Dysentery Research Articles

Dopamine receptor D2 confers colonization resistance via microbial metabolites.

The gut microbiome has major roles in modulating host physiology. One such function is colonization resistance, or the ability of the microbial collective to protect the host against enteric pathogens1-3, including enterohaemorrhagic Escherichia coli (EHEC) serotype O157:H7, an attaching and effacing (AE) food-borne pathogen that causes severe gastroenteritis, enterocolitis, bloody diarrhea and acute renal failure4,5 (haemolytic uremic syndrome). Although gut microorganisms can provide colonization resistance by outcompeting some pathogens or modulating host defence provided by the gut barrier and intestinal immune cells6,7, this phenomenon remains poorly understood. Here, we show that activation of the neurotransmitter receptor dopamine receptor D2 (DRD2) in the intestinal epithelium by gut microbial metabolites produced upon dietary supplementation with the essential amino acid L-tryptophan protects the host against Citrobacter rodentium, a mouse AE pathogen that is widely used as a model for EHEC infection8,9. We further find that DRD2 activation by these tryptophan-derived metabolites decreases expression of a host actin regulatory protein involved in C. rodentium and EHEC attachment to the gut epithelium via formation of actin pedestals. Our results reveal a noncanonical colonization resistance pathway against AE pathogens that features an unconventional role for DRD2 outside the nervous system in controlling actin cytoskeletal organization in the gut epithelium. Our findings may inspire prophylactic and therapeutic approaches targeting DRD2 with dietary or pharmacological interventions to improve gut health and treat gastrointestinal infections, which afflict millions globally.

A review of the Prevalence of Enterohemorrhagic E. coli in Iraq

Background: The Diarrhoeal illnesses were a serious public health issue and a main reason that increasing the newborn and young children morbidity and mortality in developing nations. In persons in Iraq and developing nations, Enterohaemorrhagic E. coli is a group of pathogenic E. coli that can cause diarrhea or hemorrhagic colitis. A significant contributor to pediatric acute renal failure, morbidity, and mortality in adults is hemolytic uremic syndrome (HUS), which can occasionally develop from Enterohaemorrhagic E. coli. Objective: This review focusing on the prevalence of Enterohaemorrhagic E. coli and their role in increasing the mortality and morbidity in children and adults in Iraq and developing nations. Discussion: Due to the last 30 years of surveillance, EHEC had consistently been one of the biggest dangers to foodborne pathogens globally. EHEC mostly colonizes the gastrointestinal (GI) tract of cattle, where it can spread to neighboring farms and endure for months. Generally the main reasons of the infection with EHEC were O157:H7 but later the infections caused by EHEC strains has been linked to anther serogroups than O157 like O26, O111, O103 and O145. Among the major causes of bloody diarrhea, which may resolve on its own or get complicated into (HUS), is E. coli O157.

Pathogenic Factors of Shiga Toxigenic Escherichia coli

The Shigatoxigenic Escherichia coli (STEC) are bacterial enteropathogens responsible for some intensive clinical syndromes such as bloody diarrhoea, hemorrhagic colitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and renal failure. These pathotypes come under the Enterohemorrhagic Escherichia coli (EHEC) group. Monogastric farm animals such as pigs, horses, chickens, ducks, turkeys and aquatic animals like shellfish, fishes, and wild animals can act as major spillover hosts of STEC strains and could serve as the potential source of infection. The pathogen is notorious as a quickly emergent strain with acquired characteristics like different variants of Shigatoxin, many antibiotic degrading enzymes, Intimin, Enterohemolysin, Auto-agglutination Adhesins, Catalase-peroxidase, Zinc metalloprotease, Subtilase cytotoxin, tolerance to multiple adverse conditions, and biofilm formation. The bacteria are known for its long survival in different adverse physical-chemical conditions. The formation of biofilm is one of the major factors responsible for their persistence. Multidrug resistance is another related trait contributing to the high mortality rate of these strains. STEC strains are good candidates for studying the emergence of pathogens with acquired characteristics like genes. In this article, various virulent traits and multidrug resistance that enabled the strain to emerge as a serious public health menace were reviewed.

Combatting infectious diarrhea: innovations in treatment and vaccination strategies.

