Etiopathogenesis Of Inflammatory Bowel Disease Research Articles

Outer Membrane Vesicles Derived from Adherent-Invasive Escherichia coli Induce Inflammatory Response and Alter the Gene Expression of Junction-Associated Proteins in Human Intestinal Epithelial Cells

Adherent-invasive Escherichia coli (AIEC) pathobionts, which are characterized by their ability to adhere to and invade intestinal epithelial cells, are associated with the etiopathogenesis of inflammatory bowel diseases (IBDs). Outer membrane vesicles (OMVs) released by AIEC strains can facilitate the interaction of these bacteria with host cells through delivering bacterial effectors. The aim of this study was to determine the ability of OMVs derived from AIEC strain LF82 to induce the host immune response, leading to production of proinflammatory cytokines and also altering the gene expression of junction-associated proteins in the human epithelial colorectal adenocarcinoma Caco-2 cell line. OMVs were extracted from AIEC strain LF82, and the cell viability of Caco-2 cells treated with these vesicles was assessed by MTT assay. The morphology and size distribution of vesicles were analyzed using transmission electron microscopy and dynamic light scattering, respectively. Gene expression of occludin, ZO-1, claudin-2, E-cadherin, TLR-2, and TLR-4 in response to OMVs was assessed in Caco-2 cells by RT-qPCR. Moreover, the secretion of IL-8 and TNF-α into the supernatant of Caco-2 cells upon treatment with OMVs was measured using ELISA. Our results demonstrated that OMVs upregulated the gene expression level of TLRs and also altered the gene expression level of junction-associated proteins. OMVs derived from AIEC may play a major role in the promotion of intestinal inflammation and epithelial barrier dysfunction. However, further investigations are needed to elucidate the putative role of OMVs in the pathogenesis of AIEC and IBD.

Helicobacter pylori in Inflammatory Bowel Diseases: Active Protagonist or Innocent Bystander?

Helicobacter pylori (H. pylori) infection is a prominent entity within human infectious diseases which cause chronic gastritis, peptic ulcers, gastric malignancies, and extragastric disorders. Its persistent colonization can lead to a systemic inflammatory cascade, potentially instigating autoimmune responses and contributing to the pathogenesis of autoimmune diseases. While the specific etiopathogenesis of inflammatory bowel diseases (IBDs) is still unknown, it is widely recognized that immunological, genetic, and environmental factors are implicated. Various bacterial and viral pathogens have been implicated in the pathogenesis of IBDs. Numerous studies suggest a correlation between H. pylori infection and IBDs. While subject to debate, this link suggests that the bacterium's presence somehow impacts the progression of IBDs by modifying the diversity of the gut microbiota, consequently altering local chemical profiles and disrupting the pattern of gut immune response. However, epidemiological evidence indicates a protective role of H. pylori infection against the onset of autoimmune diseases. Additionally, laboratory findings demonstrate H. pylori's capacity to promote immune tolerance and restrict inflammatory reactions. The aim of this review is to elucidate the proposed mechanisms and confounding factors that underlie the potential association between H. pylori infection and IBDs.

Gut bacteriome in inflammatory bowel disease: An update on recent advances.

Inflammatory bowel diseases (IBD) are chronic inflammatory gut disorders, majorly classified as ulcerative colitis and Crohn's disease. The complex, multifactorial etiopathogenesis of IBD involves genetic predisposition, environmental cues, aberrant mucosal immune response and a disturbed gut microbiota. Epidemiological trends, studies in gnotobiotic mice models and genome-wide association studies, identifying genes involved in microbial handling, together mount evidence in support of the gut microbiota playing a pivotal role in IBD pathogenesis. Both Crohn's disease and ulcerative colitis are characterized by severe dysbiosis of the gut microbiome, marked by an expansion of detrimental taxa and concomitant depletion of beneficial members. IBD is characterized by reduction in abundances of bacterial genera involved in production of short-chain fatty acids, bio-transformations of bile acids and synthesis of indole-based tryptophan compounds such as Faecalibacterium, Ruminococcus, Coprococcus, Dorea, Parabacteroides, Eubacterium, Oscillibacter and Prevotella and elevation in members of phyla Proteobacteria and Actinobacteria. This imbalance not only results in exaggerated immune signaling towards the microbial antigens, but also results in an altered metabolomic milieu that triggers additional inflammatory cascades. The present review provides insights into the bacterial dysbiosis observed across different intestinal sites and their metabolomic imprints participating in IBD.

