bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0047 Understanding the pathogenic role of inflammatory fibroblasts in Inflammatory Bowel Disease
Authors: Matellan C , Nwaezeigwe M , Doherty G , Manresa M 
Published: January 2025

Abstract

Background
TWEAK (TNF-like weak inducer of apoptosis), a member of the tumor necrosis factor superfamily, has been found to be upregulated in IBD biopsies and to promote chronic inflammation in in vivo murine models.
Previous work by our group has identified that TWEAK represses the expression of homeostatic factors in colonic fibroblasts, and it promotes inflammatory fibroblast-monocyte crosstalk.
The aim of this study was to translate in vitro observations into a clinical setting by investigating the presence of TWEAK in the healthy and inflamed gut and its correlation with inflammatory fibroblasts.

Methods
Fresh colonic biopsies were enzymatically digested and processed to extract single cells.
Isolated cells were analysed by flow cytometry to characterise the expression and cellular source of TWEAK, as well as changes in structural cell compartments, including inflammatory polarisation in colonic fibroblasts.
Flow cytometry was conducted on 31 colonic samples of patients with known IBD (inflamed n=11, noninflamed n=10, remission, n=10) as well as 4 healthy controls with no history of IBD

Results
We observed an increased number of TWEAK+ myeloid cells (CD45+/CD11b+/TWEAK+) in inflamed segments compared to non-involved sections, or to biopsies from healthy donors or patients in remission (Figure 1A).
Similarly, inflamed biopsies showed an increase in CD90+/PDPN+ stromal cells, which is consistent with an expansion in inflammatory fibroblasts (Figure 1B), and highly correlates with the accumulation of TWEAK+ myeloid cells (Figure 1C).

Conclusion
The accumulation of TWEAK+ myeloid cells in inflamed tissues is concomitant with the expansion of the inflammatory stroma in ulcerative colitis, positioning TWEAK as a potential driver of inflammatory fibroblast polarisation.
Understanding the effect of TWEAK in stromal remodelling is of key importance both to understanding intestinal physiology and to developing potential therapeutic strategies in diseases as diverse as inflammatory bowel disease.
P0194 Osteoporosis and osteopenia as extraintestinal manifestations in ulcerative colitis
Authors: Andronic A M , Andronic C , Toader E 
Published: January 2025

Abstract

Background
Inflammatory bowel diseases (IBD) are often characterized by associated conditions with extraintestinal manifestations that can make diagnosis and treatment difficult. It is known that chronic inflammation, nutritional deficiencies and corticosteroid treatment in IBD are the main risk factors for developing metabolic bone diseases. This study aims to evaluate ulcerative colitis (UC) patients with osteoporosis and osteopenia as extraintestinal manifestation.

Methods
We analyzed 79 patients (mean age 42 years) with UC and we measured bone mineral density by dual energy X-ray absorptiometry (DXA). Patients who received treatment with corticosteroids were not included in the study. 25(OH)D levels were also measured in all patients enrolled in the study. The patients did not follow vitamin D supplementation treatment. Disease remission was defined with partial Mayo score ≤2. Among the patients included in the study, 52 were under biologic therapy.

Results
Among the patients included in the study 55 patients (69%) were in remission and 49 patients (62%) with low vitamin D levels &lt;20 ng/ml. Osteoporosis (T score &lt;-2.5) was found in 24% of patients at the lumbar-sacral spine and in 13.9% of patients at the femoral neck; osteopenia (T score between -1.0 and -2.5) was also found in 40.5% of patients at the lumbar-sacral spine and in 35.5% of patients at the femoral neck. All patients with osteoporosis had vitamin D deficiency (p=0.01) and osteopenia was present in 61% of patients with vitamin D deficiency (p=0.05). Regarding disease activity, 23.6% patients in remission and 29.1% patients with active ulcerative colitis were diagnosed with osteoporosis (p=0.69), meanwhile in the osteopenia group, 38.1% patients were in remission and 41.6% patients were with active disease (p=0.84). From the patients included in the study, 65.8% were following biological therapy of which only 3.8% were diagnosed with osteoporosis (p=0.007) and 11.5% were diagnosed with osteopenia (p=0.006).

