Etiology Of Inflammatory Bowel Disease Research Articles

Genetic and Epigenetic Etiology of Inflammatory Bowel Disease: An Update

Inflammatory bowel disease (IBD) is a chronic disease with periods of exacerbation and remission of the disease. The etiology of IBD is not fully understood. Many studies point to the presence of genetic, immunological, environmental, and microbiological factors and the interactions between them in the occurrence of IBD. The review looks at genetic factors in the context of both IBD predisposition and pharmacogenetics.

Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study

Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and the risk of developing IBD using the Prospective Urban Rural Epidemiology cohort. This was a prospective cohort study of 133,137 individuals between the ages of 20 and 80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed up prospectively at least every 3 years. The main outcome was the development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aORs) with 95% CIs. During a median follow-up period of 11.0 years (interquartile range, 9.2-12.2 y), there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was associated significantly with baseline antibiotic (aOR, 2.81; 95% CI, 1.67-4.73; P= .0001) and hormonal medication use (aOR, 4.43; 95% CI, 1.78-11.01; P= .001). Among females, previous or current oral contraceptive use also was associated with IBD development (aOR, 2.17; 95% CI, 1.70-2.77; P < .001). Nonsteroidal anti-inflammatory drug users also were observed to have increased odds of IBD (aOR, 1.80; 95% CI, 1.23-2.64; P= .002), which was driven by long-term use (aOR, 5.58; 95% CI, 2.26-13.80; P < .001). All significant results were consistent in direction for CD and UC with low heterogeneity. Antibiotics, hormonal medications, oral contraceptives, and long-term nonsteroidal anti-inflammatory drug use were associated with increased odds of incident IBD after adjustment for covariates.

β-Myrcene Mitigates Colon Inflammation by Inhibiting MAP Kinase and NF-κB Signaling Pathways.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders that include Crohn's disease (CD) and ulcerative colitis (UC). The incidence of IBD is rising globally. However, the etiology of IBD is complex and governed by multiple factors. The current clinical treatment for IBD mainly includes steroids, biological agents and need-based surgery, based on the severity of the disease. Current drug therapy is often associated with adverse effects, which limits its use. Therefore, it necessitates the search for new drug candidates. In this pursuit, phytochemicals take the lead in the search for drug candidates to benefit from IBD treatment. β-myrcene is a natural phytochemical compound present in various plant species which possesses potent anti-inflammatory activity. Here we investigated the role of β-myrcene on colon inflammation to explore its molecular targets. We used 2% DSS colitis and TNF-α challenged HT-29 adenocarcinoma cells as in vivo and in vitro models. Our result indicated that the administration of β-myrcene in dextran sodium sulfate (DSS)-treated mice restored colon length, decreased disease activity index (DAI), myeloperoxidase (MPO) enzyme activity and suppressed proinflammatory mediators. β-myrcene administration suppressed mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways to limit inflammation. β-myrcene also suppressed mRNA expression of proinflammatory chemokines in tumor necrosis factor-α (TNF-α) challenged HT-29 adenocarcinoma cells. In conclusion, β-myrcene administration suppresses colon inflammation by inhibiting MAP kinases and NF-κB pathways.

Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice.

As the prevalence of inflammatory bowel diseases (IBD) rises, the etiology of IBD draws increasing attention. Glucoraphanin (GRP), enriched in cruciferous vegetables, is a precursor of sulforaphane, known to have anti-inflammatory and antioxidative effects. We hypothesized that dietary GRP supplementation can prevent mitochondrial dysfunction and oxidative stress in an acute colitis mouse model induced by dextran sulfate sodium (DSS). Eight-week-old mice were fed a regular rodent diet either supplemented with or without GRP. After 4 weeks of dietary treatments, half of the mice within each dietary group were subjected to 2.5% DSS treatment to induce colitis. Dietary GRP decreased DSS-induced body weight loss, disease activity index, and colon shortening. Glucoraphanin supplementation protected the colonic histological structure, suppressed inflammatory cytokines, interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α), and reduced macrophage infiltration in colonic tissues. Consistently, dietary GRP activated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α, and nuclear factor erythroid 2-related factor 2 (NRF2) pathways in the colonic tissues of DSS-treated mice, which was associated with increased mitochondrial DNA and decreased content of the oxidative product 8-hydroxydeoxyguanosine (8-OHDG), a nucleotide oxidative product of DNA. In conclusion, dietary GRP attenuated mitochondrial dysfunction, inflammatory response, and oxidative stress induced by DSS, suggesting that dietary GRP provides a dietary strategy to alleviate IBD symptoms.

