Severity Of Ulcerative Colitis Research Articles

Correlation of Blood and Intestinal Mucosa miR-34a Expressions with Disease Severity in Ulcerative Colitis Patients.

miR-34a has been implicated in many autoimmune diseases and gastrointestinal diseases. However, the expression of miR-34 in ulcerative colitis (UC) patients were not fully studied. This study was performed to in-vestigate the association of blood and intestinal tissue miR-34a expression of patients with disease severity in UC patients. Our study enrolled 82 patients with UC and 80 age- and gender- matched healthy individuals. Blood miR-34a expressions were detected using reverse transcription-polymerase chain reaction (RT-PCR). Local intestinal miR-34a, STAT3 mRNA and IL-23 mRNA expressions were also detected in the lesioned area and adjacent non-affected intestinal tissue in patients. Disease severity of UC was assessed by Mayo score. The diagnostic value of both blood and local miR-34a expression for UC patients was assessed by receiver operating characteristic (ROC) curve. Blood miR-34a was increased in UC patients in contrast with healthy individuals with statistical significance. In UC patients, local intestinal miR-34a expressions were markedly upregulated compared to adjacent non-affected intestinal tissue. Local intestinal miR-34a expressions were positively correlated with STAT3 mRNA and IL-23 mNRA. Both blood and local miR-34a expressions were significantly and positively related to Mayo scores. ROC curve analysis indicated that both blood and local miR-34a expressions may act as decent marker for Mayo grade. Blood and intestinal tissue miR-34a expressions are correlated with disease severity in UC patients. Both blood and intestinal tissue miR-34a expressions may serve as potential diagnostic and prognostic makers for UC. Therapeutic methods targeting miR-34a may act as potential ways for UC treatment.

Computational insights into colonic motility: Mechanical role of mucus in homeostasis and inflammation

Colonic motility plays a vital role in maintaining proper digestive function. The rhythmic contractions and relaxations facilitate various types of motor functions that generate both propulsive and non-propulsive motility modes which in turn generate shear stresses on the epithelial surface. However, the interplay between colonic mucus, shear stress, and epithelium remains poorly characterized. Here, we present a colonic computational model that describes the potential roles of mucus and shear stress in both homeostasis and ulcerative colitis (UC). Our model integrates several key features, including the properties of the mucus bilayer and faeces, intraluminal pressure, and crypt characteristics to predict the time-space mosaic of shear stress. We show that the mucus thickness which could vary based on the severity of UC, may significantly reduce the amount of shear stress applied to the colonic crypts and effect faecal velocity. Our model also reveals an important spatial shear stress variance in homeostatic colonic crypts that suggests shear stress may have a modulatory role in epithelial cell migration, differentiation, apoptosis, and immune surveillance. Together, our study uncovers the rather neglected roles of mucus and shear stress in intestinal cellular processes during homeostasis and inflammation.

Resveratrol ameliorates DSS-induced ulcerative colitis by acting on mouse gut microbiota.

Ulcerative colitis (UC) is a multi-faceted, recurrent immune disorder caused by dextran sulfate sodium (DSS). The intestinal microbiota has multiple functions in the host, so UC requires long-term potent medication. The effect of resveratrol (RSV) has seldom been reported, and this study researched that. Herein, the effect of RSV and Grape seed oil that anti-inflammatory ability in experimental mice was explored, also why RSV altered Gut Microbiota has been researched. In this experiment, the effects of experimental drugs on colon length in mice with DSS-induced colitis were compared. H&E Staining was performed on serial sections of colon tissues and histological scores were determined for all groups. The expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in the colon tissue of mice was detected by immunohistochemical staining. In the end, the α-diversity index, sobs index, and rarefaction curve of the cecal and colon microbiota of different groups of mice were measured. Bray-Curtis-based Venn diagram of PCoA (principal coordinate analysis) and OTUs distribution in mouse gut microbiota were obtained. The results showed that the use of 40mg/kg RSV (high dose) significantly reduced the severity of UC. The use of 10mg/kg RSV (low dose) significantly reduced the effect of shortened colon length in DSS mice. Compared with the DSS-treated group, the levels of COX-2 and TNF-α in the colon tissues of RSV + DSS-treated mice were significantly decreased. According to this experiment, 19 mouse gut microbiota species had a relative abundance greater than 0.1%, with Beerella, Bacteroides, Helicobacter, Oscillator, and cecum pylori being more abundant in the colon than in the colon. A higher relative abundance of Lachnospira NK4A136 was observed in DSS and RSV groups compared with the control group, whereas the opposite was observed for Alloprevotella. This proves that resveratrol increases the uniformity and diversity of gut microbes to a certain extent, and has a protective effect on the gut.

