bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1208 MH002, an optimized live biotherapeutic product, for the treatment of inflammatory bowel diseases, has mode-of-actions linked to restoration of intestinal dysbiosis, mucosal integrity, and immune homeostasis
Authors: Bolca S , Pinheiro I , Gottardi D , Van den Bossche L , Haazen L , Possemiers S 
Published: January 2024

Abstract

Background
MH002 is a live biotherapeutic product consisting of 6 well-characterized commensal strains, that is in clinical development for the treatment of Ulcerative Colitis (UC) and acute Pouchitis. Both are multifactorial disorders which occur through a combination of dysregulated host inflammatory mechanisms and interactions with gut microbiota.

Methods
Faecal slurries of 6 UC patients with active disease were prepared to inoculate a standardized in vitro gut model (SHIME®) which mimics the colon microbiome of patients. A total of 24 simulators were run for 8d, with a single dose administration of MH002 (human equivalent dose [HED] ~1) or vehicle on Day0. Butyrate production in the simulators was quantified daily and host response effects were assessed in in vitro cell-based assays using samples from Day1. Caco-2 cells were co-cultured with human peripheral blood mononuclear cells and treated for 48h with Day1 samples, followed by transepithelial electrical resistance (TEER) and cytokine measurements. Wound healing was assessed by imaging of monolayers of T84 cells, scratched and treated with Day1 samples.
Furthermore, the effects of MH002 (daily, 24d, HED ~30) on disease activity index (DAI; body weight [BW], stool consistency, occult blood), local inflammation, and mucosal damage were evaluated in acute dextran sulfate sodium (DSS) induced colitis, when administered to C57BL/6 mice (15/group) as from 14d prior to DSS intake, and compared to 5-aminosalicylate (5-ASA; daily, 24d, 150mg/kg) and vehicle. Animals were euthanized in the acute (Day7; 10/group) and recovery phase (Day11; 5/group).

Results
In vitro administration of MH002 to patient-derived colonic microbiomes restored within 1d butyrate production and increased efficiency to improve epithelial barrier integrity, modulate T-cell-mediated immune responses, and promote mucosal wound healing in in vitro cell cultures (Table 1).
DSS intake induced a significant decrease in relative BW and an increase in DAI. A significant recovery (BW, DAI, stool consistency) was observed at Day11 for MH002 and 5-ASA. Moreover, at Day11, macroscopic inflammation (colon weight/length ratio) and histologic scores were lower with MH002 and 5-ASA as compared to vehicle (Figure 1).

Conclusion
By restoring intestinal dysbiosis and epithelial integrity, and attenuating local inflammation, MH002 treatment should lead to lower disease activity and, ultimately, to clinical remission without immune suppression. Indeed, study MH002-UC-201 in mild-to-moderate UC was completed with favourable treatment effects (endoscopic improvement, faecal calprotectin normalization, improved stool consistency) and no safety concerns (Abstract Vermeire et al.; EudraCT 2020-004355-33).
P1211 A faecal microbial signature, in combination with faecal calprotectin, to optimise endoscopic activity monitoring in Crohn’s Disease
Authors: Taboada-López S , Malagón M , Amoedo J , Ramió-Pujol S , Busquets D , Bahi A , Gilabert P , Rodríguez-Alonso L , Mañosa M , Cañete F , Torres P F , Morales V J , Delgado-Guillena P G , Domenech E , Guardiola J , Serra-Pagès M , Garcia-Gil L J , Aldeguer X 
Published: January 2024

Abstract

Background
Monitoring Crohn's Disease (CD) endoscopic activity (EA) is crucial to identify disease progression and tailor treatment. Faecal calprotectin (FC) provides a non-invasive and cost-effective alternative to colonoscopy; however, it exhibits only a moderate correlation with EA in CD, highlighting the need for a non-invasive approach that either replaces or complements FC.
This study aimed to identify a faecal microbial signature that could offer more precise monitoring of EA in CD.

Methods
A cohort of 55 CD patients was recruited from four Spanish hospitals. All participants provided a faecal sample before undergoing colonoscopy for the analysis of FC levels and microbial markers abundances, including Eubacteria (EUB), Escherichia coli (ECO), Faecalibacterium prausnitzii (FPRA) and its phylogroups I and II (PHG-I, and PHG-II), Ruminococcus spp. (RUM), Akkermansia muciniphila (AKK), Methanobrevibacter smithii (MSM), Clostridium clusters I and XIV (CLO, and XIV), Enterococcus sp. (ENT), Roseburia sp. (ROS), and Gammaproteobacteria (GAM). The Simplified Endoscopic Score for Crohn’s Disease (SES-CD) was employed to assess EA, being remission and activity defined as SES-CD≤2 and SES-CD&gt;2, respectively.

