Occurrence Of Colitis Research Articles

Helicobacter bilis Contributes to the Occurrence of Inflammatory Bowel Disease by Inducing Host Immune Disorders

Gut microbiota coevolve with humans to achieve a symbiotic relationship, which ultimately leads to physiological homeostasis. A variety of diseases can occur once this balance is disrupted. Helicobacter bilis (H. bilis) is an opportunistic pathogen in humans, triggering multiple diseases, including inflammatory bowel disease (IBD). IBD is a chronic immunologically mediated inflammation of the human gastrointestinal tract, and its occurrence is closely related to the gut microbiota. Several studies have demonstrated that H. bilis colonization is associated with IBD, and its mechanism is related to host immunity. However, few studies have investigated these mechanisms of action. Therefore, this article is aimed at reviewing these studies and summarizing the mechanisms of H. bilis-induced IBD from two perspectives: adaptive immunity and innate immunity. Furthermore, this study provides a preliminary discussion on treating H. bilis-related IBD. In addition, we also demonstrated that H. bilis played an important role in promoting the carcinogenesis of IBD and discussed its mechanism.

Metformin use is not associated with reduced risk of older onset inflammatory bowel disease: a Danish nationwide population-based study.

Metformin has pleiotropic effects including anti-inflammatory properties and effects on the gut microbiome. It is primarily used in the older population, where the occurrence of inflammatory bowel disease (IBD) is increasing. The aim of this study was to examine whether metformin protects against development of IBD. In the setting of a Danish nationwide population-based cohort, we conducted a nested case-control study using a new-user active comparator design. For each patient with IBD, we selected 10 IBD-free individuals matched on age, sex, and duration of follow-up. Conditional logistic regression was used to estimate odds ratios (ORs) of IBD. Adjustment included educational level, other immune-mediated inflammatory diseases, and use of dipeptidyl peptidase (DPP)-4 inhibitors and statins. Among 302,863 IBD-free new users of oral glucose-lowering drugs, we identified 1271 patients who developed IBD and 12,676 matched IBD-free individuals. Mean age at IBD diagnosis was 66 (SD, 11) years. We found no association between ever use of metformin and risk of IBD, Crohn's disease or ulcerative colitis, adjusted OR 0.95 (95% CI 0.78-1.15), 0.87 (95% CI 0.60-1.26), and 1.04 (95% CI 0.83-1.31), respectively. Neither was the cumulative dose of metformin or the treatment duration with metformin associated with risk of IBD. In this population-based study, we report that despite anti-inflammatory effects and a notable impact on the gut microbiome, metformin use is not associated with reduced risk of older onset IBD.

Changes of intestinal microbiota and microbiota-based treatments in IBD.

Inflammatory bowel disease (IBD) has gained increasing attention from researchers in terms of its pathophysiology as a global disease with a growing incidence. Although the exact etiology of IBD is still unknown currently, various studies have made us realize that it is related to the dysbiosis of intestinal microbiota and the link between the two may not just be a simple causal relationship, but also a dynamic and complicated one. The intestinal microbiota has been confirmed to be closely related to the occurrence, development, and treatment of IBD. Therefore, this review focuses on the changes in the structure, function, and metabolites of intestinal bacteria, fungi, and viruses in influencing IBD, as well as various approaches to IBD treatment by changing disordered intestinal microbiota. Ultimately, more clinical studies will be needed to focus on the efficacy of intestinal microbiota-based treatments in IBD, because of the existence of both advantages and disadvantages.

Leaky Gut in IBD: Intestinal Barrier-Gut Microbiota Interaction.

