to develop new therapeutic approaches for the disease. Recently, the growing field of immunometabolism has reinforced that metabolism reprogramming is a key determinant that dictates macrophage functions and subsequent disease progression. Herein, we elaborated how metabolic alterations underlie intestinal macrophage phenotype and function during IBD, and how microenvironmental cues trigger their metabolic reprogramming processes. More importantly, we deciphered the distinguishing characteristic of macrophage immunometabolism in IBD from other inflammatory diseases, and also summarized potential therapeutic approaches for IBD by manipulating cellular metabolism of macrophages. Finally, we discussed the major opportunities and challenges of harnessing metabolism to modulate aberrant macrophage responses in IBD. Altogether, our overview provides a framework for understanding the critical roles and potential therapeutic targets of macrophage immunometabolism in IBD. 10.1016/j.pharmthera.2022.108176
Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management. Rogler Gerhard,Singh Abha,Kavanaugh Arthur,Rubin David T Gastroenterology Inflammatory bowel diseases (IBDs) are systemic diseases that manifest not only in the gut and gastrointestinal tract, but also in the extraintestinal organs in many patients. The quality of life for patients with IBD can be substantially affected by these extraintestinal manifestations (EIMs). It is important to have knowledge of the prevalence, pathophysiology, and clinical presentation of EIMs in order to adapt therapeutic options to cover all aspects of IBD. EIMs can occur in up to 24% of patients with IBD before the onset of intestinal symptoms, and need to be recognized to initiate appropriate diagnostic procedures. EIMs most frequently affect joints, skin, or eyes, but can also affect other organs, such as the liver, lung, and pancreas. It is a frequent misconception that a successful therapy of the intestinal inflammation will be sufficient to treat EIMs satisfactorily in most patients with IBD. In general, peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum can be associated with active intestinal inflammation and can improve on standard treatment of the intestinal inflammation. However, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis usually occur independent of disease flares. This review provides a comprehensive overview of epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in IBD. 10.1053/j.gastro.2021.07.042
Inflammatory Bowel Disease: Clinical Diagnosis and Surgical Treatment-Overview. Medicina (Kaunas, Lithuania) This article is an overview of guidelines for the clinical diagnosis and surgical treatment of predominantly colonic inflammatory bowel diseases (IBD). This overview describes the systematically and comprehensively multidisciplinary recommendations based on the updated principles of evidence-based literature to promote the adoption of best surgical practices and research as well as patient and specialized healthcare provider education. Colonic IBD represents idiopathic, chronic, inflammatory disorders encompassing Crohn's colitis (CC) and ulcerative colitis (UC), the two unsolved medical subtypes of this condition, which present similarity in their clinical and histopathological characteristics. The standard state-of-the-art classification diagnostic steps are disease evaluation and assessment according to the Montreal classification to enable explicit communication with professionals. The signs and symptoms on first presentation are mainly connected with the anatomical localization and severity of the disease and less with the resulting diagnosis "CC" or "UC". This can clinically and histologically be non-definitive to interpret to establish criteria and is classified as indeterminate colitis (IC). Conservative surgical intervention varies depending on the disease phenotype and accessible avenues. The World Gastroenterology Organizations has, for this reason, recommended guidelines for clinical diagnosis and management. Surgical intervention is indicated when conservative treatment is ineffective (refractory), during intractable gastrointestinal hemorrhage, in obstructive gastrointestinal luminal stenosis (due to fibrotic scar tissue), or in the case of abscesses, peritonitis, or complicated fistula formation. The risk of colitis-associated colorectal cancer is realizable in IBD patients before and after restorative proctocolectomy with ileal pouch-anal anastomosis. Therefore, endoscopic surveillance strategies, aimed at the early detection of dysplasia, are recommended. During the COVID-19 pandemic, IBD patients continued to be admitted for IBD-related surgical interventions. Virtual and phone call follow-ups reinforcing the continuity of care are recommended. There is a need for special guidelines that explore solutions to the groundwork gap in terms of access limitations to IBD care in developing countries, and the irregular representation of socioeconomic stratification needs a strategic plan for how to address this serious emerging challenge in the global pandemic. 10.3390/medicina58050567