S101 Colosplenic Fistula in Inflammatory Bowel Disease: A Scoping Review

Background: A colosplenic fistula is an extremely rare complication of Crohn’s disease (CD) first described in a 1985 case report that remains relatively poorly understood due to its infrequent incidence. With only a few colosplenic fistulas reported worldwide, the diagnosis and management of patients with colosplenic fistula is vague. Hence, we described a review of patients with colosplenic fistula due to inflammatory bowel disease (IBD) to summarize colosplenic fistula etiology, clinical features, diagnosis, management, and prognosis to help clinicians gain a better understanding of this unusual complication and provide an aid if it were to be encountered. Methods: We conducted a systematic search of articles published from 1946 to June 2022 in Ovid MEDLINE, Ovid EMBASE, Scopus, Web of Science, and Wiley Cochrane Library to identify patients with colosplenic fistulas. Studies with etiology of IBD were included. Results: The search strategy retrieved 141 references and a total of 4 studies reporting 4 patients with colosplenic fistula in the setting of IBD were analyzed. Most patients (75%) were male, with a median age of 33 years. All 4 (100%) patients had prior diagnosis of CD, with a median time of 12.5 years since diagnosis. Two patients had extraintestinal manifestations of IBD (uveitis, erythema nodosum, ankylosing spondylitis). Three patients were on long-term sulfasalazine and 2 (50%) were on corticosteroids. Etiology: Our review revealed that patients with CD formed a fistula tract from their colon to the adjacent spleen due to chronic, transmural inflammation and ulceration. Active inflammation was observed in the adjacent colon on pathology or endoscopy. Clinical features: Most patients presented with complaints of recurring fever, leukocytosis, and left upper quadrant pain or discomfort. Diagnosis: The most widely-used and effective diagnostic imaging was the computed tomography (CT) scan. CT with intravenous (IV) contrast helped identify splenic lesions and colonic thickening, while enteral contrast was useful to identify fistula tract. Chest X-rays, plain abdominal films, and colonoscopy were not essential in diagnosing a colosplenic fistula. Use of magnetic resonance imaging (MRI) was not reported in any case. Management: Most patients were promptly treated with IV fluid and broad-spectrum antibiotics. Only one patient was started on IV steroids. Most patients underwent surgical intervention of colosplenic fistulas with splenectomy and segmental resection of the affected col1on. One case offered temporary diverting loop ileostomy with plans for future splenectomy and colectomy. Prognosis: Symptoms resolved with surgical intervention. No postoperative complications or mortalities were reported. Conclusion(s): Our review revealed that patients with Crohn’s disease can form a fistula tract from their diseased colon to the adjacent spleen due to transmural inflammation. Diagnosis can be achieved with a CT scan with enteral and/or intravenous contrast. Most colosplenic fistulas can be successfully treated with laparotomy, splenectomy, and resection of the affected colon with low rate of postoperative complications. Our pooled analysis of available colosplenic fistula cases may serve as an aid for diagnosis and management of this rare entity.

Metabolomics window into the diagnosis and treatment of inflammatory bowel disease in recent 5years.

