scholarly journals Revisiting Inflammatory Bowel Disease: Pathology, Treatments, Challenges and Emerging Therapeutics Including Drug Leads from Natural Products

2020 ◽  
Vol 9 (5) ◽  
pp. 1273 ◽  
Author(s):  
Karma Yeshi ◽  
Roland Ruscher ◽  
Luke Hunter ◽  
Norelle L. Daly ◽  
Alex Loukas ◽  
...  
Keyword(s):  
Health Care ◽  
Inflammatory Bowel Disease ◽  
Natural Products ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Treatment Options ◽  
Mucosal Healing ◽  
Main Challenge ◽  
Long Term Treatment ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic and life-long disease characterized by gastrointestinal tract inflammation. It is caused by the interplay of the host’s genetic predisposition and immune responses, and various environmental factors. Despite many treatment options, there is no cure for IBD. The increasing incidence and prevalence of IBD and lack of effective long-term treatment options have resulted in a substantial economic burden to the healthcare system worldwide. Biologics targeting inflammatory cytokines initiated a shift from symptomatic control towards objective treatment goals such as mucosal healing. There are seven monoclonal antibody therapies excluding their biosimilars approved by the US Food and Drug Administration for induction and maintenance of clinical remission in IBD. Adverse side effects associated with almost all currently available drugs, especially biologics, is the main challenge in IBD management. Natural products have significant potential as therapeutic agents with an increasing role in health care. Given that natural products display great structural diversity and are relatively easy to modify chemically, they represent ideal scaffolds upon which to generate novel therapeutics. This review focuses on the pathology, currently available treatment options for IBD and associated challenges, and the roles played by natural products in health care. It discusses these natural products within the current biodiscovery research agenda, including the applications of drug discovery techniques and the search for next-generation drugs to treat a plethora of inflammatory diseases, with a major focus on IBD.

scholarly journals P059 Cytokine responsive transcriptional networks in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S164-S164
Author(s):  
A Treveil ◽  
P Pavlidis ◽  
A Tsakmaki ◽  
G Bewick ◽  
T Korcsmaros ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Mucosal Healing ◽  
Mucosal Barrier ◽  
Transcriptional Networks ◽  
Intestinal Epithelial ◽  
Transcriptomics Data ◽  
Inflammatory Bowel ◽  
Regulatory Effects

Abstract Background Interactions between the immune system and the intestinal epithelium play an important role in the pathogenesis of chronic immune mediated inflammatory diseases, including inflammatory bowel disease (IBD). In IBD, debilitating symptoms and complications including abscesses and cancer are associated with aberrant cytokine production and resulting intestinal epithelial damage. Despite the advent of biological therapies targeting key pathogenic cytokines, like tumour necrosis α (TNF), only 18% of IBD patients will achieve complete disease control and mucosal healing. Here, we provide new insights into the epithelial response to cytokines using network analysis of transcriptomics data from colonic organoids (colonoids). Methods We generated an atlas of the transcriptomic effects of cytokines by treating human-derived colonoids with IFNg, IL13, IL9, IL17A and TNF (independently). By integrating the observed transcriptional changes with previously published signalling and regulatory interactions, we generated causal networks to elucidate the effect of cytokine cues on epithelial cells. These networks comprised experimentally verified protein–protein and transcription factor (TF)–target gene interactions, forming signalling pathways linking cytokines to TFs and from TFs to differentially expressed genes. Results With this analysis, we identified previously unrecognised levels of shared and distinct transcriptional regulation of colonic epithelial function by different cytokines. While IL9 had a negligible impact on the transcriptome, the transcripts with differential expression induced by IFNg, IL13, IL17A or TNF were consistent with their recognised function in other tissues. IFNg and TNF exhibited similar magnitude and directional effects on key immune pathways while IL13 had the opposite effect. Using a network approach, we found that regulatory effects of cytokines are primarily transduced through unique signalling routes, some of which converge on the same key transcription factors; CEBPA, E2F1, E2F2, ETS1, FOS, IRF1 and MAZ. We observed independent regulatory mechanisms of the different cytokines as well as complementarity in the epithelial responses regulated by different canonical cytokines. Conclusion The generated cytokine transcriptional atlas provides a unique insight into the immune-epithelial interactome by allowing the identification of shared and distinct transcriptional pathways across different types of immunity at the mucosal barrier. In addition, it provides the unique opportunity to study cytokine responses in the context of human disease and generate novel hypotheses.

