Ulcerative Patients Research Articles

Combination Treatment in Ulcerative Colitis using 5-Aminosalysilic Acid (5-ASA) and Polysaccharide Peptide of Indonesian Ganoderma lucidum Mycelium Extract

Background: Inflammatory bowel disease (IBD) is idiopathic disease characterized by chronic inflammation of the gastrointestinal tract. Polysaccharide peptide of Ganoderma lucidum mycelium extract (PPGL) is considerably a good option for adjunctive therapy of IBD. This study aims to evaluate the benefit of PPGL in patients treated with 5-ASA.Method: A retrospective observational cohort study was conducted to examine the medical records of 124 ulcerative colitis patients. There were 80 patients in intervention group who were treated with a combination of 5-ASA and PPGL, and there were 44 patients in the control group who were treated with 5-ASA only. Clinical and laboratory endpoints were observed at the baseline and after 30, 60, and 90 days. Clinical endpoints included abdominal pain, bloody diarrhea, aphthous stomatitis, and polyarthritis; meanwhile, laboratory endpoints included hemoglobin level, ESR, CRP, fecal calprotectin, M2-pyruvate kinase (MP2K), fecal culture, C. difficile culture, and colonoscopy results. Clinical trials conducted after patient enrollment with registry number ClinicalTrials.gov NCT04029649.Results: On day-30 there was a significant difference between intervention group 45.6% and control group 2.3% in abdominal pain complaints (p 0.001). Moreover, laboratory parameters of fecal calprotectin (p 0.001), fecal MP2K (p = 0.015), and hemoglobin (p 0.001) were considerably better in intervention group on day-30. These differences were consistently found on day 60 and 90.Conclusion: The study implies potential correlation between PPGL administration and improvement of clinical and laboratory endpoints up to 90 days. A larger randomized, blinded, prospective study is required to confirm these effects in ulcerative colitis.

Trends and Complication Rates in Ulcerative Colitis Patients With and Without Helicobacter pylori Infections.

Background Previous studies have shown an inverse relationship between ulcerative colitis (UC) and Helicobacter pylori infections (HPI). Though these two conditions have opposite geographic distributions, there may also be a physiological explanation for the decreased incidence of H. pylori infections in patients with UC. The purpose of this study is to analyze trends and complication rates of ulcerative colitis patients with and without HPI. Materials and methods The National Inpatient Sample (NIS) database was queried for patients with a primary diagnosis of UC, stratified by the presence of H. pylori infection. Patient demographics, length of stay, total hospital charges, and mortality were compared by H. pylori status. Additionally, complication rates were also compared between the two groups. Chi-squared and independent t-tests were used to compare outcomes and demographics, and multiple logistic regression was used to analyze primary and secondary outcomes. Results Patients with UC and HPI had a lower mortality rate (8.22 vs. 3.48, P<0.05, adjusted odds ratio [AOR] 0.33) and lower hospital charges ($65,652 vs. $47,557, p<0.05, AOR 1) with similar length of stay. Patients with UC and HPI also had lower rates of intestinal perforation (2.16% vs. 1.12%, p=0.05, AOR 0.408) and intrabdominal abscess formation (0.89% vs. 0.12%, AOR 0.165, p=0.072), though this difference was not significant. From 2001 to 2013, the incidence of UC has increased while the incidence of HPI has decreased. Conclusions The lower hospital charges and mortality rate as well as decreased rates of intestinal perforation and abscess formation suggest that there may be a physiologic role that HPI plays in modulating UC. Further studies into the interaction of these two conditions would be beneficial in clarifying their relationship and may help guide treatment of UC.

Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair.

