Progression Of IBD Research Articles

A mitochondria-targeted nitric oxide probe with large Stokes shift for real-time imaging and evaluation of inflammatory bowel disease in situ

BackgroundInflammatory bowel disease (IBD) is a prevalent inflammatory disorder, and the abnormal expression of nitric oxide (NO) produced by biocatalysis of iNOS enzyme in mitochondria is directly associated with the occurrence and progression of IBD. Activatable fluorescent probes offer promising tools for early diagnosis of IBD, however, inadequate biodistribution and limited targeting properties of these probes in vivo severely impede accurate diagnosis of IBD and real-time evaluation of inflammatory levels in situ. Therefore, it is necessary to designed a highly efficient fluorescent probe towards NO to overcome inadequate biodistribution and achieve accurate diagnosis and evaluation of IBD in situ. ResultsWe designed a highly efficient mitochondria-targeted “turn-on” NIR fluorescent probe Cy-OMe which has excellent targeting properties and imaging ability. The response mechanism is probe Cy-OMe rapidly undergoes N-nitrosation reaction resulting in turn-on NIR fluorescence signal when exposed to NO. Cy-OMe exhibits high sensitivity and specificity in detecting NO content in vitro, owing to its large Stokes shift. Furthermore, the probe Cy-OMe not only efficiently targets mitochondria but also enables precise assessment of fluctuations in endogenous NO concertation across various cell types. Importantly, by virtue of large Stokes shift and excellent mitochondrial targeting ability, Cy-OMe has the capability to specifically evaluate dynamic fluctuations of NO in lipopolysaccharide (LPS)‐stimulated IBD mouse models in situ and Cy-OMe was achieved high-contrast imaging and precision diagnosis of intestinal inflammation diseases. SignificanceCy-OMe can accurately assess fluctuations in NO levels and show high signal fidelity in the diseased intestine region, which has prospects in the non-invasive diagnosis of intestinal inflammation in vivo. At the same time, it is expected to serve as a potential diagnose platform for investigating the physiological processes underlying NO-related inflammatory diseases and promoting understanding of the pathological functions of NO across diverse inflammatory diseases.

Dopamine β-hydroxylase shapes intestinal inflammation through modulating T cell activation

BackgroundInflammatory bowel disease (IBD) is a chronic and relapsing disease characterized by immune-mediated dysfunction of intestinal homeostasis. Alteration of the enteric nervous system and the subsequent neuro-immune interaction are thought to contribute to the initiation and progression of IBD. However, the role of dopamine beta-hydroxylase (DBH), an enzyme converting dopamine into norepinephrine, in modulating intestinal inflammation is not well defined. MethodsCD4+CD45RBhighT cell adoptive transfer, and 2,4-dinitrobenzene sulfonic acid (DNBS) or dextran sodium sulfate (DSS)-induced colitis were collectively conducted to uncover the effects of DBH inhibition by nepicastat, a DBH inhibitor, in mucosal ulceration, disease severity, and T cell function. ResultsInhibition of DBH by nepicastat triggered therapeutic effects on T cell adoptive transfer induced chronic mouse colitis model, which was consistent with the gene expression of DBH in multiple cell populations including T cells. Furthermore, DBH inhibition dramatically ameliorated the disease activity and colon shortening in chemically induced acute and chronic IBD models, as evidenced by morphological and histological examinations. The reshaped systemic inflammatory status was largely associated with decreased pro-inflammatory mediators, such as TNF-α, IL-6 and IFN-γ in plasma and re-balanced Th1, Th17 and Tregs in mesenteric lymph nodes (MLNs) upon colitis progression. Additionally, the conversion from dopamine (DA) to norepinephrine (NE) was inhibited resulting in increase in DA level and decrease in NE level and DA/NE showed immune-modulatory effects on the activation of immune cells. ConclusionModulation of neurotransmitter levels via inhibition of DBH exerted protective effects on progression of murine colitis by modulating the neuro-immune axis. These findings suggested a promising new therapeutic strategy for attenuating intestinal inflammation.

