bluuebunny/crossref_metadata_2025_split huggingface dataset:
P118 Fecal content from IBD patients disturbs epithelial functions in two model systems
Authors: Abbas Egbariya H , Elwahidi L , Braun T , Sosnovski K E , Granot M , Krauthammer A , Loberman-Nachum N , Weiss B , Gal-Mor O , Denson L , VanDussen K , Amir A , Haberman Ziv Y 
Published: January 2024

Abstract

Background
Inflammatory Bowel Diseases (IBD) result from abnormal interactions between the immune system, epithelial barrier, and gut microbiota. However, understanding the abnormal interaction between aerobic epithelia and mainly anaerobic microbiota is complicated and is limited in part by the lack of human-relevant models.

Methods
We developed a model system that is based on whole human fecal samples and human-derived epithelia to study the interactions between the gut bacteria and the epithelia. To capture patient heterogeneity, we prioritized and pooled fecal material from 10 Crohn disease (CD), 10 ulcerative colitis (UC), and 10 healthy subjects. Prioritization of samples was based on our published gut microbial health index (PMID: 35197084), matching gender and age. Monolayered epithelial cells (Caco2 cells and patient-derived colonoids) were used for the co-culturing. Measurable outputs included cell viability, epithelial integrity, and secretion of CXCL1.

Results
Fecal samples were processed by separating the supernatant, heat-killing the bacteria, and rejoining the samples (Fig. 1A). 16S sequencing showed that bacterial composition and alpha diversity (Faith) were overall preserved after the heat-killing (Fig. 1B), as seen in the original samples. The gut microbial health index was higher among the control samples and pool, compared to the IBD samples (Fig. 1C), preserving the IBD pathogenic signals. Because previous studies indicated the enrichment of salivary bacteria in IBD feces, salivary samples were also processed for comparison. We confirmed that similar amounts of bacterial DNA (as a proxy of bacterial mass) were used for coculturing as indicated by qPCR of the 16S-V4 (Fig. 1D). Co-culturing the fecal and saliva pools with Caco-2 cells revealed a significant increase in CXCL1 proinflammatory chemokine secretion to the media in comparison to no-treatment (Fig. 2A). Moreover, the UC and CD pools significantly decreased epithelial integrity [transepithelial electrical resistance (TEER)], without affecting cellular viability (Fig. 2B-D). Finally, incubation of the fecal content with colon-derived organoids (from 2 controls and 1 UC) resulted in a substantial reduction of cell viability, which was more pronounced with fecal content derived from UC patients (Fig. 2E), and this effect was noted most with the UC fecal supernatants.

Conclusion
Using a novel co-culturing system, we demonstrated the effects of fecal contents from IBD and control subjects on CXCL1 secretion and epithelial integrity in Caco2 cells, and on colonoids viability. These models will be used to identify fecal factors and interventions relevant to IBD epithelial functions.
P124 Tissue Factor and Protease-Activated Receptor 2 associated genes are upregulated in patients with Inflammatory Bowel Disease
Authors: Qiu Y , Yao L , Taylor Meadows K , Rey D , Khalid M , Travis S 
Published: January 2024

Abstract

Background
Tissue Factor (TF) is well known for its role in coagulation, but it is also a key mediator of inflammatory cellular signaling relating to myeloid cell migration and kinase activation. TF is upregulated during inflammation and has been implicated in IBD pathology. Its role as a therapeutic target has not been well characterized, due to concerns that inhibition may induce a coagulopathy. When activated, TF cleaves protease-activated receptor 2 (PAR2) and induces multiple intracellular signaling pathways. Our aim was to investigate TF gene expression and PAR2 activated genes by colonic segment with inflamed tissue in patients with IBD compared to non-inflamed regions, and tissue from healthy controls.

Methods
RNA seq data from colon biopsy samples taken from The Mount Sinai Crohn's and Colitis Registry (MSCCR) cohort containing 1188 subjects (431 UC, 505 CD and 252 healthy controls) were downloaded from GEO (GSE193677) and preprocessed by the Endpoint Health RNA seq Analysis Pipeline. Tissues from patients with UC and CD were included in the analysis if the endoscopic score indicated moderate to severe inflammation. Differential gene expression analysis was performed using the Wilcoxon rank test. Gene set enrichment analyses (GSEA) was performed for PAR2 associated genes1.