Is Helicobacter pylori Infection Associated With Ulcerative Colitis Activity?

Objectives: Epidemiological studies have shown an inverse association between <i>Helicobacter pylori</i> infection and ulcerative colitis (UC). In this study, we investigated the protective effects of H. pylori infection on the severity of UC.Methods: This single-center study included 316 patients with newly diagnosed UC based on findings of colonoscopy and upper endoscopy for H. pylori evaluation between January 1994 and December 2015. Patients’ medical records were retrospectively reviewed, and severity of UC was assessed based on endoscopic findings, clinical symptoms, treatment regimens, and Mayo scores.Results: The prevalence of <i>H. pylori</i> infection in patients with UC was 74/316 (23.4%). Based on upper endoscopic findings, the percentage of patients with duodenal ulcers was significantly higher in the H. pylori positive group than that in the <i>H. pylori</i> negative group (27.0% vs. 11.6%, <i>p</i>=0.022). Disease extent and endoscopic severity showed no significant intergroup difference (<i>p</i>=0.765 and <i>p</i>=0.803, respectively). Endoscopic severity was unaffected by the <i>H. pylori</i> infection status, based on the extent of endoscopically documented disease and endoscopic findings. Furthermore, UC-related symptom severity assessed on the basis of stool frequency, rectal bleeding severity, and rate of admission necessitated by UC aggravation was not associated with <i>H. pylori</i> infection (<i>p</i>=0.185, 0.144, and 0.182, respectively). Use of steroids as induction therapy for severe UC did not differ with regard to <i>H. pylori</i> infection (<i>p</i>=0.327). No intergroup difference was observed in disease severity of UC classified using the Mayo score (<i>p</i>=0.323).Conclusions: <i>H. pylori</i> infection was detected in approximately 25.0% of patients with UC. However, the <i>H. pylori</i> infection status was not associated with the severity of UC based on endoscopic disease activity, patients’ symptoms, steroid use, or the Mayo clinic score.

Tauroursodeoxycholic acid liposome alleviates DSS-induced ulcerative colitis through restoring intestinal barrier and gut microbiota

Ulcerative colitis (UC) is a chronic and progressive inflammatory disease that damages the colonic mucosa and disrupts the intestinal epithelial barrier. The current clinical treatment for UC is mainly chemotherapy, which has the limited effectiveness and severe side effects. It mainly focuses on the treatment of inflammation while neglecting the repair of the intestinal mucosa and the restoration of the microbiota balance. Here, we aimed to address these challenges by using an amphipathic bile acid -tauroursodeoxycholic acid (TUDCA) to replace cholesterol (CHL) in conventional liposomes. We prepared TUDCA/Emodin liposomes by incorporating the hydrophobic drug emodin. The experimental results indicated that TUDCA/Emodin Lip had uniform particle size distribution, good stability, low cytotoxicity, and exhibited good mucus permeability and anti-inflammatory activity in in vitro experiments, and was able to protect cells from oxidative stress. After oral administration, TUDCA/Emodin Lip significantly alleviated the severity of UC. This was evidenced by increased colon length, decreased inflammation and reduced colonic endoplasmic reticulum stress (ERS). Furthermore, TUDCA/Emodin Lip maintained the normal levels of the tight junction proteins Claudin-1 and ZO-1, thereby restoring the integrity of the intestinal barrier. Importantly, TUDCA/Emodin Lip also promoted the ecological restoration of the gut microbiota, increased overall abundance and diversity. Taken together, TUDCA/Emodin Lip can fundamentally restore intestinal homeostasis, this work provides a new, efficient and easily transformable treatment for UC.