Inflammatory Bowel Disease: Emerging Therapies and Future Treatment Strategies.

Inflammatory bowel disease (IBD) is a term used to represent a group of chronic, relapsing inflammatory disorders of the gastrointestinal tract. Crohn's disease (CD) and ulcerative colitis (UC) are the two major clinical forms. The global incidence and prevalence of IBD have increased over the last 2-4 decades. Despite the specific etiopathogenesis of IBD still being unknown, it is widely recognized that immunological, genetic, and environmental factors are implicated. A greater understanding of the multiple signaling pathways involved has led to the development of biologic therapies in the last two decades. Although these treatments have dramatically transformed the course of IBD, there is not a definitive cure and available therapies may cause adverse events (AEs), limiting their use, or have an inadequate effect in some patients. In this context, emerging therapies addressing new specific pathogenetic mechanisms have shown promising efficacy and safety data in early clinical trials. The purpose of this review is to highlight the available clinical trial data for these new drugs, such as more preferential JAK inhibitors, anti-IL-23 antibodies, sphingosine-1-phosphate receptor modulators, anti-integrin therapies, and other small molecules that are currently under research. We will emphasize the potential significance of these agents in shaping future treatment options.

Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients.

Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.

PPAR-Gamma Orchestrates EMT, AGE, and Cellular Senescence Pathways in Colonic Epithelium and Restrains the Progression of IBDs.

Intestinal fibrosis, the most common complication of inflammatory bowel disease (IBD), is characterized by an uncontrolled deposition of extracellular matrix proteins leading to complications resolvable only with surgery. Transforming growth factor is the key player in the epithelial-mesenchymal transition (EMT) and fibrogenesis process, and some molecules modulating its activity, including peroxisome proliferator-activated receptor (PPAR)-γ and its agonists, exert a promising antifibrotic action. The purpose of this study is to evaluate the contribution of signaling other than EMT, such as the AGE/RAGE (advanced glycation end products/receptor of AGEs) and the senescence pathways, in the etiopathogenesis of IBD. We used human biopsies from control and IBD patients, and we used a mouse model of colitis induced by dextran-sodium-sulfate (DSS), without/with treatments with GED (PPAR-gamma-agonist), or 5-aminosalicylic acid (5-ASA), a reference drug for IBD treatment. In patients, we found an increase in EMT markers, AGE/RAGE, and senescence signaling activation compared to controls. Consistently, we found the overexpression of the same pathways in DSS-treated mice. Surprisingly, the GED reduced all the pro-fibrotic pathways, in some circumstances more efficiently than 5-ASA. Results suggest that IBD patients could benefit from a combined pharmacological treatment targeting simultaneously different pathways involved in pro-fibrotic signals. In this scenario, PPAR-gamma activation could be a suitable strategy to alleviate the signs and symptoms of IBD and also its progression.

Role of prebiotics, probiotics, and synbiotics in management of inflammatory bowel disease: Current perspectives.