The escalating prevalence of infectious diseases is an important cause of concern in society. Particularly in several developing countries, infectious diarrhea poses a major problem, with a high fatality rate, especially among young children. The condition is divided into four classes, namely, acute diarrhea, invasive diarrhea, acute bloody diarrhea, and chronic diarrhea. Various pathogenic agents, such as bacteria, viruses, protozoans, and helminths, contribute to the onset of this condition. The review discusses the scenario of infectious diarrhea, the prevalent types, as well as approaches to management including preventive, therapeutic, and vaccination strategies. The vaccination techniques are extensively discussed including the available vaccines, their advantages as well as limitations. There are several approaches available to develop new-improved vaccines. In addition, route of immunization is important and aerosols/nasal sprays, oral route, skin patches, powders, and liquid jets to minimize needles can be used. Plant-based vaccines, such as rice, might save packing and refrigeration costs by being long-lasting, non-refrigerable, and immunogenic. Future research should utilize predetermined PCR testing intervals and symptom monitoring to identify persistent pathogens after therapy and symptom remission.

A74 A RARE CASE OF ANTIDEPRESSANT-INDUCED LYMPHOCYTIC COLITIS IN A TEENAGER

Abstract Background The etiopathogenesis of microscopic colitis may reflect an immunological reaction in genetically predisposed individuals exposed to an external stimulus causing gut microbiota disruption. Numerous factors such as smoking, autoimmune diseases, and medications have been linked to this condition in adults. Steroids may be required as therapy. Pediatric cases of microscopic colitis have only rarely been reported. Aims Case report. Methods Retrospective single chart review and literature review of microscopic colitis in children. Results A 17-year-old female newly diagnosed with major depression disorder following intentional acetaminophen intoxication was started on sertraline, a selective serotonin reuptake inhibitor (SSRI). Within 2 months from initiation, she began to have non bloody watery diarrhea and had a 5 kg weight loss over a 1-month period . Her laboratory workup only revealed a hypochromic, microcytic anemia. Due to severity of symptoms and reluctance of treating team to discontinue sertraline, she underwent an esophagogastroduodenoscopy and ileo-colonoscopy, both showing grossly normal mucosa. Histological assessment of the colon demonstrated increased intraepithelial lymphocytes, up to 50-60 lymphocytes/100 enterocytes (normal ≤ 20 lymphocytes/100 enterocytes), with associated reactive superficial epithelial changes including goblet cell and mucin depletion, compatible with lymphocytic colitis (Figure1). Sertraline was weaned off, and gastrointestinal symptoms resolved completely. A repeat sigmoidoscopy 5 months later confirmed complete normalization of the histology. Conclusions Microscopic Colitis encompasses two disorders, lymphocytic colitis and collagenous colitis, in which the endoscopic appearance is unremarkable, but histological changes are diagnostic. The clinical manifestations of both are similar and typically include chronic non bloody watery diarrhea, weight loss and abdominal pain. Certain medications have been implicated in causing lymphocytic colitis, including SSRIs. SSRIs historically have not been frequently prescribed in pediatrics, but their use has increased in recent years. The complete resolution of symptoms and histology, without the need for any medical therapy, strongly supports that this lymphocytic colitis was caused by sertraline. The association of lymphocytic colitis with sertraline is not well-known among pediatric practitioners: neither the pediatrician nor psychiatrist in our case were aware of such a possibility. This case highlights that medication adverse events, even if rare, should always be considered when chronology is supportive, and at times, simple discontinuation of the drug is sufficient to completely resolve the issue. Funding Agencies None

A166 STEROID-REFRACTORY ILEITIS FOLLOWING RITUXIMAB THERAPY: A CASE REPORT AND LITERATURE REVIEW

Abstract Background Rituximab, an anti-CD20 monoclonal antibody commonly used in treatment of hematologic and rheumatologic disease is generally well-tolerated from a gastrointestinal perspective however rare reported side effects include diarrhea and enterocolitis. Aims We describe a case of steroid-refractory ileitis presenting in a woman with follicular lymphoma post Rituximab therapy. Methods A case report and literature review were performed. Results A 73-year-old woman presented with a 4-week history of fevers, bloody diarrhea and abdominal pain. She had a known history of stage IV follicular lymphoma treated with six cycles of Bendamustine and Rituximab followed by four doses of maintenance Rituximab, with the last dose ending 4 weeks prior to her presentation. On examination, she had multiple peri-anal round ulcers. An abdominal CT revealed circumferential mural thickening involving the distal terminal ileum. On colonoscopy, there were multiple discrete ulcers and nodularity in the terminal ileum. Pathology showed evidence of chronic active ileitis with no signs of malignancy, lymphoproliferative disorders, or granulomas. AFB smear and cultures were negative. She was given IV steroids for 1 week and then placed on a Prednisone taper scheduled to finish in 9 weeks. 4 weeks later she presented again with fevers and abdominal pain. Inflammatory markers were elevated, and a repeat CT abdomen showed ongoing multifocal ileitis. She was put back on IV steroids and monitored. She continued to have persistent abdominal pain and fevers, and then underwent a repeat colonoscopy after 9 days of IV steroids which showed an interval increase in the size of her ileal ulcers. Pathology showed granulation tissue and reactive changes with no evidence of malignancy, lymphoma, granulomas, inclusion bodies or other viral cytopathic effects. Repeat AFB smear was negative. CMV PCR in blood was negative. She was assessed for Behcet’s disease (BD) given her peri-anal ulcers however she lacked other findings needed to fulfill the diagnostic criteria for BD. Steroids were continued with plans to initiate biological therapy. A review of literature revealed rare reports of rituximab-associated ileocolitis and development of de novo inflammatory bowel disease post rituximab therapy. Among patients who received Rituximab and underwent Colonoscopy, 4% had evidence of colitis. Rituximab-associated colitis appears to be usually mild presenting with diarrhea and requiring supportive care only, but in rare cases can lead to fulminant colitis and bowel perforation. Conclusions Rituximab-associated enterocolitis remains an under-reported entity and can lead to significant morbidity and treatment-associated challenges requiring prolonged courses of steroids and considerations for biological therapies. Important differentials to consider include malignancy, lymphoma, Tuberculosis, Bechet’s disease, and CMV enterocolitis. Ulcer in terminal ileum and ileocecal valve - Pre steroids (Left), Post steroids (Right) Funding Agencies None