Inflammatory bowel disease (IBD) is a global disease that is in increasing incidence. The gut, which contains the largest amount of lymphoid tissue in the human body, as well as a wide range of nervous system components, is integral in ensuring intestinal homeostasis and function. By interacting with gut microbiota, immune cells, and the enteric nervous system, the intestinal barrier, which is a solid barrier, protects the intestinal tract from the external environment, thereby maintaining homeostasis throughout the body. Destruction of the intestinal barrier is referred to as developing a "leaky gut," which causes a series of changes relating to the occurrence of IBD. Changes in the interactions between the intestinal barrier and gut microbiota are particularly crucial in the development of IBD. Exploring the leaky gut and its interaction with the gut microbiota, immune cells, and the neuroimmune system may help further explain the pathogenesis of IBD and provide potential therapeutic methods for future use.

The Role of Tissue-Resident Macrophages in the Development and Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a refractory disease with many immune abnormalities and pathologies in the gastrointestinal tract. Because macrophages can distinguish innocuous antigens from potential pathogens to maintain mucosa barrier functions, they are essential cells in the intestinal immune system. With numerous numbers in the intestinal tract, tissue-resident macrophages have a significant effect on the constant regeneration of intestinal epithelial cells and maintaining the immune homeostasis of the intestinal mucosa. They also have a significant influence on IBD through regulating pro-(M1) or anti-inflammatory (M2) phenotype polarization according to different environmental cues. The disequilibrium of the phenotypes and functions of macrophages, disturbed by intracellular or extracellular stimuli, influences the progression of disease. Further investigation of macrophages’ role in the progression of IBD will facilitate deciphering the pathogenesis of disease and exploring novel targets to develop novel medications. In this review, we shed light on the origin and maintenance of intestinal macrophages, as well as the role of macrophages in the occurrence and development of IBD. In addition, we summarize the interaction between gut microbiota and intestinal macrophages, and the role of the macrophage-derived exosome. Furthermore, we discuss the molecular and cellular mechanisms participating in the polarization and functions of gut macrophages, the potential targeted strategies, and current clinical trials for IBD.

Mesenchymal stem cells-derived extracellular vesicles containing miR-378a-3p inhibit the occurrence of inflammatory bowel disease by targeting GATA2.

This study sought to determine whether mesenchymal stem cells‐derived extracellular vesicles (MSCs‐EVs) carrying microRNA‐378a‐3p (miR‐378a‐3p) could affect the pathogenesis of inflammatory bowel disease (IBD) by regulating the GATA‐binding protein 2 (GATA2)/aquaporin‐4 (AQP4)/peroxisome proliferator‐activated receptor α (PPAR‐α) axis. Initially, colon mucosa biopsy tissues were harvested from healthy controls and patients with IBD for qRT‐PCR and immunohistochemistry analysis. EVs harvested from MSCs and lipopolysaccharide (LPS) were used to stimulate the M064 cells to establish an in vitro inflammation cell model. Besides, 2,4,6‐trinitrobenzene sulfonic acid intracolon administration was performed to establish in vivo IBD mouse models. After loss‐ and gain‐of‐function assays, the regulatory role of MSCs‐derived EVs loaded with manipulated miR‐378a‐3p in IBD in relation to GATA2/AQP4/PPAR‐α were explored. Upregulation of GATA2 was identified in the colon tissue of IBD patients. GATA2, which was a target gene of miR‐378a‐3p, transcriptionally upregulated AQP4. After silencing of GATA2, LPS‐induced apoptosis of M064 cells was reduced by the downregulation of AQP4. Decreased AQP4 contributed to PPAR‐α pathway inactivation and weakened the LPS‐induced apoptosis of M064 cells. MSCs‐EVs delivering miR‐378a‐3p suppressed the GATA2/AQP4/PPAR‐α pathway, which reduced LPS‐induced apoptosis of M064 cells and the occurrence of IBD in mice. Altogether, the current study illustrated that MSCs‐EVs transfer miR‐378a‐3p to reduce the GATA2 expression, which downregulates AQP4 to block the PPAR‐α signalling pathway, thus suppressing the occurrence of IBD.