Experimental evidence supports the fact that changes in the bowel microflora due to environmental or dietary factors have been investigated as implicating factors in the etiopathogenesis of inflammatory bowel disease (IBD). The amassing knowledge that the inhabited microbiome regulates the gut physiology and immune functions in IBD, has led researchers to explore the effectiveness of prebiotics, probiotics, and synbiotics in treating IBD. This therapeutic approach focuses on restoring the dynamic balance between the microflora and host defense mechanisms in the intestinal mucosa to prevent the onset and persistence of intestinal inflammation. Numerous microbial strains and carbohydrate blends, along with their combinations have been examined in experimental colitis models and clinical trials, and the results indicated that it can be an attractive therapeutic strategy for the suppression of inflammation, remission induction, and relapse prevention in IBD with minimal side effects. Several mechanisms of action of probiotics (for e.g., Lactobacillus species, and Bifidobacterium species) have been reported such as suppression of pathogen growth by releasing certain antimicrobial mediators (lactic and hydrogen peroxide, acetic acid, and bacteriocins), immunomodulation and initiation of an immune response, enhancement of barrier activity, and suppression of human T-cell proliferation. Prebiotics such as lactulose, lactosucrose, oligofructose, and inulin have been found to induce the growth of certain types of host microflora, resulting in an enriched enteric function. These non-digestible food dietary components have been reported to exert anti-inflammatory effects by inhibiting the expression of tumor necrosis factor-α-related cytokines while augmenting interleukin-10 levels. Although pro-and prebiotics has established their efficacy in healthy subjects, a better understanding of the luminal ecosystem is required to determine which specific bacterial strain or combination of probiotics and prebiotics would prove to be the ideal treatment for IBD. Clinical trials, however, have given some conflicting results, requiring the necessity to cite the more profound clinical effect of these treatments on IBD remission and prevention. The purpose of this review article is to provide the most comprehensive and updated review on the utility of prebiotics, probiotics, and synbiotics in the management of active Crohn's disease and ulcerative colitis/pouchitis.

P116 RIPK3 - a new marker for assessment of ulcerative colitis severity

Abstract Background Necroptosis is a novel form of regulated necrotic cell death that is dependent on Receptor interacting protein kinase-3 (RIPK3). It leads to cell lysis and directly triggers inflammation. Several clinical and preclinical studies have implicated necroptosis in the etiopathogenesis of inflammatory bowel disease. Methods The aim of the study was to evaluate the expression of RIPK3 according to the activity and severity of ulcerative colitis (UC). Tissue expression of RIPK3 was determined immunohistochemically in intestinal biopsies from 85 patients with ulcerative colitis. Тo evaluate the severity and activity of UC were used the Montreal classification for disease severity (S), full Mayo score (MS) and Mayo endoscopic score (MES). Results A moderate direct correlation was found between disease severity and RIPK3 expression (r=0.354; p=0.001), with severe disease (S3) being characterized by overexpression of the marker (199.67). A moderate right-proportional relationship was also found in the analysis of RIPK3 expression and UC activity, measured by the full Mayo score (r=0.481; p<0.001). RIPK3 expression increased with increasing disease activity (p<0.001), and patients with severe disease activity (MS =11-12) had overexpression of the marker (211.71). A moderate correlation between RIPK3 expression and the degree of endoscopic activity was also found (r=0.363; p=0.001), with patients with severe endoscopic activity (MES=3) having high expression of the marker (198.27). Conclusion High expression of RIPK3 in UC patients was associated with severe disease activity assessed by the Montreal classification and full Mayo score and marked endoscopic activity.

Effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats

Background and aimThe etiopathogenesis of inflammatory bowel disease (IBD) is associated with different factors such as genetic, infectious, immunological, and environmental, including modification of the gut microbiota. IBD′s conventional pharmacological therapeutic approaches have become a challenge due to side effects, complications from prolonged use, and higher costs. Kefir fermented milk beverage is a functional food that has demonstrated multiple beneficial effects including anti-inflammatory and antioxidant activity. Alternative therapeutic strategies have been used for IBD as more natural products with low-cost and easy acquisition. The aim of this study is to evaluate the anti-inflammatory effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats. MethodsWe used 4 groups to perform this study: baseline control (BC), kefir control (KC), 5% untreated DSS-induced colitis (DSS), and 5% DSS-induced colitis treated with kefir (DSSK). The animals received fermented kefir milk beverage ad libitum for six days and the disease activity index was recorded daily. Colon samples were processed for Transmission Electron Microscopy and histopathological evaluation. We analyzed short fatty chain acids through the fecal sample using gas chromatography. ResultsKefir supplementation was able to reduce the clinical activity index and inflammatory process evidenced by decreased neutrophil accumulation, decreased reticulum edema, and increased autophagosomes. Also, showed a trend to increase the levels of acetate and propionate. ConclusionsOur results suggest that kefir fermented milk beverage may have an anti-inflammatory effect minimizing the intestinal damage of DSS-induced colitis.

