IBD Activity Research Articles

Integrin αVß6 - autoantigen and driver of epithelial remodeling in colon and bile ducts in primary sclerosing cholangitis and inflammatory bowel disease.

Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified which strongly associate with ulcerative colitis (UC). We aimed to elucidate whether anti-integrin αVβ6 (anti- αVβ6) is present in primary sclerosing cholangitis (PSC), its associated inflammatory bowel disease or other cholestatic liver diseases and their persistence after proctocolectomy. We detected anti- αVβ6 by an enzyme-linked immunosorbent assay in sera collected at two German tertiary centers, including healthy controls (N=62), UC (N=36), Crohn's disease (CD, N=65), PSC-IBD (78 samples from N=41 patients), PSC without IBD (PSC, 41 samples from N=18 patients), primary biliary cholangitis (PBC, N=24), autoimmune hepatitis (AIH, N=32), secondary sclerosing cholangitis (SSC, N=12) and metabolic dysfunction-associated steatotic liver disease (MASLD, N=24). Additionally, sera after proctocolectomy were studied (44 samples / N= 10 patients). Immunofluorescent analyses were performed in tissue samples from liver, large bile duct from surgical resections and colon of PSC patients. Anti- αVβ6 occurred in 91% of UC, 17% of CD, 73% of PSC-IBD, 39% of PSC, 4% of PBC, 14% of AIH, and 0% of healthy controls, SSC or MASLD. Integrin αVβ6 is selectively expressed in disease-associated epithelia of both bile duct and colon. Anti- αVβ6 levels correlate moderately with intestinal disease activity in PSC-IBD, but only weakly with biliary disease. Anti- αVβ6 frequently occur in patients suffering from PSC, especially in PSC-IBD. Anti- αVß6 levels positively correlate to IBD activity in PSC-IBD, but may also occur in the absence of clinically manifest IBD in PSC.

Intestinal ultrasound for follow-up after 24 weeks of biological therapy in inflammatory bowel disease patients: an Egyptian center experience during the COVID-19 pandemic

BackgroundInflammatory bowel disease is a chronic inflammatory condition of the gut. It has two major subtypes Crohn’s disease and ulcerative colitis. The follow-up consists of radiologic, molecular, endoscopic, and histological assessments. Intestinal ultrasound (IUS) is a noninvasive measure that provides future hope in guiding the management of IBD patients. This study is to assess the effectiveness of IUS in IBD patients’ follow-up in our tertiary center during the pandemic. This is a prospective observational study during the COVID-19 pandemic. We used IUS to assess activity of IBD at baseline and at 6-month follow-up of patients on maintenance biological therapy using the following parameters: bowel haustrations, stratification, bowel wall thickness (BWT), Doppler sign (Limberg classification), presence of lymph nodes, or fibrofatty infiltration, echogenicity of the bowel, and presence of fistulae or abscesses. We compared the IUS with other radiologic parameters, histologic, and endoscopic scores at baseline before therapy, while we compared IUS with clinical scores and laboratory parameters before and after 24 weeks of biological treatment.ResultsThe cohort included 50 known IBD patients from June 2021 to January 2022. The laboratory studies showed a significant improvement in the hemoglobin indices, CRP, and fecal calprotectin from baseline and after 24 weeks. BWT, lumen diameter, lymph node presence, inflammatory signs, and Doppler activity signs were the most significant parameters in detecting improvement. However, there was no significant correlation between fecal calprotectin levels and ultrasound parameters. There was a positive correlation between MR and CT enterography, endoscopic parameters, and IUS parameters at baseline.ConclusionsIUS is an effective tool for follow-up of IBD patients especially during the pandemic periods.

Level of interleukin 17 in inflammatory bowel disease and its relation with disease activity

BackgroundInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract (GIT).It results in progressive intestinal epithelium structural and functional damage that necessitates lifetime medication.Thereis imbalance in the production of T helper 1 (Th1), Th2 and Th17 cytokines. This plays a crucial role in the chronic inflammatory process and the defective immune response to pathogenic agents; thus promoting the recurrence of the disease.Our aim of this study was to detect serum IL-17 levels in IBD patients and its relation with disease activity.MethodsThis was a single center case control study, conducted at hepatology and gastroenterology unit, Mansoura specialized Medical Hospital, Egypt.Patients who were included were aged 18–65 years, diagnosed either Ulcerative Colitis (UC)or Crohn’s Disease (CD) based on previous colonoscopy.IBD activity was measured for UC using the MAYO score and CD using the CD activity index (CDAI). Fifty five patients were UC, 24 patients were CD, 21 patients were control.Patients who were excluded were under 15 years old, with history of GIT malignancy, or any serious comorbidities. Study protocol was approved by Institution Research Board (IRB) of Mansoura Medical College.All patients were subjected to full history taking, routine physical examination, colonoscopy and laboratory investigations including serum IL-17 levels by ELISA besides CBC, CRP, ESR and fecal calprotectin.ResultsSerum IL-17 level was increased significantly among UC; median (min-max) = 72(21–502)pg/ml, in CD 54.5(25–260) versus control 19 (14–35), P < 0.001.However, it was not correlated to the disease activity either Mayo score of UC or CDAI of CD.There was significant correlation to the extent of inflammation in UC affecting the colon (either proctosigmoiditis, left sided colitis or pan colitis), also to the type of CD (either inflammatory, stricturing or fistulizing) by P < 0.05.It was not correlated significantly with any of the IBD activity markers (CRP, ESR, or fecal calprotectin).Yet there was negative significant correlation with Hb level (r =-0.28, p = 0.005).There was not significant association between median serum level of IL-17 & duration of disease (P = 0.6).However, median IL-17 was higher among hospitalized cases than non-hospitalized (73 & 55, pg/ml respectively; p < 0.002). AUC was significantly differentiating between IBD and control group = 0.993 with the best-detected cut off point from curve 32 pg/ml yielding sensitivity of 97.5% and specificity of 95.2%.ConclusionSerum IL-17 increases in colonic inflammation significantly more than in control group, however its increase is not correlated to IBD activity.

