bluuebunny/crossref_metadata_2025_split huggingface dataset:
A10 RESTORATION OF ARYL HYDROCARBON RECEPTOR SIGNALING IN CELIAC DISEASE BY ORAL TRYPTOPHAN SUPPLEMENTATION: AN EXPLORATORY STUDY
Authors: Kirtikar U , Rueda G H , Szeto J , Galipeau H , Constante M , Wang X , pinto-sanchez M , Bercik P , Armstrong D , Verdu E 
Published: February 2025

Abstract

Background
Celiac disease(CeD) is an autoimmune disease triggered by the ingestion of gluten in genetically predisposed individuals. The only treatment is a strict gluten-free diet(GFD), however up to 40% of remain symptomatic and have residual inflammation, highlighting the need for adjuvant therapies. We showed CeD patients exhibit impaired microbial metabolism of tryptophan, resulting in reduced activation of the aryl hydrocarbon receptor(AhR), which plays immunomodulatory roles. Increased AhR ligands and activation in the small intestine have been shown in healthy individuals after oral tryptophan, but it is unknown if this supplementation may affect treated symptomatic CeD patients.

Aims
To determine whether tryptophan supplementation improves CeD-specific symptoms, mood symptoms and quality of life in GFD non-responders.

Methods
This double-blinded, placebo-controlled trial aimed to recruit 50 CeD adults on &gt;1 year of GFD with persistent symptoms from McMaster University’s Celiac Clinic. Participants were randomized to L-tryptophan(3g/day) or placebo to be taken daily for 3 weeks. Before and post-intervention, participants completed symptom questionnaires, provided biological samples and underwent endoscopy. The primary outcome was a ≥4-point reduction in Celiac Symptom Index(CSI) from baseline, with secondary outcomes of improvement in Gastrointestinal Symptom Rating Scale(GSRS), Hospital Anxiety and Depression Scale(HADS), and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life(PAGI-QoL). An interim analysis of first 25 participants was performed to investigate early trends in symptom improvement, expressed as Odds Ratio(OR), 95% Confidence Intervals(CI).

Results
Post-intervention, CSI scores decreased in 67% of participants (8/12) in the tryptophan group compared to 30% (3/10) in the placebo group (OR=4.36; 95% CI:0.77-28.47). Similarly, GSRS improved in 75% of participants (9/12) in the tryptophan group vs 40% (4/10) in the placebo group (OR=4.5; 95% CI:0.73-27.74). HAD scores improved in 41% (5/12) of the tryptophan group vs 30% (3/10) in the placebo group (OR 1.6; 95% CI:0.28-9.82). The PAGI-QoL improved in 58.3% (7/12) of the tryptophan group vs 0% in the placebo group, p=0.0053.

Conclusions
A greater proportion of participants under the tryptophan intervention showed improvement in their gastrointestinal, mood symptoms and quality of life compared with the placebo group. We are not currently powered to establish statistical significance for these differences, however, if these results were replicated in the planned study sample size, the study could fulfil its primary outcome. These results encourage to complete recruitment, with further evaluation of the gut microbiota composition and AhR activity.
Funding Agencies:
A14 INVESTIGATING THE IMPACT OF PARKINSON’S DISEASE-ASSOCIATED GENE PINK1 ON INTESTINAL HOMEOSTASIS AND RESPONSE TO INFECTION
Authors: Pei J , Recinto S J , Kazanova A , Burns L , MacDonald A , Gavino C , Desjardins M , Stratton J A , Gruenheid S 
Published: February 2025

Abstract

Background
Intestinal epithelial cells (IECs) provide an essential physical barrier between luminal contents and host tissue. Dysregulation of IECs leads to barrier dysfunction, causing pathologies in both intestinal and extra-intestinal diseases. While Parkinson’s Disease (PD) is primarily a neurodegenerative disorder, increasing evidence links PD progression and gastrointestinal dysfunction. Our group developed a model to investigate the role of the gut in PD, demonstrating that mice with genetic ablation of the PD-associated gene Pink1 exhibited motor phenotypes only when previously infected with gram-negative Citrobacter rodentium intestinal bacteria. As Pink1 is expressed in IECs and the colonic lamina propria, we hypothesize that PD-associated gene mutations directly affect the epithelium and impact early PD pathophysiology.

Aims
1. To characterize the transcriptional profiles of Pink1 WT and KO IECs at baseline and following in vivo C. rodentium infection.
2. Use in vitro cell line and colonic organoid systems to study the effect of Pink1 on epithelial activity in an isolated system.