Results
1,030 tissue samples, including 161 UC, 409 CD and 460 healthy control samples, were analyzed from 90, 174 and 252 subjects respectively. TF was found to be upregulated in inflamed tissue compared to non-inflamed tissue in patients with UC and CD, supporting a role for TF in inflamed lesions (Figure 1). Furthermore, PAR2-induced inflammatory related gene expression was observed in the inflamed tissue biopsies from patients with UC and CD compared to health control samples.Genes involved in inflammation, which include chemokines such as CXCL8 and chemokine receptors CXCR1, were consistently upregulated in all inflamed tissue regions isolated from patients with UC and CD (Table 1).

Conclusion
TF was found to be upregulated in inflamed tissue compared to non-inflamed tissue in patients with UC and CD, which may indicate TF contributing to tissue inflammation. TF represents a novel therapeutic target for IBD, but safety concerns with inhibiting coagulation have limited its clinical utility for inflammatory disease. To address this safety concern, EP004, a human IgG1 monoclonal antibody, targets the extracellular domain of human TF, inhibiting PAR2-induced inflammatory signaling while not altering coagulation activity. Clinical studies are required to elucidate its therapeutic effect.
1. Suen, J. Y. et al. 2010. Profiling Gene Expression Induced by Protease-Activated Receptor 2 (PAR2) Activation in Human Kidney Cells. PLOS ONE 5(11): e13809.
P139 A potential protective rule of Mannose Binding lectin (MBL) against SARS-COV2 infection in IBD patients
Authors: Albertini G , Pisani L F , Bolzoni A , Annunziata M L , Porta C , Pastorelli L 
Published: January 2024

Abstract

Background
Since the beginning of the COVID-19 pandemic, IBD patients have appeared to be less susceptible to a severe form of the disease, despite undergoing immunosuppressive treatments. Mannose binding lectin (MBL) is a humoral fluid-phase pattern recognition molecule (PRM) crucial for activating the lectin complement pathway. It is capable of binding to the spike protein and blocking SARS-CoV-2 infection. Low MBL expression has been linked to poor outcomes in both SARS and SARS- CoV-2 infections. In IBD patients, the role of MBL is controversial; low concentrations seem to predispose individuals to the development of IBD, while high concentrations have been observed in severe forms of Crohn's disease.

Methods
Since April 2020, 104 IBD patients have been enrolled, with 20% treated with mesalazine, 50% with Anti-TNFa, 20% with Vedolizumab, and 20% receiving no treatment. Additionally, 45 healthy controls (HC) from North Italy were included. Serum samples and colon biopsies from inflamed and non- inflamed mucosa were collected. Serum samples underwent an ELISA test to quantify circulating MBL concentration, and MBL gene expression in biopsies was analyzed using qPCR.

Results
Both Crohn's disease and Ulcerative Colitis patients exhibited significantly higher circulating MBL levels than HC (411.6 ± 45.5 ng/ml vs. 160.9 ± 35.3 ng/ml, p &lt; 0.05). Patients treated with Anti-TNFa showed significantly higher circulating MBL levels compared to those not undergoing therapy (530.1 ± 76.5 ng/ml vs. 225.4 ± 61.6 ng/ml, p &lt; 0.05) and patients receiving Vedolizumab (530.1 ± 76.5 ng/ml vs. 155.3 ± 32.1 ng/ml, p &lt; 0.05). MBL intestinal gene expression is higher in IBD patients than HC (5.55 ± 0.9 vs. 2.36 ± 0.6; p=0.591) and tended to be elevated at similar levels in inflamed and non-inflamed mucosa (5.14 ± 1.4 vs. 5.79 ± 1.1; p=0.337), suggesting a prevalent genetic determination of MBL concentration regardless of the inflammatory background.

Conclusion
MBL appears to play a key role in SARS-CoV-2 infection. We demonstrate that IBD patients have, on average, higher circulating MBL levels than HC independently of their inflammatory status. The highest MBL levels were observed in patients treated with Anti-TNFa. These findings contribute to understanding the reported low mortality and hospitalization for COVID-19 among IBD patients treated with Anti-TNFa.
P149 Bacteroides uniformis ameliorates pro-inflammatory diet-exacerbated colitis by targeting endoplasmic reticulum stress-mediated ferroptosis
Authors: Liu C , Zhuang X , Zhan S , Tian Z , Mao R , Zhang S , Chen M , Zeng Z 
Published: January 2024

Abstract

Background
Pro-inflammatory diet is positively associated with the risk and progression of inflammatory bowel diseases. Recently, ferroptosis was observed in patients with dietary pattern-associated colitis. However, the mechanisms underlying the effects of a pro-inflammatory diet and whether it mediates ferroptosis are unknown. This study aimed to clarify the mechanisms of pro-inflammatory diet in colitis.

