bluuebunny/crossref_metadata_2025 huggingface dataset:
P1258 Disease course of inflammatory bowel disease unclassified during the first ten years following diagnosis: A prospective European population-based inception cohort – the Epi-IBD cohort
Authors: Wewer M D , Lophaven S , Lakatos P L , Gonczi L , Salupere R , Kievit H A L , Nielsen K R , Midjord J , Domislovic V , Krznarić Ž , Pedersen N , Kjeldsen J , Halfvarson J , Sebastian S , Goldis A , Arebi N , Oksanen P , Neuman A , Andersen V , Katsanos K H , Koukoudis A , Turcan S , Ellul P , Kupcinskas J , Kiudelis G , Fumery M , Kaimakliotis I P , D’Inca R , Lombardini S , Hernandez V , Fernandez A , Langholz E , Munkholm P , Burisch J ,   Epi-IBD group
Published: January 2025

Background

The Epi-IBD cohort is a prospective European population-based cohort of 1,508 patients diagnosed in 2010 and 2011 with inflammatory bowel disease (IBD) according to Copenhagen criteria in centres across 17 European countries. The study aims to describe treatment strategies, disease course and prognosis of IBD unclassified (IBDU) across Europe.

Methods

Patients with IBDU were defined as not fulfilling the Copenhagen diagnostic criteria of Crohn’s disease (CD) or ulcerative colitis (UC), but still required IBD related treatment and monitoring. They were followed prospectively from the time of diagnosis until December 31st, 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org. Patients with IBDU were categorised as CD-like, UC-like or mixed CD-UC based on disease location and continuity of the affected bowel segments at diagnosis.

Results

In total, 129 IBDU patients aged ≥15 years from 22 centres were included. They comprised 8.5% (N=129/1,508) of the total cohort. The disease location was reported in Table 1 where 4 patients had unknown disease location at baseline. At diagnosis, 16% (N=25/129) were CD-like, 52% (N=62/129) were UC-like and 32% (N=42/129) were mixed CD-UC.During the 10-year follow-up, 32% (N=41/129) were re-classified as either CD (N=16) or UC (N=25). The crude 1-, 5-, and 10-year rates for re-classification of diagnosis were 19%, 26% and 32%. The time to initiation of therapies and the distribution of therapies according to re-classification of IBDU diagnosis at baseline are presented in Figure 1 A-B . Advanced therapies were used in 13% (N=17/129) of patients over the 10-year follow-up, and was initiated after a median period of 1.9 years (inter-quartile range 0.9-8.1). An intestinal resection was required in 7% (N=9/129). After 1, 5, and 10 years, 9%, 19% and 26% of the patients diagnosed with IBDU at baseline, respectively, required hospitalisation.

Conclusion

After 10 years of follow-up, a third of patients initially diagnosed with IBDU were re-classified as either CD or UC. The disease course was in general mild with a low number of patients requiring advanced therapy, intestinal resection, and hospitalization. However, patients who were re-classified as CD or UC were more frequently treated with medical therapies.
P1267 Risk of hospital-treated infections in patients with cancer and inflammatory bowel disease
Authors: Dahl S A M , Ehrenstein V , Pedersen L , Sørensen H T , Siegel C , Erichsen R
Published: January 2025

Background

Both cancer and inflammatory bowel disease (IBD) are risk factors for infection leading to elevated infection-related mortality. We investigated the effect of IBD on infection risk in patients with cancer.

Methods

This population-based Danish nationwide cohort study included adults diagnosed with incident solid cancer between 2004 and 2021. IBD and first-time post-cancer infections were identified using discharge diagnosis codes. Patients were followed from the cancer diagnosis until the first post-cancer infection, emigration, death, or end of follow-up, whichever came first. The cumulative incidence of hospital-treated infections was calculated, considering death a competing risk. Adjusted hazard ratios (HRs) were calculated for infections in patients with versus without IBD. Among patients with cancer and IBD, we examined the effects of immunomodulatory medication on infection risk.

Results

Among 638,089 cancer patients, 7,120 (1.1%) had IBD. The overall 3-month, 1-year, and 5-year cumulative incidence of infection in patients without IBD was 3.6% (95% CI, 3.6–3.6), 8.2% (95% CI, 8.2–8.3), and 18.3% (95% CI, 18.2–1.4%), respectively, and in patients with IBD it was 4.1% (95% CI, 3.7–4.6%), 9.8% (95% CI, 9.1–10.4%), and 21.8% (95% CI, 20.8–22.8%), respectively (Figure 1). IBD was associated with 3-month, 1-year, and 5-year infection HRs of 1.06 (95% CI, 0.94–1.20), 1.13 (95% CI, 1.05–1.23), and 1.21 (95% CI, 1.15–1.28) (Figures 1 and 2). Moreover, cancer-specific HRs at three months indicated an increased risk of hospital-treated infection among individuals with oropharyngeal, digestive tract, and male genitalia cancers (Figures 1 and 2). Furthermore, among patients with IBD, corticosteroids and combination therapy were associated with increased infection risk (HR 1.54; 95% CI, 1.03–2.31 and HR 1.64; 95 CI, 1.06–2.54, respectively), while biological agents reduced it (HR 0.66; 95% CI, 0.48–0.91).

Abbreviations: IBD = inflammatory bowel disease

*Adjusted for age, sex, CCI score, highest education, index years, T, N and M status

Abbreviations: IBD = inflammatory bowel disease

Conclusion

In cancer patients, IBD was associated with an elevated long-term risk of infections. In cancer patients with IBD, the use of corticosteroids increased the infection risk, while biological agents reduced it.