Brain imaging derived phenotypes: a biomarker for the onset of inflammatory bowel disease and a potential mediator of mental complications.

Inflammatory bowel disease (IBD), mainly categorized into Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing gastrointestinal disorder that significantly impairs patients' quality of life. IBD patients often experience comorbidities such as anxiety and depression, and the underlying mechanisms and treatment strategies remain areas of investigation. We conducted a Mendelian randomization(MR) analysis utilizing brain image derived phenotypes (IDP) from the UK Biobank database to investigate the causal relationships between IBD and alterations in brain structural morphology and connectivity of neural tracts. This study aimed to identify biological evidence linking IBD to psychiatric disorders such as anxiety and depression. Specifically, the volume of grey matter in the Left Frontal Orbital Cortex exhibited a negative association with the onset of Crohn's disease (odds ratio (OR) [95% confidence interval (CI)]: 0.315[0.180~0.551], adjusted P=0.001), while the volume of the superior frontal cortex in the right hemisphere showed a positive correlation with the development of Ulcerative colitis (OR [95% CI]: 2.285[1.793~2.911], adjusted P<0.001), and the volume of lateral occipital cortex in the left hemisphere demonstrated a positive relationship with Crohn's disease onset (OR [95% CI]: 1.709[1.671~1.747], adjusted P<0.001). In the context of reverse causality, the onset of UC or CD has led to alterations in imaging derived phenotypes associated with five disorders (anxiety, depression, schizophrenia, bipolar disorder, pain) and three functions (memory, emotion, language). Our study has demonstrated a causal relationship between IBD and IDPs. IDPs may serve as potential biomarkers for the progression of IBD and as predictive intermediaries for the development of neurological diseases in IBD patients.

HUMAN β-DEFENSIN 2 ISOFORMS EXPRESSION ON PEDIATRIC IBD

Abstract Inflammatory bowel disease (IBD), which includes Ulcerative Colitis (UC) and Chron’s disease, affects a million people around the world. IBD is developed during the different stages of human life and has mostly been studied in adults. However, this disease has been observed in childhood. In the case of pediatric IBD, the causes are mostly related to genetic disorders. Human β-defensin 2 isoforms (DEFB4A and DEFB4B) are one of the families strongly related to the development of multiple diseases such as asthma and colorectal cancer. The main purpose of this study was to determine the factors that can affect the progression of pediatric IBD. Using gene expression data from 190 pediatric patients (Control= 55 samples, CD = 92 samples, and UC= 43 samples) available at the Gene Expression Omnibus (Accession code = GSE117993), the differential gene expression was determined using GEO2R tool (significant level cut-ff = 0.05 and Log 2-fold threshold= 2). The results showed that DEFB4A/B were upregulated when comparing UC and CD with Control. On the other hand, DEFB4A/B was downregulated compared to CD with UC. Human β-defensin 2 isoforms have been strongly related to the development of multiple diseases, including IBD in adult patients. In the case of pediatric patients, these isoforms could represent a potential maker to assess the progression of IBD.

P1242 Pediatric IBD microbiome and microbial profiles formed within the family

Abstract Background The rise of microbiome-focused research, reveals that the intrafamilial microbiome can be linked to specific genetic traits and be studied for its behavior during dysbiosis. It has been reported that microbiota composition is shared between cohabitating individualsand displays patterns of similarity that differ between families. Based on these observations, this study focuses on treatment-naïve pediatric IBD patients and their immediate families to identify the role of the microbiome in disease onset. Methods Families with pediatric IBD were recruited,comprising seven drug-naïve Crohn’s disease (CD) patients and two drug-naïve ulcerative colitis (UC) patients, as well as healthy siblings/parents. Fecal samples were collected for 16S ribosomal RNA gene sequencing and bioinformatics analysis. Results Our results elucidate the fact that even though family members share lifestyle and dietary habits, the patients exhibit unique microbiome patterns which could only be attributed to the disease. In addition, we studiedthe impact of the disease on specific microbial taxa and how these could serve as potential biomarkers for early detection. Conclusion We found a potential role of maternal factors in the establishment and modulation of the early life microbiome, consistent with the current literature, which may have implications for understanding the etiology and progression of IBD.

