Journal of the Canadian Association of Gastroenterology最新文献

{"title":"A262 THE EXCESS USE OF PROTON-PUMP INHIBITORS IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE","authors":"N Singh, Z. Nugent, W. El-Matary, H Singh, S. Shaffer, C. Bernstein","doi":"10.1093/jcag/gwad061.262","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.262","url":null,"abstract":"Abstract Background Proton-pump inhibitors (PPI) use can impact the gut microbiome, thus, it is possible that use in children may be associated with an increase in pediatric IBD. Aims We investigated the common gastrointestinal symptoms that result in a PPI prescription in pediatrics prior to a diagnosis of IBD and the degree to which children with IBD use excess PPIs compared to controls either prior to or post a diagnosis of IBD. Methods The University of Manitoba IBD Epidemiology Database includes all Manitobans diagnosed with IBD 1984-2018 with age, sex, and geographic-matched controls. PPI prescription data were assessed from April 1995 onwards in children diagnosed with IBD prior to age 18. Results PPI were dispensed prior to IBD diagnosis in 9% of 614 children diagnosed with IBD and 0.8% of 5718 controls (P ampersand:003C0.0001) with the median age being 15 years. Children with Crohn’s disease were no more likely to have been PPI-users pre-diagnosis (10%) than persons with ulcerative colitis (8%, p=0.57). Relative PPI use increases within 1-year of an IBD diagnosis (rate ratio, RR=22.4 (95% CI 13.6-37); P ampersand:003C 0.001) compared with 3-5 years pre-IBD (RR=4.9, 95% CI 1.4-16.7) and 1-3-year pre-IBD (RR=2.5, 95% CI 1.01-6.2). The percent of children being prescribed a PPI increased the more they visited a physician, which was associated with increased likelihood of being prescribed a PPI. PPI use was similar for the various gastrointestinal diagnoses in cases of IBD and controls. PPI users prior to a diagnosis may have less severe disease than non-PPI users. We found they were less likely to be hospitalized (HR 0.36, 95% CI 0.19 – 0.68; P = 0.002). There was no difference among children who had surgery for their IBD whether they were PPI users prior to IBD diagnosis compared to non-users. Conclusions PPI use was commonly prescribed for a variety of gastrointestinal complaints, similarly in cases and controls. Children with IBD have many more contacts for gastrointestinal diagnoses than controls even for 5 years prior to their diagnosis. This raises the possibility that PPIs are prescribed indiscriminately for gastrointestinal complaints since their use was not restricted to complaints warranting PPI use, or that PPIs are prescribed for early symptoms that are secondary to IBD. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"12 6","pages":"210 - 211"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A178 GASTROINTESTINAL STRICTURES IN A PEDIATRIC PATIENT WITH SATOYOSHI SYNDROME","authors":"K. Pohoreski, K. Pajunen, M. Brundler, I. Wrobel","doi":"10.1093/jcag/gwad061.178","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.178","url":null,"abstract":"Abstract Background Satoyoshi syndrome (SS) is a rare, progressive, multisystem disease including muscle spasms, alopecia, skeletal deformities, and diarrhea, with suspected autoimmune etiology. Treatment includes corticosteroids, immunoglobulin therapy, or immunosuppression. Reported endoscopic findings include loss of intestinal folds and nodularity in the stomach and the intestine, with histology showing gastritis cystica polyposa and lymphoplasmacytic infiltrate, as well as fibrosis noted on autopsy reports. To date, no cases of intestinal stricture have been described in SS. Aims To describe an original case of intestinal strictures in SS. Methods Case report and literature review. Results We present a case of a 10-year-old girl with chronic diarrhea and intermittent hematochezia, postprandial abdominal pain, intermittent non-bilious emesis, stunted growth, and weight loss, with acquired alopecia and severe muscle cramps. Examination showed a non-dysmorphic, small child with alopecia totalis and a distended, tender abdomen. Investigations demonstrated an unremarkable endocrine work-up, mild hypoalbuminemia, microcytic anemia, and anti-transglutaminase serology at 3-4x ULN with no improvement on the gluten-free diet. Endoscopy identified a duodenal stricture with a very distended stomach and duodenal bulb, mucosal nodularity and bridging creating a web-like appearance, and edema and friability of the left-sided colon. MR enterography confirmed an isolated duodenal stricture. Pathology displayed patchy fibrosis with crypt/glandular dilatation in the antrum, duodenum, and rectum. Skeletal imaging detected physeal