Maternal diets have effects on intestinal mucosal flora and susceptibility to colitis of offspring mice during early life

ObjectivesIntestinal flora is considered closely related to the occurrence of inflammatory bowel disease (IBD). This study aimed to discover whether diverse diet conditions during early life lead to different intestinal flora structure and impact different susceptibility to IBD. MethodsWe performed a randomized, controlled trial to investigate the relationship between maternal diet, intestinal flora, and susceptibility of IBD in offspring mice. We treated the maternal mice with different dietary conditions (maternal high fat, high protein, or normal diet, and offspring continued maternal diets or changed to normal diet), and then extracted bacterial meta-genomic DNA from the intestinal mucosa of the offspring during the early life and adult stages. We amplified and sequenced the conserved gene v3-v4 of the bacterial 16 S ribosomal RNA. After dextran sulphate sodium intervention, we evaluated the susceptibility to intestinal inflammation with hematoxylin and eosin stains and disease activity index scores. ResultsThe number of species and alpha diversity of weaning mice (3 wk old) fed a maternal high-protein diet were significantly lower than those of the control diet group (P < 0.05). Among adult (8 wk old) offspring rats, the alpha diversity of mice that continued on a high-protein diet remained significantly decreased (P < 0.05). In addition, 12 kinds of weak bacteria were found in weaning mice fed a maternal high-protein diet compared with the control group. Offspring that continued in the maternal high-protein group had increased disease activity index and pathologic scores after weaning. ConclusionsIn general, our study shows that a maternal high-protein diet during early life can negatively regulate the intestinal flora diversity of offspring mice. A high-protein diet during early life led to higher susceptibility of IBD in offspring rats.

Identification of Childhood-Onset Inflammatory Bowel Disease in Swedish Healthcare Registers: A Validation Study.

PurposeThe Swedish National Patient Register (NPR) is often used in observational studies of childhood-onset inflammatory bowel disease (IBD) (<18 years of age) and its subtypes, but the validity of previously used register-based algorithms for capturing childhood-onset IBD has never been examined.MethodsWe identified a random sample of 233 individuals with at least two first ever diagnostic listings of IBD in the NPR between 2002 and 2014. We calculated the test characteristics for different register-based definitions of IBD and its subtypes using the Copenhagen criteria and the revised Porto criteria as gold standard, both based on medical chart review. We made assumptions of the occurrence of undiagnosed IBD in the general child population based on available literature.ResultsOut of 233 individuals with at least two diagnostic listings of IBD, 216 had true IBD, resulting in a positive predictive value (PPV) = 93% (95% confidence interval (CI) 89–96), sensitivity = 88% (95% CI 83–92), specificity = 100% (95% CI 100–100), and negative predictive value (NPV) = 100% (95% CI 100–100). The PPV for the NPR-based definitions of IBD subtypes at time of first IBD diagnosis and at end of follow-up were 78% (95% CI 69–86) and 88% (95% CI 80–94), respectively, for Crohn’s disease and 74% (95% CI 63–83) and 71% (95% CI 60–80), respectively, for ulcerative colitis.ConclusionThe validity of register-based definitions of childhood-onset IBD in the Swedish NPR is high and can be used to identify patients in observational research.

Campylobacter jejuni Serine Protease HtrA Induces Paracellular Transmigration of Microbiota across Polarized Intestinal Epithelial Cells.