Selenoprotein W (Selenow) is a ~9 kDa selenoprotein suggested to play a beneficial role in resolving inflammation. However, the underlying mechanisms are poorly understood. SELENOW expression in the human GI tract using ScRNAseq Gut Cell Atlas and Gene Expression Omnibus (GEO) databases revealed its expression in the small intestine and colonic epithelial, endothelial, mesenchymal, and stem cells and correlated with a protective effect in ulcerative colitis patients. Selenow KO mice treated with 4% dextran sodium sulfate (DSS) showed exacerbated acute colitis, with greater weight loss, shorter colons, and increased fecal occult blood compared to the WT counterparts. Selenow KO mice expressed higher colonic Tnfα, increased Tnfα+ macrophages in the colonic lamina propria, and exhibited loss in epithelial barrier integrity and decreased zonula occludens 1 (Zo-1) expression following DSS treatment. Expression of epithelial cellular adhesion marker (EpCam), yes-associated protein 1 (Yap1), and epidermal growth factor receptor (Egfr) were decreased along with CD24lo cycling epithelial cells in Selenow KO mice. Colonic lysates and organoids confirmed a crosstalk between Egfr and Yap1 that was regulated by Selenow. Overall, our findings suggest Selenow expression is key for efficient resolution of inflammation in experimental colitis that is mediated through the regulation of Egfr and Yap1.

Hidradenitis suppurativa and inflammatory bowel disease in a nested case-control study.

Association between Hidradenitis Suppurativa (HS) and Inflammatory Bowel Disease (IBD) has been suggested. To assess characteristics of HS and IBD in patients with or without concomitant IBD. In a prospective, nested case-control study, each IBD patient with concomitant HS (Case) was retrospectively matched with 4 patients with HS and no IBD (Controls) for gender and age (±5 years).HS was classified according to the Hurley score and the International Hidradenitis Suppurativa Severity Score System (IHS4). Data were expressed as mean (Standard Deviation). Statistical analysis included Student-t Test or Mann-Whitney Test, χ2 test, univariate and multivariate logistic regression. The study population included 125 patients with HS: 25 with IBD, 100 matched Controls with no IBD. IBD group included 19 (76%) Crohn's disease and 6 (24%) Ulcerative Colitis patients. Obesity, familial HS and perianal HS were less frequent in Cases than in Controls (1[4%] vs 25(25%];p=0.02; 1[4%] vs 21(21%];p=0.04; 1[4%] vs 31(31%];p=0.005, respectively).HS was less severe in Cases when assessed by the IHS4 (5.9±4vs 9±6.7;p=0.04).Complete drug-induced response for HS was more frequent in IBD (13[53%] vs28 (28%]; p=0.04). Clinical characteristics of HS and of patients differed between Cases and Controls. Present findings suggest the need to appropriately search and assess skin lesions compatible with HS in IBD.

384 Alterations in the fungal microbiome in ulcerative colitis

OBJECTIVES/GOALS: Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endo-histologic activity and treatment-exposure in ulcerative colitis. METHODS/STUDY POPULATION: Our retrospective cohort was derived from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease. We evaluated the fungal composition of fecal samples from 98 ulcerative colitis patients across endoscopic activity (n=43), endo-histologic activity (n=41), and biologic-exposure (n=98). Across all subgroups, we assessed fungal diversity and differential abundance of specific taxonomic groups. RESULTS/ANTICIPATED RESULTS: We identified 504 unique fungal amplicon sequence variants across the cohort of 98 patients, dominated by phylum Ascomycota. Compared to endoscopic remission, patients with endoscopic activity had an increased global fungus load (p DISCUSSION/SIGNIFICANCE: Endoscopic inflammation in ulcerative colitis is associated with altered fungal diversity driven by expansion of Saccharomyces and Candida compared to remission. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in ulcerative colitis should be evaluated.

THE ORAL GLUTMATE CARBOXYPEPTIDASE II INHIBITOR (S)-IBD3540 ROBUSTLY ATTENUATES INFLAMMATION IN SPONTANEOUS IL10 COLITIS

Glutamate carboxypeptidase II (GCPII) is elevated in active inflamed biopsies of both Crohn’s disease and ulcerative colitis patients and is a promising therapeutic target for the treatment of IBD. We have previously presented the development and characterization of a first-in-class, gut-restricted, and orally active GCPII inhibitor, (S)-IBD3540, and have shown that oral (S)-IBD3540 attenuates disease severity in multiple murine colitis models, including acute dextran sulfate sodium (DSS)-induced colitis. Here, we extend our knowledge regarding (S)-IBD3540’s anti-inflammatory effects in spontaneously occurring colitis of interleukin 10 (IL10-/-) mice by performing longitudinal measurement of inflammatory biomarker fecal lipocalin 2 (LCN2) and terminal colon cytokine and chemokine measurements.