An atypical presentation of ulcerative colitis: case report

BackgroundBloody diarrhea in children often indicates a severe gastrointestinal illness. Although infections are the most likely cause, inflammatory bowel disease (IBD) is a close mimic. IBD generally presents with chronic and persistent symptoms requiring long-term treatment. Hence, acute or atypical presentations may mislead the physician leading to delays in diagnosis. We report the case of an atypical presentation of ulcerative colitis.Case presentationWe present the case of a 6-year-old girl with acute symptoms of bloody diarrhea, fever, abdominal pain, and tenesmus for 5 days. The child came to us after the non-resolution of symptoms after treatment from a local practitioner. The child was found to have signs of chronic malnutrition and clubbing on general examination. After ruling out infective causes, the child was evaluated further by colonoscopy, which revealed lesions suggestive of ulcerative colitis, and hence started on topical and oral treatment for the same.ConclusionAwareness about the disease and its atypical presentations like poor growth, anemia, or extraintestinal manifestations is necessary, especially in primary healthcare and resource-poor settings as it can lead to early diagnosis, referral, and treatment initiation.

Natural compounds target programmed cell death (PCD) signaling mechanism to treat ulcerative colitis: a review.

Ulcerative colitis (UC) is a nonspecific inflammatory bowel disease characterized by abdominal pain, bloody diarrhea, weight loss, and colon shortening. However, UC is difficult to cure due to its high drug resistance rate and easy recurrence. Moreover, long-term inflammation and increased disease severity can lead to the development of colon cancer in some patients. Programmed cell death (PCD) is a gene-regulated cell death process that includes apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. PCD plays a crucial role in maintaining body homeostasis and the development of organs and tissues. Abnormal PCD signaling is observed in the pathological process of UC, such as activating the apoptosis signaling pathway to promote the progression of UC. Targeting PCD may be a therapeutic strategy, and natural compounds have shown great potential in modulating key targets of PCD to treat UC. For instance, baicalin can regulate cell apoptosis to alleviate inflammatory infiltration and pathological damage. This review focuses on the specific expression of PCD and its interaction with multiple signaling pathways, such as NF-κB, Nrf2, MAPK, JAK/STAT, PI3K/AKT, NLRP3, GPX4, Bcl-2, etc., to elucidate the role of natural compounds in targeting PCD for the treatment of UC. This review used (ulcerative colitis) (programmed cell death) and (natural products) as keywords to search the related studies in PubMed and the Web of Science, and CNKI database of the past 10years. This work retrieved 72 studies (65 from the past 5years and 7 from the past 10years), which aims to provide new treatment strategies for UC patients and serves as a foundation for the development of new drugs.

Epithelial Cell Infection Analyses with Shigella.