HIGH COPY NUMBER POLYMORPHISMS OF ALPHA DEFENSIN 1-3 ARE ASSOCIATED WITH THERAPEUTIC RESPONSIVENESS IN INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND AND PURPOSE Prednisolone therapy is the first choice for the treatment of acute severe ulcerative colitis (ASUC), however, the refractory case is sometimes observed. Alpha defensin 1-3 (DEFA1A3) stored in neutrophils acts as an effector factor of innate immunity. It has been reported that the copy number variation of the DEFA1A3 gene is associated with the severity of ulcerative colitis (UC). However, the impact of DEFA1A3 in response to treatment have not been fully investigated. Therefore, we aimed to clarify the relationship between the number of DEFA1A3 copies and UC prednisolone treatment response. SUBJECTS AND METHODS Patients with UC who had attended our department and related facilities and had the number of DEFA1A3 copies measured were included between 2020 and 2022. The number of DEFA1A3 copies were measured using droplet digital PCR after DNA extraction from peripheral blood mononuclear cells. Mayo score was used to determine the response to prednisolone and severity of UC. ASUC was defined as presence of more than 6 bloody stools/d along with any one of the following: pulse rate> 90 bpm, temperature > 37.8 °C, hemoglobin < 10.5 g/dL, and/or CRP > 30mg/L. Clinical background and various parameters were extracted from medical record information. RESULTS The 47 ASUC patients were included in the study. The median DEFA1A3 copy number of the patients was 9, the median DEFA1A3 copy number in ASUC was higher than that in healthy subjects. The DEFA1A3 copy number was significantly higher in the non-remission group than in the remission group after treatment with prednisolone.There were no differences in other parameters such as CRP and WBC between the two groups. CONCLUSION DEFA1A3 copy number may be a predictive marker of prednisolone treatment response.

P098 The Endoscopic Severity Score Map (ESSM): An Artificial Intelligence scoring system providing accurate, objective and localised measurements of endoscopic disease severity in ulcerative colitis

Abstract Background Commonly used scoring schemes as the Mayo Endoscopic Subscore (MES) account for disease severity only at specific (i.e., the worst) segments and do not capture disease extent. However, for an accurate assessment of disease severity in patients with ulcerative colitis (UC), the measure of the precise extent of disease activity is necessary. Alternative systems that include disease extent have been proposed (Balint 2018), but their implementation is prohibited by the time and cost constraints of comprehensively scoring each location along the entire colon. Here, we present the Endoscopic Severity Score Map (ESSM), a scoring system based on Artificial Intelligence, capable of providing an assessment of disease severity and extent in UC in a fully automated manner. Methods The ESSM consists of 3 main elements (Fig. 1): 1) a quality algorithm which selects readable frames from a colonoscopy video, 2) a scoring system which assigns an MES to each readable frame (Gutierrez Becker 2020) and 3) a camera localisation algorithm that assigns each frame to an anatomical location within the colon (Yao 2022). The ESSM was trained and tested using 4,306 sigmoidoscopy videos from phase III Etrolizumab clinical trials (Hickory NCT02100696, Laurel NCT02165215, Hibiscus I NCT02163759, Hibiscus II NCT02171429 and Gardenia NCT02136069). Results We evaluate the performance of the ESSM by first assessing the agreement of scoring as compared to centrally read MES. The agreement between central reading and the ESSM at the colon section level was high (quadratic-weighted kappa k=0.81; Tab. 1). This was comparable to the agreement between central and local reading (k=0.84), suggesting that the ESSM shows levels of inter-rater variability comparable to experienced readers. Finally, we found correlations between the average ESSM at all anatomical locations and other disease activity markers to be moderate to high: faecal calprotectin rs=0.24, CRP rs=0.29, stool frequency rs=0.49, rectal bleeding rs=0.43 and physician global assessment rs=0.47 (Tab. 1). Conclusion Here, we introduced the ESSM, a fully-automated AI-based scoring system that enables accurate, objective and localised assessment of disease severity in UC. In brief, we show that the ESSM compares well with central reading (at the colon section level) and has clinical relevance when compared to other markers of disease activity. This tentatively suggests that the ESSM has the potential to augment the current way of assessing disease severity, both in clinical trials and everyday clinical practice.