Adjuvant nutraceuticals in the management of gastrointestinal diseases

The prevalence of gastrointestinal diseases has increased substantially in the last few years, bringing consequences not only to quality of life, but also to patients’ emotional/psychological wellbeing. Preliminary data from experimental studies suggest that using nutraceuticals as an adjuvant therapy to improve gastrointestinal symptomology may be a relevant and innovative strategy, since first line pharmacological treatments may pose severe adverse effects, drug resistance and lack of patient compliance. This narrative review aimed to explore the potential of four bioactive compounds at improving gastrointestinal symptomatology and disease management. Additionally, the mechanisms of action and dosages underlying the positive effects of these substances in improving quality of life and risk of disease relapse are also explored. According to the evidence found, peppermint oil and probiotics appear to ameliorate irritable bowel syndrome symptomatology, whereas polyphenols such as curcumin suggest a complementary effect in inducing and maintaining clinical remission among ulcerative colitis patients. Evidence regarding ginger’s effect on gastrointestinal symptoms is lacking and demonstrates little to no expression in irritable bowel syndrome nor functional dyspepsia.In conclusion, the consumption of peppermint oil, polyphenols and probiotics may be a viable adjuvant in the management of gastrointestinal diseases, associated symptomology and quality of life. However, further randomized controlled trials are warranted to elucidate on the optimal dose, safety and long-term efficacy of supplementing with these components, and particularly on the potential relevance of ginger supplementation.

Brunner gland inflammation in Crohn's disease and Celiac disease: Overlapping inflammatory patterns suggest a possible link

Similar to celiac disease, inflammatory bowel disease frequently manifests in the duodenum. Histopathologic studies focused on mucosal alterations with little attention to submucosal Brunner glands. Recently, several studies have demonstrated overlapping features between Crohn's disease and celiac disease suggesting a putative link. However, histopathologic studies evaluating this possible link are limited, and those that are focused on Brunner glands are lacking. The present study aims to explore whether Crohn's disease and celiac disease display shared or overlapping inflammatory changes in Brunner glands. We performed a retrospective review study over 17-years retrieving duodenal biopsy specimens containing Brunner gland lobules in patients with Crohn's disease, celiac disease, and ulcerative colitis. We found 10 out of 126 duodenal biopsies (8 %) in patients with Crohn's disease and 6 out of 134 (4.5 %) duodenal biopsies in patients with celiac disease sharing inflammatory patterns in duodenal Brunner gland lobules. Both diseases showed interstitial intralobular and interlobular mixed chronic inflammation with variable fibrosis. Focally enhanced active inflammation of Brunner gland lobules was more characteristic of Crohn's disease. Intralobular epithelioid granulomas and multinucleated giant cells were specific to Crohn's disease. Ulcerative colitis patients did not show similar features. The interstitial focally enhanced chronic inflammatory pattern was significantly (p < 0.05) associated with both diseases, while the other inflammatory patterns were not (p > 0.05). This overlapping inflammatory pattern in Brunner glands in patients with Crohn's disease and celiac disease is supportive of the previously reported link between the two diseases. Pathologists should pay more attention to Brunner glands when evaluating duodenal biopsies. Further studies are warranted to validate these observations and their relevance in the pathogenesis of autoinflammatory gastrointestinal diseases.

