Thrombosis in inflammatory bowel diseases: what's the link?
Ontology highlight
ABSTRACT:
SUBMITTER: Giannotta M
PROVIDER: S-EPMC4393581 | biostudies-other | 2015
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is associated with a loss or an imbalance of host-microbe interactions. Depletion-assisted deep metaproteomics was employed to reveal disease-specific networks of host-microbial protein associations in IBD.
2023-06-28 | PXD043380 | iProX
Project description:Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal mucosa and unknown etiology. In this review, we identified three main eras in the IBD history. Between the 19th and the 20th century, the primary task had been the definition of the diagnostic criteria in order to differentiate the new entity from intestinal tuberculosis. In the 20th century, an intense and prolific therapeutic research prevailed, culminating in the introduction of biological drugs in the clinical setting. Since the beginning of the 21st century, traditional definition criteria have been challenged by holistic criteria in an effort to seek a still unattained cure. Centuries of worldwide efforts on IBD etiology and therapy search have culminated in this novel strategy.
| S-EPMC6912289 | biostudies-literature
Project description:In this review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and noncoding genetic variation. In the small minority of loci where major association signals correspond to nonsynonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve noncoding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that the expression of most human genes is regulated by noncoding genetic variations. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (ie, odds ratios markedly deviating from 1) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in more severe very early onset cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility through emerging precision medical initiatives. In this article, we discuss the rapidly evolving area of direct-to-consumer genetic testing and the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect to partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and across subspecialties and disciplines will be required to fully realize the promise of genetic discovery in IBD.
| S-EPMC4915781 | biostudies-literature
Project description:Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.
| S-EPMC7409252 | biostudies-literature
Project description:The epithelium of the gastrointestinal tract is one of the most versatile tissues in the organism, responsible for providing a tight barrier between dietary and bacterial antigens and the mucosal and systemic immune system while maintaining efficient digestive and absorptive processes to ensure adequate nutrient and energy supply. Inflammatory bowel diseases (Crohn's disease and ulcerative colitis) are associated with a breakdown of both functions, which in some cases are clearly interrelated. In this updated literature review, we focus on the effects of intestinal inflammation and the associated immune mediators on selected aspects of the transepithelial transport of macronutrients and micronutrients. The mechanisms responsible for nutritional deficiencies are not always clear and could be related to decreased intake, malabsorption, and excess losses. We summarize the known causes of nutrient deficiencies and the mechanism of inflammatory bowel disease-associated diarrhea. We also overview the consequences of impaired epithelial transport, which infrequently transcend its primary purpose to affect the gut microbial ecology and epithelial integrity. Although some of those regulatory mechanisms are relatively well established, more work needs to be done to determine how inflammatory cytokines can alter the transport process of nutrients across the gastrointestinal and renal epithelia.
| S-EPMC4103619 | biostudies-literature
Project description:Inflammatory bowel diseases (IBD) are chronic intestinal disorders characterized by dysregulated immune responses to resident microbiota in genetically susceptible hosts. The activation of the cholinergic system has been proposed for the treatment of IBD patients according to its potential anti-inflammatory effect in vivo. The α-7-nicotinic-acetylcholine receptor (α7nAChR) is involved in the inhibition of inflammatory processes, modulating the production of cytokines, suppressing dendritic cells and macrophage activity, leading to the suppression of T cells. In this review, we address the most recent studies and clinical trials concerning cholinergic signaling and its therapeutic potential for inflammatory bowel diseases.
| S-EPMC8683952 | biostudies-literature
Project description:BACKGROUND:Persons with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism. We sought to examine whether the self-report of hormonal contraception (HC), as a proxy for exposure to estrogen-based contraception, was less common for women with multiple risk factors for venous thromboembolism. METHODS:We examined the prevalence of personal use of hormonal birth control in a large internet-based cohort of patients with IBD. To determine whether HC was less common among patients with IBD with increased risk of thrombosis, we estimated unadjusted and adjusted prevalence ratios (PRs) for the use of HC. RESULTS:Thousand four hundred ninety-nine female survey respondents answered optional fertility questions and were included in the analysis. The prevalence of HC was 33.7% (95% CI, 30.6%-36.9%) among women with Crohn's disease and was 32.6% (95% CI, 28.6%-36.8%) for women with ulcerative colitis. Women with one risk factor for thrombosis were not significantly less likely to receive HC (PR = 0.91, 95% CI: 0.76-1.08; adjusted PR = 0.94, 95% CI: 0.80-1.11) compared with women without risk factors nor were women with 2 or more risk factors (PR = 1.10, 95% CI 0.56-1.28; adjusted PR = 1.10, 95% CI: 0.83-1.45). The use of an intrauterine device was also similar between women with and without risk factors for venous thromboembolism. CONCLUSIONS:The prevalence of HC use in women with multiple risk factors was similar to that in women without risk factors, which represents an opportunity for prevention. Gastroenterologists should ask patients with IBD using HC about risk factors for thromboembolic disease to identify patients who may benefit from alternative contraception.