Conclusion
Our data confirm that osteoporosis and osteopenia are common extraintestinal manifestations in ulcerative colitis. Patients with vitamin D deficiency were more likely to develop metabolic bone diseases without statistically significant differences between ulcerative colitis patients with active disease or those in remission. Patients who follow biological therapy have a lower risk of developing metabolic bone disease. Screening for osteoporosis and osteopenia is indicated in UC patients and vitamin D supplements are mandatory.
P0196 Metabolic dysregulation in Crohn’s disease fibrosis: Targeting WISP1 to restore ECM homeostasis
Authors: Buck A , Widemann K , Weber M C , Friess H , Neumann P A 
Published: January 2025

Abstract

Background
In patients with Crohn’s disease (CD), homeostasis of the extracellular matrix (ECM) is significantly disrupted, frequently leading to severe complications such as intestinal stenosis. The maintenance of organ functionality depends on a delicate balance between inflammatory mediators, ECM production, and degradation processes. However, these mechanisms remain poorly understood. This study investigates the dynamic interplay between ECM homeostasis and metabolic pathways in CD, providing novel insights into their role in disease pathogenesis and potential therapeutic intervention.

Methods
Bulk RNA sequencing was performed to compare fibrotic and non-fibrotic intestinal tissues from CD patients undergoing ileocecal resection, aiming to identify key metabolic and ECM-related pathways. Primary matrix-producing fibroblasts were studied in 2D cultures and spheroids to characterize their metabolic activity, with a focus on fatty acid oxidation (FAO) and glycolysis through gene and protein analysis, metabolic assays, and fatty acid profiling (GC-FID). Chronic intestinal fibrosis was modelled in vivo using dextran sodium sulfate (DSS)-treated mice, allowing therapeutic evaluation of WISP1 neutralisation. The in vivo model was characterized using histological and clinical scoring, as well as gene and protein expression analysis.

Results
Gene set enrichment analysis revealed increased WNT signaling coupled with a reduction in fatty acid metabolism. Additionally, fibrotic tissue exhibited elevated levels of oleic acid and palmitate, indicative of increased lipid accumulation. WISP1, a WNT mediator, was identified as an adipokine and a key regulator of the metabolic shift from fatty acid oxidation to glycolysis. The disruption of FAO-related genes, including PPARγ, CPT1A, CPT2, and ACOX1, demonstrated reciprocal effects on fibroblast activity: pharmacological inhibition of FAO increased matrix production by fibroblasts, whereas activation of FAO via the PPARα agonist fenofibrate induced a catabolic fibroblast phenotype. This phenotype was characterized by suppressed ECM expression and enhanced ECM degradation via MMP1. Importantly, therapeutic neutralization of WISP1 significantly reduced fibrosis in a chronic DSS-induced colitis model.

Conclusion
This study presents a novel therapeutic strategy for managing fibrosis in Crohn’s disease. By pharmacologically neutralizing WISP1, this approach aims to correct the underlying metabolic dysfunction, thereby restoring metabolic balance and ECM homeostasis.
P0203 Unique faecal & oral microbiota signatures in first degree relatives of inflammatory bowel disease patients
Authors: Koentgen S , Zhang F , Wu N , Jayawardana T , Little R , Tavakoli P , Ghaly S , Connor S J , Hold G L 
Published: January 2025

Abstract

Background
While the aetiology of IBD is unknown, a range of genetic and environmental risk factors have been described. First-degree relatives (FDRs; siblings, parents and children) of IBD patients share many of these factors. To better understand the interplay between environmental and genetic risk factors, we evaluated the gut microbial profiles of an FDR cohort, their IBD probands and healthy controls (HC). The aim was to identify whether FDRs of IBD patients have healthy or IBD-like microbial features.

Methods
All participants were recruited as part of the Australian IBD Microbiome (AIM) study. Participants were selected based on self-reported first-degree relative status (n=68) and, where possible, affected IBD relatives (n=24) were included for comparison. All participants were antibiotic free for 3-months prior to baseline sampling. Oral and faecal samples underwent 16S rRNA sequencing. The Microbiome Research Centre 16S analysis pipeline and R studio were used for statistical analysis and data visualisation.