Inflammatory bowel disease (IBD) is a kind of chronic inflammation that occurs in gastrointestinal tract, including Ulcerative colitis (UC) and Crohn's disease (CD). Although UC and CD are associated with intestinal inflammation and epithelial damage, they are quite different. The etiology of IBD has not been fully determined, but there is extensive evidence that its pathogenesis involves environmental, genetic, immune and microbial factors. The diagnosis and treatment of IBD is challenging due to its recurrent episodes and complex evolution. Metabolomics, as a new developing technology, can be used to qualitatively and quantitatively study small metabolic molecules in samples of patients, which include stool, urine, serum, plasma and tissues, and is increasingly valued in the diagnosis and treatment of IBD. This article sums up the recent progress of metabolomics in helping to diagnose and treat IBD diseases, hoping to provide biomarkers and new targets for the diagnosis and treatment of IBD. In addition, we present the limitations of the current study of metabolomics and highlight some solutions.

An Engineered Probiotic Produces a Type III Interferon IFNL1 and Reduces Inflammations in in vitro Inflammatory Bowel Disease Models.

The etiology of inflammatory bowel diseases (IBDs) frequently results in the uncontrolled inflammation of intestinal epithelial linings and the local environment. Here, we hypothesized that interferon-driven immunomodulation could promote anti-inflammatory effects. To test this hypothesis, we engineered probiotic Escherichia coli Nissle 1917 (EcN) to produce and secrete a type III interferon, interferon lambda 1 (IFNL1), in response to nitric oxide (NO), a well-known colorectal inflammation marker. We then validated the anti-inflammatory effects of the engineered EcN strains in two in vitro models: a Caco-2/Jurkat T cell coculture model and a scaffold-based 3D coculture IBD model that comprises intestinal epithelial cells, myofibroblasts, and T cells. The IFNL1-expressing EcN strains upregulated Foxp3 expression in T cells and thereafter reduced the production of pro-inflammatory cytokines such as IL-13 and -33, significantly ameliorating inflammation. The engineered strains also rescued the integrity of the inflamed epithelial cell monolayer, protecting epithelial barrier integrity even under inflammation. In the 3D coculture model, IFNL1-expressing EcN treatment enhanced the population of regulatory T cells and increased anti-inflammatory cytokine IL-10. Taken together, our study showed the anti-inflammatory effects of IFNL1-expressing probiotics in two in vitro IBD models, demonstrating their potential as live biotherapeutics for IBD immunotherapy.

Following the Indian Immigrant: adoption of westernization results in a western gut microbiome and an increased risk of inflammatory bowel diseases.

Indians who migrate to westernized countries such as Canada, the USA, and the UK are at an increased risk of developing inflammatory bowel disease (IBD). While the underlying aetiology of IBD remains unclear, a gut microbiome, i.e. no longer symbiotic with its host, is a major player. Increasing IBD incidence in Indian immigrants may be due to the adoption of western practices that result in loss of tolerance of a symbiotic community in the gut and its underlying immune responses. However, little is known about the microbial changes in the Indian gut, including shifts in the microbiome when they migrate to westernized countries. In this Current Opinion, we discuss what is known about the Indian gut microbiome and how living in a westernized environment may be impeding what was once a symbiotic relationship with their gut microbiome and intestinal mucosae, which may be the driving factor in their increased risk of IBD.

DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon

Genetic variants in the DNA methyltransferase 3 A (DNMT3A) locus have been associated with inflammatory bowel disease (IBD). DNMT3A is part of the epigenetic machinery physiologically involved in DNA methylation. We show that DNMT3A plays a critical role in maintaining intestinal homeostasis and gut barrier function. DNMT3A expression is downregulated in intestinal epithelial cells from IBD patients and upon tumor necrosis factor treatment in murine intestinal organoids. Ablation of DNMT3A in Caco-2 cells results in global DNA hypomethylation, which is linked to impaired regenerative capacity, transepithelial resistance and intercellular junction formation. Genetic deletion of Dnmt3a in intestinal epithelial cells (Dnmt3aΔIEC) in mice confirms the phenotype of an altered epithelial ultrastructure with shortened apical-junctional complexes, reduced Goblet cell numbers and increased intestinal permeability in the colon in vivo. Dnmt3aΔIEC mice suffer from increased susceptibility to experimental colitis, characterized by reduced epithelial regeneration. These data demonstrate a critical role for DNMT3A in orchestrating intestinal epithelial homeostasis and response to tissue damage and suggest an involvement of impaired epithelial DNMT3A function in the etiology of IBD.