Methods
Single-cell RNA sequencing was performed on colonic IECs isolated from Pink1 WT and KO mice, at steady state and following in vivo C. rodentium infection. Mice were sacrificed at D6 post infection to elucidate transcriptional differences between IEC lineages of each genotype. To validate scRNAseq findings, we derived ex vivo colonoids from Pink1 WT and KO mouse crypts and used a Pink1 KO CMT-93 epithelial cell line with WT clone as control. The cultures were treated with lipopolysaccharide (LPS), or infected with gram-negative pathogens to determine how PINK1 loss-of-function affects the inflammatory response of the epithelium.

Results
At baseline, our data revealed upregulation of interferon (IFN)-signaling genes (ISGs) in Pink1 KO enterocytes (ECs) compared to WT; whereby more than 70% of upregulated differentially expressed genes were linked to type I or II IFN signaling. In vitro stimulation of Pink1 KO epithelial cell line with IFN resulted in stark upregulation of ISGs compared to WT. During infection, Pink1 KO ECs demonstrated significant alterations in actin-cytoskeleton-related GO term pathways compared to WT. Infection of Pink1 KO CMT-93 epithelial cells revealed morphological changes in F-actin structures.

Conclusions
Using in vivo and in vitro models encompassing PD-genetic susceptibility and environmental stimuli, we identified dysregulation in Pink1 KO epithelium, suggesting altered inflammatory responses at baseline and infection. By investigating PD-associated genes in IECs, we will contribute to better understanding the role of the intestine in PD initiation, progression, and pathogenesis.

Funding Agencies
CAG, CIHR
A16 ROLE OF HIPPO SIGNALING EFFECTORS YAP&TAZ IN GASTRIC METAPLASIA AND TUMORIGENESIS
Authors: Ju Z , sung J , Farag M , Fiset P , Ferri L , Gregorieff A 
Published: February 2025

Abstract
NOT PUBLISHED AT AUTHOR’S REQUEST
Please acknowledge all funding agencies listed below
Funding Agencies: CIHRstudent is supported by CIHR CGS D and TRIANGLE Canada
A19 INTERLEUKIN-6 AND INTERLEUKIN-22 MEDIATE DISTICT REGULATION OF MITOCHONDRIAL DYNAMICS IN PATHOBIONT INFECTED GUT EPITHELIA
Authors: Navaneetha Krishnan S , Wang A , Shutt T E , McKay D 
Published: February 2025

Abstract

Background
The IBD-associated pathobiont attaching-invading Escherichia coli (AIEC) strain LF82 induces mitochondrial fragmentation and depolarization in epithelial cells, resulting in impaired ATP production and reduced barrier function. Interleukin (IL)-6 and IL-22 are omnipresent in the inflamed gut, can directly affect epithelial function and both mobilize STAT-3, the serine727 phosphorylated form of which can translocate to mitochondria. Thus, we posed the question, will IL-6 or IL-22 rescue or exaggerate the mitochondrial damage evoked by exposure to E. coli-LF82?

Aims
1. To determine if IL-6 and IL-22 modulate mitochondrial function during E. coli-LF82 infection
2. To assess the mechanisms by which IL-6 and IL-22 affect mitochondrial function in model gut epithelia

Methods
Human colon-derived T84 epithelial cells were infected with E. coli-LF82 (108 CFU/mL, 4h) ± a 18h pre-treatment and then co-treatment with IL-6 or IL-22 (both 10 ng/mL). Bacterial internalization was evaluated, and mitochondrial network morphology visualized with MitoTracker Red and confocal microscopy. Mitochondrial membrane potential was evaluated using TMRE staining and flow cytometry, and ATP measured by a luminescence assay. STAT3 phosphorylation (S727 and Y705) in whole-cell extracts was determined via western blot in response to IL-6 or IL-22 during E. coli-LF82 infection.

Results
IL-6 inhibited E. coli-LF82 evoked mitochondrial fragmentation, with significantly more cells showing a fused tubular pattern: mitochondrial membrane potential was restored by ~50% and ATP depletion was less severe (n=5). IL-6 elicited increased pS727-STAT3. In contrast, IL-22 failed to prevent any of the mitochondrial changes caused by E. coli-LF82, did not cause increased pS727-STAT3 but bioactivity was confirmed by increased pY705-STAT3. IL-6, but not IL-22, reduced the number of viable intracellular bacteria without affecting bacterial growth and increased markers of autophagy activation.