Overview to Challenges in IBD 2024-2029. Inflammatory bowel diseases The mission of the Crohn's & Colitis Foundation is to cure Crohn's disease and ulcerative colitis and to improve the quality of lives of patients living with these diseases-in other words, to care and cure. To achieve these missions, there is a need to identify and prioritize research gaps and approaches to address these gaps, which is the aim of Challenges in IBD 2024. The Foundation convened close to 80 experts in inflammatory bowel disease (IBD), including researchers, clinicians, patients and caregivers, funders, industry representatives, and Foundation scientific staff and organized them into 5 workgroups, one for each of the 5 Challenges topics: Preclinical Human IBD Mechanisms, Environmental Triggers, Precision Medicine, Novel Technologies, and Pragmatic Clinical Research. The findings of these groups outline a research agenda that intends to change the research paradigm in IBD by introducing 2 concepts in the course of IBD that warrant specific focus: interception (during the preclinical phase) and restoration of normal physiology after remission is achieved. We hope these reviews will stimulate innovations in our understanding and management of IBD. 10.1093/ibd/izae092
Dilemma in post-IBD patients with IBS-D symptoms: A 2020 overview. Tozlu Mukaddes,Cash Brooks,Younes Mamoun,Ertan Atilla Expert review of gastroenterology & hepatology INTRODUCTION:Inflammatory bowel disease (IBD) patients in apparent clinical remission who present with irritable bowel syndrome (IBS)-like symptoms pose a diagnostic and therapeutic dilemma that is called post-IBD IBS. When associated with a diarrheal IBS presentation, this clinical syndrome is known as post-IBD IBS-D. AREAS COVERED:We review and describe the literature regarding the clinical overlap of IBD and IBS. We discuss prevalent theories regarding the pathophysiology of post-IBD IBS-D and whether this presentation represents coincident inherent IBS-D, IBS-D triggered by IBD, or an even more subtle level of IBD activity that is unrecognized by available laboratory modalities. We also discuss observations that post-IBD IBS-D patients harbor significantly increased colon mucosal eosinophils and appear to respond to a GI-hypoallergenic diet and budesonide therapy. EXPERT OPINION:The symptoms overlap between IBD and IBS complicates diagnosis and subsequent management of patients with post-IBD IBS-D. In addition to current theories regarding the pathophysiology of this condition such as alterations in mucosal inflammation, the microbiota, mucosal permeability, and gut-brain interactions. This new avenue of eosinophilic colopathy and therapy directed toward food-derived immune response in patients with post-IBD IBS-D deserves additional investigation. 10.1080/17474124.2021.1829469
Supportive therapy in IBD: what additional diagnoses and conditions must be treated? Swoger Jason M,Binion David G Digestive diseases (Basel, Switzerland) Despite advances in our understanding of inflammatory bowel disease (IBD) pathogenesis and increased ability to treat patients with severe and refractory disease, patients continue to suffer from disease complications, and increasing numbers of both Crohn's disease (CD) and ulcerative colitis (UC) patients are admitted annually in the USA. The rapid evolution in IBD medications and treatment paradigms has contributed to a disparity in clinical care which may vary between expert centers routinely treating large numbers of IBD patients and hospitals with low annual IBD admissions. High-volume centers handling in excess of 150 IBD annual admissions have improved operative and inpatient outcomes compared with hospitals caring for IBD patients less frequently. Although the precise reason for this disparity in clinical outcomes is not known, we hypothesize that expert centers provide superior IBD supportive therapy. This supportive care includes additional diagnostic and therapeutic approaches to help patients achieve optimal outcomes. We review information regarding disparities in the quality of IBD clinical care then focus on supportive therapy for IBD patients, including diagnostic approaches to identify confounding factors contributing to poor IBD outcome, supportive therapeutic approaches to optimize the outcome in hospitalized IBD patients, and future directions exploring brain-body interaction in the treatment of pain, stress and sleep deprivation in patients suffering from IBD. 10.1159/000320402
