bluuebunny/crossref_metadata_2025_split huggingface dataset:
P043 3-oxo-C12:2, a Quorum Sensing molecule from the gut, exerts anti-inflammatory effects through a bitter taste receptor
Authors: Coquant G , Aguanno D , Brot L , Belloir C , Briand L , Grill J P , De Sordi L , Thenet S , Seksik P 
Published: January 2022

Abstract

Background
Acyl-Homoserine Lactones (AHLs) are Quorum Sensing molecules involved in the communication network of bacteria and can also have an impact on the host’s cells. We recently showed, in the human gut ecosystem, the presence of AHLs. Among them, we identified one that has never been described: 3-oxo-C12:2. This molecule was decreased in Inflammatory Bowel Disease (IBD) patients, and its presence was correlated to normobiosis. Interestingly, 3-oxo-C12:2 is structurally close to an AHL well described and synthesized by P. aeruginosa, 3-oxo-C12. We intent to describe 3-oxo-C12:2 effects on gut inflammation and to identified which signalling pathways are involved. Given its analogous structure to 3-oxo-C12, we hypothesized that 3-oxo-C12:2 can interact with the same cellular partners, in particular a bitter taste receptor (BTR), called T2R138, which is a GPCR expressed by immune and epithelial gut cells.

Methods
To test our hypothesis, we used murine macrophages cell line RAW264.7, stimulated by interferon-γ (IFN-γ, 20U/mL) and lipopolysaccharide (LPS, 10ng/mL). Inflammatory response was monitored by measuring cytokine secretion via ELISA We performed a transcriptome analysis to identify inflammatory pathways involved in the effects and analyse pathways by capillary Western blot. Probenecid, a known allosteric inhibitor for T2R138, was used to study T2R138 role in AHL signalling. BTR screening assay was performed to extend search for 3-oxo-C12:2 receptors.

Results
After LPS/IFN-γ activation, we observed a decrease of secreted TNFα when cells were exposed to 3-oxo-C12:2, in a dose dependent manner: 15μM (-30%, p&lt;0.05), 25μM (-50%, p&lt;0.001) et 50μM (-65%, p&lt;0.0001) while no change were observed in steady state. This reflects an anti-inflammatory effect, in absence of cytotoxicity. By transcriptomic analysis, we identified the JAK-STAT pathway as differentially down-regulated. Exposing cells to 3-oxo-C12:2 prevented JAK1 and STAT1 protein phosphorylation. In addition, the observed anti-inflammatory effects were lost in presence of Probenecid, a T2R138 inhibitor. In a BTR screening assay, we confirmed that 3-oxo-C12:2 activates T2R38, but also five other BTR (T2R13, T2R8, T2R14, T2R1, T2R10).

Conclusion
3-oxo-C12:2 exerts a dose dependent anti-inflammatory effect on murine immune cells by preventing the activation of the JAK-STAT pathway. This response is partly mediated by the bitter taste receptor T2R138. This receptor is a potential target of our AHL of interest. Studying the signalling between the receptor and the anti-inflammatory response would allow us to better understand the inter-kingdom dialogue between microbiota involving AHL in IBD.
P090 Unraveling the rewiring of cytokine signalling in Inflammatory Bowel Disease using a novel network biology approach
Authors: Olbei M , Thomas J , Hautefort I , Treveil A , Bohar B , Madgwick M , Gul L , Csabai L , Modos D , Korcsmaros T 
Published: January 2022

Abstract

Background
Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of chronic immune-mediated disorders such as inflammatory bowel disease (IBD). By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available resources and studies modelling cytokine-cytokine interactions that would be important for better understanding the dysregulation of cytokine signalling in IBD, and revealing potential new therapeutic targets for patients.

Methods
Based on the workflow of a cytokine signalling resource, CytokineLink, we developed previously, in this effort we built novel interaction networks using single-cell expression data from patients with ulcerative colitis (UC) and Crohn’s disease (CD). We defined two meta-networks for each disease: a cell–cell communication network connected by cytokines; and a cytokine–cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other.

Results
The rewiring of cell–cell and cytokine–cytokine interaction networks between healthy, non-inflamed and inflamed intestinal tissues in IBD was measured using the generated meta-networks. Cytokine-cytokine interaction networks revealed that in active UC, the Th1 cytokine IFNg and the chemokines CCL28 and CCL14 were central to cytokine-mediated communication networks. In CD, IL12B and IL13 formed the central cytokines in inflamed ileal tissues. Cell–cell interaction networks identified likely main cell types mediating the signalling of these key cytokines in non-inflamed and inflamed intestinal tissues: mast cells being the main source of IL13 in both IBD patients and healthy individuals.