Figure 1: Cumulative incidence of hospital-treated infection in individuals with cancer with versus without IBD, according to cancer type, 2004–2021 (n= 638,089)

Figure 2: Adjusted HRs* (95% confidence intervals) for the association between IBD and hospital-treated infection in individuals with cancer with versus without IBD, 2004–2021 (n= 638,089)
P1268 Sexual health challenges in inflammatory bowel disease: A population-based cross-sectional study
Authors: Larimore C F , Jacobsen H , Larsen L , Graugaard C , Andersson M , Frisch M
Published: January 2025

Background

Individuals with inflammatory bowel disease (IBD) may experience impaired body image, poorer quality of life, and reduced sexual functioning compared to the general population. However, variations in sexual health across the diverse disease spectrum of IBD must be expected. This study examined sexual challenges and dysfunctions in Danish individuals with and without IBD.

Methods

In this population-based cross-sectional study, 62,675 participants from the nationally representative Project SEXUS cohort study (www.projektsexus.dk) were linked to the Danish National Patient Register to identify participants (n=655) with a first IBD diagnosis recorded between 1996 and 2017 (n=437 with ulcerative colitis (UC); n=218 with Crohn’s disease (CD)). In sex-specific analyses, the prevalence of sex life challenges and dysfunctions in participants with and without IBD and associated, confounder-adjusted odds ratios (aOR) with 95% confidence intervals (CI) were assessed. Active disease was defined by a fecal calprotectin concentration of >150 μg/g.

Results

There were few differences in how individuals with and without IBD assessed their overall sex life and current relationship quality. However, when compared with individuals without IBD, both men and women with UC were significantly more likely to report hypoactive sexual desire disorder (men: aOR=2.18; 95% CI: 1.13-4.19; women: aOR=1.66; 95% CI: 1.04-2.66), and women with UC more often reported genital pain dysfunction (aOR=2.30; 95% CI: 1.26-4.19). In IBD subgroup-specific analyses, men with active UC were more often affected by hypoactive sexual desire disorder (aOR=10.44; 95% CI: 2.29-47.57), men with UC and a stoma more often reported erectile dysfunction (aOR=22.21; 95% CI: 3.26-151.47), and men with CD and a stoma more often reported orgasmic dysfunction (aOR=7.92; 95% CI: 1.02-61.78), when compared with men without IBD. Among women, those with active UC more often reported vaginal cramp dysfunction (aOR=12.30; 95% CI: 1.25-120.59), whereas women with CD complicated by perianal involvement more often experienced genital pain dysfunction (aOR=6.39; 95% CI: 1.04-39.17), when compared with women without IBD.

Conclusion

Individuals with UC and subgroups of patients with IBD with active disease, stoma, or perianal involvement face a significantly elevated risk of various sexual challenges and dysfunctions. Healthcare providers in gastroenterology should therefore remain attentive to these potential issues and offer appropriate counselling or treatment when needed.
P1269 Assessing the prevalence and incidence of recorded fatigue codes amongst IBD patients: A nationwide study from the epi-IIRN
Authors: Focht G , Buchuk R , Loewenberg Weisband Y , Ben-Tov A , Zacay G , Matz E , Dotan I , Paltiel O , Turner D ,   The epi-IIRN
Published: January 2025

Background

Fatigue is a common and burdensome symptom experienced by patients with Inflammatory Bowel Diseases (IBD), yet it remains under-recognised and understudied. This study aimed to assess the prevalence and incidence of recorded fatigue in the first nationwide cohort investigation of this topic.

Methods

We utilised the epi-IIRN cohort, encompassing all IBD patients in Israel across the four Health Maintenance Organisations (HMOs), covering 98% of the population. These patients were matched to non-IBD controls (by birth year, sex, district, HMO). We included patients with IBD diagnosed from 2005 onwards and followed until June 2021. Fatigue was identified using ICD-9 codes for "Malaise and Fatigue" or "Chronic Fatigue". Patients with fatigue codes >2 years prior to IBD diagnosis were excluded. Prevalence of fatigue codes was compared with matched non-IBD controls, and incidence rates were analysed using Kaplan-Meier survival curves. Associations with disease activity, reflected in blood tests, and other recorded comorbidities known to contribute to fatigue were explored. Predictors of fatigue in IBD patients were assessed using a multivariate Cox model.

Results

The study comprised of 32,908 IBD patients (18,555 with Crohn’s disease [56%]; 47% female; mean age at diagnosis 35.4±18.5 years) were matched to 74,688 controls. Fatigue was recorded in 6,210 (18.9%) IBD patients compared to 9,593 (12.8%) controls (OR=1.58, 95%CI 1.52–1.63; p<0.001). Among IBD patients, fatigue was more frequent in females (OR=1.52, 95%CI 1.44–1.60). Time to fatigue onset was shorter in both male and female IBD patients compared to matched controls (p<0.001; figure).

Fatigue rates were similar between Crohn’s disease (3,548 [19.1%]) and ulcerative colitis (2,662 [18.5%]; OR=1.04, 95%CI 0.98–1.10; p=0.2).

IBD patients with fatigue had higher rates of anaemia, iron deficiency, anxiety, depression, and sleep disorders compared to those without (Table).

In a multivariate Cox model, female sex, frequent physician visits, anaemia, sleep disorders, and steroid use were associated with fatigue. In contrast, the use of 5-ASA, immunomodulators, anti-TNFs, and vedolizumab was protective (figure). Disease severity, reflected by cluster analysis of blood tests (moderate vs mild and severe vs mild), was not independently associated with fatigue (HR=1.08 95%CI 1.01-1.15 and 0.94 95%CI 0.84-1.05 respectively).