Results
FC levels showed a significant correlation with SES-CD (rs=0.778, p&lt;0.001) and a cut-off of 250 μg/g discerned EA with 86.49% sensitivity (SS), 75.65% specificity (SP), 77.06% positive predictive value (PPV) and 84.53% negative predictive value (NPV). Significant differences were identified when comparing the relative abundances of ECO (p&lt;0.005), GAM (p&lt;0.005), and RUM (p=0.026) between activity and remission. The relative abundance of ECO (rs=-0.495, p&lt;0.001), GAM (rs=-0.492, p&lt;0.001), and RUM (rs=0.274, p=0.042) also showed a significant correlation with SES-CD. None of the microbial markers alone exceeded FC performance.
The combination of FC levels with the abundances of the microbial markers ECO, RUM, GAM, PHG-II, and XIV in a unique signature outperformed FC alone in discerning EA, with 97.57% SS, 93.59% SP, 91.65% PPV, and 97.57% NPV. The false positive (FP) and negative (FN) rates were reduced by 60.00% and 75.00%, respectively, compared to FC alone. Notably, all the FN presented mild endoscopic activity, indicating accurate monitoring of patients with moderate or severe EA.

Conclusion
A new faecal microbial signature combined with FC has been defined to monitor EA in CD with higher performance than FC alone. This tool may improve clinical decision support systems in CD management, refining endoscopic allocation, and providing a more patient-friendly and cost-effective approach. Further studies are needed to validate these results.
P1213 The effects of Escherichia coli Nissle 1917 on the gut microbiota composition in ulcerative colitis patients
Authors: Puca P , Del Chierico F , Graziani C , Masi L , Coppola G , Di Vincenz F , Capobianco I , Lopetuso L R , Barbaro M R , Masucci L , Putignani L , Petito V , Marasco G , Sanguinetti M , Barbara G , Gasbarrini A , Scaldaferri F 
Published: January 2024

Abstract

Background
Escherichia coli Nissle (EcN) 1917 is a Gram-negative bacterium currently used as probiotic in the management of infectious gastroenteritis and ulcerative colitis (UC).
We evaluated the effect of administration of EcN on the composition of the gut microbiota and on intestinal permeability in patients affected by UC.

Methods
Five patients with stable UC were treated with EcN one pill daily for ten days followed by two pills per day for further twenty days. Fecal samples were collected before the treatment (T0), after ten days (T1) and after one month of treatment (T2). Alpha diversity, microbiota composition and taxonomy were analyzed.

Results
Alpha diversity increased through treatment: Good’s coverage index revealed an increase in the number of operational taxonomic units (OTUs) at T2. At phylum taxonomic level, Firmicutes relative abundance decreased at T1 compared to T0. At family level, Clostridiacae relative abundance at T1 was higher than T0 and T2. The T test on gut microbiota variations at species level reveals the variability at the two timepoints (T0 and T2), with significant increase for Actinomyces, Anaerostipes, Bacteroides, Bulleidia, Corynebacterium, Dialister, Enterobacteriaceae, Erysipelotrichaceae, Finegoldia, Granulicatella, Lactobacillaceae, Peptoniphilus, Phascolarctobacterium, Roseburia, Serratia, Veillonellaceae, Veillonella dispar.
Furthermore, the administration of EcN improved intestinal permeability, assessed on a CaCO2 monolayer.

Conclusion
Treatment with EcN leads to an improvement in the qualitative composition of the gut microbiota in patients affected by UC, in terms of both diversity and taxonomy. These effects are stronger at the end of treatment.
P1223 Lactobacillus rhamnosus GG/p40 encapsuled cationic host defense peptide play protective roles on immune-related colitis by inducing differentiation and immune suppression of regulatory T cells
Authors: Zhou Q , Liu X , Tang H , Zeng Y , Shi Q , Lu B , Qian J , Chen M , Xu Y , Wang M , Tan B 
Published: January 2024

Abstract

Background
The immune-related colitis (IRC) is the most prominent in immune-related adverse events (irAE). The association between gut microbiota and IRC development has been revealed. Our study aimed to explore the protective effect and mechanism of the probiotic Lactobacillus rhamnosus GG (LGG) and its secretory protein p40 on IRC. The self-assembled cationic host defense peptide (CHDP) hydrogel was applied to protect oral p40 protein from digestive damage and target enriched the site of colitis.