widening and sclerosis with mild slipping of the epiphyses. Auto-immune markers included positive ENA profile for anti-Sm, anti-Sm/RNP, and anti-RNP-A. The patient was treated with corticosteroids in addition to a series of endoscopic dilatations for duodenal stricture with symptomatic benefit, with addition of upadacitinib for alopecia management. Follow-up revealed intermittent worsening of symptoms with steroid taper, necessitating further duodenal dilatations, and evidence of a new anal stricture. The patient remains on corticosteroid therapy with ongoing surveillance. Conclusions This case identifies the first report of intestinal strictures in SS, which may suggest that in addition to suspected autoimmune pathogenesis, disorders of fibrogenesis may need to be considered. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"43 3","pages":"140 - 140"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A60 INVESTIGATING THE ROLE OF NUCLEOTIDE-BINDING OLIGOMERIZATION DOMAIN (NOD) PROTEINS DURING BACTERIAL INFECTIONS IN INTESTINAL EPITHELIAL CELLS","authors":"M. Nissan, S. Girardin","doi":"10.1093/jcag/gwad061.060","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.060","url":null,"abstract":"Abstract Background Inflammatory bowel disease (IBD) is a collection of conditions that result in the inflammation of the gastrointestinal tract causing diarrhea, abdominal pain, weight loss, nausea, and vomiting. With its prevalence a whopping 0.6% in Canada, there is a need to understand the targets of therapy for the disease. Crohn’s disease, which is one of the two main conditions implicated in IBD, is most often associated with polymorphisms in the NOD2 gene. NOD2 is integral to the innate immune system of mammals, and functions as a pattern recognition receptor within the cytosol of cells. It detects conserved bacterial peptidoglycans to elicit an anti-microbial response by activating the nuclear factor kappa B pathway. NOD proteins also tackle infections upon bacterial recognition by recruitment of autophagy proteins allowing for the degradation of invading bacteria. Given their roles in bacterial clearance, it is unsurprising that mice deficient for NOD1 or NOD2 show increased susceptibility to pathogens, which is also what is thought to occur with Crohn's disease patients. Aims Although NOD1 and NOD2 have been well characterized in immune cells, little research has been done to interrogate their role during bacterial dysbiosis in intestinal epithelial cells. This research aims to elucidate the global signaling landscape that these proteins modulate in intestinal epithelial cells post-infection. We hypothesize that NOD1 and NOD2 play a critical role in host defense against intracellular bacterial pathogens in intestinal epithelial cells. Methods Intestinal crypts were harvested from WT, Nlrc4-/-, and Nlrc4-/- Ripk2-/- C57BL/6 mice to generate primary ileal organoids. Organoids infected with Shigella flexneri were harvested for protein and RNA. Downstream western blot, qPCR, Immunohistochemistry, and CFU analyses were performed to ensure the efficacy of the infection. Results Upon Shigella flexneri infection, CFU counts were only able to be recorded in a non-pyroptotic background (Nlrc4-/-). When examining the organoids by Immunohistochemistry, Shigella was well visualized in the Nlrc4-/- enteroids and was absent in WT controls 4 hours post-infection. Additionally, an increase in pro-inflammatory and stress genes was seen only in Nlrc4-/- organoids compared to WT controls. Finally, Nlrc4-/- Ripk2-/- organoids experience higher bacterial loads by CFU analysis compared to Nlrc4-/-Ripk2+/+ organoids. Conclusions Our research has shown that NOD1 and NOD2 deficiencies in primary mouse epithelial cells have increased bacteria loads compared to WTs upon infections showcasing a novel epithelial-intrinsic role for NOD1 and NOD2. This new insight into an epithelium-intrinsic role may be a step towards understanding the mechanism behind NOD2-associated Crohn's disease pathogenesis. Funding Agencies CIHRCrohn's and Colitis Canada","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"81 ","pages":"39 - 40"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A43 MECHANISMS OF UNIQUE COLONIZATION DYNAMICS AND IMMUNE RESPONSES TO MURIBACULACEAE","authors":"S. Popple, D. Pepin, H. Ghezzi, C. Tropini, L. Osborne","doi":"10.1093/jcag/gwad061.043","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.043","url":null,"abstract":"Abstract Background Commercially available probiotics have a limited ability to alter the gut microbiome and establish within a pre-existing microbial community. Increases in osmolality, a condition prevalent in intestinal diseases, depletes the