Methods
Mice were fed a dietary inflammatory index-based pro-inflammatory diet for 12 weeks. Subsequently, colitis was chemically induced using 2.5% dextran sulfate sodium with or without a ferroptosis inhibitor (ferrostatin-1). Body weight, histological scores, immune response, and mucosal barrier function were evaluated to assess intestinal inflammation.Colon tissue transcriptomics, fecal microbiome, and serum metabolomics were applied to identify diet-microbe-host interactions. Dietary inflammatory index of 36 patients with Crohn’s disease were evaluated. Their intestinal specimens were also collected. The biological functions of Bacteroides uniformis were observed in vitro and in vivo.

Results
Pro-inflammatory diet induced low-grade intestinal inflammation and exacerbated colitis by activating glutathione peroxidase 4-associated ferroptosis in the endoplasmic reticulum stress-mediated pathway; ferrostatin-1 treatment reversed this pro-inflammatory potential. Additionally, the pro-inflammatory diet triggered colitis by modulating the gut microbiota and metabolites. Notably, supplementation with B. uniformis improved the pro-inflammatory diet-aggravated colitis by inhibiting endoplasmic reticulum stress-mediated ferroptosis. Co-culturing B. uniformis with intestinal epithelial cells revealed it is non-enterotoxigenic and non-enteroinvasive.

Conclusion
Pro-inflammatory diet drives colitis by targeting endoplasmic reticulum stress-mediated ferroptosis, possibly in a gut microbiota-dependent manner. Pro-inflammatory diet restriction and microbial-based therapies may be effective strategies for preventing and treating inflammatory bowel disease.
P156 Gut microbiota composition in Patients with Chron's Disease in Saudi Arabia
Authors: Alahdal H , Almuneef G , Alkhulaifi M M , Aldibasi O , Aljouie A , Alharbi O , Rejili M 
Published: January 2024

Abstract

Background
Crohn’s disease (CD) is a heterogeneous disease at the clinical, molecular, genetic, immunological, and microbial levels. The disease involves complex interactions among the host intestinal mucosa and gut microbiota, causing alterations in the microbial composition of the intestines, and leading to frequent clinical manifestations. Despite the challenge of diagnosing CD, lately, there has been an increase in the number of CD patients in Saudi Arabia. Large-scale metagenomics studies could enable the understanding of functional dysbiosis of the gut microbiome. Here, we aimed to compare the fecal microbiome of CD with the inactive form of the disease and with healthy subjects.

Methods
We analyzed 80 fecal samples from inactive CD and CD samples from Saudi patients using a 16S rRNA sequencing approach. Additionally, questionnaires were completed by CD patients, which covered multiple aspects of CD, including diagnosis, treatment, and impact on patient quality of life, further to standard demographic information.

Results
Dysbiosis was found significantly greater among CD patients compared to the inactive form of the disease, as shown with more reduced diversity. This research has also shown that certain types of bacteria (belonging to genera such as Filifactor, Peptoniphilus, and Sellimonas.) were characteristic of CD groups meanwhile, genera such as Defluviitalea, Papillibacter, and Petroclostridium) were characteristic of the control group. α. Diversity measures show that the CD groups have lower diversity and richness compared to the Control group. Smoking was found to be the most important factor affecting disease activity and microbiota dysbiosis. Age and gender were among the factors influencing the alteration of the microbiome.

Conclusion
In this project, we summarize the role of the gut microbiome and its manipulation in the development and management of Crohn's disease. This study will add great value to the amount of knowledge and help understand the relationship between microbiota and Crohn’s disease progress in Saudi Arabia.
P179 Decrease in Butyric Acid in fecal matter in patients with Inflammatory Bowel Disease is associated with the levels of secretory Immunoglobulin A and fecal calprotectin
Authors: Parra Izquierdo L V , de Avila J , Ramos A , Chila-Moreno L , Bello-Gualtero J M , Valdes A , Morantes S , Madroñero J , Bautista-Molano W , Delgado F , Florez-Sarmiento C , Romero-Sanchez C 
Published: January 2024

Abstract

Background
Accumulating evidence shows that the development of IBD is always accompanied by dysbiosis of the intestinal microbiota. Short-chain fatty acids (SCFAs) are produced by prebiotic intestinal bacteria, with mportant anti-inflammatory functions, delaying the clinical progression of IBD. The aim of this study is to compare SCFA levels in fecal matter in patients with IBD versus patients with Spondyloarthritis (SpA) and healthy controls.