Conclusion

In this nationwide, unselected cohort, fatigue was more frequently reported in IBD patients compared to controls and was associated with several disease-related and comorbid factors. The burden of fatigue is underscored by its strong association with anxiety, sleep disorders, and depression.
P1279 Associations of accelerometer-measured moderate-to-vigorous physical activity with bowel resection risk and mortality among individuals with inflammatory bowel disease: a prospective cohort study
Authors: He Z , Sun Y , Huang H , Liu Y , Dan L , Ruan X , Li Z , Wang X , Chen J , Bai Y
Published: January 2025

Background

There is limited consensus on physical activity recommendations for inflammatory bowel disease (IBD) patients due to insufficient high-quality evidence. We investigated the associations of accelerometer-measured moderate-to-vigorous physical activity (MVPA) with bowel resection risk and mortality among affected individuals.

Methods

We collected data from 1,303 UK Biobank participants with IBD diagnosis and device-measured physical activity. MVPA was classified based on data measured by wrist-worn accelerometers over a 7-day period. MVPA patterns were defined as inactive, active weekend warrior, and regularly active. Associations were estimated using multivariable Cox regression models.

Results

During a median follow-up of 7.8 years, 56 incident bowel resection cases and 86 deaths were documented. Compared to those with the lowest tertile, participants with the highest tertile of MVPA duration had lower risks of bowel resection (HR, 0.44; 95% CI, 0.22-0.86) and mortality (HR, 0.49; 95% CI, 0.27-0.89). MVPA duration is linearly associated with bowel resection (P non-linear = 0.13) while its dose-response relationship with mortality plateaus at approximately 58 min/day (P non-linear = 0.02). The active weekend warrior pattern was inversely associated with bowel resection (HR, 0.28; 95% CI, 0.12-0.65), the regularly active pattern was inversely associated with both bowel resection (HR, 0.37; 95% CI, 0.19-0.69) and mortality (HR, 0.53; 95% CI, 0.31-0.91) compared to the inactive.

Conclusion

Longer accelerometer-measured MVPA was associated with reduced bowel resection risk and mortality. The regularly active pattern may be the optimal choice for individuals with IBD, while the active weekend warrior pattern still provides health benefits compared to being inactive.
P1284 Prevalence of immune-mediated extraintestinal manifestations in paediatric Inflammatory Bowel Disease: a systematic review and meta-analysis
Authors: Colman R J , Vuyyuru S K , Solitano V , MacDonald J K , Ricciuto A , Berard R , Mohammed J , Ma C , Jairath V , Crowley E
Published: January 2025

Background

Concurrent immune-mediated extraintestinal manifestations (IM-EIMs; Table 1) are common in paediatric-onset inflammatory bowel disease (pIBD), but the overall epidemiology is unknown. This systematic review and meta-analysis aimed to summarise the prevalence and management of EIMs in pIBD.

Methods

MEDLINE, EMBASE and CENTRAL, clinicaltrials.gov and conference abstracts were searched up to May 6, 2024, for studies that included pIBD (2-17 years old) with secondarily diagnosed EIMs. The primary outcome included the prevalence of IM-EIMs among pIBD. Secondary outcomes included efficacy and adverse effects of treatment on EIMs. Meta-analysis included pooled proportions with DerSimonian-Laird random-effects analysis.

Results

The pooled proportion of IM-EIMs among pIBD was 8.4% (95% CI, 6.5-11.0%; I2=97%) among 53 eligible studies. The pooled proportion of IM-EIMs was 10.3% (95% CI, 7.3-13.8%; I2=95%) among 37 Crohn’s disease (CD) studies, compared to 11.3% (95% CI, 7.8-15.3%; I2=93%) among 39 ulcerative colitis (UC) studies. Enthesitis was the highest reported individual IM-EIM (23%, 95% CI, 4-50%; I2=94.7%) in pIBD. Arthritis was the second highest reported individual IM-EIM (8%, 95% CI, 6-10%; I2=96%) in pIBD, followed by primary sclerosing cholangitis (PSC) in UC (5%, 95% CI, 4-7%; I2=81%; Table 2). Uveitis, pyoderma gangrenosum, autoimmune hepatitis, and PSC in CD were the lowest reported IM-EIMs at 1% or less. The largest difference in reported proportions between IBD phenotypes was PSC, which was 4% higher in UC than CD. Only one eligible study described treatment response.

Conclusion

This meta-analysis identified that while musculoskeletal manifestations are relatively common, fewer than 5% of pIBD patients experience ophthalmological, dermatological, and hepatic IM-EIMs. There was significant methodological and statistical heterogeneity as expected for the relatively small number of individual paediatric studies and likely resulted in the large difference of pooled proportions between individual IM-EIMs. Multicentre collaborative efforts are needed to systematically describe the epidemiology and management outcomes of EIMs in pIBD in the current era of advanced therapies.
P1285 Incidence of venous thromboembolism in Asian patients with inflammatory bowel disease: a systematic review and meta-analysis
Authors: Song J H , Shim S R , Kim D S , Koo H S , Huh K C
Published: January 2025

Background

Although the incidence and prevalence of inflammatory bowel disease (IBD) have been gradually increasing throughout Asia, the incidence of venous thromboembolism (VTE) in Asia is relatively lower than that in Western countries and is not well known. This study aimed to evaluate the incidence of VTE in Asian patients with IBD using a systematic review and meta-analysis.

Methods

Studies were identified through a literature search of the PubMed, Embase, and Cochrane databases (from inception inclusive April 2024) for English studies. The criteria for selecting the participants were as follows: (1) studies including patients with Crohn’s disease (CD) and Ulcerative colitis (UC) in the Asian population; (2) comparisons were specified as with a control group of non-IBD patients for comparative incidence; and (3) outcomes were measured by relative risks (RR) and hazard risk (HR) for VTE incidence in nationwide cohort studies. Three independent reviewers extracted published data using a standardized procedure in accordance with the reporting guidelines. A fixed-effects model was used to estimate pooled effect sizes. Meta-regression analyses were conducted to identify the potential moderating effects of VTE risk in patients with IBD.