Results
The FDR group was predominantly female (63%) with a mean age of 49.7 years and BMI of 25.5 kg/m2. The IBD cohort was significantly different in age to FDR (mean 36.7; p &lt; 0.05) but not controls (mean 40.4 years) and BMI was comparable between groups. European Australians were the most represented ethnic group (47.6%) and 98.6% of participants were non-smokers. Oral microbiota profiles showed no significant difference in alpha diversity across FDR, IBD and HC groups. Differential abundance analysis of the oral microbiota revealed FDRs had increased abundance of Oribacterium, Granulicatella, Lachnoanaerobaculum and Rothia compared to HC, and increased levels of Capnocytophaga, Tannerella and Abiotrophia compared to the IBD group. In agreement with other studies, faecal microbial profiles in the IBD group had significantly reduced alpha diversity compared to both FDR and HC groups. All groups were compositionally different by Bray-Curtis beta dissimilarity analysis (p&lt;0.018). FDRs had higher abundance of Akkermansia, Alistipes and Monoglobus compared to IBD and HC groups. FDRs and IBD shared similar abundance of Butyricicoccus which was lower than the HCs.

Conclusion
FDR oral microbiome signatures had greater variance from HC than IBD groups. Faecal microbial analysis showed distinct differences with enrichment of key beneficial genera in the FDR group. FDR profiles however still shared significant gut microbial features with the IBD group, remaining distinct from healthy controls. FDRs oral microbiome was higher in opportunistic pathogens and IBD-like whereas faecal composition was protective, rich in beneficial metabolite producing genera.
P0206 Skin deep connections: patients with stricturing Crohn’s disease are more likely to have a history of skin scarring than those with non-stricturing Crohn’s and non-IBD controls
Authors: Mohamedrashed M , Yogakanthi S , Chauhan A , Lucas S , Robinson A , Garg M 
Published: January 2025

Abstract

Background
The mechanism and prediction of stricturing Crohn’s disease (CD) to guide medical therapy remains elusive. Formation of hypertrophic and keloid skin scars have not been previously studied in IBD. This study aimed to evaluate the nature of skin scars in patients with CD, and their association with different phenotypes.

Methods
Adult patients attending a tertiary IBD service were invited to participate in this cross-sectional observational study. Patients were divided into three groups (non-IBD controls, non-structuring/non-penetrating CD and stricturing/penetrating CD). A patient survey tool, consisting of 8 questions was administered to assess for the presence of scars and their type. Disease characteristics were ascertained using electronic medical records. The primary outcome of the study was the prevalence of either hypertrophic or keloid scarring across the 3 groups. Secondary outcomes included the rates of scarring overall as well as keloid and hypertrophic scars individually between the three groups. The chi-square test along with pair-wise comparison differences was used to assess for differences between groups.

Results
189 patients were recruited for this study with baseline characteristics presented in table 1 below. Control patients were older than the other groups (p = 0.013). Patients with stricturing/penetrating CD were more likely to be male. Patients with stricturing/penetrating CD (36.5%) were more likely to have either hypertrophic or keloid scars than those with non-stricturing/non-penetrating CD (11.1%) and non-IBD controls (6.3%), p = &lt;0.0001. Pairwise comparisons revealed differences individually between the stricturing/penetrating and non-stricturing/non-penetrating (p = 0.001) and healthy controls (p &lt; 0.001), but not between the latter two groups (p = 0.52). 8 patients with structuring/penetrating CD had a history of keloid scars, but none in the other 2 groups (p &lt; 0.001). Across the 3 groups, there was no difference in the rates of normal scars (p = 0.112).

Conclusion
In this pilot cross-sectional study, a higher rate of hypertrophic or keloid scarring was demonstrated in patients with stricturing or penetrating disease in comparison to healthy controls and those with non-stricturing/non-penetrating disease, suggesting potential underlying common pathophysiology. Future studies confirming this novel association may provide an avenue for further study of predictive and therapeutic targets for IBD.
P0207 Ex-vivo colonoids derived from ulcerative colitis patients retain epithelial inflammatory “memory” even after several passages, which may contribute to UC chronicity
Authors: Abbas-Egbariya H , Braun T , Granot M , Weiss B , Gal-Mor O , Amir A , VanDussen K , Haberman Ziv Y 
Published: January 2025

Abstract

Background
Intestinal epithelia is key in ulcerative colitis (UC) pathogenesis. However, epithelial models that capture the human variations for pre-clinical screening of epithelial-directed interventions are limited. We aimed to determine whether ex-vivo colonoids derived from different UC patients, maintain inflammatory signals associated with UC.