The human-adapted enteric bacterial pathogen Shigella causes millions of infections each year, creates long-term growth effects among pediatric patients, and is a leading cause of diarrheal deaths worldwide. Infection induces watery or bloody diarrhea as a result of the pathogen transiting the gastrointestinal tract and infecting the epithelial cells lining the colon. With staggering increases in antibiotic resistance and the current lack of approved vaccines, standardized research protocols are critical to studying this formidable pathogen. Here, methodologies are presented to examine the molecular pathogenesis of Shigella using in vitro analyses of bacterial adherence, invasion, and intracellular replication in colonic epithelial cells. Prior to infection analyses, the virulence phenotype of Shigella colonies was verified by the uptake of the Congo red dye on agar plates. Supplemented laboratory media can also be considered during bacterial culturing to mimic in vivo conditions. Bacterial cells are then used in a standardized protocol to infect colonic epithelial cells in tissue culture plates at an established multiplicity of infection with adaptations to analyze each stage of infection. For adherence assays, Shigella cells are incubated with reduced media levels to promote bacterial contact with epithelial cells. For both invasion and intracellular replication assays, gentamicin is applied for various time intervals to eliminate extracellular bacteria and enable assessment of invasion and/or the quantification of intracellular replication rates. All infection protocols enumerate adherent, invaded, and/or intracellular bacteria by serially diluting infected epithelial cell lysates and plating bacterial colony forming units relative to infecting titers on Congo red agar plates. Together, these protocols enable independent characterization and comparisons for each stage of Shigella infection of epithelial cells to study this pathogen successfully.

Clinical and public health implications of increasing notifications of LEE-negative Shiga toxin-producing Escherichia coli in England, 2014-2022.

Introduction. Shiga toxin-producing Escherichia coli (STEC) belong to a diverse group of gastrointestinal pathogens. The pathogenic potential of STEC is enhanced by the presence of the pathogenicity island called the Locus of Enterocyte Effacement (LEE), including the intimin encoding gene eae.Gap statement. STEC serotypes O128:H2 (Clonal Complex [CC]25), O91:H14 (CC33), and O146:H21 (CC442) are consistently in the top five STEC serotypes isolated from patients reporting gastrointestinal symptoms in England. However, they are eae/LEE-negative and perceived to be a low risk to public health, and we know little about their microbiology and epidemiology.Aim. We analysed clinical outcomes and genome sequencing data linked to patients infected with LEE-negative STEC belonging to CC25 (O128:H2, O21:H2), CC33 (O91:H14) and, and CC442 (O146:H21, O174:H21) in England to assess the risk to public health.Results. There was an almost ten-fold increase between 2014 and 2022 in the detection of all STEC belonging to CC25, CC33 and CC442 (2014 n=38, 2022 n=336), and a total of 1417 cases. There was a higher proportion of female cases (55-70 %) and more adults than children, with patients aged between 20-40 and >70 most at risk across the different serotypes. Symptoms were consistent across the three dominant serotypes O91:H14 (CC33), O146:H21 (CC442) and O128:H2 (CC25) (diarrhoea >75 %; bloody diarrhoea 25-32 %; abdominal pain 64-72 %; nausea 37-45 %; vomiting 10-24 %; and fever 27-30 %). Phylogenetic analyses revealed multiple events of acquisition and loss of different stx-encoding prophage. Additional putative virulence genes were identified including iha, agn43 and subA.Conclusions. Continued monitoring and surveillance of LEE-negative STEC infections is essential due to the increasing burden of infectious intestinal disease, and the risk that highly pathogenic strains may emerge following acquisition of the Shiga toxin subtypes associated with the most severe clinical outcomes.

An Unusual Case of Abdominal Pain in a Geriatric Man

BackgroundImmunoglobulin A vasculitis, historically known as Henoch-Schönlein purpura, is a rare form of autoimmune-induced vasculitis most common in children. This disease is characterized by a purpuric rash, arthritis, digestive tract complication, and renal inflammation (Hopkins). Case ReportWe present the case of a 78-year-old man in the emergency department with findings of weakness, abdominal pain, and bloody diarrhea for 3 days and a new-onset bilateral lower extremity rash. Diagnostic imaging and labs diagnosed this patient with immunoglobulin A vasculitis (IgAV) with associated acute kidney injury and abdominal mesenteric edema.Why Should an Emergency Physician be Aware of This? Recognition of IgAV by emergency physicians and assessment of multiple organ involvement is critical to expedite treatment and minimize complications. Particularly, physicians should consider and recognize the increased severity and different presentation of IgAV in adults in comparison with the more widely known manifestation in children.

ANCYLOSTOMIASIS AND ISOSPORIASIS IN SIBERIAN HUSKY DOG

Ancylostomiosis is a parasitic disease caused by infection with Ancylostoma spp. These parasites infect the digestive tract organs in dogs. Severe infection will cause death in dogs. A ten-year-old male Siberian Husky dog had complaints of bloody diarrhea, lethargy, and decreased appetite. Physical examination results showed a limp dog, pale mucous membranes, capillary refill time (CRT) of more than 2 seconds. The results of microscopic examination of feces with the floating method showed the presence of Ancylostoma spp. and Isospora spp. Based on this examination, the case dog was diagnosed with ancylostomiosis and isosporiosis. The therapy given was antihelmintic with pyrantel 15 mg/kg BW per oral (PO) with repetition on the 3rd and 7th days after the first administration, metronidazole therapy 25 mg/kg BW/12 hours per oral for seven days, symptomatic therapy with kaolin pectin per oral 7 mL/12 hours for five days and supportive therapy with vitamins and iron. On the 6th day after treatment, the dog in this case showed good results. The dog became more active and there was no diarrhea. To prevent ancylostomiosis and isosporiosis infections, routine deworming and environmental hygiene are recommended.

