bluuebunny/crossref_metadata_2025_split huggingface dataset:
P101 Circulating MicroRNA-16 in Inflammatory Bowel Disease Patients - Potential Biomarker to Assess Inflammation
Authors: Atanassova A , Georgieva A C 
Published: January 2023

Abstract

Background
miR-16 is important for the inflammatory processes and the signal pathways that participate in the immune system regulation. As there is an immune mucosal inflammation in IBD, miR-16 could also serve as a potential biomarker to assess inflammation.

Methods
The study aims to assess the expression of serum miR-16 in IBD patients and to correlate its expression with clinical parameters such as disease extent, activity and severity.
35 patients with UC and 35 patients with CD were included in the study. Serum miR-16 expression was assessed with reverse transcriptase quantitative real time PCR (RT-qPCR), and was then correlated with the miR-16 levels in a group of 30 healthy subjects.

Results
miR-16 expression is increased in patients with CD, localized in the small intestine (3.54±2.33) and in pancolitis Е3 of UC (2.01±1.54). There is a significant difference in miR-16 expression in inflammatory (B1), stenotic (B2) and penetrating (B3) form of CD (р=0.010) with higher expression levels in the more severe B2 and B3 forms. There is no significant difference in miR-16 expression according to the forms of evolution in patients with UC. In patients with CD, there is a moderate direct correlation between the expression of miR-16 and the Crohn’s disease activity index CDAI (r=0.424; p=0.015). miR-16 expression levels increase progressively in correlation with the activity of CD. Patients with moderate activity of their CD have significantly higher miR-16 expression (4.27±3.00) as compared to patients with mild activity (2.38±1.06) or in remission (2.41±1.23) of the disease (р=0.048). The increased expression levels of miR-16 are a risk factor for CDAI &gt; 150 levels (OR=4.80 (0.506-45.495); p=0.015). In patients with UC, there is no correlation between the miR-16 expression levels and the severity (S) index, measured as per the Montreal classification or the endoscopic activity, measured as per the Partial Mayo score. In patients with severe disease, measured by both S index (1.38±0.89) and Partial Mayo score (1.80±1.12), there is a decrease in miR-16, close to normal controls. MiR-16 expression levels do not correlate with any treatment that was given in patients with either CD or UC.

Conclusion
The increased miR-16 serum expression corelates with the localization of CD in the small intestine and the stenotic and penetrating form of the disease. Increased miR-16 levels are also found in extensive UC. In patients with CD there is a positive correlation between the expression of miR-16 and the activity of the disease as measured by the CDAI.
P103 Colitis-associated faecal miRNAs are mediators of host-microbiota interactions and key regulators of intestinal permeability and inflammation
Authors: Casado-Bedmar M , Roy M , Hugot J P , Le Gall M , Chassaing B , Viennois E 
Published: January 2023

Abstract

Background
Like in other chronic pathologies, evidence has shown disruption of host immune-microbial interactions and intestinal dysbiosis in the pathogenesis of Inflammatory Bowel Diseases (IBD), also characterized by chronic inflammation and increased intestinal permeability. Faecal microRNAs (miRNAs) have recently emerged as potential inter-kingdom mediators between the host and its microbiota, but the influence of its interaction on chronic intestinal disorders remains unclear. Here, we aimed to study the impact of colitis-associated miRNAs on intestinal inflammation, permeability and microbiota.

Methods
A panel of faecal miRNAs was profiled in IL10-/- mice, known as a model of spontaneous colitis. Faecal miRNAs and microbiota composition were compared between IBD and healthy controls. Identified colitis-associated miRNAs were then administered with/out antibiotics ad libitum to C57BL6 mice. Parameters of inflammation, intestinal epithelial barrier function, as well as microbiota composition, were analysed. Ex vivo and in silico studies were performed to comprehend the direct effects of the miRNAs on the gut microbiota and the host. Lastly, endogenous miRNAs were inhibited in IL10-/- mice administering miRNA-inhibitors through oral gavage.

Results
We identified in mice two colitis-associated miRNAs that were also increased in faecal samples of IBD compared to healthy controls (Graphic 1). Notably, the exogenous administration of these two miRNAs was sufficient to drive intestinal inflammation (Graphic 2) and alter the intestinal barrier function in mice. Such effects were directly impacted by the microbiota presence and composition. In humans, the measurement of faecal lipopolysaccharides and the 16S microbiota sequencing further showed strong associations between miRNAs and bacterial species, such as Faecalibacterium prausnitzii and Parabacteroides distasonis. In mice, the treatment with colitis-associated miRNAs altered the microbiota composition with a significant increase of Cyanobacteria and Verrucomicrobiota. Importantly, the inhibition of endogenous miRNAs through anti-miRNA administration prevented the emergence of severe colitis in IL10-/- mice (Graphic 3).