Results

Five studies met the inclusion criteria. The pooled RR for overall VTE incidence in Asian patients with IBD compared to that in non-IBD patients was 2.065 (95% CI: 1.905–2.238). The heterogeneity test resulted in a p-value of 0.418 for the Cochrane Q statistics, and Higgins’ I2 was 0%. There was no statistical moderating effect of the variables (number of patients, mean age, female rate, CD proportion, country, and type of risk) on the outcomes.

Conclusion

In our systematic review and meta-analysis, the VTE incidence in Asian patients with IBD was higher than that in non-IBD patients (RR 2.065). It seemed reasonable to consider prophylaxis for VTE in hospitalized patients with IBD.
P1286 Prevalence, concordance and course of disease in first-degree relatives with Inflammatory Bowel Disease
Authors: Mantzaris MD- PhD- AGAF- FEBG- MACG G
Published: January 2025

Background

The prevalence, concordance for and severity of disease in first-degree relatives (FDRs) affected by IBD has been under-reported in Greece. The aim of this study was to assess the prevalence, concordance and course of disease in FDRs affected by IBD in a cohort of consecutive IBD patients.

Methods

Consecutive patients with ulcerative colitis (UC) and Crohn’s disease (CD) who were examined in a solo practice office between 1st January 2023 and 31st October 2024 were asked for the diagnosis of UC or CD in any FDG relative (parent/children, siblings). Identified FDR were interviewed separately. A detailed medical history and physical examination was obtained from case patients and identified FDRs with IBD regarding demographic, disease and treatment characteristics, including place of birth and inhabitance, neonatal feeding attitudes, smoking and additional social habits, disease phenotype, extra-intestinal manifestations, co-morbidities, laboratory tests, imaging, endoscopy and histology reports, received medical and/or surgical treatments, and treatment outcomes until the day of interview.

Results

Overall 602 patients [380 CD/222 UC (including 28 pouch patients), 306 females, median age 35 (range 17-77 years) were interviewed. Patients geographic origin was representative of all country’s regions. Thirty pairs of FDP patients were identified (5%): all Caucasians, 11 cases mother/daughter, 1 case father/daughter, 2 cases mother/son, 3 cases father/son and 13 sibling cases (table 1). There were more cases parents/daughter than parents/son (13 vs 4) and more cases in mother/daughter than mother/son FDRs (11 vs 2). The disease was concordant for 8/17 cases parent/children, especially for UC (5/8) and in 6/13 sibling cases, especially for CD (5/6 cases). The course of disease was mild in 8/30 (26.7%) cases (5 parent/children, only 1 was concordant for UC) and in 3 sibling cases (all discordant for CD). Eight patients (6 CD/2 UC) had undergone right hemi-colectomy (4), colectomy (2, colorectal cancer and acute severe UC, respectively), parianal CD (1) and J pouch (2). One case (mother-UC/child-CD) had J pouch and stoma, respectively.

Conclusion

In this cohort of consecutive IBD-FDRs the disease was more common in females and concordant in nearly 50% of the patients, especially in siblings. The course of IBD was rather aggressive and 73% of patients had been treated with advanced therapies and/or surgical interventions.
P1287 Comparative Analysis of IBD Management: Hospital Versus Community-based Care
Authors: Israel A , Sharif K , Lahat A
Published: January 2025

Background

Our study aimed to compare disease characteristics, medication utilization, procedures performed, and hospitalizations between IBD patients treated in hospital and community settings using the Leumit Health Service database.

Methods

A retrospective cohort study was conducted using data from the Leumit Health Service, comprising 3020 patients diagnosed with IBD fBetween 2010 -2019. Patients were divided based on primary care setting: hospital-based or community-based. Data included demographic characteristics, disease type, medication usage, procedures, and outcomes.

Results

Overall 3020 patients were included, of them 1627 ( 54%) were community treated, and 1741 (57%) suffered from CD. Hospital-treated patients were significantly younger (49.4 ± 18.4 vs 40.4 ± 18.7,p<0.001 ), had higher rates of Crohn’s disease (45.9 % vs 71.4 %, p<0.001), exhibited higher inflammatory markers (calprotectin 768 ± 2182 vs 1305 ± 2526, p <0.001) , lower albumin ( 4.23 ± 0.27vs 4.12 ± 0.32, p<0.001)and Hemoglobin levels (13.4 ± 1.6 vs 12.9 ± 1.6, p <0.001) , and lower BMI (26.2 ± 5.3 vs 24.6 ± 5.6, p<0.001) compared to community-treated patients. Hospital-treated patients had more endoscopic procedures, higher medication utilization rates, shorter treatment durations, and increased hospitalizations occurrence (12.1 % vs 23.6 %, p<0.001) , length (0.67 ± 3.34 vs 1.45 ± 5.88, p<0.001), and colectomies (4.73 % vs 15.8 %,p<0.001). Table 1 displays emergency room (ER) visits, hospitalizations and colectomy among study groups,and Figure 1 displays medical treatments among study groups.