Conclusions
We have uncovered divergent effects of the STAT3 activators, IL-6 and IL-22, in the control of epithelial mitochondrial dynamics and function when challenged with a bacterial pathobiont. We speculate that IL-6 limits the effects of E. coli-LF82 via mitochondrially-directed pS727-STAT3 signaling and upregulation of autophagy. Understanding the precise role of STAT3- activating cytokines signaling in mitochondrial regulation could reveal new target to enhance epithelial barrier function.

Funding Agencies
CIHR
A22 USING AN AIR-LIQUID INTERFACE (ALI) COLONOID MODEL TO DEFINE INTESTINAL MICROBE-MUCUS INTERACTIONS: CITROBACTER RODENTIUM EMPLOYS ESPC TO PENETRATE MOUSE COLONIC MUCUS
Authors: Chen Y , Liang Q , Gilliland A , Yang H , Yu H , vallance B 
Published: February 2025

Abstract
NOT PUBLISHED AT THE AUTHOR’S REQUEST
Funding Agencies: None
A36 SERRATED POLYPOSIS SYNDROME OUTCOMES IN THE COLD SNARE RESECTION ERA
Authors: Zarrin A , Jiang S X , Taylor E , Tavakoli P , Bell S , Walia A , Pang S , Yu M , Motomura D , Enns R , Telford J , Xiong W , Shahidi N 
Published: February 2025

Abstract

Background
Surgery is indicated in patients with serrated polyposis syndrome [SPS] when the polyp burden is no longer manageable endoscopically. Evidence has emerged supporting the efficacy and safety of cold snare resection [CSR] for large sessile serrated lesions; however, the role of a primary cold snare resection algorithm [PCSRA] in patients with SPS is unknown

Aims
We aimed to evaluate the efficacy of a PCSRA in patients with SPS

Methods
Utilizing an established retrospective cohort (2013-2023), all patients with a diagnosis of SPS were evaluated, based on the 2019 World Health Organization [WHO] criteria. Patients were stratified by index colonoscopy into the pre-PCSRA (01/2013-12/2020) and the post-PCSRA (01/2021-08/2023). Outcomes included achieving clearance (complete removal of all serrated class lesions [SCL] at procedure completion), adverse events, and referral for surgery. Continuous and categorical variables were summarised using median (IQR) and frequencies respectively. Fisher Exact test was used to compare categorical variables.

Results
178 patients with SPS were included in the analysis (N=144, 80.9% pre-PCSRA; N=34, 19.1% post-PCSRA). Median age at first colonoscopy was 62 years (IQR 9 years) and 115 (64.6%) were female. In the post-PCSRA, 593 SCLs were identified: 326 diminutive (&lt; 5mm), 147 small (5-9mm), 66 medium (10-19mm), and 54 large (≥ 20mm). Among both SCLs and adenomatous lesions, 93.4% (N=627) were removed by CSR. Endoscopic clearance was achieved in 30 (88.2%) patients and 1 patient (2.9%) underwent surgery, which preceded referral for endoscopic management. In comparing the pre-PCSRA vs. the post-PCSRA: 110 (76.4%) achieved clearance in the pre-PCSRA group (P=0.09). No delayed bleeding was observed in the post-PCSRA group as opposed to 3 (2.2%) in pre-UCSRA (p = 0.50). Intra-procedural perforation was reported in 1 patient in the post-PCSRA vs. 2 in the pre-PCSRA group (p=0.47). Only 1 delayed perforation was reported in the pre-PCSRA group (p=0.81). Twenty-one (13.9%) patients underwent surgery: 20 in the pre-PCSRA (94.7%; 9 due to polyp burden and 11 for colorectal cancer) and 1 in the post-PCSRA (colorectal cancer) (p=0.08).

Conclusions
Cold snare resection should be considered as the first-line resection modality for most lesions identified in patients with SPS.

Funding Agencies
None
A50 SUCCESSFUL HEMOSTASIS WITH THROUGH THE SCOPE CLIPS FOLLOWING OVER THE SCOPE CLIP FAILURE IN DIEULAFOY LESION
Authors: Hendis S , Tomaszewski M 
Published: February 2025

Abstract

Background
Dieulafoy lesions account for 1-2% of acute GI bleeding and can be difficult to treat endoscopically.

Aims
We present a case a 59-year-old male who presented with hematemesis, melena, and hemodynamic instability.

Methods
Initial esophago-gastro-duodenoscopies (EGD) did not detect a source of active bleeding. Abdominal CT angiography revealed vascular structure in the stomach’s greater curvature, indicating a Dieulafoy lesion. Embolization via interventional radiology was unsuccessful. A third EGD finally showed the bleeding as a focal ooze localized in the proximal part of the greater curvature of the stomach. We used a padlock over-the-scope clip (OTSC). Despite successful deployment and placement of the OTSC, the bleeding persisted.