P179 Decrease in Butyric Acid in fecal matter in patients with Inflammatory Bowel Disease is associated with the levels of secretory Immunoglobulin A and fecal calprotectin

Abstract Background Accumulating evidence shows that the development of IBD is always accompanied by dysbiosis of the intestinal microbiota. Short-chain fatty acids (SCFAs) are produced by prebiotic intestinal bacteria, with mportant anti-inflammatory functions, delaying the clinical progression of IBD. The aim of this study is to compare SCFA levels in fecal matter in patients with IBD versus patients with Spondyloarthritis (SpA) and healthy controls. Methods 24 patients were evaluated for the presence of gastrointestinal symptoms, demographic data and inflammatory markers: fecal calprotectin, C-reactive protein (CRP), secretory IgA (SIgA) and erythrocyte sedimentation rate (ESR). The quantification of SCFAs (acetic-AC, propionic-AP, butyric-AB and total SCFAs-ACCC-T) from fecal matter was analyzed by ultra-high pressure liquid chromatography coupled to mass spectrometry (UHPLC-Q/ TOFMS). Results 33.3% of patients with IBD were men, with body mass index &amp;gt;25 in 16.7%; 83.3% presented more than 2 gastrointestinal symptoms at the time of sample collection, 33.3% had high levels of fecal calprotectin, 50% had CRP levels higher than 3mg/L and high ESR in 33.3% and a mean SIgA. of 27.73±5.03 g/mL. Very decreased levels of butyric acid (BA)ug/mL and T-SCFA were observed in IBD (9.45±4.89 and 121.73±65.94, respectively), compared to CS (BA 20.84±8.83 and total SCFA.12±122.09)., SpA SG (AB 13.35±10.44 and total AGCC 150.73±128.52) and SpA without OS (AB 21.13±5.68 and AGCC-T 219.51±229.65). Significant differences were found in fecal BA levels between the study groups (p=0.027). Interestingly, this metabolite in the CS group and the SpA group without OS did not show differences between them, but compared to the IBD group p=0.015 and 0.009 respectively, with a decrease in IBD. And interestingly, no differences were evident between fecal SCFA levels between the IBD group and the SpA group with OS even without a diagnosis of IBD. A principal component analysis was performed for the IBD group where two components were identified that group where COMP.1 was defined by a high correlation between the levels of each of the ACCC (AB CCF= 0.994, AA CCF= 0.935, AP= 0.610 and AGCC-TCCF= 0.910) that had an inverse relationship with COMP.2 which was made up of SIgA (CCF=0.988) and fecal calprotectin (CCF= 0.988). Conclusion SCFAs play a key role in maintaining immune homeostasis both locally and systemically. BA levels were significantly lower in patients with IBD compared to CS and those with SpA. This evidence clearly supports the hypothesis that relates the lack of BA with an exacerbated inflammatory response that could give rise to a dysfunctional intestinal epithelial barrier by regulating the production of mucosal antibodies such as SIgA.

RNA methylation in inflammatory bowel disease.

RNA modifications, including the renowned m6A, have recently garnered significant attention. This chemical alteration, present in mRNA, exerts a profound influence on protein expression levels by affecting splicing, nuclear export, stability, translation, and other critical processes. Although the role of RNA methylation in the pathogenesis and progression of IBD and colorectal cancer has been reported, many aspects remain unresolved. In this comprehensive review, we present recent studies on RNA methylation in IBD and colorectal cancer, with a particular focus on m6A and its regulators. We highlight the pivotal role of m6A in the pathogenesis of IBD and colorectal cancer and explore the potential applications of m6A modifications in the diagnosis and treatment of these diseases.