Conclusion
Overall, our findings identify an inflammatory role played by faecal miRNAs in the gastrointestinal environment, which pathogenic potential appears closely related to dysbiosis. Hence, our data suggest that miRNAs or miRNA inhibitors might be considered therapeutic agents to beneficially alter the microbiota and intestinal inflammation in IBD and other dysbiosis-associated conditions.
P104 Exploring the transcriptomic miRNA signatures of Egyptian Inflammatory Bowel Disease patients
Authors: Khaled M , Hamdy K , Abou-Aisha K , Mansour M 
Published: January 2023

Abstract

Background
Inflammatory Bowel Disease (IBD) is a chronic autoimmune gastrointestinal disease, sub-classified into Crohn’s disease (CD) and ulcerative colitis (UC). The two subclasses are characterized by a relapsing-remitting course with an increasingly high incidence and prevalence worldwide. Molecular mechanisms guarding the pathogenesis of these diseases remain, to the present day, ambiguous to researchers. MicroRNAs are 22 nucleotides long small noncoding RNAs that have been recently described as essential participants in immune cell development and the immune response to pathogens. During the past decade, genetic and epigenetic studies in IBD have been labeled as essential; since endoscopic assessment and biopsies provide limited data concerning early disease activity, factors for relapse, and response to treatment. To the best of our knowledge, IBD research has never addressed miRNA profiles in Egyptian CD and UC patients as compared to unaffected controls.

Methods
Therefore, this study aims to profile miRNAs in Egyptian patients suffering from UC and CD, using RNA-seq of total RNA extracted from colonoscopically obtained tissue pinch biopsies.

Results
The sequencing results showed that 30 miRNAs were uniquely expressed in tissue biopsies obtained from the CD patients, as compared to only 14 uniquely expressed in UC patients. Further web-based functional enrichment analysis showed that the miRNAs- in both disease groups- are mainly involved in six interlinked molecular pathways; including the JAK/STAT, WNT, PI3K/AKT, FOXO, MAPK, and NF-κB signaling pathways. One of the most interesting findings of the current study is the fact that the downregulation of the miR-204-5p in UC patients (log2 FC= 5.05)-as compared to CD patients- may be caused by the sponging effect of the MALAT1 long non-coding RNA (lncRNA); affecting related signaling pathways such as the Wnt/β-catenin signaling. This suggests an essential interplay between miRNAs and lncRNAs in shaping the molecular pathogenesis of UC vs. CD.

Conclusion
The results of the current study revealed explicit-previously undetermined- differences in the miRNA profiles of patients suffering from UC and CD. Such results are expected to impact the understanding of the difference in the molecular pathogenesis of IBD subtypes affecting patients’ response to treatment.
P105 Epithelial microRNA signatures as potential biomarkers in Crohn’s disease related to clinical and endoscopic activity
Authors: Moon J M , Kim K U , Shin S Y , Joo H J , Min H , Choi C H 
Published: January 2023

Abstract

Background
Emerging evidence suggests that epithelial cell-derived microRNAs (miRNA) are involved in the pathogenesis of inflammatory bowel disease; however, as of now specific implications in the real clinical practice, especially in relation to biologics use are yet far-fetched. Therefore, we tried to investigate specific epithelial cell derived miRNA signatures related to clinical and endoscopic activity in Crohn’s disease (CD) patients.

Methods
We prospectively collected terminal ileum tissue samples via ileocolonoscopy from healthy control (n=12), CD patients in remission (n=32) and active CD patients (n=36). CD remission was defined as clinical remission of Crohn's disease activity index (CDAI) &lt;150 and achievement of endoscopic mucosal healing. Both inflamed and non-inflamed lesions were sampled in the active CD patients. Clinical information, medication use, chemistry data were measured within a week from the tissue sample date. miRNA levels were measured by small-RNA sequencing and qRT-PCR. Diagnostic ability of specific miRNA found were evaluated by receiver operating characteristic (ROC) curve analysis.