P288 Fecal leukocyte esterase level can predict endoscopic activity for Inflammatory Bowel Disease patients

Abstract Background The urine leukocyte esterase (LE) strip is widely employed to detect leukocyte presence in human body fluids due to its simplicity, speed, and cost-effectiveness. Our previous study demonstrated that fecal LE (FLE) correlated with fecal calprotectin (FC) which serves as a surrogate marker reflecting disease activity in inflammatory bowel disease (IBD) patients. This study aims to assess the correlation between FLE and endoscopy severity. Methods This prospective study included IBD patients at National Taiwan University Hospital from December 2021 to November 2023. FLE and FC in the same stool sample, which was collected within one month of endoscopy, were analyzed. The correlation between FLC, FC, and endoscopic severity scores was assessed using the Pearson method. Active disease in ulcerative colitis (UC) and Crohn's disease (CD) patients was defined as Mayo endoscopic score (MES) ≥ 2 and simple Endoscopic Score for Crohn's Disease (SESCD) ≥ 8, respectively. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Area Under the Receiver Operating Characteristic curve (AUROC) were analyzed by using SPSS. Results A total of 177 IBD patients (93 with UC, 84 with CD) were included. The correlation between FLE and FC levels was moderately positive (r=0.305, p<0.001). The correlation between FLE and endoscopic severity in UC and CD patients was 0.442 (p<0.001) and 0.293 (p=0.007), respectively. Among UC patients, the area under the receiver operating characteristic curve (AUROC) for predicting MES ≥ 2 by FLE and FC was 0.717 and 0.787 (p=0.241), with an optimal cutoff of 2+ for FLE and 42.5 mg/kg for FC, respectively. At this cutoff point, FLE demonstrated a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for predicting MES ≥ 2 as 52.3%, 81.6%, 71.8%, and 65.6%, respectively. For CD patients, the AUROC for predicting SESCD ≥ 8 by FLE and FC was 0.761 and 0.869 (p=0.203), with an optimal cutoff of 2+ for FLE and 225 mg/kg for FC, respectively. FLE exhibited a sensitivity, specificity, PPV, and NPV of 81.8%, 64.4%, 74.3%, and 95.9% for predicting SESCD ≥8 respectively, at this cutoff. Conclusion Our results demonstrated that FLE can predict endoscopic activity, which is a cheaper and widely available monitoring tool, might be an alternative choice to FC for IBD monitoring.

P1220 Dysbiosis of the gut microbiota and decreased fecal levels of short-chain fatty acid in patients with Ulcerative Colitis: a hospital-based case-control study

Abstract Background Ulcerative Colitis (UC) is a typical intractable disease whose number of patients is increasing worldwide, and studies have suggested that the gut microbiota and its metabolites are closely involved in its pathogenesis and severity. However, to date, no study has comprehensively compared the microbiomes or metabolomes of UC patients and healthy controls after considering important confounding factors such as age, gender, race, and other lifestyle factors. Therefore, we conducted this clinical study to compare the compositions and diversity of the gut microbiota and the fecal metabolites between age-, sex-, and race-matched patients with Ulcerative Colitis (UC) and those without. Methods In total, 90 outpatients with UC (UC group) and 90 without a history of gastrointestinal diseases and their family members (without UC group) were recruited. Results The UC group had a significantly lower abundance of the genus Bifidobacterium, Faecalibacterium, and Lactobacillus than the without UC group. Furthermore, the UC group had a significantly lower alpha-diversity of the gut microbiota than the without UC group. The UC group had a significantly lower level of fecal SCFAs than the without UC group. These results remained significant after adjusting for sex, age, and smoking status. Furthermore, the expression of a group of genes encoded by the gut bacteria that are involved in the biosynthesis of tetrapyrrole was significantly lower in the UC group than in the without UC group. Conclusion Gut microbiota dysbiosis and low SCFA levels, as well as reduced tetrapyrrole biosynthetic capacity by the gut bacteria, may contribute to the development of UC. Moreover, regardless of the severity, duration, and type of UC, the gut microbiota and its metabolites were in a stable state of dysbiosis in patients with UC.