Conclusion

Hospital-based care is associated with more aggressive disease and intensive interventions, while community-based care may reflect milder disease and conservative management. Integrating specialized care models and personalized approaches across settings can optimize patient outcomes and healthcare delivery for IBD management.
P1299 Modulation of miR-31-5p expression in patients with Ulcerative Colitis treated with infliximab
Authors: Pereira J , Grillo T , Oliveira E , Baima J , Quaglio A E , Costa E , Di Stasi L , Sassaki L
Published: January 2025

Background

Biological therapy has revolutionized the treatment of Ulcerative Colitis (UC), but biomarkers that predict response are still lacking. MicroRNAs (miRNAs) are small non-coding RNA molecules that participate in cellular processes such as proliferation, differentiation, migration, maturation and apoptosis, and therefore are related to immune regulation in physiological and pathological conditions such as Inflammatory Bowel Diseases. Therefore, the objective of the study is to investigate the expression profile of miRNAs in responding and non-responding patients treated with Infliximab and to identify a profile of miRNAs that predict therapeutic response.

Methods

Twelve miRNAs: miR-21-5p, miR-31-5p, miR-192-3p, miR-192-5p, miR-215-5p, miR-326, miR-378-3p, miR-378-5p, miR-422a, miR-429, miR-551a and miR-1258-3p were evaluated in naïve patients with UC before and after treatment with Infliximab (week 54). MiRNA was extracted from formalin-fixed, paraffin-embedded (FFPE) colon tissue and qRT-PCR was performed from 12 patients, of which: 5 responding and 7 non-responding, both groups evaluated pre and post treatment (n=24 samples).

Results

Decreased expression was found for miR-31-5p (p=0.03) when comparing responding patients pre and post treatment, meanwhile miR-192-5p (p > 0.99) and miR-378-3p (p > 0.99) were suggestive but not statistically different. The other miRNAs had not had expressive results.

Conclusion

Infliximab-responding patients with UC presented decreased expression of miR-31-5p. MiR-31-5p regulates IL-25 and activates Th1/Th17 mediated inflammation in UC. Therefore, our results reinforce the importance of miR-31-5p expression in UC and indicate a relationship between this miRNA and the effectiveness of the treatment.
P1303 A machine – learning approach of therapeutic response prediction for Ustekinumab in ulcerative colitis
Authors: Koustenis K , Dovrolis N , Viazis N , Ioannou A , Bamias G , Karamanolis G , Gazouli M
Published: January 2025

Background

Ustekinumab, a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, is a promising therapeutic approach in patients with ulcerative colitis (UC), but predicting treatment response remains a challenge. In the present study, we focused to identify prognostic response markers to ustekinumab in patients with active UC, utilizing mucosal transcriptome information and machine-learning approaches.

Methods

We used 36 drug naive UC patients initiating treatment with ustekinumab. Colonic mucosal biopsies were obtained before treatment initiation. The gene expression analysis was performed using a microarray panel of 84 inflammation related genes. A differential gene expression analysis (DGEA), correlation analysis, and network centrality analysis on co-expression networks were performed to identify potential biomarkers. Additionally, machine learning (ML) models were employed to predict treatment response based on gene expression data.

Results

The genes BCL6, CXCL5, and FASLG, were among the significantly upregulated, while IL23A and IL23R were downregulated in non-responders compared to responders. The co-expression analysis revealed distinct patterns between responders and non-responders. The ML algorithms demonstrated a high predictive power, emphasizing the significance of the IL23R, IL23A, and BCL6 genes.

Conclusion

Through a variety of computational approaches, our study indicates the predictive power of mucosal expression data in predicting patient response to ustekinumab treatment.
P1306 Impact of HLA-DQA1*05 genotype in immunogenicity and response to treatment with Tumour Necrosis Factor-alpha Antagonists in Inflammatory Bowel Disease patients
Authors: Moreno Torres V , Mira C , Madero-Velázquez L , Muñoz R , Belén-Galipienso O , Cameo J I , Bernal L , García-Trueba A , Sempere L , Gutiérrez-Casbas A
Published: January 2025

Background

Carrying the HLA-DQA1*05 gene has been linked to a higher risk of developing immunogenicity in patients with inflammatory bowel disease (IBD) who are treated with tumor necrosis factor-alpha (TNF-a) inhibitors. However, studies have shown inconsistent evidence regarding its connection to a loss of response or adverse events in patients with IBD. The aim is to determine the impact of carriage of HLA-DQA1*05 allele on effectiveness, drug persistence and safety in patients diagnosed with IBD who had received antiTNF-a inhibitors.

Methods

Retrospective, single-center cohort study including IBD patients who had received anti-TNF therapy. The HLA-DQA1*05 allele was determined retrospectively from a saliva sample (kit OGD-600 de DNA Genotek Oragene) and DNA extraction with the Maxwell® RSC-Stabilized Saliva DNA kits. We evaluate drug persistence, withdrawal of antiTNF-a, clinical response/remission, primary and secondary loss of response, through antiTNF levels, development of antiTNF antibodies and adverse events in patients distributed by HLA-DQA1*05 allele presence.

Results

A total of 82 patients were included. Baseline characteristics are detailed in Table 1. HLA-DQA1*05 was positive in 35/82 (42.7%) patients. Sixty-three patients (63%) received infliximab (IFX) and 19/82(23.2%) adalimumab. AntiTNF was the first advanced therapy in 78/82(95%) of the cohort. Thirty-four out of 82 patients (41%) received an optimized antiTFN-a regimen, as well as 34/82 (41%) were treated with combo-therapy with immunosuppressants. AntiTNF-a was withdrawn in 35/82 (42.7%) patients during follow-up, and the rate of adverse events that led to discontinuation of the drug was 16% (13/82). When we compared the rate of primary and secondary non-response, persistence of the antiTNF-a therapy or use of combo-therapy, we did not find significant differences between patients by HLA-DQA1*05 status. On the other hand, the rate of infusion reactions, development of anti-TNF antibodies or adverse events that led to drug withdrawal were also similar among patients HLA-DQA1*05 positive or negative. Only the need of optimized antiTNF-a was more frequent among patients HLA-DQA1*05 positive (19(54.3%) vs. 15 (31.9%), p= 0.028).