Methods
Rectal biopsies-derived epithelial colonoids were maintained through 4-9 passages (&gt;1 month in culture) using an L-WRN-conditioned medium, differentiated for 48h, and were either left untreated or treated with inflammatory cocktails for an additional 24h. ELISA quantified CXCL1 secretion, mRNAseq and qPCR assessed mRNA levels

Results
7 controls and 9 UC colonoids were generated from different subjects (median age was 16 years, 56% females). After 4-9 passages, untreated colonoids from UC patients secreted significantly higher levels of the CXCL1 chemokine compared to colonoids obtained from non-IBD controls (Fig. 1A). This phenomenon was also observed when colonoids were treated with INFγ and TNFα to mimic gut inflammation (Fig. 1B). mRNAseq further confirmed differences between UC and non-IBD colonoids. Unsupervised PCA analyses indicated the separation of 4/8 UC organoids from control organoids on PC1 (explaining 39% variance) and toward organoids treated ex-vivo with INFγ and TNFα (Fig. 1C). Differential expression (fold change &gt;1.5 and FDR &lt;0.05) identified 800 genes significantly upregulated, and 263 genes downregulated in untreated UC compared to control colonoids following passaging (Fig. 2A). Upregulated genes included DUOX2, DUOXA2, VDAC2, TJP1 (ZO1), TGM2, CXCL1, and IL8, as previously observed in mucosal biopsies from UC (PMID: 36655602) (Fig. 2B). Functional annotation of the upregulated genes highlighted pathways related to responses to wounding, bacterial signals, and cell-cell junctions (FDR&lt;1E-10) (Fig. 2C). Conversely, downregulated genes included lipoprotein lipase (LPL), a key enzyme in lipid metabolism, the sulfate/anion transporter gene SLC26A1, and the mitochondrial coenzyme A transporter SLC25A42 (Fig. 2A-B). Functional enrichment analysis of the downregulated genes revealed associations with rRNA binding (FDR=1E-12) and mitochondrial gene expression (FDR=1E-6), all of which are relevant to UC pathogenesis (Fig. 2C). The expression of these genes and pathways were further induced with inflammatory triggering (Fig. 2D).

Conclusion
UC epithelial cells maintain a heightened inflammatory response ex-vivo after several passaging. This suggests an "inflammatory" epithelial transcriptional memory that may contribute to UC chronicity, justifying the use of this model for testing interventions targeted at the epithelium.
P0276 Psoriasis is more frequently induced and displays a distinct phenotype in patients with Inflammatory Bowel Disease.
Authors: Lhermet M , Castagna J , Puyraveau M , Gallais-Serezal I , Mauny F , Meyer F , Andre M , Clairet V , Aubin F , Toussirot E , Prati C , Vuitton L 
Published: January 2025

Abstract

Background
Specific psoriasis (Pso) phenotypes seem to emerge in inflammatory bowel disease (IBD) patients. Our study explored Pso phenotypes under and outside biologic therapy in IBD, comparing them to those in chronic inflammatory rheumatism (IRD).

Methods
From a prospective university hospital cohort of patients with IBD, IRD, and Pso, we selected those with IBD and/or IRD (axial and peripheral spondyloarthritis or rheumatoid arthritis) associated with Pso, excluding psoriatic arthritis cases. Each case was reviewed to classify psoriasis as therapy-induced or not, define prevalence with phenotype description, examine treatments responsible for induced Pso, and assess risk factors for therapy-induced Pso in IBD.