An investigation of JAK2 mutation in patients with ulcerative colitis with a history of thrombosis

Background/Aim: JAK2 is a gene that provides instructions for making a protein called Janus kinase 2, which is involved in the signaling process that regulates the growth and division of cells. Variations in the JAK2 gene have been associated with several different diseases, including certain blood disorders like myeloproliferative neoplasms (MPNs) and ulcerative colitis (UC). The exact reason for ulcerative colitis is not fully understood. This study aimed to examine the possible role of JAK2 V617F mutation in the etiopathogenesis of ulcerative colitis. Methods: The included patients were selected with UC and with signs of thrombosis. The DNA isolation was carried out from peripheral blood for all included patients. RT-qPCR methods were used to find JAK2 V617F mutations in UC patients with signs of thrombosis. Results: 73.3% of the included patients in this study had 73.3% bloody diarrhea and 80% had abdominal pain. Also, the JAK2 V617F mutation rate was detected in 6.6 % of the patients included in the study. Conclusion: In this study, it was found that the V617F mutation was relatively rare in ulcerative colitis patients and there was no correlation with the JAK2 V617F mutation in most of the ulcerative colitis cases with thrombotic symptoms.

Association of Infl ammatory Bowel Disease and Tumor Necrosis Factor-863 C/A Polymorphism in Iraq

Background: The underlying causes of infl ammatory bowel disease (IBD) are unknown, but they are thought to be a combination of genetics, environmental factors, abnormal immune responses, and disruption of the gut microbiota. This study aims to investigate the eff ect of tumor necrosis factor-alpha (TNF-α) -863 C/A(rs 1800630) single nucleotide polymorphism (SNP) in infl ammatory bowel patients and it is relation with the patient’s clinical characteristics. Methods: The study was conducted on 74 blood samples from patients of IBD including 47 patients with ulcerative colitis (UC) and 27 patients with Crohn’s disease (CD) in addition to 20 blood samples apparently healthy individuals, TNF-α-863 C&gt;A genotype was screened by PCR and Sanger sequencing techniques. Results: The results showed that the homozygous CC genotype frequency was the higher genotype frequency in 45/60 (75%) for IBD patients with less than 50 years ages compared with 7/14 (50%) the IBD patients with more than 50 years, signifi cant high association OD (CI): 2.75 (1.38–4.08), The allelic C frequency in ulcerative colitis (UC) patients was (0.83) and signifi cantly higher than the A allele frequency (0.17) and it may act as risk factor infl ammatory disease. The homozygous CC genotype of the TNF-α-863 gene was 9/27 (70.37%) in CD patients compared with 6/20 (30%) in the control group with high signifi cant diff erences (p ≤ 0.01, OR=1.00). Signifi cant diff erences also applied for the heterozygous CA genotype in -863 SNP,it was 8/27 (29.62%) compared with the control group 14/20 (70%) the odds ratio (2.62), while the homozygous AA genotype frequency showed no signifi cant association with CD (p -1.00). Conclusion: The frequency of homozygous CC genotype of the TNF-α-863 gene was higer in CD patients than in the control group with signifi cant diff erences. Signifi cant diff erences also applied for the heterozygous CA genotype while the three genotypes (CC, CA and AA) of the TNF-α-863 gene showed non-signifi cant diff erences in ulcerative patients in comparison with the control.

Single-incision laparoscopic clockwise continuous total abdominal colectomy with end ileostomy in ulcerative colitis; surgical technique and results of a 7-year experience

Total abdominal colectomy with end ileostomy is the first stage of the three-stage surgical treatment of medically refractory ulcerative colitis. Laparoscopic surgery is a safe approach offering several benefits. Single-incision laparoscopic surgery is an alternative minimally invasive approach providing excellent cosmetic results. Literature on single-incision laparoscopic clockwise continuous total abdominal colectomy in the treatment of ulcerative colitis is limited. Aim of the study is to describe our surgical technique and report the outcomes. Medically refractory ulcerative colitis patients who underwent single-incision laparoscopic clockwise continuous total abdominal colectomy with end ileostomy by a single surgeon between January 2013 and December 2020 at our tertiary care center are included. Patient charts were reviewed retrospectively. 52 patients were included in the final analysis. 51.9% patients were male with the median age of 31.5years and body mass index of 22.2kg/m2. Median duration of operation was 100min with estimated blood loss of 50ml. There were no intraoperative complications, conversions to conventional laparoscopy or open surgery. Postoperative complications were reported in 13 (25%) patients with most common being ileus (17.3%). 3 patients had surgical site infections. 2 patients had postoperative bleeding requiring blood transfusion. 2 patients had reoperation within postoperative 30days. Median length of hospital stay was 2days. No mortalities were reported. Single-incision laparoscopic clockwise continuous approach is safe and effective in ulcerative colitis patients undergoing total abdominal colectomy with end ileostomy. Further prospective randomized studies are warranted.