MUCIN MRNA ISOFORM SIGNATURES AS POTENTIAL NOVEL BIOMARKERS TO EVALUATE DISEASE STATUS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES

Abstract Mucosal barrier dysfunction and aberrant mucin expression are major hallmarks in the pathophysiology of IBD. Mucins are highly polymorphic, and the presence of genetic differences can alter gene expression, resulting in several mRNA isoforms via alternative splicing. While most isoforms encode similar biological functions, others alter protein function, potentially resulting in progression towards disease. Currently, little attention has been given to the importance of mucin mRNA isoforms in IBD. The aim of our study is to investigate the potential of mucin mRNA isoforms as novel biomarkers for the evaluation of IBD activity and subtypes. To obtain this goal, RNA was extracted from colonic and terminal ileal biopsies of IBD patients that underwent an endoscopy at the Antwerp University Hospital (UZA). Additionally, patients without a history of IBD undergoing an endoscopy due to a positive iFOBT which show no endoscopic abnormalities, were included as controls. Library preparation was performed with the PacBio Iso-Seq multiplex protocol adapted for targeted transcriptome sequencing. Targeted capture was accomplished by using a custom-designed pool of probes, developed for the capture of all mucin gene transcripts. Samples were sequenced on the PacBio Sequel platform at the University of Antwerp. The data was analyzed by using the isoseq3-pipeline and additional filtering with SQANTI3 was performed. In total 106 biopsies were sequenced on the PacBio platform. The resulting intestinal mucin transcriptome was merged with the human reference transcriptome. On this combined mucin transcriptome Illumina bulk RNA sequencing data from over 2000 intestinal biopsies (GEO dataset GSE193677) were mapped to determine mucin isoform expression. An external dataset (GEO dataset GSE165512) was used for additional validation. A classification random forest was trained on this data to distinguish inflamed IBD from non-inflamed control patients based on the mucin isoform expression alone. The model performed well on train and test datasets but decreased in the external validation (Table 1). Dividing the samples based on disease phenotype greatly increases performance on the external validation dataset (Table 1). When only training on ileal biopsies, the model proved to be excellent in distinguishing Crohn’s disease patients from controls (Table 1). Classification of inflamed ulcerative colitis from control patients based on only the biopsies from the distal colon was similar to the latter (Table 1). Our machine learning model was able to distinguish Crohn’s disease from control patients and ulcerative colitis from control patients based on mucin mRNA isoform expression. In addition, our data suggests that the mucin isoform expression may vary between different regions within the colon. Table 1 Area under the receiver operator curve (AUCROC) from a random forest classifier trained on mucin isoform expression of inflamed biopsies of IBD and non-inflamed control patients.

N45 Nurse intervention in patients with Inflammatory bowel disease: impact in their quality of life

Abstract Background Physical inactivity is considered as a modifiable risk factor in chronic diseases1 and IBD. Regular physical activity could help patients with IBD by reducing some IBD complications, such as improving immune response, increasing muscle mass and strength, and improving bone density. The aim of this study is to determine the impact of a Nurse intervention, on Physical Activity, in quality of life of IBD patients. Methods Quasi-experimental study before and after. 20 patients, both sex, with IBD from Hospital Universitario del Henares, 18-65 years old, in clinical remission or mild activity; IBD ≥ 6 months. Exclusion: physical impairment for daily activities (cardiac, orthopedic or cognitive impairment); pregnancy; surgery &amp;lt; 3 months. Nurse intervention on physical exercise: 4 group sessions of 60 minutes, 10 months follow-up. Training on strength and endurance exercises by a physiotherapist adapted to each patient’s special needs. Data were collected in Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32), Rapid Assessment of Physical Activity (RAPA), Hospital Anxiety and Depression Scale (HADS). Variables: quality of life, physical activity, IBD activity, socio-demographic, health status and lifestyle. A descriptive analysis was carried out with qualitative and quantitative variables. Four dimensions of quality of life index and impact of exercise on quality of life were calculated, before and after intervention with Students-T. Results Quasi-experimental study before and after. 20 patients, both sex, with IBD from Hospital Universitario del Henares, 18-65 years old, in clinical remission or mild activity; IBD ≥ 6 months. Exclusion: physical impairment for daily activities (cardiac, orthopedic or cognitive impairment); pregnancy; surgery &amp;lt; 3 months. Nurse intervention on physical exercise: 4 group sessions of 60 minutes, 10 months follow-up. Training on strength and endurance exercises by a physiotherapist adapted to each patient’s special needs. Data were collected in Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32), Rapid Assessment of Physical Activity (RAPA), Hospital Anxiety and Depression Scale (HADS). Variables: quality of life, physical activity, IBD activity, socio-demographic, health status and lifestyle. A descriptive analysis was carried out with qualitative and quantitative variables. Four dimensions of quality of life index and impact of exercise on quality of life were calculated, before and after intervention with Students-T. Conclusion There are non-significative differences in quality of life before and after intervention. Patients increased their physical activity after intervention. Regular physical activity is a useful tool for improving quality of life in patients with IBD.