Involvement of HHV-4 (Epstein-Barr Virus) and HHV-5 (Cytomegalovirus) in Inflammatory Bowel Disease and Colorectal Cancer: A Meta-Analysis.

Simple SummaryThe prevalence of colorectal cancer (CRC) and inflammatory bowel disease (IBD) is increasing worldwide. Understanding what factors foster these diseases’ development can help reduce their burden. Viral infections have been suggested to be involved in the genesis of these diseases, but the data is contradictory. The present study analyzed 11,413 articles on the topic and identified 196 that could provide information on the relationship between a viral infection and these gastrointestinal diseases. The Epstein–Barr virus (EBV, HHV-4) was strongly associated with IBD, and cytomegalovirus (HHV-5) with both CRC and IBD.Gastrointestinal diseases (GDs) include colorectal cancer (CRC), gastric cancer (GC), and inflammatory bowel disease (IBD). CRC and GC are typically diagnosed at later stages of development, reducing patients’ chances of survival. IBD is characterized by chronic intestinal inflammation and is a significant risk factor for the development of CRC. Chronic bacterial infections have been shown to promote some GDs, but the role of viruses in the etiology of these diseases is less clear. The present meta-analysis retrieved literature on the viral prevalence in GD patients, measuring the GD risk in odd ratios. By quantifying the study heterogeneity, the literature bias was fundamentally included in the analysis. The analysis also included 11 metagenomic studies. Our meta-analysis retrieved 11,413 studies, with 196 suitable for analysis. HHV-4 (Epstein–Barr virus) was identified as a significant risk factor for the development of IBD, and HHV-5 (cytomegalovirus) as a risk factor for both CRC and IBD. Polyomaviruses and the Hepatitis B virus were also, less strongly, involved in the risk of CRC and IBD. No relations withstanding the literature bias were identified for GC. The study discusses these findings, as well as the role of other viruses in the etiology of CRC and IBD.

The intermicrovillar adhesion complex in gut barrier function and inflammation.

The surface of intestinal epithelial cells is covered by the brush border, which consists of densely packed cellular extrusions called microvilli. Until recently, microvilli have not been known to be interconnected. In 2014, a protein complex, called the intermicrovillar adhesion complex (IMAC) which is located at the tips of the microvilli and responsible for the regular spatial organization of the brush border, was identified. Deletion of IMAC components such as cadherin-related family member-2 (CDHR2) in mice resulted in microvillus disorganization and fanning, a structural aberration that is also found in the brush border of patients with inflammatory bowel disease. The etiology of inflammatory bowel disease has been primarily associated with dysfunctional mucosal immunity, but the discovery of the IMAC may encourage theories of an epithelial origin. Here, possible effects of the brush border on the gut barrier function and intestinal inflammation are discussed proposing that the IMAC protects against inflammation through its microvillus cross-linking function.

S1046 Association of Serum IgG4 and Disease Outcomes in Patients with Inflammatory Bowel Disease