IBD Disability Index Is Associated With Both Direct and Indirect Costs of Inflammatory Bowel Disease. Inflammatory bowel diseases INTRODUCTION:We aimed to determine both direct (medical) and indirect (lost wages) costs of IBD and the association between the degree of IBD-related disability and extent of IBD-related costs. METHODS:Persons age 18-65 from the population-based University of Manitoba IBD Research Registry completed a survey including the IBD Disability Index (IBDDI) and questions related to employment, missed work (absenteeism), and reduced productivity at work (presenteeism). Administrative health data including surgeries, hospitalizations, physician claims, and prescriptions were linked to the survey and assessed. To calculate annual wage loss, number of days of missed work was multiplied by the average wage in Manitoba for the given occupation per Statistics Canada. Costs were adjusted to 2016-17 Canadian dollars. Using descriptive and regression analysis, we explored the association between IBDDI and annual direct and indirect costs associated with IBD. RESULTS:Average annual medical costs rose from $1918 among those with IBDDI 0-4 to $9,993 among those with IBDDI 80-86. Average annual cost of lost work rose from $0 among those with IBDDI 0-4 to $30,101 among those with IBDDI 80-86. Using linear regression, each additional unit of IBDDI was associated with an increase of $77 in annual medical cost (95% CI, $52-102; P < .001) and an increase of $341 in annual cost of lost wages (95% CI, $288-395; P < .001). CONCLUSIONS:Costs related to IBD are significantly associated with the degree of IBD-related disability. Among the approximate 30% of the IBD population with IBDDI scores ≥40, the indirect costs of absenteeism and presenteeism accounts for ~75% of the total IBD-related costs. 10.1093/ibd/izab248
Improving the care of inflammatory bowel disease (IBD) patients: perspectives and strategies for IBD center management. Park Jihye,Park Sinyoung,Lee Shin Ae,Park Soo Jung,Cheon Jae Hee The Korean journal of internal medicine The incidence and prevalence rates of inf lammatory bowel disease (IBD) have been increasing in East Asian countries over the past few decades. Accordingly, the general understanding and awareness of IBD among healthcare professionals has increased considerably in this region. This increase is ultimately associated with the evolving focus of IBD clinicians devoted to comprehensive patient care, especially in establishing IBD clinics/centers capable of providing multidisciplinary counseling. Comprehensive IBD care at IBD clinics/centers usually includes surgical and medication decision-making, transition from pediatric to adult clinics, care of extraintestinal manifestations, care of infectious diseases in patients undergoing immunomodulatory or biologic therapies, and nutritional, psychosocial, socioeconomic, and pharmacological care. Team members comprise specialists from various departments related to IBD and can be divided into core and ad hoc members. Usually, the scope of work in IBD clinics/centers involves patient care, patient outreach, and system management. Considering the environmental changes in IBD treatment, it is necessary to perform comprehensive IBD patient care in the form of a program based on competencies, rather than simply following the organization of previous IBD centers. The present review summarizes recent trends in IBD patient care and offers perspectives regarding IBD center management. 10.3904/kjim.2021.114
The epidemiology of inflammatory bowel disease: Clues to pathogenesis? Frontiers in pediatrics Historically, inflammatory bowel disease (IBD) was most common in North America and Europe and more common with a north-south gradient. Over the past century, there has been a marked increase in IBD in general and in childhood IBD in particular and over the past 50 years IBD has spread into the developing world. The greatest risk factor of developing IBD is an affected family member. Concordance rates between dizygotic twins is ∼4% and ∼50% in monozygotic twins, and more than half of pairs are diagnosed within 2 years of each other. Nevertheless, most patients with IBD do not have an affected family member. More than 200 genes are associated with an increased risk for IBD, but most associations are weak with odds ratios between 1.2 and 2.0 suggesting the environment plays a role. IBD is more common in urban than rural regions and is associated with "good standards" of domestic hygiene during childhood. People who migrate from areas with a low incidence to areas with a high incidence of IBD have an increased risk of developing IBD and the younger they are when they migrate, the greater their risk of developing IBD. Moreover, people who migrate from regions with a high incidence to areas with a low incidence of IBD have a decreased risk of developing IBD. Together, these findings strongly suggest particular environmental exposures occurring early in life may trigger inflammatory bowel disease in genetically susceptible individuals. The key is figuring out what those exposures might be. 10.3389/fped.2022.1103713