Results
Ultimately, hemostasis was achieved using five through-the-scope clips in a zipper fashion to the mound of tissue that had been raised by the over the scope clip. We hypothesize that although the OTSC grasped the Dieulafoy lesion, the feeding vessels were not significantly compressed to achieve hemostasis. This case demonstrates the failure of an OTSC to control bleeding from a Dieulafoy lesion, which was ultimately managed with through-the-scope clips.

Conclusions
This underscores the importance of combining traditional and novel endoscopic techniques to achieve hemostasis.

Funding Agencies
None
A51 DEFINING THE ROLE OF THE SPDEF TRANSCRIPTION FACTOR IN INTESTINAL INFLAMMATION
Authors: Jamal A , Wang H , Grondin J , Seto T , Kamal A , Khan W I 
Published: February 2025

Abstract

Background
The intestinal mucus layer prevents commensal microbes and luminal pathogens from interacting with and invading into the underlying epithelium. Goblet cells are predominantly responsible for maintaining this mucus layer through the production and secretion of mucins. Alterations in goblet cell responses are observed in various gastrointestinal disorders including inflammatory bowel disease (IBD). The differentiation and maturation of goblet cells is controlled by several genes. Recently it was shown that the SAM pointed domain ETS factor (SPDEF), an ETS family transcription factor plays a key role in terminal differentiation and maturation of goblet cells. The role of SPDEF in goblet cell responses in intestinal inflammation remains to be determined. Understanding its role in regulating goblet cell responses and mucins production will provide new insight into the mechanisms of dysregulated mucus barrier in intestinal inflammation.

Aims
This study aimed to investigate the severity of a commonly employed chemical model of colitis, dextran sodium sulphate (DSS), in SPDEF knockout (KO) mice compared to wild-type (WT) littermate controls. It was hypothesized that the SPDEF KO mice will exhibit a heightened severity of DSS-induced colitis than the WT mice.

Methods
SPDEF KO and WT mice were treated with DSS in the drinking water for seven consecutive days then euthanized. Disease activity index (DAI), comprising of body weight, stool consistency, and fecal bleeding was assessed over the course of DSS administration. The severity of intestinal inflammation was further assessed by checking macroscopic scores, histological damage scores, myeloperoxidase (MPO) assay, and various pro-inflammatory cytokines in the colonic tissues by ELISA.

Results
SPDEF KO mice exhibited a heightened sensitivity to DSS-induced colitis compared to WT controls. The SPDEF KO mice show a much more dramatic decline in body weight and a substantial increase in DAI, most prominently during the later stages of DSS administration. Additionally, SPDEF KO mice exhibited a greater degree of colonic, fecal, and rectal bleeding than the WT mice, reflected by a higher macroscopic score. Levels of MPO and certain pro-inflammatory cytokines were significantly elevated in the colon tissues of SPDEF KO as compared to WT mice. Histologically, SPDEF KO also displayed decreased goblet cell counts compared to WT mice.

Conclusions
These findings suggest that disruption of the SPDEF transcription factor aggravates DSS-colitis. Defining the role of SPDEF in intestinal inflammation provides a deeper understanding of the mechanism of dysregulated mucus barrier in colitis which may ultimately lead to identifying potential new targets to restore barrier integrity in colitis.

Funding Agencies
NRC
A54 INFLAMMATORY BOWEL DISEASE IN INDIGENOUS POPULATIONS: A SCOPING REVIEW
Authors: Munir O , Condray C , Souza Lira A P , Fowler S , Brass C , Butterworth H , Hourston A , Porter L , Porter R , Sanderson R , Peña-Sánchez J 
Published: February 2025

Abstract

Background
Globally, Inflammatory Bowel Disease (IBD) rates have surged; however, Indigenous/Native/Aboriginal populations (i.e., the original inhabitants of a geographical region) are underrepresented in research and often face unique challenges in accessing healthcare due to socioeconomic barriers stemming from historic inequities.

Aims
This scoping review aimed to synthesize available literature on IBD in Indigenous populations globally, identify research gaps, and propose recommendations to improve research inclusivity.

Methods
A literature search was conducted across eight online databases: MEDLINE, EMBASE, CINAHL, SCOPUS, Web of Science, i-portal, Native Health Database, and ASTIS. We included qualitative, quantitative, and mixed-method research in this review, as well as commentaries, editorials, and abstracts published between 1960 and 2023. Eligibility criteria included publications in English focused on IBD Indigenous populations. Two reviewers independently screened titles and abstracts. The included publications were summarized and appraised using the Joanna Briggs Institute critical appraisal tools.