Cell death pathways in inflammatory bowel disease

Intestinal inflammatory disease (IBD) is a chronic intestinal disorder that includes Crohn’s disease and ulcerative colitis. In recent years, its incidence has been increasing, but there is still no breakthrough in its treatment. Cell death was divided into programmed and nonprogrammed cell death (PCD). PCD mainly includes ferroptosis, apoptosis, necroptosis, pyroptosis, and autophagy, while non-PCD refers to necrosis. Increasing evidence shows that PCD, such as ferroptosis and autophagy, plays an important regulatory role in intestinal diseases, which may be involved in the occurrence and progression of IBD and can be used as a therapeutic target for the disease. This article reviews recent studies on ferroptosis, apoptosis, necroptosis, pyroptosis, and autophagy associated with IBD, combs the regulatory mechanisms of PCD in IBD, and summarizes the corresponding therapeutic drugs and new materials, aiming to provide new directions and treatments for IBD research.

Expression of IL-21 and IL-33 in Intestinal Mucosa of Inflammatory Bowel Disease: An Immunohistochemical Study.

Interleukins are considered to be potential therapeutic targets that can alter the prognosis and disease progression of IBD. IL-21 has proven to be involved in effector Th1, Th2 and Th17 responses. Similarly, IL-33, a newly identified cytokine, has been shown to control the Th1 effector response and the action of the colonic Tregs in animal models of colitis and patients with IBD. In this retrospective study, we have studied the expression of these interleukins, using immunohistochemistry, in 121 patients with moderate to severe IBD before and after treatment with biologics. The results were statistically processed using SPSSTM. Increased IL-21 expression was found in the UC and CD groups versus the controls. The IL-33 expression was found to be increased in the post-treatment UC and CD groups, suggesting a protective role of this interleukin against bowel inflammation. The IL-33 expression post-treatment was reversely correlated with the activity index score in CD patients, suggesting a better response to treatment in patients with higher IL-33 mucosa levels. This is the first immunohistochemical study of the expression of those interleukins in bowel mucosa before and after treatment with biologics. These data support a possibly promising future use of these interleukins as biomarkers of severe disease and response to treatment and as potential therapeutic targets for novel monoclonal antibodies.

Mucosal Genes Expression in Inflammatory Bowel Disease Patients: New Insights.

Individual differences in IBD illness severity, behavior, progression, and therapy response are evident. Since a break in the intestinal epithelial barrier causes IBD to begin, mucosal gene expression in IBD is crucial. Due to its high sensitivity and dynamic nature, molecular analysis of biomarkers in intestinal biopsies is feasible and provides a reliable means of evaluating localized inflammation. The goal of this investigation was to discover alterations in gene expression in the inflamed mucosa of IBD patients undergoing treatment with 5-amino salicylic acid (5ASA) (N = 39) or anti-TNF drugs (N = 22). The mucosal expression of numerous IBD-related genes was evaluated using qPCR. We discovered that the levels of the proteins Lipocalin-2 (LCN2), Nitric Oxide Synthase 2 (NOS2), Mucin 2 (MUC2), Mucin 5AC (MUC5AC), and Trefoil factor 1 (TFF1), which are overexpressed in untreated IBD patients compared to non-IBD subjects, are decreased by both therapy regimens. On the other hand, anti-TNF medicine helped the levels of ABCB1 and E-cadherin return to normal in IBD patients who were not receiving treatment.

Evaluation of Serum Vitamin D Level and its Effect on the Severity of Disease in Patients with Inflammatory Bowel Disease

Background: Evolving evidence indicates the role of vitamin D deficiency in the progression of IBD and its impact on the severity of the disease, but it remains unclear whether vitamin D deficiency causes IBD or vice versa.&#x0D; Methods: This cross-sectional study was conducted to determine the serum levels of vitamin D and its effects on the severity of disease in patients with inflammatory bowel disease in the Imam Khomeini Hospital complex. A questionnaire containing demographic information, records on the use of supplements and medications, disease complications, and criteria for determining the severity of the disease based on the Mayo score and Crohn’s Disease Activity Index (CDAI) and 25 hydroxy vitamin D levels was completed and evaluated.&#x0D; Results: Of the 101 participants, 21 were with Crohn’s disease and 80 had ulcerative colitis. The mean age of Crohn’s patients was 33.80±9.5 years and ulcerative colitis was 38.43±10.2 years. Among patients with ulcerative colitis, 37 (46.8%) had a mayo score less than 3 and 42 (53.2%) were 3 and more. Mean vitamin D in the mayo score less than 3 was 32.14 and the mayo score 3 and more was 23.99. Of the Crohn’s patients, 12 (57.1%) were in the recovery phase and 9 (52.9%) were in a non-recovery phase. The mean of vitamin D in the recovery phase was 29.10 and in the others was 27.04&#x0D; Conclusion: There is a significant relationship between the level of vitamin D supplementation, the final value of CDAI, and the identification of the patients with the Mayo score.