Results
Among 2,412 patients in the database, 237 (9.8%) had psoriasis associated with IBD and/or IRD: 98 with IBD, 110 with IRD, and 29 with both IBD and IRD. Pso prevalence was 12.1% in IBD vs. 8.5% in IRD (p=0.0056). After analysis, 92 (93.9%) IBD and 86 (78.2%) IRD patients had been exposed to systemic therapy (p=0.0013). The mean age for IBD+Pso and IRD+Pso was 46.4 (±15.8) and 52.8 (±15.5) years, respectively (p=0.0034); 62 (63.3%) and 49 (45%) were women (p=0.0083).
Phenotypic details of Pso were available in 97/98 IBD and 90/110 IRD cases: 70 (71.4%) vs. 33 (30%) were therapy-induced Pso, respectively (p&lt;0.0001). The main systemic therapy linked to induced Pso was biologics: adalimumab in 44 (62.9%) IBD and 15 (45.5%) IRD patients (p=0.0957).
Plaque and inverse psoriasis were noted in 72 (73.5%) and 39 (39.8%) IBD vs. 53 (48.2%) and 6 (5.4%) IRD patients (p=0.0002 and p&lt;0.0001). Lesions appeared on the face in 26 (26.5%) IBD vs. 6 (5.4%) IRD (p&lt;0.0001), on the scalp in 40 (40.8%) IBD vs. 30 (27.3%) IRD (p=0.0391), and on nasal wings in 13 (13.3%) IBD patients only (p&lt;0.0001), suggesting this as a specific site. In IBD, inverse and scalp Pso were more frequent in therapy-induced cases.
Regarding Pso treatments, biologic therapy was discontinued in 13 (13.3%) IBD patients vs. 2 (1.8%) IRD patients (p=0.0014), and a swap out of biologic class was made in 32 (32.7%) IBD patients vs. 5 (4.5%) IRD patients (p&lt;0.0001).
Factors associated to therapy-induced Pso in IBD were active smoking (OR= 2.02, 95% CI [1.14–3.56], p=0.0193), inflammatory phenotype in Crohn’s disease (OR=1.94, 95% CI [1.21;3.10], p=0.0047), and female sex (OR=2.04 [1.25–3.31], p=0.0041).

Conclusion
In this large cohort, Pso prevalence in IBD was high, with therapy-induced Pso being more frequent among women and smokers. Specific phenotypes were observed (induced, inverse, scalp, nasal wings), suggesting a common pathophysiology with the underlying inflammatory disease.
P0281 Comparison of disease characteristics and disease course between paediatric and adult onset Primary Sclerosing Cholangitis and Inflammatory Bowel Disease
Authors: Khan R , Ellen Kuenzig E , Aganya V , Tang A , Jimenez C , Crowley E , Sherlock M , Zachos M , Mulder D , Brill H , Sharma R , Otley A , El-Matary W , DeBruyn J , Abdulaziz Alkhalifa M , Alhashimalsayed Z , Wine E , Carol M , Huynh H , Murthy S , Narula N , Carman N , Griffiths A , Benchimol E , Ricciuto A 
Published: January 2025

Abstract

Background
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease that frequently coexists with inflammatory bowel disease (IBD). Data comparing the paediatric- and adult-onset PSC-IBD are lacking. We compared disease characteristics and the clinical course of PSC-IBD between Canadian children and adults.

Methods
This was a multi-center retrospective cohort study including eight paediatric centers from different provinces across Canada including (Ontario, Alberta, Nova Scotia, Manitoba) and four adult centers from the province of Ontario, including patients diagnosed with PSC-IBD from 1985-2023. Patient and disease characteristics and outcome data were extracted from the clinical charts. We compared patient demographics, disease course, laboratory and imaging results, and complications including liver transplant among paediatric- and adult-onset PSC-IBD. Continuous data were reported as median (Q1-Q3) and compared with the Wilcoxon Rank Sum test, and categorical data were reported as number (%) and compared with chi-square or Fisher exact tests. We compared the time to transplant with the log-rank test.

Results
We included 521 patients (228 children, median follow-up 3.3 (Q1-Q3 1.5-5.8) years; 293 adults, median follow-up 9.8 (Q1-Q3 4.3-16.0) years (Table-1). The interval between PSC and IBD diagnosis was longer in adults. Small duct disease and PSC with autoimmune hepatitis (AIH) features were more common in children, with corresponding higher ALT and more frequently positive autoantibodies. Rates of portal hypertension at PSC diagnosis were similar in both groups. Ulcerative colitis predominated in both groups with more IBD-unclassified in children. Colitis was most severe in the right colon in a third of children and adults. Children were more often treated with ursodeoxycholic acid, vancomycin, corticosteroids and immunomodulators. Adult patients experienced a higher proportion of adverse liver events over the entire follow-up duration, but time to event analysis showed similar rates of progression to liver transplant (log-rank p=0.075; 2- and 5-year survival with native liver in paediatric vs. adult: 97% and 90% vs. 94% and 84%). (Figure-1)

Conclusion
In this large Canadian multi-center cohort of PSC-IBD, paediatric-onset disease was characterized by more frequent small duct disease and features of AIH. The interval between IBD and PSC diagnosis was far longer in adults. Although a greater proportion of adult-onset patients experienced adverse liver outcomes overall, rates of transplant at 2 and 5 years were similar between groups, suggesting that PSC progression may in fact be similar.