Prognostic Nutritional Index (Pni) Among Ulcerative Colitis Patients With Thalassemia Minor

Prognostic Nutritional Index (Pni) Among Ulcerative Colitis Patients With Thalassemia Minor

The Role of Globularia alypum Explored Ex Vivo In Vitro on Human Colon Biopsies from Ulcerative Colitis Patients.

The existing literature indicates that Globularia alypum L. (GA) influences inflammation and oxidative stress modulation in rats and in vitro. The present study aims to investigate the effects of this plant in patients with ulcerative colitis (UC) and normal controls. In our experiments, we pretreated colon biopsies from 46 UC patients and normal controls with GA leaves aqueous extract (GAAE) used at two concentrations (50 and 100 µg/mL) for 3 h, followed by Lipopolysaccharides (from Escherichia coli) stimulation. We analyzed the effects on inflammation by studying the cyclo-oxygenase-2, the intercellular adhesion molecule-1, the nuclear factor kappa B, and p38 mitogen-activated protein kinase expression. Moreover, we assessed the levels of interleukin 6, the superoxide dismutase activity, and nitric oxide release in the supernatant of cultures. Our data showed that GAAE influences UC patients and normal controls for most studied markers and enzymes. These results acknowledge, with some scientific evidence, the traditional belief in the anti-inflammatory properties of GA and represent the first demonstration of its effect in a human in vitro model of inflammatory conditions.

Small Bowel Carcinoma in the Setting of Inflammatory Bowel Disease.

Small bowel carcinomas are rare in the general population, but the incidence is increasing. Patients with inflammatory bowel diseases (IBDs) are at significantly higher risk of small bowel adenocarcinomas than their non-IBD counterparts, with Crohn's patients having at least a 12-fold increased risk and ulcerative colitis patients with a more controversial and modest 2-fold increased risk compared with the general population. IBD patients with small bowel carcinomas present with nonspecific symptoms that overlap with typical IBD symptoms, and this results in difficulty making a preoperative diagnosis. Cross-sectional imaging is rarely diagnostic, and most cancers are found incidentally at the time of surgery performed for an IBD indication. As such, most small bowel carcinomas are found at advanced stages and carry a poor prognosis. Oncologic surgical resection is the treatment of choice for patients with locoregional disease with little evidence available to guide adjuvant therapy. Patients with metastatic disease are treated with systemic chemotherapy, and surgery is reserved for palliation in this population. Prognosis is poor with few long-term survivors reported.

Change of monocytes/macrophages in ulcerative colitis patients with symptoms of anxiety and depression

Background and aimsMonocytes/macrophages play important roles in inflammatory bowel disease and depression, but few studies had focused on the change of monocytes/macrophages in ulcerative colitis (UC) patients with psychiatric disorders.MethodsUC patients were divided into two groups based on the Hospital Anxiety and Depression Scale (HADS). Demographic and clinical data were captured. Peripheral blood samples and intestinal biopsies were collected for the analysis of monocyte immunophenotype, phagocytic function, and CD4 + T cell differentiation. Transmission electron microscopy was used to observe the ultrastructure of intestinal macrophages.ResultsA total of 139 UC patients were included. 37.41% and 32.37% of UC patients had symptoms of anxiety and depression. In patients with symptoms of anxiety/depression, mayo score, platelet count, erythrocyte sedimentation rate, and endoscopic score, histological scores were significantly higher than those in UC patients without. In patients with symptoms of anxiety/depression, the percentages of CD14 + + CD16 + monocytes and CD14 + CD16++ monocytes were higher, and the phagocytosis was decreased. Patients with symptoms of anxiety/depression had more CD68 + cells and higher M1/M2 ratios in the intestine mucosal layer compared to those without.ConclusionsMonocytes and intestinal macrophages from UC patients with anxiety/depression tended to polarize to pro-inflammatory subtypes, and their function was also impaired.