Homeostasis and Dysbiosis of the Intestinal Microbiota: Comparing Hallmarks of a Healthy State with Changes in Inflammatory Bowel Disease.

The gut microbiota, which represent a community of different microorganisms in the human intestinal tract, are crucial to preserving human health by participating in various physiological functions and acting as a metabolic organ. In physiological conditions, microbiota-host partnership exerts homeostatic stability; however, changes in intestinal microbiota composition (dysbiosis) are an important factor in the pathogenesis of inflammatory bowel disease and its two main disease entities: ulcerative colitis and Crohn's disease. The incidence and prevalence of these inflammatory conditions have increased rapidly in the last decade, becoming a significant problem for the healthcare system and a true challenge in finding novel therapeutic solutions. The issue is that, despite numerous studies, the etiopathogenesis of inflammatory bowel disease is not completely clear. Based on current knowledge, chronic intestinal inflammation occurs due to altered intestinal microbiota and environmental factors, as well as a complex interplay between the genetic predisposition of the host and an inappropriate innate and acquired immune response. It is important to note that the development of biological and immunomodulatory therapy has led to significant progress in treating inflammatory bowel disease. Certain lifestyle changes and novel approaches-including fecal microbiota transplantation and nutritional supplementation with probiotics, prebiotics, and synbiotics-have offered solutions for dysbiosis management and paved the way towards restoring a healthy microbiome, with only minimal long-term unfavorable effects.

Phylogrouping and characterization of Escherichia coli isolated from colonic biopsies and fecal samples of patients with flare of inflammatory bowel disease in Iran.

BackgroundAlthough the etiopathogenesis of inflammatory bowel disease (IBD) is still poorly understood, Escherichia coli has been described as a potential causative microorganism in IBD pathogenesis and also disease progression, offering a potential therapeutic target for disease management. Therefore, we conducted this study to investigate the pathotypes, phylogenetic groups, and antimicrobial resistance of E. coli isolates from patients with IBD in Iran.MethodsFecal and biopsy colonic samples were collected from IBD patients experiencing flare-up episodes referred to Taleghani hospital in Tehran, Iran, between August 2020 and January 2021. Identification of E. coli strains was performed based on biochemical and molecular methods. Antibiotic susceptibility testing was performed as recommended by the Clinical and Laboratory Standards Institute. Phylogrouping and pathotyping of each isolate were carried out using polymerase chain reaction (PCR) and multilocus sequence typing (MLST) assays.ResultsA total of 132 non-duplicate E. coli strains were isolated from 113 IBD patients, including 96 ulcerative colitis (UC), and 17 Crohn’s disease (CD) patients. In our study, 55% of CD-related E. coli and 70.5% of UC-related isolates were non-susceptible to at least three or more unique antimicrobial classes, and were considered as multidrug-resistant (MDR) strains. E. coli strains exhibited a high level of resistance to cefazolin, ampicillin, tetracycline, ceftazidime, ciprofloxacin, and cefotaxime. Enterotoxigenic E. coli (ETEC) and diffusely adherent E. coli (DAEC) were the most prevalent pathotypes, and groups B2 and D were the predominant phylogroups.ConclusionIn the present study, we found that E. coli strains that colonize the gut of Iranian patients with IBD most frequently belonged to phylogenetic groups B2 and D. We also conclude that E. coli isolates from IBD patients have been revealed to be resistant to commonly used antibiotics, in which most of them harbored strains that would be categorized as MDR.

The Business of T Cell Subsets and Cytokines in the Immunopathogenesis of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder and one of the most common inflammatory diseases of gastrointestinal (GI) tract in young adults. It is now equally prevalent in western countries as well as in Asian countries. Recently, there has been an increasing IBD burden in low- to middle-income countries as opposed to the earlier notion of this being a disease of the affluents. It occurs due to a variety of factors, namely, local immune alteration, disruption and inflammation of the mucosa, environmental factors, microbial commensals, and pathogen-induced genetic predisposition or genetic alteration in protective factors, etc.So far, an exact etiopathogenesis of IBD is yet to be completely elucidated. Several recent types of research have emphasized the role of altered innate and humoral immunity in its causation, many of them based on animal models of IBD. Due to the poor understanding of its etiopathogenesis, IBD is still a challenge for the treating clinicians leading to persistent and recurrent disease in many cases.Immune dysregulation in the GI tract incited by various pathogenic stimuli has gained great attention from researchers in the field of IBD. This review focuses on highlighting the role of various T cell subsets, their interplay, and associated cytokines involved in the pathogenesis of IBD along with a short description of genetic as well as other immunological factors. A better understanding of the pathogenic factors and subsequent randomized controlled trials targeting these factors is prudent for better therapeutic approaches for IBD.