P817 Incidence and risk factors of infection in patients with inflammatory bowel disease: longitudinal prospective INFEII registry of GETECCU

Abstract Background The true effect of having IBD in the development of infections has not been studied in depth since cohort studies are scarce and the results of studies are sometimes contradictory. Especially, this complication has not been addressed prospectively in an incident cohort of patients with IBD. Aims To assess, regarding infections in IBD: 1) incidence and type, 2) risk factors, 3) effect of type and the duration of IBD treatment, 4) impact in mortality 5) effect of IBD activity. Methods The INFEII registry (ClinicalTrials.gov: NCT02904590) is a prospective study promoted by GETECCU to determine the incidence and risk factors of infection in an inception cohort of patients with IBD and follow-up of at least 5 years. This longitudinal prospective study within the ENEIDA registry was conducted including incident cases with IBD. Patients were recruited between 2016 and 2020 with a planned follow-up of 5 years. All infections were detailed analysed. An infection was considered relevant when: 1) required hospital admission, 2) led to death or endangered the patient’s life, 3) was treated with specific antibiotics,4) occurred recurrently, and/or 5) required change/withdrawal of immunosuppressive treatment. Results The INFEII registry recruited 1456 patients from 28 centres throughout Spain. The median follow-up was 71 months (IQR 60-79 months). The description of the cohort is presented in Table 1. Of the 1456 patients included, 580 (40%) presented at least one relevant infection. In total, 1321 infections were collected. One-hundred and seven infections (8%) required hospitalisation and four patients died (0.3%) over infection. Ninety-nine patients were lost to follow-up (22 died and 34 changed hospitals). The most prevalent infections were: ear-nose-throat in 238 cases, urinary tract infections in 237, respiratory in 234, COVID-19 in 133, skin infections in 127, dental in 64 and colitis/enteritis in 64 (Figure 1). From the whole cohort and at some point, in time, 756 (52%) patients received 5ASA, 481 (33%) steroids (369 (25%) oral, 112 (7.7%) intravenous), 568 (39%) azathioprine, 72 (4.9%) methotrexate, 21 (1.4%) tofacitinib, 533 (37%) antiTNF, 141 (9.9%) ustekinumab and 77 (5.3%) vedolizumab. The effect of treatment and IBD activity in each infection is being analysed. Conclusion Infections are frequent complications in patients with IBD, presented in 40% of them. Being a woman, having a history of past serious infections or occupational risk may be associated with infection occurrence. It has to be determined if IBD activity and treatment suppose a greater risk for infections. This is a paradigmatic study that implies the first use of the ENEIDA registry in prospective research.

P619 Sleep disruption is associated with reduced quality of life in inflammatory bowel disease through its interaction with pain

Abstract Background Quality of life is reduced in people with inflammatory bowel disease. Poor sleep is prevalent in people with inflammatory bowel disease. This study aimed to investigate the influence of sleep on quality of life in people with inflammatory bowel disease. Methods An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn’s Colitis Australia. The questionnaire included the EQ-5D-5L measures of health-related quality of including EQ-5D utility score, EQVAS – visual analogue scale from 0-100 of quality of life and domains mobility, selfcare, activities, pain and depression and anxiety. Measures of sleep included the insomnia severity index (ISI), and the Pittsburgh sleep quality index (PSQI). IBD activity was assessed using validated patient reported scores. Demographic data and mental health scores were also obtained. Results Quality of life was lower in people IBD than the general South Australian population (utility score mean (SD) 0.79 (0.15) v 0.91(0.14)). Poor sleep and clinically significant insomnia were associated with lower quality of life (utility score 0.77 (0.15) and 0.71 (0.16) respectively, cohort 0.79 (0.15), p&amp;lt;0.0001). Sleep quality scores moderately correlated with EQ-5D domains pain (Ro=0.35), usual activities (Ro=0.32), and depression-anxiety (Ro=0.37) but not domains self-care or mobility. After adjusting for demographic variables, IBD anxiety, depression, and anxiety the pain domain continued to be influenced by sleep quality, sleep disturbance and sleep duration, and the usual activities domain continued to be influenced by daytime dysfunction (see table 1). Clinically significant insomnia was associated with a reduction of 13.6 (10.42-16.91) (univariate regression) in quality of life measured by EQVAS. Following introduction of demographic and IBD activity the reduction in EQVAS for clinically significant insomnia remained significant (10.11 (6.96-13.27)). Health related quality of life scores (EQVAS) were significantly worse in those with clinically significant insomnia and active IBD than with active IBD alone (see Figure 1). Conclusion Health related quality of life in IBD is influenced by aspects of sleep quality irrespective of IBD activity and mental health conditions. The presence of insomnia is associated with a significant decline health related quality of life. Consideration should be given to sleep targeting interventional studies in an IBD population.