highly abundant bacterial family Muribaculaceae (Mb) from the gut microbiome in a mouse model of short-term osmotic laxative use. Excitingly, despite microbial community re-equilibration in its absence, Mb supersedes other bacterial colonizers to its original abundance if reintroduced, suggesting unique colonization attributes and a potential privileged immune interaction. Aims We aimed to investigate whether and how Mb colonization affects intestinal innate and adaptive immune homeostasis, including the generation of Mb-specific antibodies. Methods To examine interactions between Mb and the immune system that allows for efficient colonization, we used the osmotic laxative polyethylene glycol (PEG) to clear Mb and then generated mice with complex microbiomes that either lack Mb completely (Mb naïve) or were introduced to 8 murine-derived Mb strains (Mb+). The same strains were then introduced to Mb naïve mice (primary exposure to the immune system). To model secondary exposure, Mb+ mice were treated with PEG, and Mb re-introduced 3 weeks later. Leukocytes from the small and large intestinal lamina propria and gut-draining mesenteric lymph nodes (mLNs) were profiled over 21 days to characterize colonization and recolonization dynamics. Results High-throughput 16SrRNA sequencing showed no significant difference between relative abundance of Mb isolates during colonization or recolonization, indicating that Mb is capable of establishing in mice that have never been colonized with it before, making up to 20% of the relative abundance. Broad immunophenotyping demonstrated robust CD11b-CD103+ dendritic cell and Germinal Centre B cell responses in the mLNs of mice seeing Mb for the first time, yet no subsequent plasmablast accumulation in the mLN or lamina propria. We also observed significantly increased type two innate lymphoid cells in the small intestine upon primary exposure to Mb. Recolonization elicited no detectable changes in the monitored populations. Conclusions The lack of immune reactivity upon reintroduction to Mb suggests Mb may evade immune detection upon repeat exposure and contribute to its robust colonization abilities. Determining mechanisms involved in Mb colonization and its impact on host immune responses could increase our understanding of colonization dynamics and highlights the potential of Mb as a model for microbiota reintroduction in therapeutic applications. Funding Agencies Weston Family Foundation","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"13 6","pages":"25 - 26"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A265 BARRIERS TO DIETARY MODIFICATION IN INFLAMMATORY BOWEL DISEASE (IBD): A MIXED-METHODS ASSESSMENT OF PATIENT PERCEPTIONS","authors":"J. Szeto, C. V. Noejovich, R. Verma, P. Miranda, M. Pinto-Sanchez, Eduardo Verdu, D. Armstrong","doi":"10.1093/jcag/gwad061.265","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.265","url":null,"abstract":"Abstract Background Many patients living with IBD identify diet as a key factor in managing their disease, symptoms and general health, and many report implementing dietary restrictions in response to disease activity and symptoms. Despite increasing data on the role of diet, IBD patients face a variety of challenges that can compromise adherence to dietary recommendations in clinical practice. Aims To identify IBD patients’ perceptions regarding barriers to dietary modification and to understand their experiences and expectations of dietary advice from gastroenterologists (GI) or dietitians (RD). Methods A mixed-method qualitative data collection strategy with semi-structured focus group and individual one-on-one interviews moderated by a clinical psychologist over a web-based, video communication platform (Zoom). Adult IBD patients (between 18 to 75 years old) attending the McMaster University Medical Centre IBD Clinic were invited to join a focus group consisting of 2-6 individuals or a one-on-one interview. All participants were asked to complete a demographics survey (REDCap) before the session. Recorded audio files for all sessions were transcribed, de-identified and reviewed for accuracy by 2 reviewers with an independent adjudicator to resolve discrepancies followed by thematic analysis (NVIVO). Results Between May to December 2022 and May 2023, 38 of 90 invitees took part in 11 focus groups and 9 chose individual interviews. Most participants (mean age 42 years; 60% female) were Caucasian (87%); 42% had a self-reported history of mental health disorders. Mean IBD duration was 16 years (min-max: 0.5–44 years); 73% were in remission and 68% had Crohn’s disease. Thematic analysis identified 5 primary and 11 secondary barriers to dietary adoption (Table). Participants reported positive and negative experiences with dietary advice from GIs and RDs; expectations included GI referral to a specialist RD and integration of an RD into the health care team. Conclusions IBD patients report multiple, varied barriers to dietary adoption and identify a need for improved access to dietary advice and other resources, including integration of RDs into primary and IBD Clinic care teams. The identification of multiple, varied patient-reported barriers offers an opportunity to develop personalized dietary advice for IBD patients to enhance health, well-being and quality of life. Thematic map of barriers experienced by patients when adopting dietary modifications Primary Barriers Secondary Barriers Difficulty identifying foods or diets affecting IBD Lack of guidance in identifying foods or diets Difficulty correlating symptoms with diet Barriers to accessing IBD diet foods Limited availability of IBD-friendly food options Expense of speciality food items Psychological Factors Anxiety in relation to food Aversive attitude to food Personal struggles with diet adherence Challenges with diet protocol complexity Changing habits and lifestyle Avoiding food cravings","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"111 3","pages":"213 - 214"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A189 INVESTIGATING THE ROLE OF BACTERIAL HISTAMINE METABOLISM IN VISCERAL HYPERALGESIA","authors":"T. Ross, J. Pujo, M. Hall-Bruce, S Collins, S. Vanner, D E Reed, P. Bercik, G. De Palma","doi":"10.1093/jcag/gwad061.189","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.189","url":null,"abstract":"Abstract Background Intestinal microbiota have been implicated in the expression of irritable bowel syndrome (IBS) as patients present with altered gut microbial profiles and microbial metabolic activity. We have previously identified bacterial histamine to strongly influence mast cell accumulation through only IBS activation of the H4 receptor, leading to visceral hyperalgesia in a subset of patients with IBS. We hypothesize that a subset of IBS patients with high histamine-producing microbiota exhibit an aberrant histamine metabolism. Investigating the microbiota-driven pathways involved in histamine metabolism is key to understanding abdominal pain pathophysiology in IBS patients. Aims 1. To study whether variations of histamine levels are due to bacterial metabolism using in vitro and in vivo approaches. 2. To identify the prevalence of high histamine-producing and histamine-degrading bacteria in a clinical cohort via in silico analyses. Methods Using in vitro approaches, stool samples from healthy control (HC) donors and IBS patients were inoculated in minimal media in aerobic/anaerobic conditions, with/without excess histidine or added histamine. Bacterial histamine production and degradation were assessed in culture supernatants by ELISA. After identification through Sanger sequencing, individual colony capacity to degrade and produce histamine was assessed. Host and microbial contributions to histamine metabolism will be identified through analyses of germ-free mice colonized with IBS and HC stool samples. Results IBS patients (n=23) tested were found to consistently produce higher levels of histamine compared to HC (n=3). Among the tested isolated colonies from IBS patients (n=179) 61% produced histamine compared to 33% of HC (n=54), and 20% degraded histamine compared to 11% of HC. Of these colonies, 13% of only IBS isolates demonstrated the capacity to both degrade and produce histamine. Facultative anaerobes were found to possess both higher production and degradation capacity. Both pH and histamine concentration determine bacterial ability to produce or degrade histamine. Conclusions Based on these findings, both healthy and IBS individuals exhibit varying levels of histamine production/degradation, most prominently through facultative anaerobes. The intestinal environment and bacterial community composition are major regulators of bacterial histamine metabolism. The observed in vitro capacity to produce/degrade histamine, and its biological implications, will be confirmed with gnotobiotic humanized mice, ultimately aiding in designing microbiota-directed therapies for the management of visceral hypersensitivity. Funding Agencies CIHRFarncombe Innovation Fund","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"749 ","pages":"148 - 149"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A253 BEHAVIOUR CHANGE CONSIDERATIONS TO IMPROVE PHYSICAL ACTIVITY PARTICIPATION AMONG INDIVIDUALS WITH QUIESCENT AND MILDLY ACTIVE IBD – A QUALITATIVE STUDY","authors":"B. Oketola, S. Webber, H