Risk factors of developing inflammatory bowel diseases

Introduction: The pathogenesis of inflammatory bowel disease (IBD) is still unknown. It is known to be multi-factorial. The world is seeing an ever increasing number of new cases of these diseases. Ulcerative colitis and Crohn's disease are the main representatives of inflammatory bowel diseases.
 Aim: The aim of the study was to analyze risk factors for inflammatory bowel diseases.
 Materials and methods: The results were obtained on the basis of a questionnaire survey.
 Results: 95 people took part in the survey aged 16 to 72 years old. 35.8% were men and 64.2% were women. 78% lives in cites, only 22% are rural residents. 56.4% of them suffer from ulcerative colitis and 43.6% from Crohn's disease. 40.4% of respondents smoked cigarettes in the past, but currently only 12.6% are still struggling with the addiction. Only 4 people declare brushing their teeth after each meal. 18 people confirm the presence of NCDH in their families, 19 suffer from other autoimmune diseases at the same time. 2 people from among the respondents - also celiac disease. One person had Salmonella and Shigella infection. Conclusions: Due to the mutual cause-effect relationships between genetic predisposition and the influence of environmental factors, it is currently difficult to state which of the above factors plays a decisive role. Environmental factors that play a role in the etiopathogenesis of IBD include, first and foremost, the intestinal bacterial flora, diet, human environment and smoking. There is a clear tendency for the coexistence of autoimmune diseases in the group of patients with NCJ and a predisposition to the disease in the family. There is also a need to educate patients about the benefits of taking probiotics and taking care of proper eating habits. Key words: inflammatory bowel diseases, risk of developing the disease, irresponsible patient

Prevalence of small intestinal bacterial overgrowth syndrome among patients with inflammatory bowel disease and its impact on nutritional status and clinical manifestations

Background. In recent years, there has been high interest in the prevalence of small intestinal bacterial overgrowth (SIBO) syndrome in various populations. Chronic inflammatory bowel disease (IBD) is known to be a heterogeneous group of disorders, with a high degree of geographical variability in terms of symptoms, nature of progression, clinical manifestations, or combination with other types of pathologies. Since the involvement of the intestinal microbiome plays an important role in the etiopathogenesis of inflammatory bowel disease, the combination of SIBO and IBD is increasingly being considered and studied recently. Since the symptoms of both pathological conditions are significantly echoed, and therefore exacerbated by the combination, the manifestations of malnutrition become more pronounced, which negatively affects the nutritional status of patients with IBD. The purpose of the study is to determine the frequency of SIBO in patients with IBD depending on the nosological forms and to investigate its effect on clinical and laboratory indicators of nutritional status and clinical manifestations. Materials and methods. We examined 100 patients with IBD, aged 19 to 79 years, on average (42.54 ± 1.50) years, including 70 patients with ulcerative colitis (UC), and 30 — with Crohn’s disease (CD). All patients underwent general clinical examination, anthropometric measurements, general and biochemical blood tests (with the determination of total protein, albumin, prealbumin). To characterize the state of the small intestine microbiota (presence of SIBO), all patients underwent a hydrogen breath test with glucose loading using a Gastro+ Gastrolyzer gas analyzer from Bedfont Scientific Ltd (UK). Results. The analysis of SIBO frequency showed the changes in the state of the small intestinal microflora in 45 % of patients with IBD. The prevalence of SIBO was higher in the group of patients with CD — 53.3 % (16) than in the group with UC — 41.4 % (29). The presence of SIBO in the group of patients with UC had statistical significance and a direct correlation with the duration of the disease — (9.3 ± 6.2) versus (2.9 ± 3.1) years (p = 0.001, r = 0.55). There was a decrease in weight and body mass index (BMI) in patients with SIBO, especially in patients with Crohn’s disease, and accounted for (19.8 ± 3.5) kg/m2. There was a significant difference between the levels of total protein in patients with SIBO and without it, both in the basic group and in the group of UC: (65.8 ± 8.4) vs. (70.2 ± 8.2) g/l (p=0.009, r = –0.232) and (66.5 ± 8.3) vs. (70.7 ± 7.4) g/l (p = 0.029), respectively, and albumin levels were reduced in both nosological groups. No relationship was found between the severity of abdominal pain and the presence of SIBO. When SIBO was detected, the manifestations of flatulence significantly prevailed in patients with UC — 75.8 % (n=22), and diarrheal syndrome in patients with CD — 75 % (n = 12). Conclusions. The obtained results indicate a high prevalence of SIBO in patients with IBD. Patients with CD suffered from SIBO more often (53.3 %) than patients with UC (41.4%) (with a predominance of patients with severe disease). A direct correlation of SIBO with the disease duration in patients with UC (r = 0.55, р < 0.05) was revealed, which is explained by the violation of physiological barriers that prevent the emergence of SIBO, due to more episodes of exacerbation, long-term use of drugs and concomitant pathology with time. The negative impact of SIBO on nutritional status manifested in weight loss, reduced BMI and other anthropometric (mid-upper arm circumference, mid-arm muscle circumference, triceps skinfold) and laboratory (total protein, albumin, prealbumin) parameters in these patients. The most common symptoms in patients with IBD with SIBO were abdominal pain, diarrhea, and flatulence that reflected the typical clinical picture of SIBO.