P220 IBD-Disk: italian translation and validation in a population-based cohort

Abstract Background As an objective endpoint in IBD Disease-Modification Trials, measures of disability and health-related quality of life have been proposed. IBD-DISK is an easy-to-use, and self-administered analogic visual tool designed for assessing disability. However, successful dissemination of this tool will require a cultural adaptation and translation process. To date, the IBD-Disk has not been validated in Italian clinical practice. Hence, we aimed to validate the IBD-Disk in an Italian population-based cohort according to the COSMIN recommendations. Methods The IBD-Disk italian translation and validation study was a cross-sectional multicentre study conducted in 8 Italian IBD referral centres. After forward-backward translation into Italian, patients were consecutively recruited from February 2023 to October 2023. Patients completed the following questionnaires: IBD-Disk (at baseline, T0, and after seven days, T1) and IBD-Disability Index (IBD-DI) for disability, IBDQ-32, and SF-36 for quality of life. Validation included assessment of validity, reproducibility, internal consistency. We further investigated the correlation between IBD-Disk and IBD activity and clinical factors associated with IBD-Disk. Results At baseline, 513 patients (237,46.2% CD; 276,53.8% UC) completed the IBD-Disk[Table.1]. Internal consistency was excellent with a Cronbach’s α of 0.93. The intraclass correlation coefficient (ICC) was 0.94 for test-retest (T0 and T1) (p&amp;lt; 0.001). To evaluate construct validity, the IBD-Disk was compared with the IBD-DI, revealing a significant positive correlation (r = 0.70; p &amp;lt; 0.001). Furthermore, it exhibited a positive correlation with both IBDQ-32(r=0.82, p&amp;lt; 0.001) and SF-36(r=0.093, p= 0.035). The overall IBD-Disk median score was 32(12-52), with 219(42.7%) reporting moderate-to-severe disability (IBD-DISK ≥ 40). The IBD-Disk score was significantly higher in patients with active CD disease based on HBI ≥ 5 compared to patients with inactive disease(p &amp;lt; 0.001). Similarly, for UC, patients with active disease, measured with a partial Mayo score ≥2, showed a higher IBD-DISK score than those in clinical remission[Fig.1]. Additionally, moderate-to-severe disability significantly increased in female [OR =2.83; 95% CI(1,97-4,07)] and in patients with active extraintestinal manifestations [OR = 1,71; 95%CI(1,23-2,81) p=0.04]. Conclusion This study validated the IBD-Disk in a large cohort of Italian IBD patients, demonstrating that it is a valid, reliable and responsive tool for quantifying disability. This validation enables the broad implementation of IBD-DISK across Italy, facilitating its integration into the daily clinical management of IBD patients.

P533 Photo Biomodulation treatment in patients with Ulcerative Colitis

Abstract Background Current UC treatment options still fall short in both effectiveness and safety. Rectal inflammation may be particularly difficult to treat. Photo-biomodulation (PBM) involves the irradiation of specific non-ionizing, non-thermal light exerting an anti-inflammatory effect. PBM has demonstrated efficacy in various dermatologic and mucosal inflammatory conditions. These observations combined with ex-vivo mucosal healing studies suggest a potential efficacy of this therapy in inflammatory bowel diseases. Therefore, we aimed to assess the safety and efficacy of PBM treatment in UC patients with significant rectal inflammation. Methods The PhotoPill-ProctCare system comprises a rectal tube that delivers therapeutic 850nm, illumination to the rectal mucosa, at ~1 J/cm2. UC patients with clinical and endoscopic evidence of rectal inflammation were enrolled to the study. The rectal device was inserted and activated for 4 minutes. The study included two parts. Part 1 involved 6 treatment sessions over 14 days. Part 2 included up to 6 additional treatments over 6 weeks. Primary endpoint was treatment safety. Secondary endpoints were clinical, biochemical, endoscopic, histologic, and microbiome composition parameters during and following the intervention. Results Five patients were recruited for the part 1 of the study and 6 to part 2. All patients tolerated the treatment well. Two patients reported adverse events related to intervention; these were mild in severity and spontaneously resolved (mild abdominal discomfort up to 2 hours post-treatment). Two unrelated events included COVID infection and URTI. In part 2, two patients dropped out after 6 sessions due to lack of efficacy. Overall, 4/11 patients (36%) achieved clinical remission. Response was observed in 7/11 patients (63%). Mayo score decreased from 7.82±1.4 at baseline, to 4.91±1.93 post treatment (p&amp;lt;0.01). Rectal bleeding sub-score decreased from 1.91±0.61 to 1.09±0.67 (p=0.03), and stool frequency sub-score decreased from 2.09±1 to 1±0.74 (p&amp;lt;0.01) respectively. Mean Ulcerative Colitis Endoscopic Index of Severity decreased from 6.75±1.33 to 5.9±1.5 (p=0.02). The number of host (human genome) reads within microbiome samples (likely indicative of shedding of epithelial cells) decreased post-treatment significantly in 4 patients and did not increase significantly in any of the patients. Moreover, several gut bacteria species (e.g. Bacteroides species) and bacterial pathways that are known to be associated with IBD activity, decreased significantly post-treatment. Conclusion This pilot study demonstrated the safety and efficacy of rectal Photo-Biomodulation for induction of response and remission in UC patients. Further studies are needed to confirm these preliminary results.