Conclusion

In our real-life cohort of IBD patients treated with antiTNF-a, being an HLA-DQA1*05 carrier did not act as a predictor of loss of response, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the variant. However patients HLA-DQA1*05 positive required optimized antiTNF-a regimen more frequently.
P1311 Mucosal Microbiome Signatures Associated with Postoperative Endoscopic Recurrence in Paediatric Crohn’s Disease
Authors: Breton MDCM- MSTR J , Tanes C , Wilson N , Kachelries K , Bittinger K , Mattei P , Baldassano R
Published: January 2025

Background

Following ileocecal resection (ICR) for Crohn’s disease (CD), recurrence is frequent even in the biologic era. Gut microbiota is involved in this setting and a few adult studies have suggested that bacterial recolonization after surgery may predict recurrence. Given the inherent risk of postoperative recurrence associated with age and disease duration, studies investigating the role of the gut microbiota in predicting relapse in children undergoing ICR appears critical. We aimed to identify changes in the mucosal microbiome associated with, and predictive of, endoscopic CD recurrence within the first year post-ICR in a paediatric population.

Methods

Microbiota composition (16S rDNA sequencing) was assessed from ileal and colonic mucosa at the time of ICR and later during endoscopic evaluation from above and below the surgical anastomosis in 33 patients (26 with paired samples) prospectively recruited at a tertiary care paediatric IBD center.

Results

The study included 33 children (mean age 16±2.7 years) undergoing ICR. At the time of ileo-colonoscopy, 9 (35%) patients had endoscopic recurrence (Rutgeerts’ score≥ i2). ICR strongly modified the gut mucosal microbiota composition with significant changes in β-diversity (R2= 0.03, PERMANOVA test, p=0.01). Bacterial recolonization post-ICR differed according to recurrence status (Figure 1). Post-operatively, recurrence was associated with an increase in Fusobacterium, Dialister genera and in members of the Lachnospiraceae family, and a decrease in Faecalibacterium, Lactobacillus genera and members of the Streptococcaceae family. Microbiota colonizing the neoterminal ileum and subanastomotic colon differed in children with recurrence and showed, compared to remission, elevated and reduced bacterial abundance of the Enterobacter (q=0.1) and Ruminococcaceae (q=0.05) families in colonic samples respectively while the ileal mucosa exhibited profound depletion in Faecalibacterium (q=0.01). Postoperative colonic mucosal relative abundance of Enterobacteriaceae (q=0.06) and Ruminococcaceae (q=0.06) correlated positively and negatively with length of intestinal resection. At the time of surgery, several bacterial taxa able to predict relapse were identified (Figure 2).

Conclusion

Predicting postoperative CD relapse remains challenging, although several clinical risk factors of recurrence have been identified. Our study demonstrates that bacterial recolonization following ICR might pave the way towards remission or recurrence. Our results highlight, for the first time in a paediatric population, target species that may help clinicians to better define patients at risk of relapse and allow precise modulations of the overall microbial ecosystem towards remission pattern.
P1315 Decoding microbiome-metabolome interactions: gaining insights into Gastric Cancer, Inflammatory Bowel Disease and Colon Cancer
Authors: Philip D , Hodgkiss R , Kollampallath Radhakrishnan S , Acharjee A
Published: January 2025

Background

The gut microbiome and its metabolites are key to understanding the pathogenesis of gastrointestinal diseases (GID) like gastric cancer (GC), inflammatory bowel disease (IBD), and colon cancer (CC), aiding in the identification of shared and disease-specific biomarkers for personalised interventions. This study used machine learning (ML) models, metabolic modelling and network analysis methods to assess the risk of developing one GID following another, especially as IBD patients are at higher risk of CC, and GC patients can develop CC.

Methods

Microbiome and metabolome datasets from Erawijantari et al. (GC), Franzosa et al. (IBD), and Yachida et al. (CC) were subjected to three ML models, eXtreme gradient boosting (XGBoost), Random forest (RF) and Least absolute shrinkage and selection operator (LASSO). The models were refined using Recursive Feature Elimination & Cross-Validation (RFECV) and LASSO. Trained models were applied for within and cross disease analyses using common microbes and metabolites. Microbial abundance analysis was conducted to identify compositional differences between the diseased and healthy patients. Microbial Community Modelling (MICOM) simulated microbial interactions to evaluate contributions to metabolite production. Using Weighted Gene Co-expression Network Analysis (WGCNA), A cluster dendrogram was generated to identify modules of highly correlated metabolic features based on co-expression patterns.

Results

ML models for the GC model had LASSO, achieving the highest AUC 0.96 [0.85-1.00]. For IBD, RF performed the best at AUC 0.93 [0.86-0.98]. CC model had XGBoost as the top performer AUC 0.85 [0.75-0.94]. Biomarkers from the GC model were used to predict CC and IBD outcomes, while biomarkers from IBD and CC models were similarly tested across diseases, having strong performance scores (Figure 2). Abundance analysis had lower levels of Bacteroidaceae in GC compared to healthy patients and higher Ruminococcaceae and Lachnospiraceae in IBD and CC. MICOM identified six metabolites in GC (adenosine, alanine, glycerophosphate, methionine, methionine sulfoxide, nicotinate), two in IBD (cholate, cytosine) and seven in CC (1-methyladenosine, alanine, glutamate, histidine, lactate, nicotinamide, tryptophan) all differentially produced by the selected microbes. WGCNA revealed four modules for GC (β=18,R²=0.91), eight modules for IBD (β=16,R²= 0.56), and two modules for CC (β=19,R²=0.27).