Atherosclerotic Cardiovascular Disease in Inflammatory Bowel Disease: The Role of Chronic Inflammation and Platelet Aggregation.

Background and Objectives: Atherosclerosis is one of inflammatory bowel disease's most significant cardiovascular manifestations. This research aimed to examine the relationship between biochemical, haemostatic, and immune parameters of atherosclerosis and ulcerative colitis patients and its relationship to platelet aggregation. Materials and Methods: A clinical, observational cross-sectional study was performed, during which the tested parameters were compared in the experimental and control groups. The patients were divided into four groups. The first group had 25 patients who had ulcerative colitis and atherosclerosis. The second group included 39 patients with ulcerative colitis without atherosclerosis. The third group comprised 31 patients suffering from atherosclerosis without ulcerative colitis, and the fourth group comprised 25 healthy subjects. Results: In our study, we registered statistically higher levels of inflammatory markers like SE, CRP, Le, fecal calprotectin, TNF-α, and IL-6, as well as the higher value of thrombocytes and thrombocyte aggregation in the group of patients with ulcerative colitis compared to the control group. Lower levels of total cholesterol and LDL were also recorded in patients with ulcerative colitis and atherosclerosis and ulcerative colitis without atherosclerosis compared to healthy control. Triglyceride and remnant cholesterol were higher in patients with ulcerative colitis and atherosclerosis when compared to patients with ulcerative colitis and healthy control but lower than in patients with atherosclerosis only. Conclusions: Several inflammatory markers and platelet aggregation could be good discrimination markers for subjects with ulcerative colitis with the highest risk of atherosclerosis.

Prospective randomized comparison of three-dimensional (3D) versus conventional laparoscopy in total colectomy for ulcerative colitis.

3D laparoscopy has been proposed with the aim of improving the depth perception and overall operative performance. To aim of this study is to compare 3D laparoscopy with conventional 2D laparoscopy in terms of operative time and visual parameters. This is a prospective, randomized, single-center trial designed to determine 10% reduction in the mean operative time. Ulcerative colitis patients >18 years of age who underwent laparoscopic total abdominal colectomy with end ileostomy between 2015 and 2020 were included. Patients were randomized into 3D and 2D laparoscopy groups. Duration of operation and surgeons' evaluation of the visualization system were the primary outcomes. Fifty-three subjects (26 in 2D, 27 in 3D group) were included in the analysis, with 56% being male. Mean age and body mass index were 40 (16.3) years and 23.5 (4.7) kg/m2 , respectively. Twenty-five subjects underwent single port laparoscopic surgery, of whom 13 were in 3D and 12 in 2D group. Mean operative time was 75.3 (30.8) versus 82.7 (38.6) minutes (P=0.4) for 3D and 2D groups, respectively. Operative times spent for individual steps were comparable. Post-operative minor complications (8 in 3D versus 8 in 2D, P=1) and median number of times for scope maintenance were also similar between the groups. 69% of the visual evaluation survey results favoured 3D over 2D (P=0.014). Three-dimensional laparoscopy for total colectomy in ulcerative colitis patients is safe and feasible option providing better visualization with no difference in operative time.