N10 Evaluation of the impact of an IBD nurse in an Inflammatory Bowel Disease Center

Abstract Background In some European countries, IBD nurse is not a recognized status. IBD nurses are general care nurses who wants to improve their knowledges and get involved in the « Care and Support » of IBD patients. An increasing number of IBD centers are using the services of IBD nurse. The aim of this study was to evaluate prospectively the activity and impact of IBD nurse on the management of IBD patients in an IBD center. Methods From March 13th to June 13th, 2023, all patients having interacted with IBD nurse in an expert center, were prospectively recorded. The main points were, the number and characteristics of patients, means and reasons of contact, actions implemented, follow-up and, finally, patient satisfaction assessed using a standardized questionnaire (visual analog scale from 0 to 10). Results During three months, 132 patients, 69 women and 63 men (47% Ulcerative Colitis, 52% Crohn's disease and 1% indeterminate colitis), with a median age of 40 years (16 to 87), had contacted the IBD nurse. The means of contact were phone call: n =131 (42%), text messages: n = 25 (8%), e-mail: n = 69 (22%), face-to-face consult: n = 86 (27.5%) and teleconsulting: n = 1 (0.5%). The reasons for contact were: Three hundred and twelve contacts had led to 315 actions divided into seven groups: Over this period, IBD nurse was contacted 22 times by 19 patients for a real or perceived emergency. These situations were managed by a multidisciplinary team, and resulted in reinsurance (68%), referral to others medical specialist (18%) or hospitalization (14%). Overall satisfaction with the IBD nurse intervention was 10/10 for 78% of patients and 9/10 for 11%. To the question: “do you think that the intervention of the IBD nurse improves disease management?”: 78.5% agreed at 10/10 and 7% at 9/10. To the question: “do you think contact with the IBD nurse improves access to care: 67.5% agreed at 10/10 and 3.5% at 9/10. The main patients’ advice / reviews to improve care were: to adjust levels of follow-up according to the patient and his/her needs, to strengthen the IBD Nurse coordination team to limited days off, to have explanation sheets and reports of IBD Nurse intervention, to develop more workshops for patients in the Education program. Conclusion This pilot study showed the importance of the IBD Nurse activity in an expert center. The patients who benefited from this care were very enthusiastic about it.

P1219 Changes in gut microbiota of patients with inflammatory bowel disease receiving biologic therapy

Abstract Background Inflammatory bowel disease (IBD), comprising the predominant forms Crohn’s disease (CD) and ulcerative colitis (UC), is associated with compositional and metabolic changes in the intestinal dysbiosis. The aim of this study is to evaluate the composition in the microbiota of IBD patients who received biologic therapy Methods This is a prospective study recruited 14 patients with IBD received biologic therapy and 13 IBD controls who received conventional treatment . The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The stool samples at baseline, weeks 6 and 48 after biologic therapy initiation were assessed. We also evaluated the level of inflammation and treatment response of biologics by BD activity score (CD patient by Crohn’s disease activity index [CDAI] and in UC patient by Mayo score). Results In CD group, we recruited 7 CD patients receiving biologic therapy (Anti-tumor Necrosis Factor for 4 and anti-integrin for 3) and 6 controls.In UC group, we recruited 7 UC patient receiving biological therapy (Anti-tumor Necrosis Factor for 2 and anti-integrin for 5) and 7 controls. Community α-diversity was lower in patients at baseline of biologics group compare to controls significantly but increase abundance and richness after achieving remission in trend at week 6 and week 48, respectively. In Top 10 taxon bacterial distribution, the Firmicutes were increase its abundances gradually ( relative abundance in biologics W0,W6,W48 and controls were 46.3%, 51.7%,62.0%, and 66.4%, respectively). Conversely, the Bacteroidetes were decrease its abundances ( relative abundance in biologics W0,W6,W48 and controls were18.3%, 18.8%, 10.2% and 6.4%, respectively). Increased F/B ratio significantly after biologics therapy also found in our study. (F/B ratio were 9.4, 12.5,64.0,and 84.3,respectively). Patients in control group had higher abundance of Firmicutes of the phylum.By contrast, Enterobacteriaceae and Bacteroidaceae were significantly more abundant in patients of biologics group at W0 . Conclusion Treatment with biologic therapy induced improvement of community diversity and increased F/B ratio in IBD patients which seemed correlate the level of clinical inflammation. The dysbiosis-representative bacteria, such as Enterobacteriaceae, could induce colonic inflammation,were more abundant in patients who had higher activity of IBD. Further larger prospective studies are needed to determine whether the biologic therapy could induce long-term changes of intestinal microbiome.