Conclusion

Despite study limitations, results suggest that the gut microbiome and its metabolites influence disease progression and aid in optimising therapeutic strategies, such as faecal microbiota transplantation (FMT), particularly in IBD and CC, potentially addressing both disease prevention and progression.
P1318 Temporal Changes of Gut Microbiota and Micro-RNAs according to Disease Activity in Chronic Colitis
Authors: Eun C S , Jeong H W , Lee A R , Jung B W , Han D S
Published: January 2025

Background

Both gut microbiota and micro-RNAs (miRNAs) have been implicated in the pathogenesis of inflammatory bowel disease. We aimed to investigate the temporal changes and their interactions between gut microbiota and miRNAs according to the disease activity using multi-omics analysis in a murine chronic colitis model.

Methods

Chronic colitis was induced in the C57BL/6 mice by three rounds of 2.5% DSS exposure. Mice were divided into three groups (n= 8 per group): control group, active group (sacrified at 3 days after the third DSS), and recovery group (sacrificed at 80 days after the third DSS). Clinical activities including weight change and histologic findings of colonic segments were examined. DNA was extracted from mouse feces, and 16S rRNA gene sequencing was performed to evaluate changes in gut microbiota. miRNA expression levels were measured by microarray analysis from mouse colonic tissues. Correlation and network analyses were performed to evaluate the interactions between gut microbiota and miRNAs.

Results

Alpha diversity indices were increased in the active group compared to control and recovery group. PCoA of metagenomic sequencing showed that the gut microbial profile of the active group was distinctly different from the control group, while the gut microbial profile of the recovery group was similar to the control group. On the other hand, PCoA of miRNA microarray showed that the active group had a significantly different miRNA expression pattern compared to the control group, while the recovery group had a similar miRNA expression pattern to the active group. In taxonomic and miRNA analyses, 147 differential abundant bacterial ASVs and 30 differential expressed miRNAs were identified in the active group compared to the recovery group. Spearman correlation and network analysis between gut microbiota and miRNAs, which showed significant differences between the active and the recovery groups, revealed significant associations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p.

Conclusion

In the active phase of chronic colitis, the gut microbial composition and miRNA expression were significantly altered, while in the recovery phase of chronic colitis, the gut microbial profile was similar to that of control, but a significantly different miRNA expression pattern was observed. Specific miRNAs were associated with specific bacterial ASVs, suggesting the interactions between miRNAs and gut microbiota in the development of chronic colitis. Our data suggested significant correlations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p in the active phase of chronic colitis.
P1319 Multi-omic modelling of antibiotic perturbed faecal microbial communities demonstrates reduced microbial resilience in IBD
Authors: Koentgen S , Zhang F , O’Brien C , Grimm M , Allen-Vercoe E , Hold G L
Published: January 2025

Background

Excessive antibiotic use is a risk factor in IBD, due to the impact on the gastrointestinal microbiota, but the extent of impact on microbial metabolite production is unknown. Here we investigate the impact of ciprofloxacin (CIP) and metronidazole (MTZ) on gut microbiota structure/function in a healthy donor and a new-onset therapeutic naïve IBD patient. We also investigate the use of autologous faecal microbiota transplant (aFMT) as a microbial therapeutic to assist recovery of the gut ecosystem.

Methods

Donor faecal specimens (IBD or healthy) were used to inoculate twin chemostat vessels. Following community stabilisation, vessels were dosed daily with CIP or MTZ for 7 days. In the healthy donor vessel, 4 doses of aFMT were administered over 7 days (post antibiotics) followed by a 7-day recovery. In the IBD vessels no FMT was administered. Vessels were sampled daily to monitor microbial profiles (16S rRNA sequencing) and short chain fatty acid (SCFA) profiles (GC-MS).

Results

CIP in the healthy vessel caused a significant depletion of acetate, butyrate and propionate, remaining significantly depleted during aFMT. CIP dosing also resulted in an enrichment of Escherichia-Shigella and Enterobacter and a loss of Akkermansia, Faecalibacterium and Bacteroides. During recovery acetate and propionate recovered whilst butyrate remained depleted (p=0.004). In the healthy MTZ vessel, acetate increased during antibiotic dosing and was restored following aFMT. Butyrate decreased during MTZ dosing and remained significantly decreased (p<0.031). Propionate levels also reduced following MTZ but were found in highest abundance during aFMT and recovery phases (p<0.038). Parabacteroides increased during MTZ dosing which subsequently decreased to stable abundance. Akkermansia was significantly increased in recovery phase compared to aFMT and stability phases.

In the IBD donor, CIP caused a significant reduction in 10 SCFAs and several taxa including Bacteroides and Dialister genera alongside an enrichment of Enterococcus, Lachnospiraceae, Anaerofilum and Eisenbergiella. MTZ treatment resulted in a less dramatic reduction in SCFAs. Microbial community changes included an enrichment of Escherichia-Shigella, Enterococcus and Parasutterella and a depletion of Alistipes and Dialister.

Conclusion

CIP and MTZ significantly depleted levels of beneficial genera and reduced the abundance of SCFAs. Neither donor community was able to fully restore composition or function. aFMT modulated the healthy donor microbial communities to a "new healthy". Further investigation into long-term antibiotic treatment and the use of microbial therapeutics is needed to fully understand this relationship in the context of IBD.
P1320 Oral highly-virulent pathogenic isolates aggravated colitis through gut microbiota-equol-ERβ axis
Authors: Chen J , Yang C , Xu Y , Zhao Y , Wu J , Liu Y , Chen N
Published: January 2025

Background

We isolated potential oral pathogens from IBD patients saliva and analyzed their virulence differences, hoping to elucidate the mechanism of different disease patterns in IBD patients.