REAL-WORLD EFFECTIVENESS OF USTEKINUMAB IN PATIENTS WITH ULCERATIVE COLITIS IN THE UNITED STATES OF AMERICA

Abstract BACKGROUND Primary treatment goals for ulcerative colitis (UC) are to induce and maintain long-term disease remission and reduce the prevalence of symptoms such as bowel urgency and abdominal pain. Ustekinumab (UST) is a biologic approved for treating adult patients with moderate-severe UC, but real-world effectiveness data remain limited. OBJECTIVE We aimed to assess real-world effectiveness of UST in patients with UC. METHODS Data were drawn from the Adelphi Real World UC Disease Specific Programme™, a cross-sectional survey with retrospective data collection of gastroenterologists and their patients in the United States of America (USA) from December 2022–September 2023. Two samples were utilised; a sample where physicians provided data for their next six consecutive patients with UC, and an oversample where physicians provided data for their next four consulting patients with UC receiving UST. Patients receiving UST for >1 day at time of consultation (assumed to have received ≥1 UST dose) from either sample were included in the analysis. Data collected included clinical status, disease duration and location, symptoms and treatment profiles. Remission defined by Mayo score was reported separately for advanced therapy (AT)-naïve (UST received as first AT) and AT-experienced (UST received as second or later line of AT) patients. Descriptive statistics for each variable were reported for patients with known data. McNemar’s test was used for symptom prevalence and disease severity comparisons. RESULTS Data for 160 patients were included in this study from 50 physicians. Patients had been diagnosed with UC for median (interquartile range; IQR) of 2.2 (0.5, 4.5) years; mean (standard deviation) age was 39.7 (13.0) years and 50.0% of patients were male. UST was received as first AT for 68.1% of patients, second AT for 18.1% and third AT for 11.3%. Median (IQR) time on UST was 8.7 (4.1, 18.6) months, with 83.9% of patients receiving UST for ≥3 months. For patients in maintenance phase of treatment, 65.8% were on UST USA label dose, 17.9% were receiving an increased and 16.3% decreased dose. According to Mayo scores, 53.6% of AT-naïve and 58.3% of AT-experienced patients were in remission at consultation (Table 1). Improvement in disease severity was evidenced by a reduced proportion of patients with moderate/severe disease at consultation (34.4%) compared to prior to initiation of UST (90.9%; p<0.01). Similarly, there was a significantly lower prevalence of all symptoms between UST initiation and consultation, including abdominal pain (72.1% vs 30.2%), bowel urgency (55.1% vs 22.0%) and bloody diarrhea (54.4% vs 17.6%) (all p<0.01; Figure 1). CONCLUSION Our study showed real-world effectiveness of UST in patients with UC in the USA; most patients receiving UST achieved remission and demonstrated reduced prevalence of symptoms following UST initiation. Table 1 Physician-reported characteristics of patients receiving ustekinumab at the time of consultation. Figure 1 Physician-reported prevalence of (A) symptoms and (B) moderate/severe disease severity prior to initiation of ustekinumab and at time of consultation.

P1139 Lymphocytic Colitis: A large case series in the United Kingdom

Abstract Background Lymphocytic colitis, a type of microscopic colitis, was previously thought to be a rare condition. It is a histological diagnosis characterised by chronic loose stools and normal findings on endoscopy. It is now thought that it could be implicated in up to 10% of people with chronic diarrhoea, and has traditionally been associated with certain medications. We conducted a retrospective case analysis of patients diagnosed with the condition on histology between January 2018 till December 2022. Methods A list of patients who had undergone colonoscopy and biopsy for chronic diarrhoea, with no evidence of inflammatory bowel Disease (IBD), was generated. The patient’s electronic health records were then manually analysed, and data was collected using certain parameters including presence of autoimmune disease, faecal calprotectin levels/QFIT, smoking status, medication use (NSAIDS, PPI, Statins or SSRIs), colonoscopy findings, treatment choice and treatment outcomes. 121 patients were eligible based on histopathology consistent with a diagnosis of lymphocytic colitis. Results The median age was 63, with a 3:2 split of female to male patients. 63% reported painless, chronic diarrhoea lasting more than 6 weeks. 10.7% had painless and bloody diarrhoea, 23% had diarrhoea with abdominal pain. 25.4% had evidence of autoimmune disease. 43% were taking a PPI, 6.6% and NSAID, 41% a statin and 25.6% an SSRI. 27% were active smokers at the time of presentation. 62.8% of patients had a normal colonoscopy report, with the rest having ‘’abnormal reports” due to polyps. Faecal calprotectin levels ranged from 20-954. QFIT was positive in 35% of patients. 34% of patients were treated under a gastroenterologist. Of those who received budesonide only: 46% recovered with no relapse, 20% had relapsed in under 6 months, 16% relapsed after 6 months, 16% did not present again. Of the patients who received loperamide only, 66% reported resolution of symptoms. All histology demonstrated lymphocytosis in the lamina propria, 16% had expansion of the subepithelial collagen band, often termed ‘incomplete Microscopic colitis’. Conclusion Use of PPIs, statins and SSRIs are highly represented in the data, compared with general population usage. Treatment with either budesonide or loperamide generally lead to better symptom control, indicating patients should be referred to gastroenterology upon diagnosis. Clinicians should judiciously prescribe the above medications with clear indication and avoid prescribing indefinitely.