Introduction: The etiology of Inflammatory bowel disease (IBD) is multifactorial and is thought to be influenced by inappropriate activation of the gut mucosal immune system. Immunoglobulin G (IgG) humoral immune response specifically subclasses 1, 2, & 3 activate the classical complement pathway to clear infection. IgG subclass 4 (IgG4) cannot activate the classical complement cascade. The role of IgG4 in IBD pathophysiology as an immunomodulator is controversial. This study aims to characterize the association of low, normal, and high IgG4 levels on the outcomes of patients with IBD. Methods: This was a retrospective chart review of a multisite tertiary care center database evaluating all patients with IBD who had an IgG4 level drawn between 2014 and 2021. Subjects were divided into low, normal, and high IgG4 level groups. Demographic and clinical data stratifying IBD activity and severity was collected by manual chart review. The SPSS program was used for data analysis. Categorical variables were summarized using the number and percent, and continuous variables were summarized by mean and standard deviation. Associations were done using the chi-square or Fishers exact test for categorical variables, and ANOVA or Mann Whitney for continuous variables. P-value of 0.05 was set to indicate statistical significance. Results: 284 patients with IBD had an IgG4 level checked. Of these patients, 22 had a low IgG4 level (7.7%), 16 had a high IgG4 level (5.6%) and 246 (86.6%) had a normal IgG4 level. There was no difference in IBD subtype (Crohn’s disease vs. ulcerative colitis), mean age, age at diagnosis with IBD, or smoking between the 3 groups or either group compared to the other separately. There was no difference in number of hospitalizations, C-reactive protein levels, need for intestinal resection, or in presence of primary sclerosing cholangitis, pancreatitis, or perianal disease between the groups. Regarding medication use, significantly more patients in the low IgG4 group had previous exposure to vedolizumab compared to the other groups and more patients in the low IgG4 group received vedolizumab, azathioprine, and prednisone during the 5-year follow up after IgG4 level was checked. Conclusion: A low serum IgG4 level is associated with increased rates of vedolizumab, azathioprine, and steroid use. Study limitations include potential bias in ordering IgG4 levels which in our practice is reserved for patients not responding to therapy.

Protective Effects of Natural Antioxidants on Inflammatory Bowel Disease: Thymol and Its Pharmacological Properties.

Inflammatory bowel disease (IBD) is a gastrointestinal disease that involves chronic mucosal or submucosal lesions that affect tissue integrity. Although IBD is not life-threatening, it sometimes causes severe complications, such as colon cancer. The exact etiology of IBD remains unclear, but several risk factors, such as pathogen infection, stress, diet, age, and genetics, have been involved in the occurrence and aggravation of IBD. Immune system malfunction with the over-production of inflammatory cytokines and associated oxidative stress are the hallmarks of IBD. Dietary intervention and medical treatment suppressing abnormal inflammation and oxidative stress are recommended as potential therapies. Thymol, a natural monoterpene phenol that is mostly found in thyme, exhibits multiple biological functions as a potential adjuvant for IBD. The purpose of this review is to summarize current findings on the protective effect of thymol on intestinal health in the context of specific animal models of IBD, describe the role of thymol in the modulation of inflammation, oxidative stress, and gut microbiota against gastrointestinal disease, and discuss the potential mechanism for its pharmacological activity.

Inflammatory bowel disease therapeutic strategies by modulation of the microbiota: how and when to introduce pre-, pro-, syn-, or postbiotics?

Inflammatory bowel diseases (IBD), a heterogeneous group of inflammatory conditions that encompass both ulcerative colitis and Crohn's disease, represent a major public health concern. The etiology of IBD is not yet fully understood and no cure is available, with current treatments only showing long-term effectiveness in a minority of patients. A need to increase our knowledge on IBD pathophysiology is growing, to define preventive measures, to improve disease outcome, and to develop new effective and lasting treatments. IBD pathogenesis is sustained by aberrant immune responses, associated with alterations of the intestinal epithelial barrier (IEB), modifications of the enteric nervous system, and changes in microbiota composition. Currently, most of the treatments target the inflammation and the immune system, but holistic approaches targeting lifestyle and diet improvements are emerging. As dysbiosis is involved in IBD pathogenesis, pre-, pro-, syn-, and postbiotics are used/tested to reduce the inflammation or strengthen the IEB. The present review will resume these works, pointing out the stage of life, the duration, and the environmental conditions that should go along with microbiota or microbiota-derived treatments.

Insight into the Relationship between Oral Microbiota and the Inflammatory Bowel Disease.