Methods
24 patients were evaluated for the presence of gastrointestinal symptoms, demographic data and inflammatory markers: fecal calprotectin, C-reactive protein (CRP), secretory IgA (SIgA) and erythrocyte sedimentation rate (ESR). The quantification of SCFAs (acetic-AC, propionic-AP, butyric-AB and total SCFAs-ACCC-T) from fecal matter was analyzed by ultra-high pressure liquid chromatography coupled to mass spectrometry (UHPLC-Q/ TOFMS).

Results
33.3% of patients with IBD were men, with body mass index &gt;25 in 16.7%; 83.3% presented more than 2 gastrointestinal symptoms at the time of sample collection, 33.3% had high levels of fecal calprotectin, 50% had CRP levels higher than 3mg/L and high ESR in 33.3% and a mean SIgA. of 27.73±5.03 g/mL. Very decreased levels of butyric acid (BA)ug/mL and T-SCFA were observed in IBD (9.45±4.89 and 121.73±65.94, respectively), compared to CS (BA 20.84±8.83 and total SCFA.12±122.09)., SpA SG (AB 13.35±10.44 and total AGCC 150.73±128.52) and SpA without OS (AB 21.13±5.68 and AGCC-T 219.51±229.65). Significant differences were found in fecal BA levels between the study groups (p=0.027). Interestingly, this metabolite in the CS group and the SpA group without OS did not show differences between them, but compared to the IBD group p=0.015 and 0.009 respectively, with a decrease in IBD. And interestingly, no differences were evident between fecal SCFA levels between the IBD group and the SpA group with OS even without a diagnosis of IBD. A principal component analysis was performed for the IBD group where two components were identified that group where COMP.1 was defined by a high correlation between the levels of each of the ACCC (AB CCF= 0.994, AA CCF= 0.935, AP= 0.610 and AGCC-TCCF= 0.910) that had an inverse relationship with COMP.2 which was made up of SIgA (CCF=0.988) and fecal calprotectin (CCF= 0.988).

Conclusion
SCFAs play a key role in maintaining immune homeostasis both locally and systemically. BA levels were significantly lower in patients with IBD compared to CS and those with SpA. This evidence clearly supports the hypothesis that relates the lack of BA with an exacerbated inflammatory response that could give rise to a dysfunctional intestinal epithelial barrier by regulating the production of mucosal antibodies such as SIgA.
P191 Inflammatory bowel disease type unclassified in paediatric-onset IBD: A nationwide cohort study in Scotland with up to 20 years follow-up shows reclassification in the majority and mild course in those remaining as IBDU
Authors: Wands D , Gianolio L , Cameron F , Hansen R , Russell R , Wilson D 
Published: January 2024

Abstract

Background
Inflammatory bowel disease type unclassified (IBDU) is the least common subtype of IBD accounting for around 10% of incident cases in children. There are a lack of long-term longitudinal data to fully elucidate both disease course and reclassification rate in IBDU. Our aim is to clarify disease course and reclassification rate by presenting nationwide data of an IBDU cohort with long-term (9-20 years) follow-up.

Methods
In a nationwide study, we analysed our prospectively identified 11 year cohort of IBDU patients diagnosed 01/01/03-31/12/13 via all Scottish paediatric IBD centres (Aberdeen, Edinburgh, Glasgow) and followed-up into adult services until 01/01/23. All had a diagnosis of IBDU based on the Porto diagnostic criteria and Paris PIBD phenotypic classification using a combination of clinical, endoscopic, histological and radiological findings. Follow-up data were obtained retrospectively from electronic medical records (demographics, diagnostic plus all repeat endoscopic and radiological assessments, longitudinal disease severity based on defined global clinician assessment, medical treatment and surgical outcomes) at fixed time points (5 and 10 years post-diagnosis) and at the last follow-up.