Campylobacter jejuni represents an eminent zoonotic germ responsible for foodborne infections causing campylobacteriosis. In addition, infections with C. jejuni constitute a risk factor for the occurrence of inflammatory bowel disease (IBD). In the latter case, patients show inflammatory reactions not only against C. jejuni, but also against the non-infectious microbiota. However, the involved mechanisms and molecular basis are still largely unclear. We recently reported that C. jejuni breaches the intestinal epithelial barrier by secretion of serine protease HtrA (high temperature requirement A), which cleaves several major tight and adherens junction proteins. In the present study, we aimed to study if HtrA-expressing C. jejuni may also trigger the transepithelial migration of non-pathogenic gastrointestinal microbiota. Using confocal immunofluorescence and scanning electron microscopy, we demonstrate that C. jejuni wild-type (wt) as well as the isogenic ∆htrA mutant bind to the surface of polarized intestinal Caco-2 epithelial cells, but do not invade them at the apical side. Instead, C. jejuni wt, but not ∆htrA mutant, disrupt the cellular junctions and transmigrate using the paracellular route between neighboring cells. Using transwell filter systems, we then co-incubated the cells with C. jejuni and non-invasive microbiota strains, either Escherichia coli or Lactococcus lactis. Interestingly, C. jejuni wt, but not ∆htrA mutant, induced the efficient transmigration of these microbiota bacteria into the basal compartment. Thus, infection of the intestinal epithelium with C. jejuni causes local opening of cellular junctions and paracellular translocation in an HtrA-dependent manner, which paves the way for transmigration of microbiota that is otherwise non-invasive. Taken together, these findings may have impacts on various Campylobacter-associated diseases such as IBD, which are discussed here.

Homemade diet as nutritional support for a dog suffering from chronic pancreatitis and inflammatory bowel disease

AbstractA spayed Boston terrier was referred for nutritional advice after failing to respond to long‐term medical and dietary treatment for chronic pancreatitis. Based on clinical appearance, consecutive bloodwork and ultrasound examination, the concomitant occurrence of inflammatory bowel disease was likely. An exclusion diet (novel protein approach) and a stepwise balancing schedule were formulated to address combined nutritional recommendations, as well as the possibility for hypersensitivity to play a role. After initiation of the exclusion diet, the patient relapsed twice. Once due to non‐compliance of the owner, once due to reaction to an added supplement. After correction, no major relapses were noted for at least 1 year. To the authors’ knowledge, this report is the first to describe the successful supportive care of chronic pancreatitis and concurrent inflammatory bowel disease by prescribing a homemade diet.

A Broad m6A Modification Landscape in Inflammatory Bowel Disease.

Background and Aims: N6-Methyladenosine (m6A) is the most common post-transcriptional modification on eukaryotic mRNA, affecting the mRNA’s fate. The role of m6A regulation in inflammatory bowel disease is unclear. Here, we investigated the m6A landscape in inflammatory bowel diseases (IBD). Methods: Eleven human IBD microarray datasets were recruited from the Gene Expression Omnibus database and four were selected as discovery cohorts. An RNA-seq dataset from the Inflammatory Bowel Disease Multi’omics Database was used as a validation cohort. m6A regulators were measured in volunteers’ colonic samples. Consensus clustering and immune scoring were used to estimate the characteristics of m6A regulation in IBD. m6A-related characteristics of different sub-phenotypes, sample sources, and biological therapeutic responses were determined using seven independent datasets. Results: m6A modification involves methyltransferases (writers), demethylases (erasers), and methylation-reading proteins (readers). A wide interaction exists between m6A regulators and IBD risk genes. The IBD risk loci can also be modified by m6A modifications in the public m6A sequencing data. Furthermore, m6A regulators displayed extensive differential expression in four independent discovery cohorts that share common differential genes (IGF2BP2, HNRNPA2B1, ZCCHC4, and EIF3I). In the validated cohort and enrolled volunteers’ colonic biopsy samples, the differential m6A regulators were reconfirmed. Two clusters of consensus clustering exhibit different immune phenotypes. m6A-modified positions exist in the core IBD immune cytokines. Another set of IBD datasets revealed m6A-related differences across clinical phenotypes, biological samples, and therapeutic response subgroups in IBD patients. Conclusion: Regulation of m6A methylation is widely involved in IBD occurrence and development. m6A modifications in risk variants, core cytokines, immune cells, and other proteins may deeply influence the pathophysiology and clinical phenotypes. Further studies are needed to determine its role in IBD.