Conclusion
We generated interaction networks aimed at capturing the most prevalent cell–cell and cytokine–cytokine interactions using disease specific single-cell expression data. Using the generated interaction networks we identified the condition-specific rewiring of cytokine mediated signalling in IBD, and key cytokines that could be targeted for ameliorating inflammatory responses. The data can be used by the community as a platform for hypothesis-generation. Potential use cases are deconvoluting the complexities of cytokine signalling in IBD to reveal potential cytokine drug targets, or predicting the downstream effects of drugs on cytokine responses.
P114 SARS-CoV-2 infection in IBD: pandemic waves and predictors of severe or persistent COVID-19
Authors: Taxonera Samso C , Olivares D , Blanco I , Velasco E , Molina S , López G , López-García O N , Alba C , Rey E 
Published: January 2022

Abstract

Background
This study aimed to compare the risk of COVID-19 in patients with IBD versus the general population, and to evaluate predictors of infection acquisition, progression to severe forms, and risk of developing persistent COVID-19. We also assess the differences between cases across the different COVID-19 pandemic waves in our target population.

Methods
This single-centre prospective, cohort study included consecutive IBD patients diagnosed of COVID-19 either by a positive polymerase chain reaction test and/or antigen test in nasopharyngeal swabs, or by anti-SARS-CoV-2 antibodies, and that they had a follow-up of at least 4 months. Using logistic regression, we evaluated cases versus IBD controls included in the IBD Unit database for predictors of COVID-19 acquisition. COVID-19 cases were distributed according to pandemic waves. Cox regression analysis was used for predictors of severe and persistent COVID-19.

Results
By May 31, 2021, 160 out of 1911 IBD patients (8.3%) were diagnosed with COVID-19. IBD patients had a similar adjusted incidence of COVID-19 (OR 0.94; 95% CI 0.86–1.02; P=0.42), and a similar associated mortality ratio (OR 0.83; 95% CI 0.6–1.06; P=0.48), compared to the general population. In multivariable analysis, treatment with biologics was associated with a higher risk (OR 2.22, P&lt;0.001), and treatment with salicylates with a lower risk (OR 0.71, P=0.048) of contracting COVID-19.(Table 1) 62 COVID-19 cases were diagnosed during the first wave of pandemic (until the end of June 2020), and 54 and 44 cases during the second and third waves (until the end of December 2020 and May 2021, respectively).(Figure 1) In multivariate analysis, first wave cases were associated with a higher risk of progression to severe forms of infection (OR 4.76, 95% CI 1.83–12.37, P=0.001), and development of persistent COVID-19 (OR 2.4, 95% CI 1.16–4.95, P=0.018). 29 patients (18.1%) required hospitalisation and were classified as severe COVID-19, which was associated in multivariable analysis with age&gt;48 (HR 3.68, P=0.007), cases diagnosed in the first wave (HR 6.04, P&lt;0.001), and comorbidities (evaluated with Duke Severity of Illness Checklist [DUSOI], P&lt;0.001).(Table 2) During a median follow-up of 8.4 months, 68 patients (42.5%) were diagnosed with persistent COVID-19. Multivariable analysis identified UC (P=0.053), comorbidities (P=0.090), and being diagnosed during the first wave (P=0.011) as risk factors for persistent COVID-19.(Table 3)

Conclusion
IBD patients have a similar risk of COVID-19 and associated mortality as the general population. Cases diagnosed during the first wave of the pandemic had severe and persistent forms of COVID-19 more frequently. Age and comorbidity were the main risk factors for severe forms of the disease.
P130 Comparison of the clinical course of Ulcerative Colitis according to the presence or absence of clinical symptoms at the time of diagnosis
Authors: Madarame A , Fukuzawa M , Uchida K , Nemoto D , Shinohara H , Yamanishi F , Matsumoto S , Suzuki Y , Muramatsu T , Kagawa Y , Matsumoto T , Morise T , Yamaguchi H , Sugimoto A , Kono S , Yamauchi Y , Naito S , Kawai T , Itoi T 
Published: January 2022

Abstract

Background
Asymptomatic ulcerative colitis (UC) is increasingly detected by improved screening tests such as the fecal immunochemical test. However, there have been few reports on the difference in the clinical course of UC according to the presence or absence of symptoms at diagnosis. The purpose of this study was to compare the clinical course of UC according to the presence or absence of clinical symptoms at the time of diagnosis.