Results
The study cohort was followed up until January 2022. Mean follow-up period of the prospective CD cohort was 13.06 months. In comparing to the healthy control, CD patients in remission and active state revealed specific miRNA profiles in small-RNA sequencing. Through RT-PCR validation, we found that the expression levels of miR-141-3p, miR-338-3p, miR-378a-3p, and miR-200b-3p were significantly decreased, while miR-125b-5p, miR-29b-3p and miR-155-5p were significantly increased in the inflamed tissue of active CD patients. Moreover, in case of active CD patients, expressions of miR-150-5p, miR-200b-3p and miR-155-5p were significantly down-regulated in those using biologics, compared with biologics naïve patients. This may suggest that these miRNAs were not only as biomarkers of CD patients, but also as biomarkers related to inflammation and biologics response. ROC curve analysis suggested miRNAs with different diagnostic activity related to both clinical disease activity and endoscopic inflammation status. MiR-338-3p, miR-141-3p and miR-378a-3p demonstrated area under curve of greater than 0.9 in predicting active CD patients.

Conclusion
We report specific miRNA biomarkers identifying CD and its disease inflammation activity with relation to biologics use, suggesting potential treatment target in CD pathogenesis. These miRNA signatures could also be of potential clinical use in positioning biologics, which we intend to explore in the near future.
P110 activation protein is strongly expressed in intestinal fibrosis in inflammatory bowel disease patients
Authors: Lartey D , van Roest M , Verhoeff J , Grootjans J , Buskens C , van der Bilt J , Wildenberg M , D'Haens G , Löwenberg M 
Published: January 2023

Abstract

Background
Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD) with limited diagnostic modalities to detect and determine the degree of fibrosis. Fibroblast activation protein alpha (FAP) is a protein with both dipeptidyl peptidase and endopeptidase properties which is virtually absent in healthy tissues and has increased expression in chronic inflammatory and fibrotic diseases. In this study, we investigated the presence of FAP in intestinal fibrosis caused by Crohn’s disease (CD) and ulcerative colitis (UC).

Methods
For this study, transmural surgical resection specimens were retrieved from the Tytgat institute IBD biobank located at Amsterdam University Medical Center. IBD patients undergoing an ileocecal resection for stricturing CD or a subtotal colectomy for therapy-refractory disease, and patients undergoing a right-sided hemicolectomy or ileocecal resection for dysplasia or non-metastasized colorectal cancer (CRC), were included. All patients had an established diagnosis of (CD, UC, dysplasia or CRC) by previous endoscopy and biopsies and had provided informed consent prior to surgery.
FAP protein and gene expression levels were determined using immunohistochemistry staining and quantitative polymerase chain reaction (qPCR). Mass cytometry was used to identify FAP–expressing cells.

Results
In total, 59 ileal and 35 colonic samples were stained and quantified to asses FAP expression (figure 1). A 1.7-fold and 1.9-fold increase of FAP protein expression was seen in inflamed (mean 22.3, p=0.0069); and stenotic (mean 25.5 p=0.0002) CD ileum compared to healthy non-IBD tissue (mean 13.1). Inflamed UC colon (mean 26.8, p = 0.0406) showed a 1.4-fold increase compared to healthy colon (mean 19.2).
For the gene expression, 66 ileal and 42 colonic samples were processed and used for qPCR analysis. A 5-fold and 6.4-fold increase of FAP was found in inflamed (mean 0.011, p=0.0475) and stenotic (mean 0.014, p=0.0042) CD ileum, and a 1.7-fold increase was seen in inflamed UC colon (mean 0.278, p=0.0195) compared to controls (means: ileum 0.002; colon 0.165).

Conclusion
This is the first study reporting the potential of FAP as a fibrotic biomarker not only in stricturing CD, but also in therapy-refractory UC. Significantly increased FAP protein and gene expression is found in inflamed and stenotic ileum in CD and inflamed colon in UC. Additionally, CD90+GP38+ cells have been identified as the most present FAP expressing cells.
P113 Protein fingerprint biomarkers of collagen remodeling can evaluate fibrogenesis in an in vitro colonic scar-in-a-jar model
Authors: Pehrsson M , Sorokina Alexdottir M , Asser Karsdal M , Høg Mortensen J 
Published: January 2023

Abstract

Background
Intestinal fibrosis affects most inflammatory bowel disease (IBD) patients, resulting in severe clinical complications and reduced treatment response. With no treatments approved for intestinal fibrosis, there is a need for preclinical models to investigate the pathobiology and novel treatments. Myofibroblasts are the main drivers of intestinal fibrosis and the excessive accumulation of extracellular matrix in IBD patients. We investigated a prolonged scar-in-a-jar model of colonic fibrogenesis to validate protein fingerprint (PF) biomarkers of collagen formation for clinical use and the in vitro model as a screening tool.