P324 Urine metabolite profile characterizes clinical activity and disease extent in patients with inflammatory bowel disease

Abstract Background Inflammatory Bowel Disease (IBD), which comprises Crohn's Disease (CD) and Ulcerative Colitis (UC), is a disorder in which complex interactions between genetic, environmental, and microbial factors trigger alterations in the immune intestinal response. On the other hand, nutrient catabolism from the diet carried out by the microbiota results in the formation of metabolites that also impact immune responses on the intestinal mucosa. Considering that IBD patients have altered microbiota compared to healthy controls (HC) and that the urinary metabolic profile of an individual is the result of a combination of genetic, dietary, and microbial components, we propose the hypothesis that the urinary metabolic profile distinguishes IBD patients from HC. The aim of the study was to compare metabolomic analysis of urine samples from HC and IBD patients. Methods 27 patients were included [HC (n=10), UC (n=10), and CD (n=7)]. Clinical IBD activity was evaluated with partial Mayo score (UC) and Harvey-Bradshaw index (CD). Metabolites in urine were measured using gas chromatography-mass spectrometry (GC-MS). Metabolomic analysis and machine learning were performed using the MetaboAnalyst software. PLS-DA was used for multivariate analysis, and clustering separation was performed using hierarchical clustering. To identify and interpret patterns of metabolite concentration changes in a biologically meaningful way we perform Over Representation Analysis. Results In total, 62 organic acids were detected. Comparing UC and HC revealed 11 significantly altered metabolites (9 increased and 2 decreased). Main increased metabolites comprised lactic acid (p=0.0015), pyroglutamic acid (p=0.0147), isocitric acid (p=0.0325), and phosphoric acid (p=0.0091). Interestingly, the value of adipic and suberic acids were higher in remission vs. active patients. Furthermore, adipic acid was higher in UC patients with proctitis compared to left-side colitis/extensive colitis. Comparing CD and HC revealed only 2 significantly altered metabolites, glycolic acid (p=0.0214), and lactic acid (p=0.0111). Oxalic acid was more concentrated in CD patient with perianal disease. Finally, propionic and phosphoric acid were able to discriminate UC from CD patients. The most affected metabolic pathways were related to energy metabolism and oxidative stress, including the Warburg effect (p=0.0016), gluconeogenesis (p=0.0106), pyruvate metabolism (p=0.0197) and glutathione metabolism (p=0.0039) (Fig.1). Conclusion We found that the urinary metabolic profile of IBD patients differs from the HC, particularly for UC patients. These metabolites profile could be used to improve diagnosis and monitoring in patients with IBD.

Formylated Peptide Receptor-1-Mediated Gut Inflammation as a Therapeutic Target in Inflammatory Bowel Disease.

Formylated peptide receptor (FPR)-1 is a G-coupled receptor that senses foreign bacterial and host-derived mitochondrial formylated peptides (FPs), leading to innate immune system activation. We sought to investigate the role of FPR1-mediated inflammation and its potential as a therapeutic target in inflammatory bowel disease (IBD). We characterized FPR1 gene and protein expression in 8 human IBD (~1000 patients) datasets with analysis on disease subtype, mucosal inflammation, and drug response. We performed in vivo dextran-sulfate sodium (DSS) colitis in C57/BL6 FPR1 knockout mice. In ex vivo studies, we studied the role of mitochondrial FPs and pharmacological blockade of FPR1 using cyclosporin H in human peripheral blood neutrophils. Finally, we assess mitochondrial FPs as a potential mechanistic biomarker in the blood and stools of patients with IBD. Detailed in silico analysis in human intestinal biopsies showed that FPR1 is highly expressed in IBD (n = 207 IBD vs 67 non-IBD controls, P < .001), and highly correlated with gut inflammation in ulcerative colitis (UC) and Crohn's disease (CD) (both P < .001). FPR1 receptor is predominantly expressed in leukocytes, and we showed significantly higher FPR1+ve neutrophils in inflamed gut tissue section in IBD (17 CD and 24 UC; both P < .001). Further analysis in 6 independent IBD (data available under Gene Expression Omnibus accession numbers GSE59071, GSE206285, GSE73661, GSE16879, GSE92415, and GSE235970) showed an association with active gut inflammation and treatment resistance to infliximab, ustekinumab, and vedolizumab. FPR1 gene deletion is protective in murine DSS colitis with lower gut neutrophil inflammation. In the human ex vivo neutrophil system, mitochondrial FP, nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) is a potent activator of neutrophils resulting in higher CD62L shedding, CD63 expression, reactive oxygen species production, and chemotactic capacity; these effects are inhibited by cyclosporin H. We screened for mitochondrial ND6 in IBD (n = 54) using ELISA and detected ND6 in stools with median values of 2.2 gg/mL (interquartile range [IQR] 0.0-4.99; range 0-53.3) but not in blood. Stool ND6 levels, however, were not significantly correlated with paired stool calprotectin, C-reactive protein, and clinical IBD activity. Our data suggest that FPR1-mediated neutrophilic inflammation is a tractable target in IBD; however, further work is required to clarify the clinical utility of mitochondrial FPs as a potential mechanistic marker for future stratification.