Guanylin ligand protects the intestinal immune barrier by activating the guanylate cyclase-C signaling pathway

Inflammatory bowel disease (IBD) impacts patient quality of life significantly. The dysfunction of intestinal immune barrier is closely associated with IBD. The guanylate cyclase-C (GC-C) signaling pathway activated by the guanylin (Gn) ligand is involved in the occurrence and development of IBD. However, how it regulates the intestinal immune barrier is still unclear. To investigate the effect of the GC-C pathway on intestinal mucosal immunity and provide experimental basis for seeking new therapeutic strategies for IBD, we focused on Caco-2 cells and intestinal intra-epithelial lymphocytes (IELs), which displayed inflammatory responses induced by lipopolysaccharide (LPS). GC-C activity was modulated by transfection with Gn overexpression or GC-C shRNA plasmid. Levels of Gn, GC-C, and CFTR; transepithelial electrical resistance (TER); paracellula r permeability; and levels of IL-2, IFN-γ, and secretory IgA (sIgA) were examined. The study found that after stimulation with LPS, Gn, GC-C, CFTR, TER, and sIgA levels were all significantly reduced, IL-2 and IFN-γ levels as well as paracellular permeability were significantly increased. These indicators changed inversely and significantly after transfection with the Gn overexpression vector. Compared to the vector controls, GC-C-silenced cells displayed significantly decreased levels of GC-C, CFTR, and TER and increased levels of IL-2, IFN-γ, and paracellular permeability stimulated by LPS. The results show that Gn ligand can protect the intestinal immune barrier by activating the GC-C signaling pathway, which may be helpful for the development of new treatments for IBD. Data availability statementThe data used to support the findings of this study are available from the corresponding author upon request.

Immunological Aspect in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic inflammation in the alimentary tract due to improper immune response toward external and internal antigens. The disease consists of 2 entities: ulcerative colitis (UC) and Crohn’s disease (CD). The disease’s prevalence is increasing worldwide due to westernization and industrialization. Europe still holds the highest prevalence of IBD in the world. There are 2 peaks of disease incidence. The first is in the third decade of life and the second is in the fourth decade. Slight male predominance is observed in IBD. Internal and external risk factors play important role in the occurrence of IBD including genetic, smoking, reduced fibre intake, less or absent breastfeeding, sedentary occupation, pollution exposure, and medications. The disease carries heavy economic burden and hampers patient’s quality of life. The immune concept of IBD was hypothesized in 1950s since the symptoms resolved with the administration of steroid. Innate and adaptive immune systems are involved in the pathogenesis of IBD. Antigen presenting cells are found hyperactive, intestinal barrier is disrupted, and autophagy activity is increased. Molecular mimicry occurs between foreign and self antigen. The activity of T helper (Th)1, Th2, and Th17 is amplified while regulatory T cell’s activity is suppressed. Pro-inflammatory cytokine production is elevated but anti-inflammatory cytokines is lowered. Finally, there is increased immunoglobulin G level in intestinal mucosa and imbalance of gut microorganism. All the above immune disturbances lead to chronic inflammation in IBD.

Fecal microbiota profiling in irritable bowel syndrome and inflammatory bowel disease patients with irritable bowel syndrome-type symptoms

