In assessing the best evidence for optimizing management of inflammatory bowel disease (IBD), the focus is typically on anti-inflammatory agents and therapies that modulate the immune system. The ...intestinal immune response remains the key focus of developing therapies as well. In the past decade, the concept of dysbiosis of the gut microbiome has emerged as a potential pathogenetic focus in IBD, and with this a burgeoning interest in manipulating the microbiome as a means of controlling the disease has emerged. In this review, anti-inflammatory, immune-modulating, and microbiome-modulating therapies will be covered in terms of what is known today, as well as treatments that may be part of the therapeutic armamentarium in the near future. Concurrent with the evolution of our understanding of the basic biology of IBD, there is an increasing appreciation for the disconnect between patients' symptoms and inflammatory disease. As clinical trials have simultaneously addressed both symptom scores and mucosal healing, investigators and clinicians have gained a greater appreciation for the fact that many symptoms may not be driven by active inflammation, and hence focusing only on immunomodulatory therapies would not serve patients' needs fully. Furthermore, there is an emerging recognition of the importance of stress and psychological health in symptom experience and treatment needs. In this review, approaches to managing patients' symptoms as well as other adjunctive approaches to improving well-being will also be discussed. Finally, throughout this review, important research questions regarding different aspects of treatment will be proposed.
The brain-gut axis serves as a circuit that incorporates the human experience, the state of mind, the gut microbiome, and the immune response that ultimately drives the phenotypic expression of ...inflammatory bowel disease (IBD). There are several biological pathways through which stress can play a deleterious role, including through increasing intestinal permeability, which can facilitate intestinal translocation of bacteria. Stress has an impact on symptoms in IBD; however, there is limited evidence that stress triggers increased intestinal inflammation. Although attention to stress and psychiatric comorbidity is important in the management of IBD, there are few clinical trials to direct management.
Brain-Gut Interactions in Inflammatory Bowel Disease Bonaz, Bruno L; Bernstein, Charles N
Gastroenterology (New York, N.Y. 1943),
2013, January 2013, 2013-Jan, 2013-01-00, 20130101, 2013-01, Letnik:
144, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Psycho-neuro-endocrine-immune modulation through the brain-gut axis likely has a key role in the pathogenesis of inflammatory bowel disease (IBD). The brain-gut axis involves interactions among the ...neural components, including (1) the autonomic nervous system, (2) the central nervous system, (3) the stress system (hypothalamic-pituitary-adrenal axis), (4) the (gastrointestinal) corticotropin-releasing factor system, and (5) the intestinal response (including the intestinal barrier, the luminal microbiota, and the intestinal immune response). Animal models suggest that the cholinergic anti-inflammatory pathway through an anti–tumor necrosis factor effect of the efferent vagus nerve could be a therapeutic target in IBD through a pharmacologic, nutritional, or neurostimulation approach. In addition, the psychophysiological vulnerability of patients with IBD, secondary to the potential presence of any mood disorders, distress, increased perceived stress, or maladaptive coping strategies, underscores the psychological needs of patients with IBD. Clinicians need to address these issues with patients because there is emerging evidence that stress or other negative psychological attributes may have an effect on the disease course. Future research may include exploration of markers of brain-gut interactions, including serum/salivary cortisol (as a marker of the hypothalamic-pituitary-adrenal axis), heart rate variability (as a marker of the sympathovagal balance), or brain imaging studies. The widespread use and potential impact of complementary and alternative medicine and the positive response to placebo (in clinical trials) is further evidence that exploring other psycho-interventions may be important therapeutic adjuncts to the conventional therapeutic approach in IBD.
The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and ...microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID.
LINKED CONTENT
This article is linked to Hawthorne et al papers. To view these articles, visit https://doi.org/10.1111/apt.17042 and https://doi.org/10.1111/apt.17077
While it is widely accepted that chronic diseases such as inflammatory bowel disease (IBD) may trigger negative psychological emotions such as distress and even depression, it is unknown if this ...response to a chronic illness like IBD is solely a psychological response to an adverse situation or whether it also represents a biological response, that is, the active inflammatory state of IBD intersecting with the pathobiology of what mediates mood and anxiety disorders. There is a bi-directionality between psychological comorbidity and IBD with each influencing the course of the other when they coexist. Furthermore, there is much to learn in terms of the underlying pathobiology of depression and anxiety and how this may impact on the pathobiology of IBD. Several important questions in regards to psychological comorbidity and IBD will be reviewed in this chapter.