| S-EPMC5064836 | biostudies-literature
Project description:Background: The human gut microbiota is a dynamic community of microorganisms that mediate important biochemical processes. Differences in the gut microbial composition have been associated with inflammatory bowel diseases (IBD) and other intestinal disorders. In this study, we quantified and compared the frequencies of eight genotoxic and/or pro-inflammatory bacterial genes found in metagenomic Whole Genome Sequences (mWGSs) of samples from individuals with IBD vs. a cohort of healthy human subjects. Methods: The eight selected gene sequences were clbN, clbB, cif, cnf-1, usp, tcpC from Escherichia coli, gelE from Enterococcus faecalis and murB from Akkermansia muciniphila. We also included the sequences for the conserved murB genes from E. coli and E. faecalis as markers for the presence of Enterobacteriaceae or Enterococci in the samples. The gene sequences were chosen based on their previously reported ability to disrupt normal cellular processes to either promote inflammation or to cause DNA damage in cultured cells or animal models, which could be linked to a role in IBD. The selected sequences were searched in three different mWGS datasets accessed through the Human Microbiome Project (HMP): a healthy cohort (N = 251), a Crohn's disease cohort (N = 60) and an ulcerative colitis cohort (N = 17). Results: Firstly, the sequences for the murB housekeeping genes from Enterobacteriaceae and Enterococci were more frequently found in the IBD cohorts (32% E. coli in IBD vs. 12% in healthy; 13% E. faecalis in IBD vs. 3% in healthy) than in the healthy cohort, confirming earlier reports of a higher presence of both of these taxa in IBD. For some of the sequences in our study, especially usp and gelE, their frequency was even more sharply increased in the IBD cohorts than in the healthy cohort, suggesting an association with IBD that is not easily explained by the increased presence of E. coli or E. faecalis in those samples. Conclusion: Our results suggest a significant association between the presence of some of these genotoxic or pro-inflammatory gene sequences and IBDs. In addition, these results illustrate the power and limitations of the HMP database in the detection of possible clinical correlations for individual bacterial genes.
| S-EPMC5902703 | biostudies-literature
Project description:Alexithymia is usually described by three main dimensions difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT). The most commonly used questionnaire investigating alexithymia, the Toronto Alexithymia Scale (TAS-20), supports this three-factor structure. One important assumption is that alexithymia severity is associated to vulnerability to somatic diseases, among them gastrointestinal disorders. However, the association between alexithymia and gastrointestinal disorders is not systematic, thus questioning the role of alexithymia as a vulnerability factor for those illnesses. A recent factor analysis suggested another four-factor structure for the TAS-20: difficulties in awareness of feelings (DAF), difficulties in interoceptive abilities (DIA), externally oriented thinking (EOT), and poor affective sharing (PAS). We assume that DIA and DAF might be more relevant to investigate the association between alexithymia and gastrointestinal disorders. The rationale is that DIA and DAF reflect impairments in emotion regulation that could contribute to an inappropriate autonomic and HPA axis homeostasis in irritable bowel syndrome (IBS), ulcerative colitis (UC), or Crohn's disease (CD). The aim of this study was to investigate whether DIA and DAF are associated with the presence of IBS, UC or CD, while checking for anxiety, depression, parasympathetic (vagus nerve) activity and cortisol levels. We recruited control participants (n=26), and patients in remission who were diagnosed with IBS (n=24), UC (n=18), or CD (n=21). Participants completed questionnaires to assess anxiety, depression, and alexithymia. A blood sample and an electrocardiogram were used to measure the level of cortisol and parasympathetic activity, respectively. Logistic regressions with the four-factor structure of the TAS-20 revealed that DIA was a significant predictor of IBS (W(1)=6.27, p=.01). Conversely, DIA and DAF were not significant predictors in CD and UC patients. However, low cortisol level was a significant predictor of UC (W(1)=4.67, p=.035). Additional logistic regressions based on the original 3-factor structure of TAS-20 (DIF, DDF, and EOT) showed that only DDF was a significant predictor of CD [W(1)=6.16, p < .001]. The present study suggests that DIA is an important dimension for assessing potential risk for gastrointestinal diseases, in particular for IBS.
| S-EPMC7142209 | biostudies-literature
Project description:Methotrexate (MTX) is an established therapy for patients with steroid-dependent Crohn's disease (CD). MTX is also frequently used in combination with anti-TNF agents to suppress anti-drug antibody formation. It has been suggested in the past that MTX lacks any clinical effectiveness in patients with ulcerative colitis (UC); however, newer data at least partially contradict this assumption. The following review will discuss recent data for the use of MTX in CD, UC and in combination with anti-TNF agents.
| S-EPMC4820247 | biostudies-literature