Revisiting the Role of Valeric Acid in Manipulating Ulcerative Colitis.

Ulcerative colitis (UC) is characterized by a complicated interaction between mucosal inflammation, epithelial dysfunction, abnormal activation of innate immune responses, and gut microbiota dysbiosis. Though valeric acid (VA), one type of short-chain fatty acids (SCFAs), has been identified in other inflammatory disorders and cancer development, the pathological role of VA and underlying mechanism of VA in UC remain under further investigation. Studies of human clinical specimens and experimental colitis models were conducted to confirm the pathological manifestations of the level of SCFAs from human fecal samples and murine colonic homogenates. Valeric acid-intervened murine colitis and a macrophage adoptive transfer were applied to identify the underlying mechanisms. In line with gut microbiota dysfunction in UC, alteration of SCFAs from gut microbes were identified in human UC patients and dextran sodium sulfate -induced murine colitis models. Notably, VA was consistently negatively related to the disease severity of UC, the population of monocytes, and the level of interluekin-6. Moreover, VA treatment showed direct suppressive effects on lipopolysaccharides (LPS)-activated human peripheral blood mononuclear cells and murine macrophages in the dependent manner of upregulation of GPR41 and GPR43. Therapeutically, replenishment of VA or adoptive transfer with VA-modulated macrophages showed resistance to dextran sodium sulfate-driven murine colitis though modulating the production of inflammatory cytokine interleukin-6. In summary, the research uncovered the pathological role of VA in modulating the activation of macrophages in UC and suggested that VA might be a potential effective agent for UC patients.

The Role of Akkermansia muciniphila and Faecalibacterium prausnitzii in the Pathogenesis of Ulcerative Colitis and Crohn's Disease.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases with uncertain etiology. We aimed to determine the amounts of Akkermansia muciniphila and Faecalibacterium prausnitzii in the intestinal microbiota of these patients and to correlate their amounts with blood IL-8, IL-10, and IL-12 cytokine levels. Thirty UC, 30 CDs, and 46 healthy controls were included. IL-8, IL-10, and IL-12 levels of blood samples were analyzed by ELISA. The amounts of Akkermansia muciniphila and Faecalibacterium prausnitzii were determined by the LightCycler 480 qPCR system. F. prausnitzii, A. muciniphila, IL-10, and IL-12 decreased in patient groups, while IL-8 decreased in UC but increased in CD. A significant difference was detected between the patient and control groups in terms of F. prausnitzii, A. muciniphila, and IL-8, but not for others. The amount of F. prausnitzii was correlated with IL-8 and IL-10 in UC and with IL-10 in CD patients. The decrease in the amount of F. prausnitzii was associated with the increase in UC disease severity. A. muciniphila and F. prausnitzii were detected in lower amounts in both diseases. F. prausnitzii decreased more with the severity of UC, suggesting that these bacteria may have complex roles in their etiopathogenesis.

Development and validation of a blood routine-based extent and severity clinical decision support tool for ulcerative colitis

Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin’s model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin’s model was free with open access at http://jinmodel.com:3000/. Jin’s model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.