P1186 Unveiling the reality of Collagenous colitis: Beyond its Benign Façade

Abstract Background Microscopic colitis is a cause of chronic watery, non-bloody diarrhoea diagnosed mainly on histology after taking biopsy from essentially normal colonoscopy. Thereby mainly two subtypes can be identified: Lymphocytic and collagenous colitis. So far, no biomarkers for the diagnosis of microscopic colitis have been identified. Hower, despite being benign nature of this disease .it often trigger Two weeks wait (cancer path way) of the in the UK. Methods In this study, we analysed all cases of collagenous colitis diagnosed from 2018-2022 in the Northeast London from 5 different teaching hospitals. 104 cases were identified and their electronic health record from hospital and from the primary care physicians (GP) were manually reviewed. Results In this cohort, 24% male, 76% female with ratio of (1:3), with mean age of 65 years. Forty percent were active or ex-smoker. Painless watery diarrhoea was the main cause for referral in 90% of cases, 7% had painless bloody diarrhoea, whilst 3% complaint painful bloody diarrhoea. Abdominal pain noted in only 39% cases. Thirty-five (35%) cases noted to have history of weight loss. Among these patients, 27% had Haemoglobin < 130g/L, including 7% had <105g/L. Twenty nine percent had Faecal calprotectin (FCP) > 50 microgram/gm of stool and 14% had FCP >200. Seventeen percent had serum inflammatory marker raised CRP (normal 0-10). Thirteen percent (13%) of these patient trigger two weeks pathway referral as they had positive Faecal immunochemical test (FIT) which used for bowel cancer screening test, Twenty-seven (27%) presents did not require any treatment, got better after stopping suspected medication as a cause, while 73 % require treatment, of whom 5% require treatment with immunomodulator/ Biologics. Conclusion In this large series of collagenous colitis, we found that, despite being benign condition, it can present with alarming features which both health care provider and patient should be aware of, in order to avoid unnecessary anxiety. Further studies are needed to identify biomarker of this condition.

P302 Diagnostic Delayed is Associated with a Poor Prognosis in Patients with Crohn's Disease

Abstract Background The studies show that diagnostic delay, especially in Crohn’s disease (CD), is associated with a higher risk of complications and major surgery. We aimed to investigate timing of the diagnostic delay (DD) and its impact on the CD outcomes. Methods We retrospectively evaluated demographic and clinical features of CD patients between June 1993 and October 2023. Diagnostic delay was defined as the time interval from the onset of the first symptoms to the making of the CD diagnosis. The first CD related symptoms were evaluated by a review of the physician’s notes and medical record. Specific symptoms of CD included chronic or recurrent bloody or non-bloody diarrhea, and/or abdominal pain accompanied by noticeable weight loss, general weakness, and fever. Results 514 patients with CD were included in the study. The median age of disease onset was 34.14 years (16–84 years). Male sex was 299 (58.2%). DD was detected median 13 months (5-47) (14 months in male and 12 months in female). DD was 12 months for diseases with onsets before the age of 40 and 15 months for diseases with onsets after the age of 40. DD was 25 months in isolated ileal involvement, in terminal ileal involvement was 21.5 months, ileo-colonic involvement was 20 months, and colonic location was 10 months. Ileal involvement was found to have a longer duration for DD than colonic involvement. Compared to stenosing behavior (20 months) and penetrating behavior (17 months), DD was shorter in non-stenosing non-penetrating behavior (12 months). DD was longer in perianal disease (18 months) than in those without (12 months). Current smokers had a longer duration of the DD (20 months) compared to non-smokers (11.5 months) and ex-smokers (10 months). The duration of DD (18 months) was longer in CD patients with extraintestinal manifestations than in those without (12 months). Regarding the biological treatment, CD patients who experienced multiple biologics and resistance had longer DD (24 months) than those who experienced biologic monotherapy and responded (12 months). Compared to patients who had not had surgery (12 months), DD was longer in CD patients who had undergone surgery (15 months). Conclusion Our study showed that ileal involvement, stenosing-penetrating behavior, perianal disease, current smoking and existing extraintestinal manifestations were connected with DD. DD was also associated with multiple biologic needed and surgery. DD may have a role a significantly increased risk of bowel damage.