Inflammatory bowel disease has been a growing concern of lots of people globally, including both adults and children. As a chronic inflammatory disease of the intestine, even though the etiology of inflammatory bowel disease is still unclear, the available evidence from clinic observations has suggested a close association with microorganisms. The oral microbiota possesses the characteristics of a large number and abundant species, second only to the intestinal microbiota in the human body; as a result, it successfully attracts the attention of researchers. The highly diverse commensal oral microbiota is not only a normal part of the oral cavity but also has a pronounced impact on the pathophysiology of general health. Numerous studies have shown the potential associations between the oral microbiota and inflammatory bowel disease. Inflammatory bowel disease can affect the composition of the oral microbiota and lead to a range of oral pathologies. In turn, there are a variety of oral microorganisms involved in the development and progression of inflammatory bowel disease, including Streptococcus spp., Fusobacterium nucleatum, Porphyromonas gingivalis, Campylobacter concisus, Klebsiella pneumoniae, Saccharibacteria (TM7), and Candida albicans. Based on the above analysis, the purpose of this review is to summarize this relationship of mutual influence and give further insight into the detection of flora as a target for the diagnosis and treatment of inflammatory bowel disease to open up a novel approach in future clinical practice.

Inflammatory Bowel Disease Is Associated With Prediagnostic Perturbances in Metabolic Pathways

Circulating metabolites integrate environmental, genetic, and microbiome data and can serve as illustrative proximal markers of complex diseases. Accordingly, metabolomics profiling has emerged as a novel approach for building mechanistic bridges that link diverse biological pathways to disease phenotype. Alterations in metabolomic profiles have been described in patients with established inflammatory bowel disease (IBD).1 However, metabolomic studies to date have used postdiagnosis samples, where it is impossible to discriminate between signatures associated with IBD etiology and those resulting from IBD.

Histone deacetylase 1 and 3 inhibitors alleviate colon inflammation by inhibiting Th17 cell differentiation.

BackgroundThe etiology of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is not completely clear, but its pathogenesis is closely related to T helper 17 (Th17) cells. Several histone deacetylase (HDAC) inhibitors have been shown to exert potent anti‐inflammatory effects and modulate Th17 cell polarization. Owing to the large variety and broad expression of HDACs, finding specific therapeutic targets for IBD is of clinical importance.MethodsThe proportions of Th17 cells and interleukin (IL)‐17A produced between patients with UC and healthy volunteers were compared. The differentiation of human peripheral blood mononuclear cells (PBMCs) into Th17 cells was induced in vitro. Differentiated Th17 cells were treated with RGFP109 (RG), a selective inhibitor of HDAC1 and 3, to observe its effects on these cells. Subsequently, colitis was induced in mice and treated with RG. The proportion of Th17 cells, the severity of colitis in mice, and colon histopathology and immunohistochemistry were evaluated respectively.ResultsThe proportion of Th17 cells and IL‐17A production was significantly increased in patients with UC than in healthy individuals. RG inhibited the differentiation of human PBMCs into Th17 cells and reduced IL‐17A secretion in vitro. RG‐treated colitis mice had a lower Th17 ratio, mild colon inflammation, and decreased expression of HDAC1 and 3 in the colon.ConclusionsHDAC1 and 3 inhibitors can modulate the differentiation of inflammatory Th17 cells, downregulate IL‐17A levels, and exert anti‐inflammatory effects in experimental colitis mice, indicating that HDAC1 and 3 may be potential therapeutic targets for patients with IBD.