The Management Approach to the Adolescent IBD Patient: Health Maintenance and Medication Considerations. Current gastroenterology reports PURPOSE OF REVIEW:Inflammatory bowel disease (IBD) is often diagnosed during adolescence and can have a deep impact on the physical, hormonal, developmental, and psychosocial changes associated with this life period. The purpose of this review is to address the particular manifestations of IBD (such as growth and pubertal delay), health maintenance issues, and treatment considerations in the adolescent. RECENT FINDINGS:The need for a multidisciplinary approach to recognize and address growth and pubertal delay, bone health, as well as the psychosocial impact of IBD on the adolescent has been increasingly recognized as an integral part of IBD care in this population. Vaccinations schedule, preventive health measures, and promoting compliance with care are particularly important during adolescence. Replacing nutrients deficits is also crucial: in particular, vitamin D has been shown to play a role in the gut immune system, and adequate vitamin D levels might promote IBD remission. Iron replacement should be done by intravenous route since oral iron is poorly absorbed in chronic inflammatory states. Finally, recent data have shed light on the increased risk of particular types of lymphoma in adolescent on thiopurines, whereas biologic therapies, in particular, anti-TNF, now are positioned as a preferred and effective steroid-sparing agents in moderate to severe IBD. Management of adolescents with IBD is not without significant challenges. An early implementation of steroid-sparing therapies, a multidisciplinary treatment approach, and a dynamic physician-patient relationship are essential to achieve remission, prevent disease-related complications but also optimize developmental, physical, and psychosocial health, and encourage compliance and transition to adult care. 10.1007/s11894-019-0739-9
Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-analyses. Piovani Daniele,Danese Silvio,Peyrin-Biroulet Laurent,Nikolopoulos Georgios K,Lytras Theodore,Bonovas Stefanos Gastroenterology BACKGROUND & AIMS:Multiple environmental factors have been associated with the development of inflammatory bowel diseases (IBDs). We performed an umbrella review of meta-analyses to summarize available epidemiologic evidence and assess its credibility. METHODS:We systematically identified and appraised meta-analyses of observational studies examining environmental factors and risk of IBD (Crohn's disease [CD] or ulcerative colitis [UC]). For each meta-analysis, we considered the random effects estimate, its 95% confidence interval, the estimates of heterogeneity, and small-study effects, and we graded the evidence according to prespecified criteria. Methodologic quality was assessed with AMSTAR (ie, A Measurement Tool to Assess Systematic Reviews) 2. RESULTS:We examined 183 estimates in 53 meta-analyses of 71 environmental factors related to lifestyles and hygiene, surgeries, drug exposures, diet, microorganisms, and vaccinations. We identified 9 factors that increase risk of IBD: smoking (CD), urban living (CD and IBD), appendectomy (CD), tonsillectomy (CD), antibiotic exposure (IBD), oral contraceptive use (IBD), consumption of soft drinks (UC), vitamin D deficiency (IBD), and non-Helicobacter pylori-like enterohepatic Helicobacter species (IBD). We identified 7 factors that reduce risk of IBD: physical activity (CD), breastfeeding (IBD), bed sharing (CD), tea consumption (UC), high levels of folate (IBD), high levels of vitamin D (CD), and H pylori infection (CD, UC, and IBD). Epidemiologic evidence for all of these associations was of high to moderate strength; we identified another 11 factors associated with increased risk and 16 factors associated with reduced risk with weak credibility. Methodologic quality varied considerably among meta-analyses. Several associations were based on findings from retrospective studies, so it is not possible to determine if these are effects of IBD or the results of recall bias. CONCLUSIONS:In an umbrella review of meta-analyses, we found varying levels of evidence for associations of different environmental factors with risk of IBD. High-quality prospective studies with analyses of samples from patients with recent diagnoses of IBD are needed to determine whether these factors cause or are results of IBD and their pathogenic mechanisms. 10.1053/j.gastro.2019.04.016
Morphology of inflammatory bowel diseases (IBD). Ceskoslovenska patologie Inflammatory bowel diseases (IBD) represent a group of chronic systemic inflammatory conditions with predilection to gastrointestinal tract and include Crohns disease and ulcerative colitis. If the IBD cannot be further specified, a term unclassified IBD is used. Histopathological diagnosis of IBD relies on identifying a chronic inflammatory pattern in proper topographic distribution, showing structural abnormalities of the intestinal mucosa and characteristic cellular composition of the inflammatory infiltrate. The intestinal involvement in Crohns disease is typically segmental, with predilection for terminal ileum and presence of epithelioid granulomas in histology. Ulcerative colitis shows a diffuse pattern of the inflammation and usually affects a rectum, with variable extension towards a terminal ileum. However, there is an expanding knowledge about etiopathogenesis, morphology and clinical presentation of IBD, which led to detailed phenotypic subclassification and defined many atypical variants. As a result, diagnosis of IBD became complex multidisciplinary process. The aim of this work is to present an overview of IBD morphology and to provide a base for histopathological diagnosis of IBD on both bioptic samples and surgical resections.