P072 LDN-071, a novel first-in-class amino acid-based PAI-1 inhibitor, significantly reduces the severity of experimental colitis in mice

Abstract Background Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders characterised by alterations of acute relapses and remission. The past decades have brought substantial advances in the pharmacological management of IBD by wide range of medicines. Although, the sustained efficacy of the currently available anti-inflammatory therapies is still far from optimal. Therefore, the development of novel therapies represents a major unmet clinical need in this field. Recently the enrichment of the coagulation pathway genes and among these, Plasminogen activator inhibitor 1 (PAI-1) was described in IBD, whereas PAI-1 emerged as a link between the epithelium and inflammation. Moreover, the genetic deletion of PAI-1 impaired the severity of experimental colitis in mice. Based on these, our aim was to develop and test novel PAI-1 inhibitors for the treatment of IBD. Methods Novel, amino acid-based PAI-1 inhibitors were synthetized by A3SMO® platform. The inhibitory potential and cytotoxicity effects of the peptides were determined by in vitro assays. Based on the in vitro results LDN-071 was selected for further analysis. Experimental colitis was induced in mice with 3% DSS and after the induction of colitis 10 mg/bwkg LDN-071 was administered per os for four consecutive days. The changes of body weight, spleen weight and colon length were measured. Haematoxylin eosin (HE) and Periodic acid-Schiff (PAS) staining were performed for histology. ELISA and qRT-PCR measurements were applied to analyse the mucosal cytokine expressions. In vivo toxicity of LDN-071 was determined in mice. Results LDN-071 significantly inhibited PAI-1 in vitro without decreasing the cell viability in a concentration range of 1µM-1mM. The administration of 10 mg/bwkg LDN-071 in the DSS-treated mice prevented the body weight loss, the development of bloody diarrhoea, the decrease of colon length and increase of the spleen weight, which were displayed by the DSS+vehicle-treated animals. The histological analysis of the colon revealed that DSS treatment induced a severe transmural inflammation, ulceration, loss of crypt structures and goblet cell depletion. Importantly, all of these parameters were significantly impaired by the administration of 10 mg/bwkg LDN-071. Additionally, mucosal gene and protein expressions of TNF-α, IL-1β and IL-6 were significantly impaired by PAI-1 inhibition. Importantly, no signs of toxicity were LDN-071 observed in mice exposed to 100 mg/bwkg LDN-071 for 7 days. Conclusion Our results showed that LDN-071, a novel amino acid-based inhibitor of PAI-1. It significantly reduces the severity of experimental colitis in mice. We propose that the inhibition of PAI-1 could be a potential novel therapeutic strategy in IBD.

P935 Remission rates of biologics and small molecules in extension studies of moderate to severe Ulcerative Colitis; A systematic review and Network Meta-analysis

Abstract Background Ulcerative colitis is a relapsing and remitting inflammatory bowel disease characterised by symptoms of bloody diarrhoea and abdominal pain. In recent years, newer therapies have emerged such as biologics and small molecule therapies. However, these therapies have not been compared head-to-head in the longer term, and the choice in clinical practice is often at the discretion of the clinician. In this study we aim to compare these biologics and small molecule therapies across outcomes such as remission (as defined by the Mayo score) as well as histological, endoscopic and corticosteroid free remission in data beyond 52 weeks of medication administration. Methods Medical databases including MEDLINE, EMBASE and Cochrane were searched for phase III and IV randomised control trials examining efficacy of biologic and small molecule therapies in adults with moderate to severe ulcerative colitis beyond 52 weeks. A network meta-analysis was performed using the frequentist model to compare the aforementioned outcomes with pooled relative risk, heterogeneity and P values used to rank treatments. Results 13 randomised control trials (RCT) were included for analysis from a screen of 2516 abstracts. Of these 13 RCTs, there were 8 treatments directly compared to placebo beyond week 52. In terms of remission as defined by the Mayo score, Upadacitinib 30mg was found to be the best treatment for moderate-severe ulcerative colitis when compared to Upadacitnib 15mg, Vedolizumab and Etrolizumab in consecutive order. In achieving histological remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg) and Etrolizumab. For endoscopic remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg), Vedolizumab, Etrolizumab and Golimumab. For corticosteroid free remission, Filgotinib 200mg was superior to Golimumab, Upadacitinib (30mg and 15mg), Vedolizumab and Etrolizumab. Conclusion Large head-to-head trials of biologic and small molecule therapies in the treatment of moderate to severe ulcerative colitis beyond 52 weeks have not been performed. However, our results show Upadacitinib 30mg to be efficacious in terms of remission defined by the Mayo score as well as histologic, endoscopic and corticosteroid free remission when compared to other biologics and small molecule therapies. Whilst these newer therapies show promise, their overall performance over an extended period remains unclear and their use often precludes the efficacy of subsequent biologic or small molecule therapies. As such, the first choice of therapy must be made carefully to increase the probability of remission whilst also balancing the burden of adverse events.