Results
A total of 116 patients were initially identified as IBDU, with 14 patients excluded as they emigrated out of the area before the first time point. 102 patients were included in the analysis (57/102 (56%) male, median (IQR) age at diagnosis 11.5 (9.1-13.2) years) with a median (IQR) length of follow-up of 10.5 (8.6-14.0) years. A change of diagnosis was made in 61/102 (60%) patients with 30/102 (29%) reclassified as Crohn’s disease (CD) and 31/102 (30%) as ulcerative colitis (UC) after a median (IQR) disease duration of 5.0 (2.0-8.2) and 4.7 (1.8 – 7.7) years respectively. Patients who remained as IBDU had a milder disease course compared to those reclassified as CD/UC with higher 1-5 year remission rates (30/39 (77%) in IBDU vs 16/57 (28%) in CD/UC-reclassified, p&lt;0.05), lower rates of moderate-to-severe disease (3/39 (8%) in IBDU vs 31/57 (54%) in CD/UC-reclassified, p&lt;0.05), less need for biologics across all time points (all p&lt;0.05) and a higher proportion managed on aminosalicylates or no medication (all p&lt;0.05). Higher rates of surgical resections were observed by last documented FU in CD/UC-reclassified patients (IBDU 1/41 (2%) vs CD/UC-reclassified 11/61 (18%), p=0.02).

Conclusion
In our nationwide paediatric IBDU cohort the majority (60%) of patients were reclassified as either UC or CD over the longest published median follow-up (10.5 years); those who remained with an IBDU classification had a milder disease course and decreased need of biologic escalation.
P214 Effects of rectal stump proctitis on short-term postoperative complications after proctectomy and ileal pouch-anal anastomosis for Ulcerative Colitis
Authors: Calini G , Catalioto C , Dajti G , Cardelli S , Rizzello F , Gionchetti P , Poggioli G , Rottoli M 
Published: January 2024

Abstract

Background
Inflammation of the rectal stump (proctitis) after subtotal colectomy with ileostomy for ulcerative colitis (UC) is common. Proctitis may affect the postoperative outcomes of ileal pouch-anal anastomosis (IPAA). This study aims to explore associations between rectal stump proctitis and short-term postoperative complications (POCs) after proctectomy and IPAA for UC.

Methods
This retrospective single-centre study included patients who underwent proctectomy, IPAA and protective ileostomy for UC from 2000-2023. Data were retrieved from our prospectively-maintained database. Exclusion criteria were dysplasia or cancer (103 pts), missing pathology results (50 pts), undetermined colitis or Crohn’s Disease features at proctectomy (18 pts). All patients underwent three-staged IPAA and were divided into four groups according to the rectal stump proctitis status at pathology: remission, mild, moderate, and severe proctitis. A stepwise binary logistic regression analysis was performed for each short-term outcome. Models included variables with a different distribution according to the outcome (p-value ≤0.1).

Results
We included 785 patients who underwent proctectomy and IPAA. At pathology, remission was achieved by 162 (20.6%) patients, while proctitis of the rectal stump was mild in 211 (26.9%), moderate in 246 (31.3%), and severe in 166 (21.1%) patients, respectively. Table 1 details population characteristics and outcomes according to the proctitis status. Patients with moderate and severe proctitis received more preoperative biologics and ongoing systemic steroids at surgery. While they underwent previous abdominal surgery less frequently, the laparoscopy rate was lower with a longer postoperative length of stay. At multivariate (Table 2), Medical POCs were independently associated with ongoing antibiotics (OR 2.29 [1.01-5.20] p=0.047) and ASA score≥3 (OR 1.93 [1.11-3.35] p=0.019). Surgical POCs were independently associated with ongoing systemic steroids (OR 2.09 [1.19-3.68] p=0.011, while ongoing antibiotics (OR 0.2 [0.04-0.86] p=0.031) and laparoscopy (OR 0.53 [0.28-1.00] p=0.049) were protective. Intra-abdominal septic complications (IASCs) and abdominal/pelvic abscesses were independently associated with the proctitis status (OR 1.1 [1.06-2] p=0.018 and OR 1.56 [1.08-2.25] p=0.017, respectively).

Conclusion
Rectal stump proctitis was independently associated with postoperative abdominal and pelvic abscesses and IASCs after proctectomy and IPAA for UC. The association between proctitis and IPAA’s long-term outcomes and pouch failure need to be further explored.