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1.
Synergic interactions between polyphenols and gut microbiota in mitigating inflammatory bowel diseases.
Li, H, Christman, LM, Li, R, Gu, L
Food & function. 2020;(6):4878-4891
Abstract
Inflammatory bowel diseases (IBD) are a group of chronic and recurring inflammatory conditions in the colon and intestine. Their etiology is not fully understood but involves the combination of gut dysbiosis, genetics, immune functions, and environmental factors including diet. Polyphenols from plant-based food synergistically interact with gut microbiota to suppress inflammation and alleviate symptoms of IBD. Polyphenols increase the diversity of gut microbiota, improve the relative abundance of beneficial bacteria, and inhibit the pathogenic species. Polyphenols not absorbed in the small intestine are catabolized in the colon by microbiota into microbial metabolites, many of which have higher anti-inflammatory activity and bioavailability than their precursors. The polyphenols and their microbial metabolites alleviate IBD through reduction of oxidative stress, inhibition of inflammatory cytokines secretion (TNF-α, IL-6, IL-8, and IL-1β), suppression of NF-κB, upregulation of Nrf2, gut barrier protection, and modulation of immune function. Future studies are needed to discover unknown microbial metabolites of polyphenols and correlate specific gut microbes with microbial metabolites and IBD mitigating activity. A better knowledge of the synergistic interactions between polyphenols and gut microbiota will help to devise more effective prevention strategies for IBD. This review focuses on the role of polyphenols, gut microbiota and their synergistic interactions on the alleviation of IBD as well as current trends and future directions of IBD management.
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2.
Therapeutic drug monitoring with vedolizumab in inflammatory bowel disease.
Pugliese, D, Privitera, G, Pizzolante, F, Gasbarrini, A, Guidi, L, Armuzzi, A
Minerva gastroenterologica e dietologica. 2019;(4):280-290
Abstract
Therapeutic drug monitoring (TDM) is a useful tool for decision-making process in patients with inflammatory bowel disease (IBD) treated with anti TNF-α drugs, especially when experiencing loss of response. Growing evidences support the existence of exposure-response relationship with vedolizumab, but the utility and the appropriate use of TDM in clinical practice is still under debate. In this review, we summarize all evidences supporting a TDM-guided approach for patients treated with vedolizumab, suggesting three potential scenarios: 1) early prediction of long-term outcomes; 2) verifying the best strategy in case of loss of response; 3) maximizing therapeutic efficacy during maintenance treatment. Vedolizumab through concentrations <20 µg/mL at week 6 and >12 µg/mL seem to be associated with more favorable outcomes. No comparative studies have been conducted so far to demonstrate the advantage of adopting a TDM-guided versus an empirical approach for managing primary or secondary nonresponses. The frequency of antibodies to vedolizumab detection is quite low (up to 4% in pivotal trials), suggesting, unlike of anti TNF-α agents, a low probability of experiencing an immune-mediated pharmacokinetic failure in clinical practice. Future prospective and controlled studies are warranted to establish the guidance on the use of a TDM-guided approach with vedolizumab in clinical practice.
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3.
Inflammatory bowel disease and immunonutrition: novel therapeutic approaches through modulation of diet and the gut microbiome.
Celiberto, LS, Graef, FA, Healey, GR, Bosman, ES, Jacobson, K, Sly, LM, Vallance, BA
Immunology. 2018;(1):36-52
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Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, thought to at least in part reflect an aberrant immune response to gut bacteria. IBD is increasing in incidence, particularly in populations that have recently immigrated to western countries. This suggests that environmental factors are involved in its pathogenesis. We hypothesize that the increase in IBD rates might reflect the consumption of an unhealthy Western diet, containing excess calories and lacking in key nutritional factors, such as fibre and vitamin D. Several recent studies have determined that dietary factors can dramatically influence the activation of immune cells and the mediators they release through a process called immunonutrition. Moreover, dietary changes can profoundly affect the balance of beneficial versus pathogenic bacteria in the gut. This microbial imbalance can alter levels of microbiota-derived metabolites that in turn can influence innate and adaptive intestinal immune responses. If the diet-gut microbiome disease axis does indeed underpin much of the 'western' influence on the onset and progression of IBD, then tremendous opportunity exists for therapeutic changes in lifestyle, to modulate the gut microbiome and to correct immune imbalances in individuals with IBD. This review highlights four such therapeutic strategies - probiotics, prebiotics, vitamin D and caloric restriction - that have the potential to improve and add to current IBD treatment regimens.
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4.
Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders.