Singh, M. Kredentser, K. Reynolds, G. Restall","doi":"10.1093/jcag/gwad061.253","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.253","url":null,"abstract":"Abstract NOT PUBLISHED AT AUTHOR’S REQUEST Please acknowledge all funding agencies listed below Funding Agencies CAGPfizer","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"521 5","pages":"203 - 204"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A196 CSF2 AUTOANTIBODIES AS A SEROLOGICAL MARKER FOR CROHN'S DISEASE","authors":"S. Tai, D. Del Valle, R. Urango, K. Croitoru, S. Gnjatic, J. Korzenik, J. Colombel, A. Mortha","doi":"10.1093/jcag/gwad061.196","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.196","url":null,"abstract":"Abstract Background Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that severely affects quality of life. Despite technological advances, CD diagnoses remain difficult and invasive, with delayed diagnoses correlated with worse prognosis and complications. CD is multifactorial, involving complex interactions between genetic and environmental risk factors, which leads to difficulty in identifying a cause and cure. However, research alludes to an underlying dysregulation of immune activity that leads to chronic intestinal inflammation. Mononuclear phagocytes (MNP) are essential immune cells that promote intestinal homeostasis through supporting immune tolerance, antimicrobial activity, and barrier integrity. A crucial cytokine that promotes the survival and function of intestinal MNP is Colony Stimulating Factor 2 (CSF2). Intriguingly, previous work in our lab demonstrated that CSF2 autoantibodies (CSF2-Ab) can be detected in the serum of every third CD patient and antedate the onset of CD by up to 6 years. In contrast, these titers are not seen in healthy donors or ulcerative colitis. Moreover, CSF2-Ab were predictive of disease location and severity, and are able to neutralize CSF2 by binding to glycosylations, impacting downstream signaling in MNP. These data suggest a role for CSF2-Ab in promoting intestinal immune dysregulation in CD. Aims Our work aims to characterize CSF2-Ab and their role in CD. Methods We developed a bead-based flow cytometric assay to screen CD patient serum for CSF2-Ab in several cohorts that contain samples at time points prior to, at, and after diagnosis. Results Our preliminary data demonstrate that our assay is rapid and specific for detecting CSF2-Ab of various isotypes in human serum and can be validated using ELISA. Furthermore, we show that this assay can be used to determine the epitope specificity of CSF2-Ab in CD patients in just one single sample. Conclusions We have developed a rapid and accessible assay to predict CD development years before diagnosis using minimal serum samples. Moreover, this screen will enable subclassification of patients based on their autoantibody reactivity to glycovariants of CSF2. Glycovariants that escape recognition by CD-specific CSF2-Ab could potentially be used as a therapeutic to ameliorate disease. Beyond treatment, understanding how CSF2-Ab epitope specificity and isotypes may change over the course of disease development will serve as a roadmap for elucidating the role of CSF2-Ab in CD. Funding Agencies CAG, CIHR","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"415 1","pages":"154 - 155"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A297 EXAMINING THE IMPACT OF INFLAMMATORY BOWEL DISEASE IN PRIMARY SCLEROSING CHOLANGITIS PATIENTS POST LIVER TRANSPLANTATION","authors":"G. Malhi, L. A. Diaz, G. Punchhi, R. Mortuza, M Khan, M. Brahmania, V. Jairath, J. Arab","doi":"10.1093/jcag/gwad061.297","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.297","url":null,"abstract":"Abstract Background Primary sclerosing cholangitis (PSC) is an immune-mediated disease that is characterized by biliary inflammation and fibrosis. It is associated with inflammatory bowel disease (IBD) in 80% of cases. To date, the impact of IBD in liver transplantation (LT) recipients is not completely understood. Aims To assess the impact of IBD in individuals with PSC who underwent liver transplantation (LT) in terms of graft survival, infections, and mortality. Methods This was a retrospective cohort study that included individuals with PSC who received a LT between 1999–2021. Statistical analysis included Kaplan-Meier survival curves, a binary logistic regression to estimate infection risk, and a competing-risk analysis to estimate post-LT mortality (with re-transplantation being a competing risk). Results 122 LT recipients were included. Mean age at LT was 44.9±12.6 years old. The median MELD-Na at LT was 22 [17–28]. Twenty-nine (23.8%) LT recipients died during follow-up (median 1,248 [413–3,857] days) and 5 (4.1%) required