Methods
Human colonic fibroblasts (CCD-18co) purchased from ATCC were grown in EMEM supplemented with 10% FBS and 1% P/S in culture flasks with 200 µg/cm3 gelatin to reduce cell activation. At 80% confluency, the cells were seeded at 30,000 cells/well in a 48-well plate noted as day -2. The cells were either unstimulated or stimulated with a 2-fold dilution of TGF-β starting at 800 pM to 50 pM starting at day 0 and then every fourth day, terminating at day 12. At termination, the wells were decellularized and the collagen matrix was stained with Sirius Red for visual confirmation of collagen formation. Imaging was done using light microscopy at X20 magnification using similar settings for all images. Fibrogenesis was quantitatively determined by measuring the biomarkers PRO-C1, PRO-C3, and PRO-C6 in the supernatants. The biomarkers reflect type I, type III, and type VI collagen formation, respectively. We applied Šídák’s multiple comparisons test for differences in the collagen formation biomarker levels by comparing stimulated with unstimulated cells.

Results
Stimulation with TGF-β significantly increased type I and type III collagen formation at days 4, 8, and 12 compared to unstimulated cells, with the stimulation inducing a 297.4% increase of type III collagen at day 12 (table 1 + fig.1). Irrespective of the TGF-β concentration, a 426.8% spike in the fibrotic hormone endotrophin (PRO-C6) was observed on day 4, which declined to unstimulated levels at days 8 and 12 (table 1 + fig.1). All concentrations of TGF-β induced a significant release of the collagen formation biomarkers to the supernatant (fig. 1). Collagen deposition was confirmed by Sirius Red (fig. 2). No significant increase was observed in the unstimulated cells determined by biomarker measurements and Sirius Red (fig. 1 + 2).

Conclusion
PF biomarkers can be applied in vitro to objectively quantify fibrogenesis, demonstrating a significant increase following TGF-β stimulation of colonic fibroblasts. The model may be combined with the biomarkers to evaluate drug targets of intestinal fibrosis.
P124 Risk of surgery in inflammatory bowel disease: A systematic review and meta-analysis of sex-based differences
Authors: Rasmussen N F , Gregersen L H K , Hikmat Z , Moos C M , Green A , Andersen V , Madsen G I , Jess T , Kjeldsen L J 
Published: January 2023

Abstract

Background
Inflammatory bowel diseases (IBDs) are chronic diseases that require routine hospital visits and long-term medical treatment for control of disease activity. Factors such as gender may impact the use and need for healthcare. This systematic review aimed to summarize what is known about sex differences in the risk of bowel surgery in patients with IBD.

Methods
Embase, Medline, CINAHL, and Web of Science abstracts (January 2012 to January 2022) were searched systematically for observational studies examining associations between sex and risk of bowel surgery. Screening and data extraction were performed independently by two reviewers using Covidence. Study data were analysed and reported in accordance with the PRISMA guidelines. Quality assessment of included studies was conducted using the Newcastle-Ottawa Scale for cohort studies. Pooled hazard ratios (HRs) were calculated using random effects model meta-analysis for the risk of surgery. In addition, meta-analysis was undertaken to assess the risk of surgery by IBD subtype. The between-study heterogeneity was assessed by calculating the tau-squared and the I-squared statistics.

Results
Of 9,902 screened articles, 36 studies were included in the review. Most studies were retrospective by design (74.6%). In total, 21 of 36 studies found statistically significant sex-based differences in the risk of bowel surgery for IBD patients. A pooled estimate of HRs for the 13 studies eligible for meta-analysis showed a statistically significant increased risk of bowel surgery among male patients (HR: 1.43 [95% confidence interval (CI): 1.09;1.86]) compared to female patients. The between-study heterogeneity was high (I2=88.60 [60.60;96.33] and tau2=0.17 [0.03;0.58]) indicating that the pooled estimate should be interpreted with caution. These findings were consistent with the subgroup analysis for ulcerative colitis (HR: 1.78 [1.16;2.72]), but no statistically significant sex difference in the risk of surgery in Crohn’s disease patients was found (HR: 1.26 [0.82;1.93]).