Hirten, RP, Iacucci, M, Shah, S, Ghosh, S, Colombel, JF
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018;(9):1374-1384
Abstract
Current therapies used in the treatment of inflammatory bowel disease (IBD) are not effective in all patients. Biologic agents result in approximately 40% remission rates at 1 year in selected populations, prompting a growing interest in combining biologic therapy to improve outcomes. There are limited published data regarding the efficacy and safety of combination targeted therapy in IBD specifically, which include only 1 exploratory randomized control trial and 3 case reports or series. This review evaluates the published literature regarding this therapeutic paradigm in IBD and its extensive utilization in the treatment of other immune-mediated inflammatory disorders. The combination of biologic therapies demonstrates variable degrees of efficacy and highlights some safety concerns, depending upon the agents used and the disease state treated. A trial (Clinical Trials.gov Identifier: NCT02764762) combining vedolizumab and adalimumab is currently underway evaluating the effectiveness and safety of this approach in patients with Crohn's disease, which should provide further insight into this treatment concept. While combination biologic therapy is an attractive strategy, the lack of consistent superior efficacy as well as safety concerns militates the need for further trials prior to its general application in IBD.
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5.
Interplay of Immunity and Vitamin D: Interactions and Implications with Current IBD Therapy.
Abdo, J, Rai, V, Agrawal, DK
Current medicinal chemistry. 2017;(9):852-867
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) are classified under inflammatory bowel disease (IBD) which has been linked to a multifaceted etiology involving both environmental and genetic factors that intersect with the vitamin D pathway. Dysfunctions in innate immune defense mechanisms in the epithelial compartment of the intestine play a crucial role in the pathogenesis of IBD. Symptoms of IBD are caused by excessive immune responses to luminal bacteria, and vitamin D has been shown to play a role in intestinal defense by aiding in the suppression of microbial invasion into the epithelium. Vitamin D, as an immunomodulator, can modify the innate immune response of the body. Vitamin D attenuates the transcription of pro-inflammatory cytokines that are upregulated in the event of epithelial stress common in patients with IBD. Vitamin D deficiency was identified in 82% of IBD patients compared to the 31% national average and has been linked to defective epithelial processes at both genomic and proteomic levels. Mucosal damage and an impaired immune response are at the center of IBD, and vitamin D aids in sustaining the structural integrity of epithelial cells while enhancing innate immune responses in the mucosa. Here we provide a systematic review of the pathophysiological effects of cytokines in IBD in the presence of vitamin D deficiency. Also, analysis of the immunomodulatory effect of vitamin D in regulating immunopathogenic factors like chemokines, growth factors, and human defensins will enhance knowledge of the underlying molecular mechanisms of the therapeutic role of vitamin D in IBD and thus aid in the development of better patient management strategies.
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6.
Resveratrol and inflammatory bowel disease.
Shi, Y, Zhou, J, Jiang, B, Miao, M
Annals of the New York Academy of Sciences. 2017;(1):38-47
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, comprising ulcerative colitis (UC) and Crohn's disease (CD). Progression of IBD leads to long-term impairment of intestinal structure and function. The pathogenesis of IBD is complex, involving environmental, immunological, genetic, microbial, and psychological factors. The conventional therapies and many existing biopharmaceuticals for IBD have limited efficacy or adverse effects. As a promising safe and effective therapy for IBD, resveratrol has been studied widely, as it has shown anti-inflammatory and antioxidant activity. Resveratrol's mechanism of action involves multiple immune responses and signaling pathways; it is absorbed quickly and metabolized into various derivatives. However, the poor water solubility and low bioavailability of resveratrol limit its clinical applications. Further research should attempt to improve the stability and oral bioavailability of resveratrol by modification and various delivery systems.
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Association Between Adipokines Levels with Inflammatory Bowel Disease (IBD): Systematic Reviews.
Morshedzadeh, N, Rahimlou, M, Asadzadeh Aghdaei, H, Shahrokh, S, Reza Zali, M, Mirmiran, P
Digestive diseases and sciences. 2017;(12):3280-3286
Abstract
BACKGROUND A combination of genetic and environmental factors is involved in the etiology of inflammatory bowel disease (IBD). Recent studies have shown that adipocytes play a crucial role, by actively participating in systemic immune responses in IBD patients. But findings remain controversial. To the best of our knowledge, no systematic review has evaluated the roles of adipokines in IBD, considering which this systematic review was undertaken to summarize the effects of these adipokines in IBD pathogenesis. METHODS For this review, articles published between 1980 and 2016 were identified from the PubMed, EMBASE, Scopus, and Cochrane and Google scholar databases. Thirteen articles were ultimately selected for inclusion in this systematic review. RESULTS Findings of the present study indicate that some of the adipokines such as leptin, adiponectin and resistin are associated with disease severity, body composition and glucose hemostasis in IBD patients, although some of these associations are stronger than others. CONCLUSIONS Overall findings indicate that some adipokines may play a crucial role in IBD severity or other IBD related outcomes. Further studies are recommended to confirm the results.
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8.