Methods
Data were obtained from a retrospective chart review of 64 consecutive patients with UC diagnosed at our hospital between 2014 and 2020. Patients were grouped according to the presence or absence of clinical symptoms at the time of UC diagnosis, and clinical characteristics (age, sex, extent of disease, Mayo Score, endoscopic severity, and hematological findings) at the time of diagnosis were subjected to univariate and multivariate analyses. In the clinical characteristics, propensity score matched analysis was performed, and systemic steroids use, hospitalization within 1 year, and the introduction of therapies for refractory UC were evaluated. Patients with a clinical course of less than 1 year after UC diagnosis, patients intolerant to 5-aminosalicylic acid, patients with carcinoma, pregnant women, and patients under 15 years of age were excluded.

Results
Eligible patients were 64 UC patients (19 asymptomatic and 45 symptomatic) diagnosed at our hospital during the period of the study. The symptomatic group included 32 cases of bloody stools, 30 cases of diarrhea, 7 cases of abdominal pain, and 4 cases of fever. Multivariate analysis of clinical features at diagnosis showed significant differences in Mayo Score (p=0.003, odds ratio: 3.650, 95% confidence interval: 1.541–8.647) and serum hemoglobin level (p=0.021, odds ratio: 0.367, 95% confidence interval: 0.157–0.859). As a result of propensity score matched analysis, 24 patients (12 asymptomatic, 12 symptomatic) were selected. There were no significant differences in the rates of systemic steroid use (16.7% vs. 16.7%), hospitalization within 1 year (16.7% vs. 8.3%), and the introduction of therapies for refractory UC (16.7% vs. 8.3%) between the two groups (p=1.000 in all items).

Conclusion
There was no difference in the prognosis of the asymptomatic group compared with the symptomatic group using propensity score matched analysis. The results suggest that asymptomatic UC detected by colonoscopy may be acceptable for follow-up without treatment.
P152 Impact of disease location on burden of illness in patients with moderate-severe Crohn’s disease: A real-world survey in the United States, France, Germany, Italy, Spain, and United Kingdom (5EU)
Authors: Sikirica M , Lynch J , Kershaw J , Lukanova R , Baker S , Milligan G 
Published: January 2022

Abstract

Background
Presentation and risks of progression and complications differ according to Crohn’s disease (CD) location. The objective of this study was to investigate how disease burden differs based on CD location, from physician and patient perspective.

Methods
Data drawn from the Adelphi Inflammatory Bowel Disease (IBD) Disease Specific Programme™, a point-in-time survey of gastroenterologists (GEs) and their IBD patients from two waves (Nov 2014-Mar 2015; Sep 2017-Jan 2018) in the United States, and 5EU. GEs completed physician-reported questionnaires for 5–10 consecutively consulting patients with CD, covering demographics, treatment, symptoms, and CD location. Same patients completed voluntary patient-reported questionnaire including outcome measures such as Short IBD Questionnaire (SIBDQ), EuroQol 5-dimension questionnaire (EQ-5D), and Work Productivity and Activity Impairment questionnaire.
Comparisons were drawn between patients with CD in 3 locations: ileal only (IL), ileocolonic (IC), and colonic only (CO). Outcomes such as patient-reported level of pain, sleep disturbance, and fatigue, were compared between locations using linear regression analyses that included potential confounding variables age, gender, body mass index, comorbidities (using Charlson Comorbidity Index [CCI]) and severity at diagnosis. Least square (LS) means were generated for each location and compared using a p-value generated from Wald tests. Variables such as current treatment and symptoms, were compared using univariate tests (ANOVA, chi2 test). Base sizes varied due to the voluntary nature of patient participation.

Results
686 GEs collected data on 2354 patients with moderate-severe CD, identifying patients with IL (28.3%), IC (45.7%), and CO (26.0%) location. Overall demographic characteristics were similar, mean age 39 years, proportion of male patients 51.4%, mean Body Mass Index 24.0, mean CCI 0.14.
Differences were observed between the 3 groups (Table 1). Patients with ileal involvement (IL and IC) were prescribed biologics more often and had greater symptom burden than CO patients, except for rectal urgency. IL patients tended to have slightly greater burden overall in terms of symptomatology and severity. There was similarity across SIBDQ and EQ-5D scores; however, absenteeism was higher amongst IL and IC patients, compared with CO patients.