Natural Products: Experimental Efficient Agents for Inflammatory Bowel Disease Therapy

2020 ◽  
Vol 25 (46) ◽  
pp. 4893-4913 ◽  
Author(s):  
Fan Cao ◽  
Jie Liu ◽  
Bing-Xian Sha ◽  
Hai-Feng Pan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Natural Products ◽  
Immune System ◽  
Bowel Disease ◽  
Therapeutic Potential ◽  
Adaptive Immune System ◽  
Receptor Protein ◽  
Intestinal Epithelia ◽  
Inflammatory Bowel ◽  
The Individual

: Inflammatory bowel disease (IBD) is a chronic, elusive disorder resulting in relapsing inflammation of intestine with incompletely elucidated etiology, whose two representative forms are ulcerative colitis (UC) and Crohn’s disease (CD). Accumulating researches have revealed that the individual genetic susceptibility, environmental risk elements, intestinal microbial flora, as well as innate and adaptive immune system are implicated in the pathogenesis and development of IBD. Despite remarkable progression of IBD therapy has been achieved by chemical drugs and biological therapies such as aminosalicylates, corticosteroids, antibiotics, anti-tumor necrosis factor (TNF)-α, anti-integrin agents, etc., healing outcome still cannot be obtained, along with inevitable side effects. Consequently, a variety of researches have focused on exploring new therapies, and found that natural products (NPs) isolated from herbs or plants may serve as promising therapeutic agents for IBD through antiinflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic effects, which implicates the modulation on nucleotide- binding domain (NOD) like receptor protein (NLRP) 3 inflammasome, gut microbiota, intestinal microvascular endothelial cells, intestinal epithelia, immune system, etc. In the present review, we will summarize the research development of IBD pathogenesis and current mainstream therapy, as well as the therapeutic potential and intrinsic mechanisms of NPs in IBD.

scholarly journals Optimal Range of Fecal Calprotectin for Predicting Mucosal Healing in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-11
Author(s):  
Bing-Jie Xiang ◽  
Min Jiang ◽  
Ming-Jun Sun ◽  
Cong Dai
Keyword(s):  
Inflammatory Bowel Disease ◽  
Diagnostic Accuracy ◽  
Likelihood Ratio ◽  
Sensitivity And Specificity ◽  
Bowel Disease ◽  
Meta Analysis ◽  
Positive Likelihood Ratio ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
Inflammatory Bowel

<b><i>Objective:</i></b> Fecal calprotectin (FC) is a promising marker for assessment of inflammatory bowel disease (IBD) activity. However, the utility of FC for predicting mucosal healing (MH) of IBD patients has yet to be clearly demonstrated. The objective of our study was to perform a meta-analysis evaluating the diagnostic accuracy of FC in predicting MH of IBD patients. <b><i>Methods:</i></b> We systematically searched the databases for studies from inception to April 2020 that evaluated MH in IBD. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. <b><i>Results:</i></b> Sixteen studies comprising 1,682 ulcerative colitis (UC) patients and 4 studies comprising 221 Crohn’s disease (CD) patients were included. The best performance of FC for predicting MH in UC was at cut-off range of 60–75 μg/g with area under the curve (AUC) of 0.88 and pooled sensitivity and specificity of 0.87 and 0.79, respectively. The pooled sensitivity and specificity values of cutoff range 180–250 μg/g for predicting MH in CD were 0.67 and 0.76, respectively. The AUC of 0.79 also revealed improved discrimination for identifying MH in CD with FC concentration. <b><i>Conclusion:</i></b> Our meta-analysis has found that FC is a simple, reliable noninvasive marker for predicting MH in IBD patients. FC cutoff range 60–75 μg/g appears to have the best overall accuracy in UC patients.

scholarly journals A183 TELEHEALTH USE IN RURAL SASKATCHEWAN AND INFLAMMATORY BOWEL DISEASE OUTCOMES

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 197-199
Author(s):  
M Patterson ◽  
M Gozdzik ◽  
J Peña-Sánchez ◽  
S Fowler
Keyword(s):  
Health Care ◽  
Inflammatory Bowel Disease ◽  
Health Care Utilization ◽  
Bowel Disease ◽  
Postal Code ◽  
Care Utilization ◽  
Specialist Care ◽  
Disease Characteristics ◽  
Significant Difference ◽  
Inflammatory Bowel