DOP08 Cellular and molecular interaction of MAIT in mucosal tissue and their role in inflammatory bowel disease

Abstract Background Inflammatory bowel disease (IBD) manifests as chronic inflammation of the gastrointestinal tract and is characterized by a deregulated immune response targeting the gut microflora. Mucosal-associated invariant T (MAIT) cells have been identified as a possible key player in IBD. Activated MAIT cells produce cytokines including IL-26, a newly discovered cytokine involved in the pathology of IBD. Interestingly, IL-26 is not expressed in mice and therefore its effect on the course of inflammation has not been yet fully investigated. Similarly, studies employing human cell cultures often provide limited results as they cannot fully mimic the complex three-dimensional structure of the intestinal tissue. A great hope is placed in the development of models of human diseases using organoids - 3D structures that better recapitulate the architecture and functionality of tissues. Methods Our laboratory recently described a model of intestinal inflammation based on human iPSCs-derived intestinal organoids (IOs). Taking advantage of this model, we investigate the influence of the cytokine IL-26 on the course of IBD. Moreover, we elucidate the influence of MAIT cells on the pathogenesis of IBD by studying their pathways of activation in vitro, and subsequently their interaction with inflamed tissues through the co-culture with IOs. Results After stimulation, IOs mimic the pro-inflammatory microenvironment and express various cytokines and chemokines. Moreover, IOs express MR1 which is recognised by the invariant TCR receptor of the MAIT cells. IOs express functional IL-26 receptor and respond to this cytokine. MAIT cells isolated from human blood show production cytokines including IL-26 and effector molecules upon in vitro activation. Their response differs depending on the origin of the stimuli. Conclusion IOs form complex structures and immunocompetent environment allowing to study of intestinal inflammation. IOs consist of various cell types, but not immune cells. Taken together with MR1 and cytokines expression we show that IOs can activate MAIT cells, and they serve as a relevant model for in vitro study of their biology. Moreover, IOs respond to IL-26, so they also provide a relevant model to elucidate the role of this cytokine. We expect that this study will contribute to our understanding of the processes underlying the progression of IBD, and lead to the design of new therapeutic targets for the treatment of idiopathic intestinal inflammation.

DOP03 Unfermented β-fructan fibres can induce gut inflammation and tumorigenesis in select Inflammatory Bowel Disease patients mediated by gut microbiota

Abstract Background Dietary fibres are not digested in the bowel; they are fermented by microbes, typically promoting gut health. However, IBD patients have altered gut microbiota composition and can experience sensitivity to consumption of fibres. Our previous findings offered the first mechanistic evidence that if dietary β-fructans (inulin and oligofructose) are not fermented by gut microbes in IBD patients, these fibres can induce inflammation. This diet-induced inflammation could have serious repercussions as chronic inflammation creates a mutagenic environment that promotes progression to colorectal cancer (CRC). We hypothesized that unfermented β-fructans cause tumorigenesis and promotion of IBD progression to CRC. Methods We examined pathways associated with response to β-fructan in a randomized controlled trial examining β-fructan supplementation (15g/day) in UC patients in remission (RNA sequencing). We validated pathways of interest in IBD patient colonic biopsies cultured ex vivo with β-fructans (targeted proteomics and mesoscale discovery). We examined structural changes (microscopy; e.g., tumorigenic architecture) in these biopsies. Further, cell invasion, migration, and proliferation were examined using scratch wound assays and chick chorioallantoic membrane assays (CAM; n=10 embryos per treatment). Results CRC-related pathways (SLIT2/MAPK and SOS1) were induced and anti-tumour gene RPS27A was reduced only in biopsies from remission UC patients who entered relapse following consumption of β-fructans (endpoint versus baseline), not those in the placebo arm who relapsed. Pathways were validated in IBD patient colonic biopsies cultured ex vivo demonstrating oligofructose produced more significant effects than inulin; response correlated with disease severity. Inulin and oligofructose further influenced the processes of migration and invasion reflective of the tumorigenic process of epithelial to mesenchymal transition and risk of CRC. Conclusion Our findings suggest that intolerance and avoidance of fibres in select IBD patients occurs specifically in patients whose gut microbiota do not support fermentation of dietary fibres resulting in increased presence of unfermented dietary fibres in the gut. Here we show that these β-fructan fibres commonly touted as beneficial prebiotics can elicit gut inflammation and tumorigenesis in this subset of IBD patients, suggesting consumption of these fibres should be avoided in these patients.