Establishment of a dextran sulfate sodium-induced ulcerative disease mouse model

Inflammatory bowel diseases (IBD) are multifactorial chronic intestinal disorders. Currently, mesalamine etc. and therapeutic strategies were suggested for IBD therapy. However, the etiology of IBD remains unclear which is an ongoing challenge and side effects of therapeutic drugs must be also considered. Thus, the aim of this study was to establish an optimal mouse model of IBD for the drug and therapeutic strategy investigations. Herein, 12 mice with 2% dextran sulfate sodium (DSS)-induced colitis (the negative control group) were via oral administration. Twelve mice were administered with drinking water without 2% DSS (the normal control group) via the same method as DSS-induced mice. At the end of the experiment, the body weight (BW), the stool appearance/status, the macroscopic and microscopic colonic injuries, and myeloperoxidase (MPO) activity were monitored, measured, and scored. The results showed that BALB/c mice’ BW decreased on D6-D8 of 2% DSS induction and then BALB/c mice’ BW continuously increased until D13 of the experiment. The stool appearance/status was seen soft stool on D2 of 2% DSS induction. The soft stool was mainly occurred on D2-D6 of 2% DSS induction. In addition, the watery stool was occurred on D4 of 2% DSS induction and was continuous until the end of the experiment (D14). The macroscopic colonic injuries were showed that colon length of the negative group (2% DSS-induced group) was significantly shorter than that of the normal control group (p &lt; 0.001). The colon weight of the negative group was significantly increase than that of the normal control group (p &lt; 0.001). The colon weight / length ratio in the negative group was significantly higher than that of the normal control group (p &lt; 0.001). According to the histopathologic scores (evaluation of the microscopic colonic injuries), the scores of area, ulceration, inflammation, and edema in the colon tissues of the negative group was significantly higher than that of the normal control group (p &lt; 0.001). The total histopathologic scores in the negative group was significantly higher than that of the normal control group (p &lt; 0.001). The myeloperoxidase (MPO) activity in the inflamed colon tissue of the negative group was significantly higher than that of the normal control group (p &lt; 0.001). Taken all results together, a DSS-induced ulcerative disease mouse model was successfully established. We hope that this animal model may be a useful tool for the research of the better therapeutics for IBD.

Opportunities and challenges for synthetic biology in the therapy of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a complex, chronic intestinal inflammatory disorder that primarily includes Crohn’s disease (CD) and ulcerative colitis (UC). Although traditional antibiotics and immunosuppressants are known as the most effective and commonly used treatments, some limitations may be expected, such as limited efficacy in a small number of patients and gut flora disruption. A great many research studies have been done with respect to the etiology of IBD, while the composition of the gut microbiota is suggested as one of the most influential factors. Along with the development of synthetic biology and the continuing clarification of IBD etiology, broader prospects for novel approaches to IBD therapy could be obtained. This study presents an overview of the currently existing treatment options and possible therapeutic targets at the preclinical stage with respect to microbial synthesis technology in biological therapy. This study is highly correlated to the following topics: microbiota-derived metabolites, microRNAs, cell therapy, calreticulin, live biotherapeutic products (LBP), fecal microbiota transplantation (FMT), bacteriophages, engineered bacteria, and their functional secreted synthetic products for IBD medical implementation. Considering microorganisms as the main therapeutic component, as a result, the related clinical trial stability, effectiveness, and safety analysis may be the major challenges for upcoming research. This article strives to provide pharmaceutical researchers and developers with the most up-to-date information for adjuvant medicinal therapies based on synthetic biology.

The Rising Burden of Inflammatory Bowel Disease in Denmark Over Two Decades: A Nationwide Cohort Study

Shifts in epidemiological stages of inflammatory bowel disease (IBD) carry implications toward understanding IBD etiology and managing clinical care. We conducted a temporal analysis of the epidemiology of IBD between 1995 and 2016 in the Danish nationwide cohort. We used the Danish registers to obtain data on demographics and IBD-related outpatient and inpatient contacts between 1995 and 2016. IBD diagnosis was defined as having ≥2 registrations related to Crohn's disease (CD) or ulcerative colitis (UC) within a 2-year period. We estimated overall and annual incidence rates and prevalence of CD and UC standardized with respect to age and sex. A total of 47,830 individuals met the criteria for IBD diagnosis, of which 33% were diagnosed with CD and 67% with UC. Between 1995 and 2016, the incidence rate (95% confidence interval) per 100,000 person-years rose from 9.1 (8.3-10.0) to 17.8 (16.8-19.0) for CD, and from 21.0 (19.8-22.3) to 28.4 (27.0-29.8) for UC. The highest increase in CD and UC incidence rates occurred in children and young adults, respectively. The prevalence of IBD doubled from 1995 to 2016; the greatest increase (2.5-fold) was in UC prevalence among individuals aged >40 years. During this period, the median age of the IBD population increased by 6 to 7 years. In Denmark, the incidence and prevalence of IBD have increased during the last 2 decades. The IBD population is shifting toward an older age. These findings have implications towards understanding environmental shifts as well as preparing health care systems for an aging IBD population.