Abstract Background Appropriate management of inflammatory bowel disease (IBD) often requires multiple specialist appointments per year. Living in rural locations may pose a barrier to regular specialist care. Saskatchewan (SK) has a large rural population. Prior to COVID-19, telehealth (TH) in SK was not routinely used for either patient assessment or follow up. Furthermore, TH was exclusively between hospitals and specific TH sites without direct contact using patient’s personal phones. Aims The objective of this study was to assess the differences in demographics, disease characteristics, outcomes, and health care utilization between patients from rural SK with IBD who used TH and those who did not. Methods A retrospective chart review was completed on all rural patients (postal code S0*) with IBD in SK who were followed at the Multidisciplinary IBD Clinic in Saskatoon between January 2018 and February 2020. Patients were classified as using TH if they had ever used it. Information on demographics, disease characteristics, and access to IBD-related health care in the year prior to their last IBD clinic visit or endoscopy was collected. Data was not collected for clinic visits after March 1, 2020 as all outpatient care became remote secondary to the COVID-19 pandemic. Mean, standard deviations, median and interquartile ranges (IQR) were reported. Mann-Witney U and Chi-Square tests were used to determine differences between the groups. Results In total, 288 rural SK IBD patients were included, 30 (10.4%) used TH and 258 (89.6%) did not. Patient demographics were not significantly different between the two groups; although, there was a statistically significant difference in the proportion of ulcerative colitis patients (17% TH vs. 38% non-TH, p=0.02). The percentage of patients with clinical remission was 87% for TH patients and 74% for non-TH patients (p=0.13). There were no significant differences in health care utilization patterns and biochemical markers of disease, including c-reactive protein (CRP) and fecal calprotectin (FCP) (p&gt;0.05). Conclusions Prior to the pandemic, a small percentage of patients with IBD in rural SK ever used TH. A small proportion of UC patients used TH. No significant differences in disease characteristics, outcomes, or health care utilization were identified. Further study is warranted to identify barriers to use of this technology to tailor care to this patient group and improve access to care, especially now as the COVID-19 pandemic has drastically changed the use of virtual care. Funding Agencies None

scholarly journals Health care and patients' education in a European inflammatory bowel disease inception cohort: An ECCO-EpiCom study

2014 ◽  
Vol 8 (8) ◽  
pp. 811-818 ◽  
Author(s):  
J. Burisch ◽  
Z. Vegh ◽  
N. Pedersen ◽  
S. Čuković-Čavka ◽  
N. Turk ◽  
...  
Keyword(s):  
Health Care ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inception Cohort ◽  
Inflammatory Bowel

scholarly journals Socio-anamnestic and clinical analysis of pregnant women with ulcerative colitis

2021 ◽  
Vol 25 (1) ◽  
pp. 65-69
Author(s):  
I. V. Oleksiienko
Keyword(s):  
Ulcerative Colitis ◽  
Health Care ◽  
Inflammatory Bowel Disease ◽  
Pregnant Women ◽  
Bowel Disease ◽  
Clinical Analysis ◽  
Chronic Inflammatory Bowel Disease ◽  
Care Providers ◽  
History Of ◽  
Inflammatory Bowel