The Multiple Faces of Integrin-ECM Interactions in Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD) comprises a series of chronic and relapsing intestinal diseases, with Crohn’s disease and ulcerative colitis being the most common. The abundant and uncontrolled deposition of extracellular matrix, namely fibrosis, is one of the major hallmarks of IBD and is responsible for the progressive narrowing and closure of the intestine, defined as stenosis. Although fibrosis is usually considered the product of chronic inflammation, the substantial failure of anti-inflammatory therapies to target and reduce fibrosis in IBD suggests that fibrosis might be sustained in an inflammation-independent manner. Pharmacological therapies targeting integrins have recently shown great promise in the treatment of IBD. The efficacy of these therapies mainly relies on their capacity to target the integrin-mediated recruitment and functionality of the immune cells at the damage site. However, by nature, integrins also act as mechanosensitive molecules involved in the intracellular transduction of signals and modifications originating from the extracellular matrix. Therefore, understanding integrin signaling in the context of IBD may offer important insights into mechanisms of matrix remodeling, which are uncoupled from inflammation and could underlie the onset and persistency of intestinal fibrosis. In this review, we present the currently available knowledge on the role of integrins in the etiopathogenesis of IBD, highlighting their role in the context of immune-dependent and independent mechanisms.

The Gut Microbiome and Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host-microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions.

Probiotics, Prebiotics and Synbiotics in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the digestive tract with periods of remission and relapses. The etiopathogenesis of IBD is multifactorial and has not been fully understood. Hence, only symptomatic treatment of these diseases is possible. The current pharmacological treatment has variable efficacy and is associated with the risk of significant side effects. Therefore, there is a constant need to search for new types of therapies with a high safety profile. Considering that the qualitative and quantitative profile of the gastrointestinal microbiome is often different in patients with IBD than in healthy individuals, there is a need for looking for therapies aimed at restoring intestinal microbiome homeostasis. Thus, the use of strictly defined probiotics, prebiotics and synbiotics may become an alternative form of IBD therapy. There is evidence that treatment with certain probiotic strains, e.g., VSL#3 and Escherischia coli Nissle 1917, is an effective form of therapy to induce remission in patients with mild to moderate UC. So far, the effectiveness of the use of probiotics, prebiotics and synbiotics in inducing or maintaining remission in patients with CD has not been confirmed. There are also reports of possible beneficial effects of fecal microbiota transplantation (FMT) on the course of IBD, especially UC. Further, well-planned studies on a large group of patients are needed to determine the role of specific probiotic strains, prebiotics, synbiotics and FMT in the treatment of IBD in adults and in children.