P643 Magnifying Endoscopy with Narrow Band Imaging for Graft Failure and Disease Recurrence in Patients with Crohn’s Disease after Intestinal Transplantation

Abstract Background Crohn’s disease (CD) is one of the common causes of short bowel syndrome (SBS) and intestinal failure (IF). Intestinal transplantation (IT) is sometimes needed for patients with CD who develop IF after multiple intestinal resections due to CD-related complications, such as uncontrollable bleeding and penetrating diseases. However, there have been limited case reports concerning the endoscopic surveillance of CD patients after IT. Methods We retrospectively investigated two patients with CD who underwent IT because of SBS-IF after multiple intestinal resection. We administered post-transplantation immunosuppressants and conducted regular magnifying endoscopy with narrow-band imaging (ME-NBI) via ileostomy chimney for surveillance of grafte rejection. Endoscopic prediction of rejection were based on our previously published "VENCH" score which is composed of five parameters: "V" (villi appearance), "E" (erythema), "N" (capillary network), "C" (crypt widening), and "H" (heterogeneity). Endoscopic biopsy were taken for histologic confirmation of graft rejection severity. Results Case 1 was a 60-year-old male patient with CD who received three times of intestinal resection for small bowel stricture and perforation, followed by IT due to SBS-IF. He lived uneventful until seven years thereafter with bloody diarrhea presented. Endoscopic surveillance revealed normal VENCH score of background mucosa but deep longitudinal ulcers which was indicative of recurrence of CD rather than graft rejection. Anti-tumor necrosis factor alpha with adalimumab was prescribed and his diarrhea and graft ulcers improved. Case 2 was a 39-year-old male patient with CD who received extensive intestinal resection due to multiple perforations, followed by IT because of SBS-IF. Endoscopic surveillance revealed normal VENCH score without histologic graft rejection two years thereafter. Both enrolled cases demonstrated favorable outcomes after endoscopic surveillance of intestinal graft with ME-NBI and management accordingly. Conclusion The post IT follow-up of CD patients remains challenging. We highlight the usefulness of the ME-NBI using VENCH score for early detection of graft rejection and its value in monitoring CD patients after IT. Additionally, ulcerations without changes in morphology of surrounding villi should take into consideration the disease recurrence of underlying CD. Further research is needed in endoscopic follow-up and molecular genetics to better understand CD after IT.

Prophylactic Oral Application of Activated Charcoal Mitigates Acute Campylobacteriosis in Human Gut Microbiota-Associated IL-10-/- Mice.

The incidence of human Campylobacter jejuni infections is increasing worldwide. It is highly desirable to prevent campylobacteriosis in individuals at risk for severe disease with antibiotics-independent non-toxic compounds. Activated charcoal (AC) has long been used as an anti-diarrheal remedy. Here, we tested the disease-mitigating effects of oral AC versus placebo in human gut microbiota-associated (hma) IL-10-/- mice starting a week prior to C. jejuni infection. On day 6 post-infection, the gastrointestinal C. jejuni loads were comparable in both infected cohorts, whereas campylobacteriosis symptoms such as wasting and bloody diarrhea were mitigated upon AC prophylaxis. Furthermore, AC application resulted in less pronounced C. jejuni-induced colonic epithelial cell apoptosis and in dampened innate and adaptive immune cell responses in the colon that were accompanied by basal concentrations of pro-inflammatory mediators including IL-6, TNF-α, IFN-γ, and nitric oxide measured in colonic explants from AC treated mice on day 6 post-infection. Furthermore, C. jejuni infection resulted in distinct fecal microbiota shift towards higher enterobacterial numbers and lower loads of obligate anaerobic species in hma mice that were AC-independent. In conclusion, our pre-clinical placebo-controlled intervention study provides evidence that prophylactic oral AC application mitigates acute murine campylobacteriosis.