Methods

A series of in vitro and in vivo experiments, whole-genome sequencing, 16S rRNA sequencing and non-targeted metabolomics sequencing were used to explore the pathogenicity of Streptococcus mutans (S.m) isolates.

Results

Our previous study indicated that the abundance of streptococcus in ulcerative colitis (UC) patients saliva was higher than healthy people. After over 1 year follow-up, we found that UC patients with poor disease state had higher proportion of S.m in saliva, and 31 S.m strains were further isolated from 25 UC saliva. Whole-genome sequencing showed that the virulence genes of S.m strains were related to immunity, metabolism and exotoxins. 9 strains with greater pro-inflammatory effects and barrier destroying ability were obtained based on microbe-cell co-culture. Subsequent animal experiments suggested that pro-inflammatory S.m strains significantly exacerbated intestinal inflammation of DSS mice, while non-pro-inflammatory S.m strains didn’t induce above effects.

The pro-inflammatory effects of pro-inflammatory S.m strains on DSS mice disappeared after the depletion of gut microbiota by antibiotics, and fecal bacteria transplantation (FMT) found that the intestinal inflammation of DSS mice transplanted with pro-inflammatory strains groups feces was more severe than that of non-proinflammatory mice, suggesting that intestinal microbiota is essential for the proinflammatory effects of S.m strains. 16S rRNA sequencing showed that α diversity of intestinal microbiota of pro-inflammatory strains groups mice was lower than that of non-proinflammatory mice. The level of equol was lower in pro-inflammatory groups compared to non-pro-inflammatory groups through non-targeted metabolomics sequencing. Subsequently, we further confirmed S-equol/R-equol both ameliorated DSS mice colitis, while estrogen receptor β (ERβ) antagonist inhibited the protective effect of equol partially. Molecular docking also confirmed the combination of equol and ERβ protein, of which the binding sites were GLU-305, Ph-356 and HIE-475.

Conclusion

This study found for the first time that the pro-inflammatory effects of S.m isolates are different, which may be related to gut microbiota-equol-ERβ axis.
P1325 Metabolic dynamics of the small intestinal microbiota upon nutritional interventions
Authors: Jordi S , Li J , Bärtschi I , Fasel N , Jacqueline W , Stecher B , Sauer U , Andrew M , Yilmaz B , Misselwitz B
Published: January 2025

Background

The human small intestinal microbiota, which plays a crucial role in intestinal function, remains poorly investigated due to limited accessibility.

Methods

We utilise the access via Ileostomies in a randomised cross-over trial with two nutritional interventions (high carb vs. high fat). Stoma effluent samples are collected from 70 stoma patients hourly (0-6h) after the intervention, along with blood and urine samples (0h, 3h, 6h). Stoma effluent samples from each study day are anaerobically cultured to generate a collection of small intestinal bacteria strains.

Results

We characterise the small intestinal microbiota through taxonomy (16S sequencing), biomass, and metabolome analysis. Shotgun metagenomic and mRNA sequencing are performed at selected timepoints. Our comprehensive “multi-omics" analysis involves identifying bacterial networks, interpreting their dynamics. In parallel, we have created a bacterial isolate catalogue (>1000 isolates, ~200 species) form human samples to reproduce key interactions in vitro.

Conclusion

This study aims for a comprehensive analysis of small intestinal microbiota dynamics in the context of different nutritional interventions. The data and samples collected will enable hypothesis testing in vitro and lay the groundwork for future disease-specific investigations. Additionally, by establishing an extensive catalogue of well-characterised human-derived bacterial isolates, we created a resource for future experimental research projects.
P1329 Longitudinal study of the gut microbiome in patients with ulcerative colitis on biological treatment with vedolizumab
Authors: Robles Alonso V , Herrera-deGuise C , Mayorga L , Varela E , Martín Arranz M D , Margolles A , Sabater C , Casellas F , Guarner F , Borruel N
Published: January 2025

Background

In inflammatory bowel disease, altered microbial states of the gut microbial ecosystem could influence response to treatment. Our objective was to investigate the possibility of predicting response to vedolizumab using markers of the gut microbiome.

Methods

To this end, we analysed the characteristics of the gut microbiome using shotgun metagenomic sequencing in 21 patients with active ulcerative colitis, eligible for treatment with vedolizumab. The protocol included assessment of clinical activity and analysis of the microbiome in faecal samples prior to treatment and at weeks 12, 30, and 52 after initiation, and endoscopy at week 12. Remission was defined by SCAI < 4, calprotectin < 150 μg/g, C-reactive protein < 0.5 mg/L, and Mayo index of 0 or 1. Sustain clinical remission was defined as previously at 52 weeks.

The study was funded by Takeda Farmacéutica España, S.A. EPIMUC study code: IISR-2015-101160 (FGA-VED-2016-01

Results

There were 9 responders and 12 non-responders. None of the patients with low microbial diversity (Chao1 <75) achieved remission at week 14. The microbiomes of patients who did not achieve remission were more heterogeneous in taxonomy and metabolic pathways than the microbiomes of those who remitted (p<0.05), which showed a stable microbiome composition profile during the remission induction phase. During treatment with vedolizumab, a progressive and significant increase (p<0.05) in the relative abundance of some anti-inflammatory commensals (Bacteroides uniformis, Roseburia intestinalis, R. inulinivorans, R. faecis, Lachnospiraceae spp.) was only observed in patients who achieved sustained remission.

Conclusion

The stability and responsiveness of the gut microbial ecosystem could be a precondition, among others, for a satisfactory response to anti-integrin treatment