COMMENSAL GUT BACTERIA REGULATE HIF ACTIVITY TO PROMOTE INTESTINAL HOMEOSTASIS

Abstract Inflammatory bowel disease (IBD) is a disorder marked by chronic, relapsing inflammation of the gastrointestinal tract. Although the precise etiology of IBD is unclear, pathogenic immune response to the gut microbiota is considered a contributing factor. The importance of the gut microbiota in the development of intestinal inflammation has been previously shown through associative studies that correlate dysbiosis of the gut microbiota with active IBD, particularly through the loss of fiber-fermenting obligate anaerobes, an increased presence of pathobionts, and an overall decrease in microbial species diversity. Although the gut microbiota clearly plays an essential role in the development and progression of IBD, the mechanisms by which these micro-organisms regulate gut homeostasis remain to be fully elucidated. Previously, we found that Salmonella Typhimurium (STm), a model invasive pathogen, activated hypoxia inducible factor-1α (HIF-1α) in intestinal epithelial cells (IECs) to regulate anti-bacterial autophagy. HIF-1α is a member of a transcription factor family that senses and responds to environmental stressors, in particular low oxygen tensions. Such stressors stabilize HIF-1α in the cytoplasm and prevent its usual oxygen-dependent degradation. Of note, HIF-1α has been previously shown to be essential for intestinal homeostasis in animal models of IBD, and stabilization of HIF has been demonstrated to be protective during various models of colitis in mice. As an extension of these studies, we asked whether bacterial stabilization of HIF was unique to STm in the intestinal epithelium. We found that stabilization of HIF in IECs was not restricted to STm but was, surprisingly, recapitulated by a wide variety of bacteria, including bacteria rendered non-invasive by genetic manipulation and nonpathogenic/commensal enteric bacterial isolates. Further, we observed that stabilization of HIF was dependent on live bacteria and not due to a secreted factor, suggesting an innate HIF response by the intestinal epithelium to enteric bacteria. Finally, we found modulation of HIF signaling by enteric bacteria including regulation of numerous genes previously implicated in gut homeostasis. These results, taken together, suggest that commensal bacteria regulate intestinal homeostasis through activation of the transcription factor HIF.