BackgroundThe intestinal microbiota is thought to be involved in the occurrence of inflammatory bowel disease in remission with irritable bowel syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. This cross-sectional study aims to investigate the fecal microbiota profiling in patients with these diseases.MethodsFecal samples from 97 subjects, including Crohn’s disease patients in remission with IBS-type symptoms (CDR-IBS+) or without IBS-type symptoms (CDR-IBS−), ulcerative colitis patients in remission with IBS-type symptoms (UCR-IBS+) or without IBS-type symptoms (UCR-IBS−), IBS patients and healthy controls, were collected and applied 16S ribosomal DNA (rDNA) gene sequencing. The V4 hypervariable regions of 16S rDNA gene were amplified and sequenced by the Illumina MiSeq platform. The differences in the sample diversity index in groups were analyzed with R software.ResultsThe richness of the intestinal microbiota in the CDR-IBS group was markedly lower than those in the control and IBS groups based on the analysis of observed species and the Chao index (P < 0.05). The observed species index in the CDR-IBS+ group was higher than that in the CDR-IBS− group (median index: 254.8 vs 203, P = 0.036). No difference was found in alpha diversity between UCR patients with IBS-type symptoms and those without related symptoms. At the genus level, the number of Faecalibacterium in CDR patients with IBS-type symptoms increased significantly, while Fusobacterium decreased versus those without such symptoms (mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P < 0.05; Fusobacterium: 1.51% vs 5.2%, P < 0.05). However, compared with the UCR-IBS− group, the number of Faecalibacterium in the UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no significant difference in the genus structure. The abundance and composition of the microbiota of IBS patients were not distinct from those of healthy controls.ConclusionsThe IBS-type symptoms in CD patients in remission may be related to an increase in Faecalibacterium and a decrease in Fusobacterium. The IBS-type symptoms in UC patients in remission cannot be explained by changes in the abundance and structure of the intestinal microbiota.

Transplantation of fecal microbiota from patients with inflammatory bowel disease and depression alters immune response and behavior in recipient mice

Gut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and physiological effect between IBD patients with (IBD/D+) or without depression (IBD/D−), we analyzed the fecal microbiota composition of patients with IBD with (/D+) or without depression (/D−) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D+ or IBD/D− caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1β and IL-6 expression, and NF-κB+/CD11c+ cell population in the colon. Transplantation of the IBD/D+ patient feces (IBD/D+-F) caused IBD-like colitis more strongly than that of IBD/D−-F. FMTs from patients with IBD/D+ also caused anxiety-/depression-like behaviors, increased the NF-κB+/Iba1+ and lipopolysaccharide (LPS)+/Iba1+ cell populations, and decreased the BDNF+/NeuN+ cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D− caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D+-F vs. IBD/D−-F. However, the transplantation of HV-F into mice previously transplanted with IBD/D+-F significantly reduced depression-like behaviors, NF-κB+/Iba1+ and LPS+/Iba1+ cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1β expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.

S1110 Hepatopancreatobiliary Malignancy and Inflammatory Bowel Disease Occurrence in Black and White Patient Populations With Primary Sclerosing Cholangitis Seen in a Large U.S. Health Care Network

S1110 Hepatopancreatobiliary Malignancy and Inflammatory Bowel Disease Occurrence in Black and White Patient Populations With Primary Sclerosing Cholangitis Seen in a Large U.S. Health Care Network

Crohn's Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes.

The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 patients with IBD, including children, and 888 controls. Imaging or endoscopy with a histopathological confirmation was used to diagnose IBD. Genotyping was performed to assess the differences in genotypic and allelic frequencies. Linkage disequilibrium was analyzed, and associations between haplotypes and clinical data were evaluated. We emphasized the prevalence of risk alleles in all analyzed loci in patients with Crohn disease (CD). Interestingly, c.2722G>C and c.3019_3020insC alleles were also overrepresented in ulcerative colitis (UC). T-C-G-C-insC, T-C-G-T-insC, and T-T-G-T-wt haplotypes were correlated with the late-onset form of CD (OR = 23.01, 5.09, and 17.71, respectively), while T-T-G-T-wt and C-C-G-T-wt were prevalent only in CD children (OR = 29.36, and 12.93, respectively; p-value = 0.001). In conclusion, the presence of c.3019_3020insC along with c.802C>T occurred as the most fundamental contributing diplotype in late-onset CD form, while in CD children, the mutual allele in all predisposing haplotypes was the c.2798 + 158T. Identifying the unique, high-impact haplotypes supports further studies of the NOD2 gene, including haplotypic backgrounds.