Previous studies have reported colectomy rates of over 50% in ulcerative colitis (UC), although changes in management may have influenced the rates of colectomy in the modern era. We sought to ...determine the incidence of colectomy in UC and identify risk factors associated with early colectomy (EC) and late colectomy (LC).
We used the University of Manitoba Inflammatory Bowel Disease Epidemiology Database, a population-based data set including UC patients with up to 25 years of post diagnosis follow-up. We tracked the occurrence of total colectomy in all patients with known UC, subdivided into EC (≤90 days from diagnosis date) and LC (>90 days from diagnosis). Survival curves were created and stratified by age, sex, era of diagnosis, and inpatient/hospital diagnosis. Cox proportional hazards modeling was used to determine which risk factors were predictive of either EC or LC.
Among 3,752 patients with UC, 367 underwent colectomy. The 5-, 10- and 20-year actuarial risk of requiring colectomy was 7.5%, 10.4%, and 14.8%, respectively. Male sex (hazard ratio (HR): 2.63, corrected 95% confidence interval (CI): 1.58-4.36) and being initially diagnosed during a hospitalization (HR: 12.46, 95% CI: 7.40-21.0) were predictive of EC after adjustment for confounders. In-hospital diagnosis was predictive of LC, whereas being diagnosed more recently was protective against LC (HR: 0.96, 95% CI: 0.93-0.98).
The cumulative incidence of colectomy in UC is lower than previously reported, and appears to be decreasing further among more recently diagnosed cohorts of patients. Male sex and hospitalization at the time of diagnosis are major risk factors for EC and LC.
The development of commensal flora in infants has been shown to be sensitive to antibiotic use. Altered intestinal flora is thought to contribute to the etiology of inflammatory bowel disease (IBD), ...an idiopathic chronic condition. We aimed to determine if early use of antibiotics was associated with the development of IBD in childhood.
Nested case-control analysis of the population-based University of Manitoba Inflammatory Bowel Disease Epidemiologic Database was carried out. IBD status was determined from a validated administrative database definition. A total of 36 subjects diagnosed between 1996 and 2008 were matched to 360 controls, on the basis of age, sex, and geographic region. Antibiotic data were drawn from the Manitoba Drug Program Information Network, a comprehensive population-based database of all prescription drugs for all Manitobans dating back to 1995. Antibiotic use in the first year of life was compared between IBD cases and controls.
The mean age at IBD diagnosis was 8.4 years. Twenty-one cases (58%) had one or more antibiotic dispensations in their first year of life compared with 39% of controls. Crohn's disease was diagnosed in 75% of IBD cases. Those receiving one or more dispensations of antibiotics were at 2.9 times the odds (95% confidence interval: 1.2, 7.0) of being an IBD case.
Subjects diagnosed with IBD in childhood are more likely to have used antibiotics in their first year of life.
Venous thromboembolism (VTE) is known to be increased in inflammatory bowel disease (IBD). We aimed to determine whether rates of VTE in IBD have reduced over the past 30 years.
We used the ...population-based University of Manitoba IBD Epidemiology Database (1984-2018) to determine the incidence of VTE in IBD and the incidence rate ratio vs matched controls. In persons with IBD with and without VTE, we assessed for variables that were associated with an increased risk of VTE on multivariate logistic regression.
The incidence of VTE in the IBD cohort was 7.6% which was significantly greater than in controls (3.3%, P < 0.0001). The overall age-standardized incidence rate of VTE was 433 per 100,000 in IBD and 184 per 100,000 in controls. The incidence of VTE was higher in Crohn's disease (8.4%) than in ulcerative colitis (6.9%, P = 0.0028). The incidence rate ratio in IBD vs controls was 2.36 (95% confidence interval 2.16-2.58). The increased risk was similar in males and females and in Crohn's disease compared with ulcerative colitis. The incidence rate among persons with IBD from 1985 to 2018 decreased very slowly, with annual percent change of -0.7% (P = 0.0003). Hospital admission, high comorbidity, use of antibodies to tumor necrosis factor for less than 3 years up until the time of the VTE, and the combination of steroid and antibodies to tumor necrosis factor increased the risk of VTE.
Despite advancements in IBD management in the past 30 years, the rates of VTE have only been slowly decreasing and remain significantly increased compared with controls.
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