Lower urinary tract symptoms in patients with inflammatory bowel diseases: A cross-sectional observational study

BackgroundInflammatory Bowel Diseases (IBD), Crohn's Disease (CD), and Ulcerative Colitis (UC) may have extraintestinal manifestations, including disorders of the urinary tract. The prevalence of lower urinary tract symptoms (LUTS) in IBD patients remains unclear. AimsAssess the prevalence of LUTS in patients with CD or UC, evaluate the variables implicated in any difference in LUTS prevalence between CD or UC, and assess any relationship between disease activity and LUTS MethodsLUTS were evaluated in 301 IBD patients through standardised questionnaires: Bristol Female Lower Urinary Tract Symptoms (BFLUTS), NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), and International Prostate Symptom Score (IPSS). IBD activity was determined through the Crohn's Disease Activity Index (CDAI), Partial Mayo Score (PMS), and Total Mayo Score (TMS). ResultsBFLUTS total score for females was 6 (3–11). Patients with a higher age at diagnosis had worse filling symptoms (p = 0.049) and a worse quality of life (p = 0.005). In males, 67.1% had mild, 28.5% moderate, and 4.4% severe IPSS symptom grades. The overall NIHCPSI prevalence of chronic prostatitis-like symptoms was 26.8%. The questionnaires revealed some significant differences in the subgroups analysed. ConclusionLUTS should be evaluated in IBD patients by urologic-validated questionnaires for prompt diagnosis and early treatment.

Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases.

Crohn's disease [CD] and ulcerative colitis [UC] require lifelong treatment and patient monitoring. Current biomarkers have several limitations; therefore, there is an unmet need to identify novel biomarkers in inflammatory bowel disease [IBD]. Previously, the role of plasminogen activator inhibitor 1 [PAI-1] was established in the pathogenesis of IBD and suggested as a potential biomarker. Therefore, we aimed to comprehensively analyse the selectivity of PAI-1 in IBD, its correlation with disease activity, and its potential to predict therapeutic response. Blood, colon biopsy, organoid cultures [OC], and faecal samples were used from active and inactive IBD patients and control subjects. Serpin E1 gene expressions and PAI-1 protein levels and localisation in serum, biopsy, and faecal samples were evaluated by qRT-PCR, ELISA, and immunostaining, respectively. The study population comprised 132 IBD patients [56 CD and 76 UC] and 40 non-IBD patients. We demonstrated that the serum, mucosal, and faecal PAI-1 concentrations are elevated in IBD patients, showing clinical and endoscopic activity. In responders [decrease of eMayo ≥3 in UC; or SES-CD 50% in CD], the initial PAI-1 level decreased significantly upon successful therapy. OCs derived from active IBD patients produced higher concentrations of PAI-1 than the controls, suggesting that epithelial cells could be a source of PAI-1. Moreover, faecal PAI-1 selectively increases in active IBD but not in other organic gastrointestinal diseases. The serum, mucosal, and faecal PAI-1 concentration correlates with disease activity and therapeutic response in IBD, suggesting that PAI-1 could be used as a novel, non-invasive, disease-specific, faecal biomarker in patient follow-up.

Correlation of Circulating Cathelcidin Level and Inflammatory Bowel Disease Activity

Abstract Background Inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are a group of idiopathic, chronic and relapsing inflammatory disorders of the gastrointestinal tract, whose incidence and prevalence has been increasing in the last decade. Objective To correlate circulating cathelicidin levels with mucosal disease activity in patients with IBD. Patients and Methods This case control cross sectional study was conducted on 45 adult subjects referred to Gastrointestinal Endoscopy and Liver Unit, EL-Haram Hospital.40 of the patients had IBD, the other 40 were non IBD patients studied as case control. All subjects were submitted to complete medical history, physical examination, laboratory investigations, colonoscopic examination and cathelicidin serum level. Results Our results showed that there was no statistically significant difference between both studied groups regarding both age and sex distribution. In this study we found highly significant decrease in Hemoglobin level in cases group compared to control group (p value &amp;lt; 0.001). Also, there was significant increase in platelets level among cases group compared to control (p value &amp;lt; 0.05). Also, we found that serum albumin was decreased among IBD patients compared to control. Conclusion Serum Cathelicidin has shown significant increase in patients with IBD activity. Serum cathelicidin levels showed statistically significant reverse correlation with Partial Mayo Scores of severity in UC patients. Serum cathelicidin levels showed Non-statistically significant correlation with Harvey Bradshaw Indices of severity in CD patients. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients.

Clinical Significance of Serum Cholinesterase in the Diagnosis and Assessment of Clinical Activity in Patients with IBD

Abstract Background Inflammatory bowel diseases (IBD), including Crohn’s disease and Ulcerative colitis, witnessed dramatic rise in incidence in the past few decades. Fecal calprotectin has been widely established as laboratory marker in assessment, diagnosis and severity of IBD. It showed low specificity and high number of false positive results. Cholinesterase (ChE) enzymatic glycoprotein used in hydrolosis of acetylcholine, showed significant correlation with IBD activity, it showed also potential role in diagnosis and assessing clinical severity in IBD patients. We will evaluate the role of serum cholinesterase in diagnosis and assessment of severity in IBD patients. Aim of the Work The aim of this study is to evaluate the role of serum cholinesterase (ChE) in diagnosis and assessment of activity in IBD patients Patients and Methods A Case control study in outpatients and inpatients in departments of Internal Medicine, Ain Shams University Hospital for Six months since beginning of data collection (till fulfilling the sample size) on 70 subjects divided into 3 groups: Group A: 25 patients with Crohn’s disease evidenced by colonoscopy and tissue biopsy, group B: 25 patients with Ulcerative Colitis disease evidenced by colonoscopy and tissue biopsy, group C: 20 age-matched, sex-matched healthy controls Results Our results confirmed that, compared with healthy controls, serum ChE levels were decreased in patients with IBD, and the decline in serum ChE levels was more pronounced as clinical activity in IBD increased. We also found that the serum ChE levels of patients with CD and those with UC were significantly different. It needs to be further clarified the relationship between serum ChE and endoscopic activity in the future. Conclusion Serum ChE levels can be used as a simple, economical method to help diagnose and distinguish the different stages of IBD. With the increasing biomedical research on the cholinergic anti-inflammatory pathway and ChE, serum ChE is expected to become a new immunotherapy target for IBD.