Mirikizumab (Omvoh)


 CADTH recommends that Omvoh be reimbursed by public drug plans for the treatment of moderately to severely active ulcerative colitis (UC) if certain conditions are met.
 Omvoh should only be covered for patients who are eligible for the reimbursement of other advanced drugs for the treatment of moderately to severely active UC (i.e., biologics and Janus kinase [JAK] inhibitors) based on the criteria used by each public drug plan.
 Omvoh should only be reimbursed if prescribed by a physician experienced in the diagnosis and management of UC but should not be reimbursed if used in combination with biologic therapies or JAK inhibitors for UC. For ongoing treatment to keep UC under control, Omvoh should only be reimbursed if initial treatment reduces the severity of UC after 24 weeks. Patients should be reassessed every year for renewal. The cost of Omvoh should not exceed the drug program cost of treatment with the least costly biologic reimbursed for the treatment of UC.

Correlation between the Eosinophil Colonic Mucosa Density and Severity of Ulcerative Colitis

Background: The inflammatory process of ulcerative colitis (UC) involves eosinophils. Eosinophils are not only related to the severity of UC but also to clinical improvement. The role of eosinophils in colonic mucosa has not been fully understood. This study aims to determine the correlation between the density of eosinophils in the colonic mucosa and the severity of ulcerative colitis.Method: This is a prospective cross-sectional study with consecutive sampling between August 2020 and July 2021. The subjects were UC inpatients/outpatients at Dr. Sardjito Hospital who met the inclusion and exclusion criteria. The number and location of the biopsies are determined based on a colonoscopy performed by a Gastroenterology-Hepatology Consultant. An Anatomic Pathology Specialist examined the eosinophil colonic tissue. The severity of UC was classified using the Truelove Witts score. Data analysis using a computer program with a p-value 0.05 was considered statistically significant.Results: There are 3 UC severity categories according to the Truelove Witts score: 22 mild (45.8%), 9 moderate (18.8%), and 17 severe (35.4%). Seven participants (14.6%) had eosinophilia, with a median eosinophilia score of 203.33 cells/microL (0–1470 cells/microL). Five participants (10.4%) with colonic mucosal eosinophilia, with a median value of 14.13 cells/HPF (0–172 cells/HPF). The density of colonic mucosal eosinophils and the severity of UC had a moderate connection (r = 0.396; p = 0.005).Conclusion: There is a significant correlation between the density of eosinophils in the colonic mucosa and the severity of UC.

Altered fecal bile acid composition in active ulcerative colitis

BackgroundDisturbed bile acid homeostasis associated with a rise of primary and a decline of secondary bile acids is a consistent finding in inflammatory bowel diseases (IBDs). Whether fecal bile acids may emerge as biomarkers for IBD diagnosis and disease severity is less clear. Our study aimed to identify associations of 18 fecal bile acid species with IBD entity and disease activity.MethodsStool samples of 62 IBD patients and 17 controls were collected. Eighteen fecal bile acid species were quantified by LC–MS/MS using stable isotope dilution. Lipid levels normalized to a dry weight of the fecal homogenates and ratios of single bile acid species to total bile acid levels were used for calculations.ResultsIBD patients exhibited altered primary and secondary bile acid ratios in stool, with notable distinctions between ulcerative colitis (UC) compared to Crohn’s disease (CD) and healthy controls. Fecal calprotectin was negatively correlated with glycolithocholic acid (GLCA) and hyodeoxycholic acid (HDCA) in UC. These bile acids were reduced in stool of UC patients with fecal calprotectin levels > 500 µg/g compared to UC patients with low calprotectin levels. Moreover, negative associations of six secondary bile acids with C-reactive protein (CRP) existed in UC. In CD patients, fecal bile acids did not correlate with CRP or fecal calprotectin. Diarrhoea is common in IBD, and UC patients with diarrhoea had reduced deoxycholic acid (DCA), glycine conjugated DCA (GDCA) and lithocholic acid in stool in contrast to patients with normal stool consistency. Fecal bile acid levels were not associated with diarrhoea in CD patients. UC patients treated with mesalazine had increased levels of fecal GDCA whereas no such changes were observed in CD patients. Bile acid levels of CD and UC patients treated with biologicals or corticosteroids did not change. Relative levels of GHDCA (specificity: 79%, sensitivity: 67%) and glycochenodeoxycholic acid (specificity: 74%, sensitivity: 63%) were the most specific to distinguish UC from CD.ConclusionDisrupted fecal bile acid homeostasis is associated with disease severity and disease symptoms in UC but not in CD, potentially aiding in distinguishing IBD subtypes and classifying the pathophysiology of diarrhoea in UC.