ASSESSMENT OF THE IMMUNE CELL LANDSCAPE IN INFLAMMATORY BOWEL DISEASE

Abstract INTRODUCTION Inflammatory Bowel Disease (IDB) is a chronic and sometimes refractory group of gastrointestinal conditions that can cause enormous medical and socioeconomic burdens. [1] Both, innate and adaptive immune cells play a crucial role in the pathogenesis of IBD, but the exact mechanisms are not totally well understood [2] An improved understanding of the immune cell landscape behind IBD is necessary for identifying novel diagnostic and therapeutic targets. OBJECTIVE The aim of this study was to evaluate and compare the immune cell composition between healthy patients and patients with Ulcerative Colitis (UC) and Chron’s Disease (CD) in peripheral blood and colon biopsy samples. METHODOLOGY The immune cell landscape in peripheral blood and colon biopsy samples was determined using CIBERSORT and gene expression data from the study submitted by Argmann et al obtained via Gene Expression Omnibus (peripheral blood: GSE186507 and colon biopsies: GSE193677). In this study the biopsies were obtained from ileum, colon, and rectum. T-test was used to estimate the differences among the groups. RESULTS The immune cell landscape of peripheral blood showed more resting T CD4 memory cells in the control group (p=0.009), while the number of activated T CD4 memory cells was greater in IBD patients (p= 0.01). The frequency of B cells naïve was higher in CD than in UC (p= 0.03), and CD8 T cells were more in UC (p=0.04). In terms of biopsies, the samples from the rectum showed the highest infiltration of immune cells. Macrophages M1 are present with higher numbers in rectum samples from CD vs UC (p=0.0026) and CD vs control group (p=8e-10). CONCLUSIONS The results showed significant differences in the immune cell composition among the control group, UC, and CD patients, not only in peripheral blood but also in biopsy samples. In both cases, Macrophages M1 were the most common cells found. These findings suggest that immune cell landscape could be used as a potential biomarker of the progression of IBD.

Updated immunomodulatory roles of gut flora and microRNAs in inflammatory bowel diseases.

Inflammatory bowel disease is a heterogeneous intestinal inflammatory disorder, including ulcerative colitis (UC) and Crohn's disease (CD). Existing studies have shown that the pathogenesis of IBD is closely related to the host's genetic susceptibility, intestinal flora disturbance and mucosal immune abnormalities, etc. It is generally believed that there are complicated interactions between host immunity and intestinal microflora/microRNAs during the occurrence and progression of IBD. Intestinal flora is mainly composed of bacteria, fungi, viruses and helminths. These commensals are highly implicated in the maintenance of intestinal microenvironment homeostasis alone or in combination. MiRNA is an endogenous non-coding small RNA with a length of 20 to 22 nucleotides, which can perform a variety of biological functions by silencing or activating target genes through complementary pairing bonds. A large quantity of miRNAs are involved in intestinal inflammation, mucosal barrier integrity, autophagy, vesicle transportation and other small RNA alterations in IBD circumstance. In this review, the immunomodulatory roles of gut flora and microRNAs are updated in the occurrence and progression of IBD. Meanwhile, the gut flora and microRNA targeted therapeutic strategies as well as other immunomodulatory approaches including TNF-α monoclonal antibodies are also emphasized in the treatment of IBD.

MicroRNA-9a-5p-NOX4 inhibits intestinal inflammatory injury by regulating the M1 polarization of intestinal macrophages.

We found that the expression of microRNA (miRNA)-9a-5p decreased in inflammatory bowel diseases (IBD; ulcerative colitis and Crohn's disease). Further, we revealed the effects and mechanisms of miRNA-9a-5p for regulatingIBD progression. In C57BL/6N mice, IBD was induced with dextran sodium sulfate (DSS), and the effects of endogenous miRNA-9a-5p were mimicked/antagonized through intraperitoneal injection of miRNA-9a-5p agomir and antagomir. In animal experimentation, agomir could inhibit intestinal inflammation and tissue damage, and reduce the mucosal barrier permeability. Antagomir, on the other hand, could promote barrier damage, whose effect was associated with the M1 macrophage polarization.This study finds that miRNA-9a-5p targets NOX4 to suppressROS production, which plays an important role in mucosal barrier damage in IBD.

Age-related and Gender Aspects of Inflammatory Bowel Diseases in the Republic of Dagestan

Aim: Creation of a patient registry in the Republic of Dagestan to study various aspects of the course and outcomes of IBD, depending on the age and gender of patients.Materials and methods. We have created a register of IBD patients in the Republic of Dagestan. It included 168 IBD patients aged 17 to 70 years, 69 males and 99 females, the average age of patients with IBD was 38.1 ± 2.5 years with an average duration of illness of 6.19 ± 0.71 years. The diagnosis of IBD was established on the basis of the characteristic clinical picture of the disease, objective status, results of laboratory, endoscopic, X-ray and morphological research in accordance with Russian Clinical GuidelinesResults. The prevalence of IBD in the Republic of Dagestan is 5.41 cases per 100,000 population. The progression of IBD is more often observed in women, aged 30 to 39 years, residents of rural areas. Anemia (mainly chronic iron deficiency) was registered in 66.1 %, more often in women, its maximum frequency was noted in patients aged 20–29 years (80 %). Disability due to IBD was registered in 55.4 % of patients.Conclusions. The creation of a register of IBD patients in the Republic of Dagestan is aimed at monitoring the state of health, timely monitoring of the effectiveness of therapy and improving the quality of medical care.