A85 ASSESSING THE IMPACT OF A DEDICATED RAPID INTERDISCIPLINARY IBD CLINIC ON PATIENT WAIT TIMES, REPORTED OUTCOMES, AND SATISFACTION OF CARE

Abstract Background Inflammatory bowel disease (IBD) is a chronic fluctuating condition where patients can experience periods of active disease and remission. Timely access to care has been shown to be impactful on important disease outcomes. In January 2020, we implemented a rapid assessment IBD program consisting of expedited access to interdisciplinary care and close monitoring of patients. Purpose To assess the impact of the rapid assessment program on access to care, disease activity, and patient satisfaction. Method Once informed consent was obtained, patients were enrolled into the RAPID IBD program. This program consisted of four close monitoring time points at baseline, 1, 2, and 3 months, as well as two follow up time points at 6 and 12 months. At each timepoint patients completed questionnaires that evaluated disease activity, using the Modified Harvey Bradshaw Index (mHBI) for Crohn’s disease (CD), partial Mayo (pMayo) score and Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis patients. At baseline, 3, 6, and 12 months, patients were also assessed on mental health, using the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7), and satisfaction of care, using the CACHE questionnaire. Result(s) Between January 2020 – August 2021, 216 patients were referred to the RAPID IBD program. The mean time from referral to clinical assessment was 8.1 days. Of those referred, 143 (71 CD, 62 UC, 6 IBDU, and 4 Query IBD) patients consented to and completed the 12-month RAPID IBD study. 34.9% of patients who had active disease at baseline achieved remission by 3 months (Table 1). At baseline 44.8% and 28.4% of patients experienced moderate to severe depression and anxiety, respectively. The greatest improvement in mental health was seen at 2 months where the proportion of patients experiencing moderate to severe depression and anxiety decreased to 27.5% and 18.3%, respectively (Table 2). Patient satisfaction, specific to clinical care, improved from a baseline score of 69.1% to 74.1% at 3 months (Table 3). Image Conclusion(s) Implementation of a dedicated RAPID IBD clinic program reveals shorter wait times to be seen in clinic. By three months of enrollment, patients demonstrate improvements in clinical response, mental health, and satisfaction of care. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; AMO Innovation Funding Disclosure of Interest None Declared

A165 FCGBP IN THE COLON IS SPATIALLY DEPENDENT ON MUC2 EXPRESSION AND IS DEGRADED IN DEXTRAN SULFATE SODIUM-INDUCED COLITIS

Abstract Background The colonic mucus bilayer is an integral innate host defense mechanism that provides a physical barrier separating the lumen and its contents from the underlying epithelium. This essential barrier is produced by specialized secretory goblet cells of which Muc2 mucin is its primary product. IgG-Fc-binding protein (Fcgbp) is the second most abundant protein produced by goblet cells, which has a suggested function of crosslinking with Muc2 to stabilize the structural integrity of mucus. FCGBP is observed to decrease preceding the onset of inflammation in ulcerative colitis patients, leading to spatially distinct structural mucus weakening to contribute to the pathogenesis of the disease. Purpose Fcgbp is altered regionally in the gut and plays a role in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. The specific aims are: To characterize the spatial expression of Muc2 and Fcgbp basally in goblet cells To quantify alterations in Muc2 and Fcgbp in response to DSS-induced colitis and at restitution of disease Method mRNA and protein expression in Muc2+/+ and Muc2-/- C57BL/6 littermates were analyzed by RT-qPCR and Western blotting, respectively. Mucin granules were isolated from colonic goblet cells and the proteome quantified by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Colitis was induced in Muc2+/+ mice with 3.5% (w/v) DSS in tap water for five days, whereas Muc2-/- littermates were given 1.5% (w/v) DSS in tap water for three days, ad libitum. Mice were given regular tap water for the remainder of the experiment to allow restitution of inflammation. Disease activity index (DAI) was scored based on weight loss. Mice were sacrificed at various time points up to 10 days, and colons excised and sectioned for histopathology analysis. Result(s) LC-MS/MS of mucin granules run under reducing and non-reducing conditions confirmed that Muc2 and Fcgbp were the most abundant proteins in mucin granules and were non-covalently bound to each other. mRNA and protein expression of Muc2 and Fcgbp were highly expressed in the mid colon, and regulation of Fcgbp was unaffected in Muc2-/- littermates. In response to DSS-induced colitis in Muc2+/+ mice, Muc2 transcription rapidly increased in all regions of the colon with highest expression in the mid colon. In contrast, Fcgbp transcription increased in the mid and distal colons and peaked during highest disease activity. Interestingly, Fcgbp protein expression was abrogated in the mid colon even at restitution. In Muc2-/- mice, Fcgbp transcription decreased during disease onset but returned to normal levels following removal of DSS. Image Conclusion(s) This study demonstrates that in response to DSS, Fcgbp expression was spatially degraded at the onset of disease and remained low at restitution. The disappearance of Fcgbp in the mid colon of Muc2+/+ littermates, despite Muc2 restoration, suggests that the mucus barrier remains structurally altered and functionally impaired at restitution. Supported by CIHR Disclosure of Interest None Declared