Diagnosis of Crohn’s disease and ulcerative colitis using the microbiome

BackgroundInflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disease resulting from dysregulation of the mucosal immune response and gut microbiota. Crohn's disease (CD) and ulcerative colitis (UC) are difficult to distinguish, and differential diagnosis is essential for establishing a long-term treatment plan for patients. Furthermore, the abundance of mucosal bacteria is associated with the severity of the disease. This study aimed to differentiate and diagnose these two diseases using the microbiome and identify specific biomarkers associated with disease activity.ResultsDifferences in the abundance and composition of the microbiome between IBD patients and healthy controls (HC) were observed. Compared to HC, the diversity of the gut microbiome in patients with IBD decreased; the diversity of the gut microbiome in patients with CD was significantly lower. Sixty-eight microbiota members (28 for CD and 40 for UC) associated with these diseases were identified. Additionally, as the disease progressed through different stages, the diversity of the bacteria decreased. The abundances of Alistipes shahii and Pseudodesulfovibrio aespoeensis were negatively correlated with the severity of CD, whereas the abundance of Polynucleobacter wianus was positively correlated. The severity of UC was negatively correlated with the abundance of A. shahii, Porphyromonas asaccharolytica and Akkermansia muciniphilla, while it was positively correlated with the abundance of Pantoea candidatus pantoea carbekii. A regularized logistic regression model was used for the differential diagnosis of the two diseases. The area under the curve (AUC) was used to examine the performance of the model. The model discriminated UC and CD at an AUC of 0.873 (train set), 0.778 (test set), and 0.633 (validation set) and an area under the precision-recall curve (PRAUC) of 0.888 (train set), 0.806 (test set), and 0.474 (validation set).ConclusionsBased on fecal whole-metagenome shotgun (WMS) sequencing, CD and UC were diagnosed using a machine-learning predictive model. Microbiome biomarkers associated with disease activity (UC and CD) are also proposed.

Serum albumin levels as a useful complementary marker for erectile dysfunction in ulcerative colitis: A cross-sectional study.

Recently, a close association between ulcerative colitis (UC) and erectile dysfunction (ED) was reported. An inverse relationship between serum albumin and ED is found in patients with chronic disease. However, the association between serum albumin levels and ED in patients with UC is unclear. This study aims to investigate this issue in Japanese patients with UC. One hundred and thirty-six Japanese male UC patients were enrolled in this study. Information on serum albumin levels and medications for UC from medical records, Sexual Health Inventory for Men (SHIM) score information from self-administered questionnaires and information on the severity of UC from physician reports were obtained from medical records, self-administered questionnaires, and reports from physicians. The participants were divided into tertiles based on the total protein, serum globulin, serum albumin, aspartate aminotransferase, and C-reactive protein levels. The definition of ED and severe ED was SHIM score < 22 and SHIM score < 8, respectively. The association between these serum markers and ED was assessed by multivariate logistic regression. The prevalence of severe ED in the low, moderate, and high albumin groups was 66.0%, 51.0%, and 28.3%, respectively. After adjusting for confounding factors, the low albumin group was independently and positively associated with severe ED (adjusted odds ratio: 2.74, 95% confidence interval: 1.03-7.48, p for trend =0.044). No association between other marker and ED was found. Serum albumin was independently inversely associated with severe ED in Japanese patients with UC. Hypoalbuminemia might be a useful complementary marker for assessing the prevalence and severity of ED in UC patients.

Artificial intelligence quantifying endoscopic severity of ulcerative colitis in gradation scale.