Methods
The IRC model mice were intervened with LGG by gavage (i.g.), p40 by enema (en.), or p40 encapsuled by CHDP (i.g.). The T cell phenotype of colonic lamina propria mononuclear cells (LPMC) was measured by flow cytometry. The indocyanine green (ICG) encapsuled by CHDP was gavage in IRC model mice, the distribution of CHDP was monitored by fluorescence signals imaging via IVIS, to assess the adhesive effect of CHDP in mice colitis. In vitro, the proportion of regulatory T cells (Treg) differentiated was measured by LGG supernatant co-cultured with CD4+ naïve T cells, and the division index of CD4+T cells was measured by LGG supernatant co-cultured with CD4+T cells and Treg (CD4+T cells: Treg=1:1) by carboxyfluorescein succinimidyl ester (CFSE) staining test.

Results
Compared with DSS+anti-PD-1+anti-CTLA-4 IRC model group, LGG (i.g.) group had lower weight loss, DAI score, histopathological score, relative IL-6 and TNF-α mRNA level, IL-6 and TNF-α concentration and higher colon length (P&lt;0.05) (Fig.1A-L). P40 (en.) group had lower weight loss, DAI score, histopathological score and higher colon length (P&lt;0.05) (Fig.1M-T). CHDP+p40 (i.g.) group had lower weight loss, DAI score, histopathological score, relative IL-6 and TNF-α mRNA level, IL-6 concentration and higher colon length (P&lt;0.05) (Fig.1M-W). The percentages of CD25+FoxP3+Treg/CD4+T cells of colonic LPMC in LGG, p40 (en.), and CHDP+p40 (i.g.) group were significantly higher than IRC model group (P&lt;0.05) (Fig.1X-Z, α). The average 28hr-residual rate of fluorescence imaging radiance in IRC-CHDP+ICG group was higher than both NC-CHDP+ICG and IRC-ICG group (Fig.2β-δ), and the average radiance of colon in IRC-CHDP+ICG group was also the highest (P&lt;0.05) (Fig.2ε-ζ). In vitro, LGG 107 CFU/mL, 108 CFU/mL and 5 × 108 CFU/mL (P&lt;0.05) could significantly promote Treg differentiation with concentration dependent manner (Fig.2η-ι), and the suppression of Treg on CD4+T cells with lower division index compared with control group (Fig.2κ).

Conclusion
LGG/p40 played protective role by promoting the differentiation and immune suppression of Treg cells in IRC. CHDP hydrogel could protect p40 protein from the digestive damage, and target enriched the inflamed lesion to improve the efficacy.
P1228 The EISER Study: Identifying Microbial Factors Associated with Subclinical Gut Inflammation in Psoriatic Arthritis Patients Who Develop Inflammatory Bowel Disease
Authors: Marín Jimenez I , Boix-Amorós A , Blank R B , Cantor A , Sanz Sanz J , Gutiérrez-Casbas A , Gratacós J , Rodríguez-Lago I , Trujillo E , Plaza Z , Domínguez-Álvaro M , Díaz-González F , Cañete J D , Scher J U , Clemente J C 
Published: January 2024

Abstract

Background
Nearly 8% of patients with spondyloarthritis (SpA) manifest symptoms that are compatible with active inflammatory bowel disease (IBD). It is well established that microbial dysbiosis is associated with different immune-mediated diseases. We therefore hypothesized that the gut microbiome could be a modulator of intestinal inflammation and factor in the pathogenesis of IBD in SpA patients.

Methods
As part of the EISER study, we selected a subset of 193 subjects diagnosed with psoriatic arthritis (PsA), a form of SpA, who had no prior diagnosis of IBD. The presence of subclinical symptoms compatible with IBD was evaluated at time of enrollment. For patients with fCAL levels of 80 µg/g or higher, colonoscopy was performed and histological analysis of biopsies collected during the procedure were used to diagnose IBD. Capsule endoscopy was performed on those patients with a negative colonoscopy result. Stool samples were collected from all participants, and microbial DNA was extracted for shotgun metagenomic sequencing using the Illumina HiSeq platform. Sequenced data was processed using MetaPhlAn 4 to estimate taxonomic composition, MMEDS for overall microbiome analysis, and R for additional statistical analyses.