Conclusion
Differences were observed between IL, IC, and CO CD location groups. Despite IC patients experiencing the greatest burden overall, there were key distinctions between IL and CO patients, particularly in medication, symptoms, and work productivity impairment, suggesting that disease management with attention to CD location could lead to better patient outcomes.
P160 Pan-enteric mucosal inflammation in CD patients treated with vedolizumab – interim results of a prospective observational study using a panenteric capsule (PiilCam CD)
Authors: Kopylov U , Lipkin M , Ungar B , Haj O , Shachar E , Lahat A , Ben-Horin S , Eliakim R 
Published: January 2022

Abstract

Background
Mucosal healing is associated with improved short- and long-term outcomes in Crohn’s disease (CD). However, the likelihood of reaching mucosal healing differs between segments of the mucosal tract. The prevalence of panenteric mucosal healing is scarcely described. Capsule endoscopy is the prime modality for evaluation of the entire small bowel. Recently, a combined pan-enteric capsule (PillCam Crohn’s capsule (PCCD) that enables evaluation of mucosal inflammation in the entire digestive tract in a single procedure, has been developed.
The main aim of our study was to evaluate the rate of panenteric mucosal healing in Crohn’s disease patients treated with vedolizumab (VDZ) after 52 weeks of therapy. The current interim report focuses on the rates of mucosal improvement after 14 weeks of VDZ treatment.

Methods
This was a prospective open- label observational study. Patients starting vedolizumab (VDZ) for Crohn’s disease underwent a patency capsule (PC) and if it was excreted within 30 hours, enrolled in the study. The patients were evaluated with PCCD at week 0, 14 and 52 of VDZ treatment. Mucosal inflammation was quantified using the Lewis score (LS) and the panenteric Pillcam score (PS). In addition, fecal calprotectin (FC) and CRP levels were measured at each visit. Patients without active mucosal inflammation on week 0 PCCD were excluded from further participation

Results
We enrolled 30 patients; 5/30 failed PC and were dropped out of the study.Twenty five patients underwent PCCD at week 0 and 19/25 (78%)% -at week14 (six patients were dropped out for either absence of active mucosal inflammation at week 0 (1 patient), treatment discontinuation before week 14 (2 patients) endoscopic activity – 1, withdrawal of consent (1 patient) or loss to follow-up (1 patient)).
After 14 weeks of VDZ treatment, there was a significant improvement in LS (median of 900 (interquartile ration (IQR)- 1143)), vs 450 (IQR-750), p=0.013), ES (15 (IQR-18) vs 10 (IQR-11), p=0.012) and FC (996 (IQR-455) vs 742 (IQR -740), p=0.012), while CRP levels were not significantly different.

Conclusion
VDZ induces significant improvement in mucosal inflammation evaluated by panenteric capsule endoscopy, in addition to a significant improvement in FC levels, after 14 weeks of therapy
*The study was supported by IIR grant from Takeda and Medtronic
P165 Characterization and risk of sarcopenia in patients with Ulcerative Colitis, compared with older and younger adults. Cross-sectional study
Authors: Alison S C , Ylse G G , Viridiana M M , Bueno Hernández N 
Published: January 2022

Abstract

Background
Ulcerative colitis (UC) is characterized by being associated with a large number of extraintestinal manifestations that can affect any organ before or during the course of the disease, one of which is sarcopenia. Which is a progressive disorder of the generalized skeletal muscle that causes a decrease in muscle mass, muscle strength, and physical performance. In a patient with UC, it can cause an increased risk of falls and fractures, impaired ability to perform daily activities, and increased mortality. The objective of this study was to characterize and measure the risk of sarcopenia in UC patients compared to elderly people.

Methods
The study included 78 people of both genders and treated in the gastroenterology service of the Hospital General de México “Dr. Eduardo Liceaga ”. This was a cross-sectional study in patients with UC, elderly people, and healthy volunteers. Sarcopenia was diagnosed through measurement of muscle mass (bioelectric impedance), muscle strength (dynamometry), and physical performance (gait speed and Sit to Stand Test). And all the participants were divided into presarcopenia, sarcopenia, and severe sarcopenia.