Conclusion
Sex differences exist in the risk of bowel surgery in IBD patients, and further research is needed to address the underlying causes and consequences of these disparities. It is unclear whether differences are due to underlying biologic mechanisms or are associated with healthcare system related factors such as differential access to care. Surgical procedures or the lack or delay thereof, will have consequences for the further disease trajectory.
P128 The role of small bowel capsule endoscopy as a diagnostic tool in isolated complex perianal disease
Authors: Avni Biron I , Ollech J E , Toth E , Nemet A , Wurm Johansson G , Schweinstein H , Kopylov U , Margalit Yehuda R , Dotan I , Yanai H 
Published: January 2023

Abstract

Background
Isolated complicated perianal disease (cPD) might be the sole representation of Crohn’s disease (CD). We aimed to evaluate the impact of small bowel capsule endoscopy (SBCE) as a diagnostic tool for CD in this population.

Methods
A multicenter, retrospective cohort study from three tertiary centers. Patients with cPD who had a negative workup for CD (Ileocolonoscopy and cross-sectional imaging) and underwent evaluation with SBCE were included. Demographics, biomarkers, and the Lewis inflammatory score (LS) were recorded and analyzed. A LS≥135 was considered a positive SBCE.

Results
Ninety-one patients were included: 65 males (71.4%), mean age 40 (14) years, median duration of cPD 25.13 months (12.53-66.1). SBCE was positive in 24 patients (26.37%). Median LS was 675 (222-1518). Fecal calprotectin (FC) positively correlated with LS (r=0.81; p&lt;0.0001): patients with a positive vs. negative SBCE had a significantly higher mean FC level (255 [389] vs 97[180], p=0.02), Figure 1. Correspondingly, a FC level ≥ 300 mg/kg had a specificity of 90% for a positive SBCE, while a cutoff of FC level &lt;100 mg/kg or &lt;50 mg/kg had a sensitivity of only 40% or 50% to rule out small bowel CD, respectively.

Conclusion
SBCE was positive in over a quarter of patients with cPD and a negative workup for CD. FC levels correlated with the degree of inflammation defined by the LS. However, the sensitivity of low FC to rule out CD was low. These results suggest that SBCE is an essential diagnostic tool for patients with cPD even after negative workup.
P136 Multidimensional assessment of visceral hypervigilance in patients with IBD
Authors: Atanasova K , knoedler L L , Schmitteckert S , Ebert M , Reindl W , Thomann A 
Published: January 2023

Abstract

Background
Persons with inflammatory bowel diseases (IBD) can suffer from irritable bowel syndrome (IBS-like) symptoms in the absence of inflammation. Also, the prevalence of anxiety symptoms and disorders is increased in IBD. Both IBS-like and anxiety symptoms impair quality of life and are challenging to treat as well as poorly understood in IBD. Visceral hypervigilance (VH) as a specific form of anxiety and a common feature of disorders of gut-brain interaction may be a relevant symptom in IBD and could relate to IBS-like symptoms. This study aimed at investigating clinical, psychological and biological factors associated with VH in persons with IBD.

Methods
We used the visceral sensitivity index (VSI) to investigate VH in 308 patients with different states of IBD disease activity (as determined by Harvey Bradshaw Index or partial Mayo Score). We further assessed demographic (age, sex), clinical (disease duration, CRP levels) and psychological (anxiety and depression, HADS) characteristics. Genetic and metabolic parameters related to serotonin metabolism were analyzed in subsamples with active disease (single nucleotide polymorphisms in genes related to serotonin signaling (n=83) and serum tryptophan metabolites (n=70)). We used multiple regression analyses to examine which factors could predict patients’ VH levels and to explore genetic and metabolic predictors of VH.

Results
The strongest predictors for VH were anxiety, depression and disease activity (all p &lt; .001, Fig.1, left). Explorative analyses revealed polymorphisms in the HTR3A (p = .028) and SERT gene (p = .030) to predict VH (Fig.1, middle). While clinical disease activity was related to VH, there was no association between VH and inflammatory biomarkers or tryptophan metabolites (Fig.1, left and right).

Conclusion
VH as a specific type of anxiety strongly relates to psychopathology in persons with IBD. Anxiety was found to be the strongest predictor of VH, contributing to a greater extent to VH than disease activity. Possible genetic predispositions of VH should be investigated in larger studies. Screening patients for VH could help to detect disturbances in gut-brain-interactions and improve individualized treatment.