The Role of Environmental Factors in the Pathogenesis of Inflammatory Bowel Diseases: A Review.
Shouval, DS, Rufo, PA
JAMA pediatrics. 2017;(10):999-1005
Abstract
IMPORTANCE Inflammatory bowel diseases (IBD), such as Crohn disease and ulcerative colitis, are chronic relapsing conditions that affect a growing number of children worldwide. The pathogenesis of these disorders is complex and thought to be mediated by the interplay between genetic susceptibility, microbial dysbiosis, and environmental factors that result in a dysregulated immune system. This dysregulation ultimately mediates intestinal inflammation and clinical symptoms typically observed in patients with IBD including abdominal pain, diarrhea, and poor growth. A dramatic increase in the incidence of IBD has been observed in the past 2 decades, mainly in developed countries but also in developing regions. This increased incidence has paralleled changes in diet, sanitation conditions, and lifestyle habits. OBSERVATIONS The increased incidence of IBD can likely be attributed to more than evolving genetic diversity alone and strongly suggests that environmental factors are playing an increasingly critical role in the development of these disorders and in the modulation of IBD clinical phenotypes over time. Here, we review the data suggesting how different environmental factors may modulate the risk of developing IBD including diets, smoking, lifestyle choices, enteric infections, appendectomy, air pollution, and the use of medications, with an emphasis on antibiotics. We will also discuss how early-life events can influence the subsequent likelihood of developing one of these diseases and suggest directions that can help decrease the risk of IBD in particularly high-risk populations. CONCLUSIONS AND RELEVANCE Dramatic lifestyle changes in the last century have substantially improved the quality of life but are also associated with increased risk of various diseases. Pediatricians should be aware of the changing epidemiology of IBD and environmental factors that modulate the risk of developing these conditions.
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9.
Vitamin D signaling in intestinal innate immunity and homeostasis.
Dimitrov, V, White, JH
Molecular and cellular endocrinology. 2017;:68-78
Abstract
The lumen of the gut hosts a plethora of microorganisms that participate in food assimilation, inactivation of harmful particles and in vitamin synthesis. On the other hand, enteric flora, a number of food antigens, and toxins are capable of triggering immune responses causing inflammation, which, when unresolved, may lead to chronic conditions such as inflammatory bowel disease (IBD). It is important, therefore, to contain the gut bacteria within the lumen, control microbial load and composition, as well as ensure adequate innate and adaptive immune responses to pathogenic threats. There is growing evidence that vitamin D signaling has impacts on all these aspects of intestinal physiology, contributing to healthy enteric homeostasis. VD was first discovered as the curative agent for nutritional rickets, and its classical actions are associated with calcium absorption and bone health. However, vitamin D exhibits a number of extra-skeletal effects, particularly in innate immunity. Notably, it stimulates production of pattern recognition receptors, anti-microbial peptides, and cytokines, which are at the forefront of innate immune responses. They play a role in sensing the microbiota, in preventing excessive bacterial overgrowth, and complement the actions of vitamin D signaling in enhancing intestinal barrier function. Vitamin D also favours tolerogenic rather than inflammogenic T cell differentiation and function. Compromised innate immune function and overactive adaptive immunity, as well as defective intestinal barrier function, have been associated with IBD. Importantly, observational and intervention studies support a beneficial role of vitamin D supplementation in patients with Crohn's disease, a form of IBD. This review summarizes the effects of vitamin D signaling on barrier integrity and innate and adaptive immunity in the gut, as well as on microbial load and composition. Collectively, studies to date reveal that vitamin D signaling has widespread effects on gut homeostasis, and provide a mechanistic basis for potential therapeutic benefit of vitamin D supplementation in IBD.
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10.
Probiotics: The scientific evidence in the context of inflammatory bowel disease.
Celiberto, LS, Bedani, R, Rossi, EA, Cavallini, DC
Critical reviews in food science and nutrition. 2017;(9):1759-1768
Abstract
Inflammatory bowel disease (IBD) generally comprises Crohn's disease (CD) and ulcerative colitis (UC), and their main characteristic is the intestinal mucosa inflammation. Although its origin is not yet fully known, there is growing evidence related to genetics, intestinal microbiota composition, and the immune system factors such as precursors for the initiation and progression of intestinal conditions. The use of certain probiotic microorganisms has been touted as a possible and promising therapeutic approach in reducing the risk of inflammatory bowel disease, specifically ulcerative colitis. Several mechanisms have been proposed to explain the benefits of probiotics, indicating that some bacterial strains are able to positively modulate the intestinal microbiota and the immune system, and to produce metabolites with anti-inflammatory properties. The aim of this paper is to bring together the various results and information, based on scientific evidence, that are related to probiotics and inflammatory bowel disease, emphasizing the possible mechanisms involved in this action.