re-transplantation (median 1,460 [923–2,563] days). Estimated graft survival was 93.2% (95%CI: 86.9%–96.6%) at 1 year and 81.3% (95%CI: 72.5%–87.6%) at 5 years. An adjusted competing-risk model demonstrated that increasing age (sHR 1.05, 95%CI: 1.01–1.10; p=0.018), baseline MELD-Na (sHR 1.07, 95%CI: 1.02–1.12; p=0.005), and ERCP requirements before LT (sHR 6.33; 95%CI: 1.63–24.65; p=0.008) were associated with higher post-LT mortality, while IBD was not associated with post-LT mortality (sHR 1.02, 95%CI: 0.38–2.70; p=0.962). The incidence of infections after LT was 50.8% at 30 days. IBD was not associated with development of infections at 30 days (OR 1.01, 95%CI: 0.98–1.04; p=0.615) post-LT. Conclusions Based on this retrospective review, an older age, higher MELD-Na at LT and prior ERCP requirements were independently associated with a higher mortality post-LT in PSC patients. However, a background history of IBD was not associated with higher mortality or with infections post-LT. Table 1: Baseline Demographics Category Number (%) PSC 122 (100) Classic PSC 104 (85.3) PSC-AIH Overlap 17 (13.9) Small Duct PSC 1 (0.8) Age ampersand:003C30 17 (13.9) 30-50 59 (48.4) ampersand:003E50 46 (37.7) Sex Male 91 (74.6) Female 31 (25.4) IBD History IBD Present 99 (81.2) No IBD 23 (18.8) Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"163 ","pages":"240 - 242"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A15 LEVERAGING CULTURE-DEPENDENT AND -INDEPENDENT METAGENOMICS TO IDENTIFY ENTEROBACTERIACEAE GENES ASSOCIATED WITH ACTIVE ULCERATIVE COLITIS","authors":"D. Tertigas, F. Rinawi, P. Moayyedi, A. Griffiths, M. Surette","doi":"10.1093/jcag/gwad061.015","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.015","url":null,"abstract":"Abstract Background Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that is restricted to the large intestine and is characterized by mucosal inflammation. There is evidence that pathogenic bacteria contribute to UC pathogenesis in at least some patients and the bacterial family Enterobacteriaceae are prime suspects. Some strains of Enterobacteriaceae carry virulence genes important for colonizing the gut (e.g. fimH) and disrupting the intestinal epithelium (e.g. hemolysins). We hypothesize that key virulence genes carried by strains of many Enterobacteriaceae species contribute to disease activity in some UC patients. As we predict virulence genes are strain-specific, the detection of the species alone (e.g. Escherichia coli) is insufficient to predict pathogenic potential and this has confounded previous studies to identify infectious agents in UC. Aims We aim to use culture-dependent and -independent sequencing approaches to identify Enterobacteriaceae genes in the UC gut microbiome associated with active disease. Methods UC patient stool samples collected throughout enrolment in randomized control trials of fecal microbiota transplantation (FMT) for adult UC (n=10) and microbiome studies in early-onset pediatric UC (n=25) were cultured on MacConkey (MAC) agar to enrich for Enterobacteriaceae. Strains were isolated from baseline stool samples cultured on MAC agar for whole genome sequencing and virulence gene characterization. Baseline and post-treatment stool samples cultured on MAC agar were sent for metagenomic sequencing. Using a subset of 11 pediatric patients, I developed a metagenomic pipeline to identify Enterobacteriaceae genes enriched during active UC compared to periods of remission or milder disease. Results Known virulence genes, including fimH and hemolysins, were present in some strains across multiple Enterobacteriaceae species. Using an unbiased metagenomic approach with the pediatric cohort, we identified 42 genes enriched at baseline with the criteria they must be elevated in at least three of the 11 patients. The majority of the 42 genes were distributed into six gene clusters, including a small plasmid. Conclusions Our approach allows us to identify genes enriched in active UC that have not been previously described in the literature and our analysis will be repeated with our adult cohort. Genes that are enriched in active UC in the pediatric and/or adult cohort will be validated in publicly available metagenomic datasets that consist of both IBD patients and healthy controls. Furthermore, culture-dependent approaches allow us to test mechanisms in vivo that are informed by our bioinformatics. Leveraging microbiome and clinical data provides a unique window to guide future diagnostics and treatments to improve outcomes for UC patients. Funding Agencies CIHROGS","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"396 2","pages":"8 - 9"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}