The dietary practices and beliefs of British South Asian people living with inflammatory bowel disease: a multicenter study from the United Kingdom

Background/AimsEpidemiological associations have implicated factors associated with Westernization, including the Western diet, in the development of inflammatory bowel disease (IBD). The role of diet in IBD etiopathogenesis, disease control and symptom management remains incompletely understood. Few studies have collected data on the dietary habits of immigrant populations living with IBD. Our aim was to describe the dietary practices and beliefs of British South Asians with IBD.MethodsA 30-item questionnaire was developed and consecutively administered to 255 British South Asians with IBD attending gastroenterology clinics in the United Kingdom.ResultsFifty-one percent of participants believed diet was the initiating factor for their IBD and 63% felt diet had previously triggered disease relapse. Eighty-nine percent avoided certain dietary items in the belief that this would prevent relapse. The most commonly avoided foods and drinks were spicy and fatty foods, carbonated drinks, milk products, alcohol, coffee, and red meat. A third of patients had tried a whole food exclusion diet, most commonly lactose- or gluten-free, and this was most frequently reported amongst those with clinically active IBD (P = 0.02). Almost 60% of participants avoided eating the same menu as their family, or eating out, at least sometimes, to prevent IBD relapse.ConclusionsBritish South Asians with IBD demonstrate significant dietary beliefs and food avoidance behaviors with increased frequency compared to those reported in Caucasian IBD populations. Studies in immigrant populations may offer valuable insights into the interaction between diet, Westernization and cultural drift in IBD pathogenesis and symptomatology.

Субпопуляции Т-хелперов, ключевые цитокины и хемокины в патогенезе воспалительных заболеваний кишечника (часть 2)*

Studies in recent decades have identified the role of various T-helper cell subsets in the pathogenesis of inflammatory bowel diseases (IBD) and have shown the importance of cytokine-mediated regulation of the immune response in patients with ulcerative colitis (UC) and Crohn’s disease (CD). The imbalance between pro-inflammatory and anti-inflammatory cytokines in IBD prevents resolution of inflammation and leads to chronic course, disease progression and tissue destruction. In the review article, the role of key cytokines that are important in the development and progression of IBD is discussed. Of the pro-inflammatory mediators involved in the pathogenesis of IBD, special attention is currently paid to chemokines – cytokines belonging to chemoattractants. Chemokines are responsible for directed migration and attraction of cells expressing a certain set of receptors to organs, tissues and foci of inflammation. The article provides unique data on the importance of some chemokines in IBD. Cytokines, chemokines and their receptors are considered as potential therapeutic targets in IBD. Cytokine-targeted therapy using antibodies against TNF-α and antibodies to IL-12/IL-23 have already shown high efficiency and safety in randomized clinical trials, as well as in real clinical practice in patients with IBD. The data presented by the authors are important for clarifying the role of immunological processes, including microbiome-dependent ones, in the etiopathogenesis of IBD. Key words: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, T-helper cell subsets, cytokines, chemokines, gut microbiome

Dietary Strategies for Maintenance of Clinical Remission in Inflammatory Bowel Diseases: Are We There Yet?

The etiopathogenesis of Inflammatory bowel disease (IBD) is a result of a complex interaction between host immune response, the gut microbiome and environmental factors, such as diet. Although scientific advances, with the use of biological medications, have revolutionized IBD treatment, the challenge for maintaining clinical remission and delaying clinical relapse is still present. As exclusive enteral nutrition has become a well-established treatment for the induction of remission in pediatric Crohn’s disease, the scientific interest regarding diet in IBD is now focused on the development of follow-on dietary strategies, which aim to suppress colonic inflammation and delay a disease flare. The objective of this review is to present an extensive overview of the dietary strategies, which have been used in the literature to maintain clinical remission in both Crohn’s disease and Ulcerative colitis, and the evidence surrounding the association of dietary components with clinical relapse. We also aim to provide study-related recommendations to be encompassed in future research studies aiming to investigate the role of diet during remission periods in IBD.