Expression of microribonucleic acid 1228 in inflammatory bowel disease patients

Introduction Knowledge in the field of microribonucleic acids (miRNAs) can be used both to reveal the mechanisms of occurrence of inflammatory bowel diseases (IBDs) and to predict the response to a particular treatment. Aim The aim of this article is to assess the serum expression of miR-1228 in IBD patients. Materials and Methods A total of 35 patients with ulcerative colitis (UC), 35 patients with Crohn’s disease (CD), and a control group of 30 healthy individuals were studied. Serum expression of miR-1228 was tested in all through reverse transcriptase-quantitative real-time polymerase chain reaction (RT-qPCR). Results The expression in CD patients (1.91 ±2.21) was significantly higher compared to the expression in UC patients (1.15±0.64) and healthy controls (1.14±0.59). In CD patients, increased expression of miR-1228 was observed in cases with active disease, intestinal localization (L1–2.28) and penetrating phenotype (B3–3.92). In UC patients, no difference in miR-1228 expression was observed with regards to the localization and the course of the disease. Serum expression of miR-1228 correlates positively with CRP in UC patients. Conclusion In the present study, increased expression of miR-1228 was observed in cases with active disease (UC, CD), intestinal localization (CD), and penetrating phenotype (CD), while decreased expression correlated to immunosuppressive (CD) and biological (UC) therapy.

Enterotoxigenic Bacteroidesfragilis Promotes Intestinal Inflammation and Malignancy by Inhibiting Exosome-Packaged miR-149-3p

Enterotoxigenic Bacteroides fragilis (ETBF) is strongly associated with the occurrence of inflammatory bowel disease (IBD), colitis-associated colorectal cancer, and colorectal cancer (CRC). However, the mechanism of ETBF-induced intestinal inflammation and tumorigenesis remains unclear. microRNA sequencing was used to detect the differentially expressed microRNAs in both ETBF-treated cells and exosomes derived from ETBF-inoculated cells. Cell Counting Kit 8 assays were used to evaluate the effect of ETBF and exosomes on CRC cell proliferation. The biological role and mechanism of ETBF-mediated miR-149-3p in colitis and colon carcinogenesis were determined both invitro and invivo. ETBF promoted CRC cell proliferation by down-regulating miR-149-3p both invitro and invivo. ETBF-down-regulated miR-149-3p depended on METTL14-mediated N6-methyladenosine methylation. As the target gene of miR-149-3p, PHF5A transactivated SOD2 through regulating KAT2A messenger RNA alternative splicing after ETBF treatment in CRC cells. miR-149-3p could be released in exosomes and mediated intercellular communication by modulating T-helper type 17 cell differentiation. The level of plasma exosomal miR-149-3p was gradually decreased from healthy control individuals to patients with IBD and CRC. miR-149-3p, existing in plasma exosomes, negatively correlated with the abundance of ETBF in patients with IBD and CRC. Exosomal miR-149-3p derived from ETBF-treated cells facilitated T-helper type 17 cell differentiation. ETBF-induced colorectal carcinogenesis depended on down-regulating miR-149-3p and further promoting PHF5A-mediated RNA alternative splicing of KAT2A in CRC cells. Targeting the ETBF/miR-149-3p pathway presents a promising approach to treat patients with intestinal inflammation and CRC with a high amount of ETBF.

Identify Inflammatory Bowel Disease-Related Genes Based on Machine Learning.

The patients of Inflammatory bowel disease (IBD) are increasing worldwide. IBD has the characteristics of recurring and difficult to cure, and it is also one of the high-risk factors for colorectal cancer (CRC). The occurrence of IBD is closely related to genetic factors, which prompted us to identify IBD-related genes. Based on the hypothesis that similar diseases are related to similar genes, we purposed a SVM-based method to identify IBD-related genes by disease similarities and gene interactions. One hundred thirty-five diseases which have similarities with IBD and their related genes were obtained. These genes are considered as the candidates of IBD-related genes. We extracted features of each gene and implemented SVM to identify the probability that it is related to IBD. Ten-cross validation was applied to verify the effectiveness of our method. The AUC is 0.93 and AUPR is 0.97, which are the best among four methods. We prioritized the candidate genes and did case studies on top five genes.