A mean platelet volume in inflammatory bowel disease: A systematic review and meta-analysis.

BackgroundInflammatory bowel disease (IBD) is a chronic gastrointestinal tract inflammatory state, which is affecting millions of individuals in the world. It can affect alimentary canals such as colon, rectum, ileum and other parts. In IBD, platelet parameters underwent several changes. Therefore, the aim of this review was determining the estimated pooled mean platelet volume and mean difference in inflammatory bowel disease to elucidate its potential diagnostic value.MethodsArticles were extensively searched in bibliographic databases using Medical Subject Heading and entry phrases or terms. In addition, articles were directly searched in Google Scholar to account for the studies omission in searching bibliographic databases. Observational (cohort, cross-sectional and case-control) studies, published in English language and conducted on IBD were included. For studies meeting the eligibility criteria, the first author’s name, publication year, population, study design, study area, sample size, mean platelet volume and standard deviation were extracted and entered in to Microsoft-excel. The analysis was done by Stata version 11. In order to estimate the pooled mean platelet volume and mean difference, random effect model was done. The heterogeneity was quantified using Higgin’s I2 statistics. Publication bias was determined using Egger’s test statistics and funnel plot. Sub-group analysis based on population carried to reduce heterogeneity.ResultsA total of 17 relevant articles with 2957 participants (1823 IBD cases and 1134 healthy controls) were included to this study. The pooled estimated MPV was 9.29fl; 95% CI: 9.01–9.57 and 9.50fl; 95% CI: 8.81–10.20 in IBD and control groups, respectively. The standardized pooled estimate of mean difference in mean platelet volume was -0.83fl; 95% CI: -1.15, -0.51; I2: 93.1%; P-value < 0.001. In subgroup analysis based on population, the highest estimated mean difference in MPV was observed among patients of CD; -2.30; 95% CI: -3.46, -1.14; I2: 97.8%; P-value < 0.001.ConclusionAccording to the current systematic review and meta-analysis, mean platelet volume was lower in IBD compared to control. The decreased mean platelet volume could be attributed to platelet consumption or sequestration associated with the progression of IBD. As a result, in IBD, mean platelet volume can provide diagnostic and prognostic information.

Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates the severity of DSS colitis

BackgroundInflammatory bowel diseases (IBDs) including Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by chronic and debilitating gut inflammation. Altered bacterial communities of the intestine are strongly associated with IBD initiation and progression. The gut virome, which is primarily composed of bacterial viruses (bacteriophages, phages), is thought to be an important factor regulating and shaping microbial communities in the gut. While alterations in the gut virome have been observed in IBD patients, the contribution of these viruses to alterations in the bacterial community and heightened inflammatory responses associated with IBD patients remains largely unknown.ResultsHere, we performed in vivo microbial cross-infection experiments to follow the effects of fecal virus-like particles (VLPs) isolated from UC patients and healthy controls on bacterial diversity and severity of experimental colitis in human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred to HMA mice, resulting in treatment-specific alterations in the gut virome. VLPs from healthy and UC patients also shifted gut bacterial diversity of these mice, an effect that was amplified during experimental colitis. VLPs isolated from UC patients specifically altered the relative abundance of several bacterial taxa previously implicated in IBD progression. Additionally, UC VLP administration heightened colitis severity in HMA mice, as indicated by shortened colon length and increased pro-inflammatory cytokine production. Importantly, this effect was dependent on intact VLPs.ConclusionsOur findings build on recent literature indicating that phages are dynamic regulators of bacterial communities in the gut and implicate the intestinal virome in modulating intestinal inflammation and disease.EQTzi7uzN3oVQtNZuyDoLGVideo