Results
Eighteen publications were included in the review, with most originating from Canada (n=7), New Zealand (n=5), and Australia (n=4). There was one study from Chile and another from the United States. Results showed a lower prevalence of IBD in Indigenous populations compared to the general population, but some recent studies reported an increasing prevalence of IBD among Indigenous populations from different countries. These changes are hypothesized to result from urbanization, changes in diet, sanitation, or other environmental changes. Also, a study from Canada showed that Indigenous peoples face inequities in accessing IBD care. Apart from 3 papers from Canada, 15 of the 18 publications had no evidence of working with Indigenous community members during the research process.

Conclusions
This scoping review highlights gaps in the literature about IBD in Indigenous populations. While the prevalence of IBD among Indigenous peoples is low, evidence demonstrates that rates are rising. Further research is required to continue studying the rising rates of IBD in Indigenous populations, alongside the genetic and environmental factors contributing to these trends. A focus on patient-centered research should also be emphasized. Indigenous peoples must be included as research partners and Indigenous research protocols must be followed to address health inequities and improve the health and well-being of Indigenous peoples living with IBD.

Funding Agencies
None
A56 THE ROLE OF THE STERILE ALPHA MOTIF (SAM) POINTED DOMAIN ETS FAMILY TRANSCRIPTION FACTOR (SPDEF) ON GOBLET CELL BIOLOGY AND INTESTINAL MUCUS PRODUCTION IN THE CONTEXT OF PARASITIC HOST DEFENSE.
Authors: Seto T , Haider Z , Grondin J , Wang H , Haq S , Banskota S , Khan W I 
Published: February 2025

Abstract

Background
The intestinal mucus layer in the gastrointestinal (GI) tract acts as a physical protective barrier against luminal contents and potential invaders. Goblet cells, a specialized subset of intestinal epithelial cells, play a large role in synthesizing and secreting mucins, which are the structural building blocks of the intestinal mucus layer. The terminal differentiation and maturation of these goblet cells are regulated by sterile alpha motif (SAM) pointed domain ETS family transcription factor (SPDEF). Goblet cell biology and the intestinal mucus barrier is one of the most effective host response mechanisms against enteric parasitic infections, including Trichuris muris. However, no study has evaluated the relationship between SPDEF, goblet cell biology, and mucus production in the context of parasitic host defense.

Aims
To identify the relationship between SPDEF, goblet cell biology, and mucus production during T. muris infection and how this contributes to parasitic host defence.

Methods
For infection experiments, BALB/c mice were gavaged with ~300 T. muris eggs in 200 µl autoclaved distilled water. To explore the role of SPDEF in goblet cell and mucin responses during T. muris infection, SPDEF-/- and SPDEF+/+ mice were administered ~300 T. muris eggs and were sacrificed at days 14 and 21 post-infection (p.i) along with uninfected controls. Periodic Acid Schiff (PAS) staining was used to quantify goblet cells and immunofluorescence was used to identify Muc2+ and SPDEF+ cells. Enzyme-linked immunosorbent assays were used to evaluate Th2 cytokines, and qPCR was used to evaluate Muc2 and SPDEF expression.

Results
BALB/c mice infected with T. muris displayed increased SPDEF expression. On days 14 and 21 p.i., SPDEF-/- mice harboured significantly more worms than their SPDEF+/+ counterparts. These mice also displayed diminished levels of IL-4 and IL-13 at day 14 p.i. as well as decreased PAS+ and MUC2+ goblet cell numbers. Compared to SPDEF+/+ mice, on day 21 p.i., IL-4 was increased in infected SPDEF-/- mice, whereas levels of PAS+ and MUC2+ goblet cells retained a similar pattern to that of day 14 p.i. Interestingly, the number of PAS+ goblet cells, MUC2+ cells and Muc2 expression significantly increased after infection in SPDEF+/+ mice at day 14 and day 21 p.i.

Conclusions
Together, these results suggest that SPDEF is an important regulator of goblet cell function and mucus production during T. muris infection, ultimately contributing to parasitic host defense.
Funding Agencies:
A58 LOW TTG-IGA ASSOCIATED WITH ISOLATED BULB PATHOLOGY IN PEDIATRIC CELIAC DISEASE: IMPLICATIONS IN A NO-BIOPSY APPROACH ERA
Authors: Wang Q , Jantchou P , Dirks M , Lavoie S , Oligny L , Dal Soglio D , Patey N 
Published: February 2025

Abstract
NOT PUBLISHED AT AUTHOR’S REQUEST
Funding Agencies: None