Existing endoscopic scores for ulcerative colitis (UC) objectively categorize disease severity based on the presence or absence of endoscopic findings; therefore, it may not reflect the range of clinical severity within each category. However, inflammatory bowel disease (IBD) expert endoscopists categorize the severity and diagnose the overall impression of the degree of inflammation. This study aimed to develop an artificial intelligence (AI) system that can accurately represent the assessment of the endoscopic severity of UC by IBD expert endoscopists. A ranking-convolutional neural network (ranking-CNN) was trained using comparative information on the UC severity of 13,826 pairs of endoscopic images created by IBD expert endoscopists. Using the trained ranking-CNN, the UC Endoscopic Gradation Scale (UCEGS) was used to express severity. Correlation coefficients were calculated to ensure that there were no inconsistencies in assessments of severity made using UCEGS diagnosed by the AI and the Mayo Endoscopic Subscore, and the correlation coefficients of the mean for test images assessed using UCEGS by four IBD expert endoscopists and the AI. Spearman's correlation coefficient between the UCEGS diagnosed by AI and Mayo Endoscopic Subscore was approximately 0.89. The correlation coefficients between IBD expert endoscopists and the AI of the evaluation results were all higher than 0.95 (P < 0.01). The AI developed here can diagnose UC severity endoscopically similar to IBD expert endoscopists.

Levetiracetam attenuates experimental ulcerative colitis through promoting Nrf2/HO-1 antioxidant and inhibiting NF-κB, proinflammatory cytokines and iNOS/NO pathways

Ulcerative colitis (UC) is a serious inflammatory disease of the colon. The pathogenic mechanisms of UC involve the activation of inflammatory and oxidative stress responses in the colon. Levetiracetam is an antiepileptic drug with anti-inflammatory and antioxidant effects. The aim of this study was to investigate the potential protective effect of levetiracetam against UC in a mouse model. UC was induced in mice by intrarectal administration of acetic acid and then mice were treated with levetiracetam (50 or 100mg/kg/day, i.p.) for three days. The colonic tissue samples were dissected for biochemical, RT-PCR and immunofluorescence analysis. Results showed that levetiracetam treatment significantly decreased colonic mucosal injury as evidenced by the macroscopic and histopathological analysis. Levetiracetam induced Nrf2/HO-1 and antioxidants while reduced lipid peroxidation and myeloperoxidase activity in colon tissue. Levetiracetam treatment decreased NF-κB activity and the expression of proinflammatory mediators TNF-α, IL-6, IL-1β, IFN-γ, MCP-1 and ICAM-1. The colonic levels of anti-inflammatory cytokines IL-10 and TGF-β1 were increased by levetiracetam treatment. Furthermore, levetiracetam significantly diminished iNOS expression and NO production in colon tissue. These findings suggest that levetiracetam ameliorates the severity of UC in mice through the regulation of inflammatory and oxidative responses.

Banxia Xiexin decoction ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis via inhibiting serine-threonine protein kinase (Akt)/mitogen-activated protein kinase (MAPK) signaling pathway.

Banxia Xiexin decoction (BXD), a traditional Chinese medicine, was widely used in treating ulcerative colitis (UC). However, the active components of BXD and its mechanism in UC remain elusive. Therefore, we used network pharmacology in vivo experiments, molecular docking, and surface plasmon resonance strategy (SPR) to uncover BXD's potential mechanism. A UC rat model was established by orally administering 7% dextran sulfate sodium (DSS) in drinking water, BXD and palmatine were orally administered for 7days. Network pharmacology was used to investigate the main bioactive components and crucial targets of BXD in treating UC. Molecular docking was used to investigate interactions between components and crucial targets, verifying the results by SPR. By network pharmacology predicting, 20 active components and 44 candidate anti-UC targets of BXD were identified, and the crucial proteins were screeded from PPI network, including extracellular regulated protein kinases (ERK), AKT1, and tumor necrosis factor-α (TNF). In addition, some key active components (palmatine, sexangularetin, and skullcapflavone II) were screened out from the active components-targets network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and in vivo experiments showed that protein-serine-threonine kinase (Akt)/MAPK pathway was involved in BXD treatment for UC; BXD and palmatine significantly ameliorated the severity of DSS-induced UC in rats. Our study might assist in further investigation of the active components in Chinese medicine.