Annotation. At the turn of the 21st century, chronic inflammatory bowel disease (CIBD) has become a global disease with accelerating morbidity in industrialized countries with a prevalence exceeding 0.3%. These data underscore the need for research into the prevention of inflammatory bowel disease and innovations in health care systems to manage this complex and costly disease. The information from a personal anamnesis of 40 women patients with ulcerative colitis (clinical group (main). In the second group (control), 30 practically healthy pregnant women with a physiological course of gestation were included, which did not have in their history of inflammatory intestinal diseases. Statistical processing of research results was performed using the software package Statistica 6.0. The arithmetic mean (M) and the standard deviation error (± m) (p<0.05) were determined, as well as the odds ratio (OR), confidence interval (CI) at p=95%. It was found that for women with ulcerative colitis is characterized by the presence of a history of obstetric pathology, such as: spontaneous miscarriage of OR 3.33, 95% CI [1.06-10.53], p=0.04 and blood secretions of OR 3.0, 95% CI [1.00-8.98], p=0.0496; among extragenital pathology in the anamnesis: children's infectious diseases of OR 4.85, 95% CI [1.25-18.85], p=0.02, chronic bronchitis of OR 7.54, 95% CI [1,56-36, 41], p=0.01, varicose veins OR 4.33, 95% CI [1.11-16.95], p=0.035, chronic gastritis OR 6.0, 95% CI [1,23-29, 31], p=0.03, anemia of OR 15.0, 95% CI [4.53-49.68], p<0.0001, allergy history of OR 6.65, 95% CI [1.73-25.60], p=0.006; among gynecological complications – premenstrual syndrome OR 6.0, 95% CI [1.55-23.15], p=0.009, algomenorrhea OR 8.14, 95% CI [2.12-31.24], p=0.002 , salpingo-oophoritis, OR 7.54, 95% CI [1.56-36.41], p=0.01. Because CIBD during pregnancy is associated with an increased risk of adverse effects on the mother and fetus, information on socio-anamnestic and clinical analysis of pregnant women with ulcerative colitis will be useful to health care providers in making decisions about CIBD during pregnancy.

scholarly journals Cardiovascular risks in patients with inflammatory bowel disease: what should be taken into account?

2021 ◽  
Vol 1 (6) ◽  
pp. 112-120
Author(s):  
G. B. Bikbavova ◽  
M. A. Livzan
Keyword(s):  
Cardiovascular Disease ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Treat To Target ◽  
Steady Increase ◽  
Cardiovascular Risks ◽  
Specialized Care ◽  
Pathogenetic Therapy ◽  
Inflammatory Bowel

In recent years, there has been a steady increase in the incidence of inflammatory bowel disease (IBD) worldwide. Treatment of ulcerative colitis and Crohn’s disease has become more effective thanks to the emergence of biological therapies, increased access to specialized care and a “treat to target” approach. However, with an increase in the life expectancy of patients with IBD, there is an increase in the number of persons with comorbidity, primarily with a combination of IBD with cardiovascular pathology. Environmental factors lead to a change in the diversity and density of colonization of the intestinal microbiota, a violation of its barrier function, immune dysregulation, which in turn leads to the development of chronic inflammatory diseases and atherosclerosis. Levels of proinflammatory cytokines, C-reactive protein, and homocysteine increase in IBD, leading to endothelial dysfunction and atherosclerosis. In addition, inflammatory processes in IBD promote hypercoagulation, which occurs both in the thromboembolic complications and in the pathogenesis of the disease itself. It has been suggested that medical pathogenetic therapy for IBD is also associated with the risk of cardiovascular disease. In this review, we systematize the available data on the risks of cardiovascular diseases in patients with IBD. A literature search containing information on relevant studies was carried out in PubMed and Google Scholar systems with the keywords: inflammatory bowel disease, cardiovascular disease, inflammation, atherosclerosis.

scholarly journals Emerging roles of the Hedgehog signalling pathway in inflammatory bowel disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhuo Xie ◽  
Mudan Zhang ◽  
Gaoshi Zhou ◽  
Lihui Lin ◽  
Jing Han ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Critical Role ◽  
Signalling Pathway ◽  
Hedgehog Signalling Pathway ◽  
Inflammatory Bowel ◽  
Effective Drugs

AbstractThe Hedgehog (Hh) signalling pathway plays a critical role in the growth and patterning during embryonic development and maintenance of adult tissue homeostasis. Emerging data indicate that Hh signalling is implicated in the pathogenesis of inflammatory bowel disease (IBD). Current therapeutic treatments for IBD require optimisation, and novel effective drugs are warranted. Targeting the Hh signalling pathway may pave the way for successful IBD treatment. In this review, we introduce the molecular mechanisms underlying the Hh signalling pathway and its role in maintaining intestinal homeostasis. Then, we present interactions between the Hh signalling and other pathways involved in IBD and colitis-associated colorectal cancer (CAC), such as the Wnt and nuclear factor-kappa B (NF-κB) pathways. Furthermore, we summarise the latest research on Hh signalling associated with the occurrence and progression of IBD and CAC. Finally, we discuss the future directions for research on the role of Hh signalling in IBD pathogenesis and provide viewpoints on novel treatment options for IBD by targeting Hh signalling. An in-depth understanding of the complex role of Hh signalling in IBD pathogenesis will contribute to the development of new effective therapies for IBD patients.

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