Verification of the Bühlmann fCAL turbo faecal calprotectin assay on the Binding Site Optilite benchtop analyser

ObjectivesInflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are increasingly prevalent disorders. Faecal calprotectin is useful in the differential diagnosis of IBD from IBS and monitoring IBD activity. We verified the Bühlmann fCAL turbo faecal calprotectin assay on the Binding Site, Optilite benchtop analyser. DesignAccuracy, precision, lower limit of quantitation (LLoQ), and linearity of the Bühlmann fCAL turbo faecal calprotectin assay on the Binding Site, Optilite benchtop analyser were ascertained. Comparison with the Bühlmann Quantum Blue fCAL extended and DiaSorin, Liaison calprotectin assays were also undertaken. Difference between assays was evaluated using the Wilcoxon signed-rank test and method comparison was undertaken using Spearman’s rank correlation (rs), difference plots and Passing-Bablok regression analyses. ResultsThe fCAL turbo assay was linear between 25 and 10,000 μg/g, and the LLoQ was 25 μg/g. Intra-, and inter-assay imprecision was <5%. There was a good agreement (rs = 0.96) and no significant bias (3%, p = 0.10) present between the fCAL turbo and Quantum Blue extended assays. Between the fCAL turbo and DiaSorin, liaison assays there was a good agreement (rs = 0.97), but a significant bias (53%, p = <0.01) was present. ConclusionsThe fCAL turbo assay performs well on the Binding Site, Optilite benchtop analyser. Calprotectin results are commutable between with Bühlmann fCAL turbo and Quantum Blue fCAL extended assays, but not between Bühlmann and DiaSorin calprotectin assays.

Optimizing maternal and neonatal outcomes through tight control management of inflammatory bowel disease during pregnancy: a pilot feasibility study

A home point-of care FCP test (IBDoc) and a self-reported clinical disease activity program (IBD Dashboard) may improve routine monitoring of IBD activity during pregnancy. We aimed to evaluate the feasibility of tight control management using remote monitoring in pregnant patients with IBD. Pregnant patients (< 20 weeks) with IBD were prospectively enrolled from Mount Sinai Hospital between 2019 and 2020. Patients completed the IBDoc and IBD Dashboard at three core time points. Disease activity was measured clinically using the Harvey–Bradshaw Index (mHBI) for CD and partial Mayo (pMayo) for UC, or objectively using FCP. A feasibility questionnaire was completed in the third trimester. Seventy-seven percent of patients (24 of 31) completed the IBDoc and IBD Dashboard at all core time points. Twenty-four patients completed the feasibility questionnaires. All survey respondents strongly preferred using the IBDoc over standard lab-based testing and would use the home kit in the future. Exploratory analysis identified discordance rates of more than 50% between clinical and objective disease activity. Tight control management using remote monitoring may be feasible among pregnant patients with IBD. A combination of both clinical scores and objective disease markers may better predict disease activity.

Risk of colorectal neoplasia according to histologic disease activity in patients with inflammatory bowel disease and colonic post-inflammatory polyps.

While post-inflammatory polyps (PIPs) have historically been a risk factor for colorectal neoplasia (CRN), histologic activity may explain this association. We aimed to assess the impact of histologic activity on CRN occurrence in IBD patients with colonic PIPs. Patients with PIPs on surveillance colonoscopy at Saint-Antoine hospital between 1 January 1996 and 31 December 2020 were included and subsequent colonoscopies were assessed. Histologic IBD activity was assessed by the Nancy histologic index. Survival and Cox regression analysis were performed to assess the strength of the association of PIPs and other patient variables with progression to CRN. A total of 173 patients with at least two surveillance colonoscopies with PIPs at index colonoscopy were compared to a similar group of 252 patients without PIPs. In survival analysis, the presence or PIPs at index colonoscopy did not impact the risk of CRN in patients with histological inflammation (p = 0.83) and in patients without histological inflammation (p = 0.98). The risk of CRN was associated with increasing Nancy index score of 3 or 4 (HR: 4.16; 95% CI 1.50-11.52 and HR: 3.44; 95% CI 1.63-7.24), age (HR per 10-year increase: 1.37; 95% CI 1.13-1.66) and first-degree family history of colorectal cancer (HR: 5.87; v 1.31-26.26), but not PIPs (HR: 1.17; 95% CI 0.63-2.17). After controlling for histologic activity, PIPs do not increase the risk of CRN in IBD patients. Histologic activity rather than PIPs should be considered in the risk assessment of CRN.