Results
In this study 26 patients with UC, 22 older adults, and 30 healthy volunteers were included. In the UC group, there was a mean age of 40±10, in the elderly people group had a mean of 68±9.09 and healthy volunteers was 39±9.16. We can see that in the three groups there was a greater presence of women (UC: 57.7%; elderly 68.2% and healthy volunteers: 73.3%). The prevalence of sarcopenia was significantly higher in the UC group (27%) than in the elderly people (14%) and healthy volunteers (3%) group (P&lt;0.05). However, the presence of presarcopenia was higher in elderly people (41%), compared to UC (23%) and healthy volunteers (17%) (P&lt;0.05). The risk of developing sarcopenia was higher in UC patients compared to elderly people (OR=12.8; 95%CI=1.4–11.8; P=0.008). In UC patients there was lower physical performance (m/s=7.52±1.15) compared to the elderly people (m/s=7.72±1.39) and healthy volunteers (m/s=4.66±0.74).

Conclusion
Sarcopenia has a high prevalence in patients with UC. Patients with a diagnosis of UC have a higher risk of presenting sarcopenia compared to older adults. Sarcopenia manifests with physical deterioration in UC patients. A multidisciplinary approach is necessary for the early detection of sarcopenia to avoid the risk of falls, fractures, impaired movement capacity, increased mortality, and poor response to treatment.
P169 Delayed diagnosis of inflammatory bowel disease in women: Characterization and use of health resources
Authors: Sempere Robles L , Bernabeu P , Cameo Lorenzo J I , Laveda R , García M F , Aguas M , Belén O , Zapater P , van-der Hofstadt C , Jover R , Gutiérrez A , Ruiz M T 
Published: January 2022

Abstract

Background
Delayed diagnosis of IBD is associated with increased complications. Female gender is one of the factors most frequently associated with delayed diagnosis. Higher prevalence of functional gastrointestinal disorders in women probably hinders the diagnosis of IBD. The aim of this study is to explore delayed diagnosis of IBD and assess differences between women and men in healthcare access routes.

Methods
This multicentre prospective cohort study included 190 patients with newly diagnosed IBD. Data were collected on clinical and demographic characteristics, IBD activity and systematic reconstruction of the diagnostic process in a semi-structured interview together with a review of their medical record.

Results

Figure 1 shows clinical and demographic characteristics. In CD, patients’ symptoms were similar between both genders, except for a higher incidence of bowel incontinence, arthralgias, asthenia and other symptoms in women. In UC, there was no gender difference in clinical presentation. Overall, the median time from symptom onset to IBD diagnosis was 4.5(2.1–12.9) months, being significantly longer in women than in men, 7.8(3.3–18.9) vs. 3.8(1.7–7.8) p&lt;0.001. In diagnostic process, the time from symptom onset to initial physician visit was 0.7(0.26–2) months with no statistically significant differences between women and men. While the time from initial physician visit to IBD diagnosis was 3.4(1.1–7.4) months with a longer time in women than in men 4.2(1.9–11.1) vs 2.2(0.82–5.1) p&lt; 0.001. Figure 2 shows the different diagnostic times by sex in CD and UC. Misdiagnosis were reported in 61.6%, women had a higher percentage of misdiagnosis than men, 77.3% vs 48% (OR 3.6; 95% CI 1.9–6.9). These differences between women and men were maintained in CD 83% vs 55.3 (OR 3.9; 95% CI 1.5–9.9) and in UC 68.6% vs 41.8% (OR 3; 95% CI 1.2–7.4). Misdiagnosis were observed in 66/120 (55%) patients evaluated in Emergency Department, 89/166 (53.6%) in Primary Health Care, 25/122 (20.5%) in Gastroenterology Outpatient Clinics, 4/11(36.5) in another medical specialist, and 14/84 (16.7) in Hospital Admission. Women had a higher percentage of misdiagnosis, in Emergency Department 66.1%/44.3% (OR 2.4; 95% CI 1.1–5.1), Primary Health Care 65.1%/42.2% (OR 2.5; 95% CI 1.3–4.7), Gastroenterology Outpatient Clinics 29.5%/11.5% (OR 3.2; 95% CI 1.2–8.4) and Hospital Admission 25.6%/7.3% (OR 4.3; 95% CI 1.1–16.9). Figure 3 shows the distribution of the most frequently misdiagnosed pathologies prior to IBD diagnosis.

Conclusion
Delayed diagnosis of IBD in women affects both CD and CU, due to a longer delay in the diagnostic process since the patient consults for the first time. Gender biases in the misdiagnosis of IBD patients occur at all levels of health care.