A179 MECHANISMS OF ACTION INVOLVED IN THE WOUND HEALING EFFECT OF THE DIETARY FIBRE RHAMNOGALACTURONAN

Abstract Background Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions associated with impaired intestinal epithelial barrier. Mucosal healing is the primary goal for IBD treatment since it is a good predictor of clinical remission. We previously showed the direct beneficial effects of rhamnogalacturonan (RGal), a polysaccharide isolated from the plant Acmella oleracea, on intestinal epithelial barrier function with participation of TLR4 and PKC activation. RNAseq data and pathway analysis have indicated the involvement of the canonical nuclear factor kB (NF-kB) signaling pathway. Purpose We hypothesize that RGal increases intestinal epithelial wound healing through FAK-Src/PI3K/NF-kB signaling pathways. Method Caco-2 and T84 cells, and human primary cell monolayers grown from ulcerative colitis patient-derived organoids, were wounded and treated with vehicle (media or 0.5% DMSO in media) or RGal (1000 μg/ml) for 48 h. Wound healing was assessed using either the IncuCyte or ImageXpress Pico live cell imaging systems. Proliferation and apoptosis of cells were evaluated using EdU and TUNEL assays, respectively. Inhibitors were added at the same time (transcription inhibitor Actinomycin D, 5 μg/ml) or 1 h (FAK inhibitor FAK-14, 10 μM, Src inhibitor PP2, 5 μM, PI3K inhibitor LY294002, 20 μM, NF-kB inhibitors Bay 11-7082 and JSH-23, 10 and 20 μM, respectively, or COX-2 inhibitor NS-398, 20 μM) before RGal treatment. Unwounded Caco-2 monolayers treated with RGal (1000 μg/ml) were collected for Western blotting for COX-2 protein. Result(s) In the wound healing assay, RGal (1000 μg/ml) enhanced wound healing by 12.5% at 48 h in Caco-2 cells and by 14.7% at 24 h in T84 cells, compared to control group. RGal (1000 μg/ml) also accelerated the wound closure in colonoid monolayers obtained from ulcerative colitis patient biopsies by 81.3% at 48 h. Neither proliferation nor apoptosis were involved in the RGal effect on wound healing. Treatment of cells with FAK14 (10 μM), PP2 (5 μM), and PI3K (20 μM) significantly prevented the RGal-induced wound healing. Actinomycin D (5 μg/ml), Bay 11-7082 (10 μM) or JSH-23 (20 μM) treatment significantly reversed the effect of RGal on wound healing, showing that the response was transcriptionally dependent and involved NF-kB signaling. Treatment of cells with NS-398 (20 μM) also reversed the effect of RGal on wound healing. COX-2 protein expression was significantly increased at 6 and 12 h after RGal addition to Caco-2 monolayers. Conclusion(s) These data suggest that the plant-based polysaccharide RGal increases intestinal epithelial cell wound healing by increasing cell migration. The RGal effect is dependent on the activation of the FAK-Src/PI3K signaling pathways and subsequently the transcription factor NF-kB and downstream COX-2 protein expression and activity. Our findings show a novel mechanism of action of RGal in wound healing that could help in the resolution of intestinal inflammation and mucosal healing. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; NSERC Disclosure of Interest None Declared