Results
Twenty-five out of 193 subjects in our cohort (12.95%) had symptoms that were compatible with subclinical IBD (sIBD) and five patients (2.6% of total) were confirmed to have clinical IBD (cIBD). The use of nonsteroidal anti-inflammatory drugs (NSAIDs) resulted in significant differences in overall alpha (Shannon entropy, p=0.03) and beta microbial diversity (PERMANOVA, p=0.043), while the use of proton-pump inhibitors (PPI) resulted in significant differences in beta diversity (PERMANOVA, p= 0.036). Patients with cIBD had significantly higher abundance of taxa including Prevotella copri and Prevotella stercorea. P. copri, P. stercorea and fCAL were all significantly elevated in cIBD patients (Wilcoxon’s p=0.0278, 0.0007, 0.0161), although with a larger effect size in P. copri and P. stercorea (Cohen’s D: P. copri = 1.074; P. stercorea = 1.269; fCAL= 0.629). fCAL was also significantly elevated in patients who used PPIs (p= 4.456e-11), while P. copri and P. stercorea abundances were not impacted (Wilcoxon’s p: P. copri = 0.2394; P. stercorea = 0.0643).

Conclusion
Microbiome composition was impacted by the use of NSAIDs and PPI. We identified taxa differentially enriched in cIBD patients, including Prevotella copri and P. stercorea. Importantly, while fCAL was significantly higher in cIBD patients, its discriminatory power was not as strong as that of P. copri and P. stercorea, suggesting that these taxa could be potentially used as biomarkers of co-morbid IBD in patients with PsA.
N12 The Experience of Post-traumatic Growth Process in Newly Diagnosed Chinese Patients with Crohn’s Disease: A Longitudinal Qualitative Study
Authors: Chen L , Zhou Y , Liu J 
Published: January 2024

Abstract

Background
The impact of Crohn’s disease (CD) is not purely negative, it may become an opportunity for patients to undergo positive psychological adjustments and achieve personal growth. To date there has been limited in-depth research to understand the patients’ experiences of post-traumatic growth (PTG) process following an CD diagnosis using a qualitative study with a longitudinal perspective.

Methods
A longitudinal qualitative design was adopted. Sixteen newly diagnosed Chinese patients with CD were recruited through purposive sampling. Semi-structured interviews were conducted on three occasions: 3, 6 and 12 months post-diagnosis. Data were collected between November 2021 and December 2022. Data analysis of each time point was based on conventional content analysis. Afterwards, all data were combined for a comprehensive re-analysis to capture change.

Results
Four themes and fifteen sub-themes were formed through analysis (table 1). The process of PTG was shown in Figure 1. Within the first year post-diagnosis, patients with CD experienced considerable physical discomforts and psychological distress. Their personal development was also limited. With increased disease knowledge, and driven by a strong sense of responsibility and external support, the patients’ disease acceptance transformed from "difficult to accept" to "have to accept" to "should accept" then to "be able to accept". Living with CD, they actively engaged in monitoring disease condition, cooperating with treatment, exploring patterns of flare-ups, relieving stress and focusing on problem solving to eliminate negative emotions, and regaining hope and positively planning for future. Over time, the impact of CD on the patients’ lives became smaller, they integrated their disease as a part of themselves, and achieved personal growth. This growth was manifested by "developing closer relationships with others", "increasing personal strength", "changing in life philosophy" and "emerging new possibilities". Overall, as disease duration increased, the disease related sufferings diminished, and CD patients’ disease acceptance improved. In addition, as time goes by, the patients’ ability to self-manage disease enhanced, and their experience of personal growth increased.

Conclusion
The process of PTG in patients with CD within the first year of diagnosis primarily consists of four stages: "enduring hardships", "accepting illness", "living with illness", and "achieving personal growth". This growth was not linear, but rather cyclical. Nurses could provide targeted guidance to patients based on the trajectory identified in this study, helping them unearth inner resources and create conditions for PTG.
N23 Incorporating a patient facing application and home calprotectin based patient initiated follow up and monitoring in IBD Home® digital care
Authors: Schranz J , Whitehead E , Peaks H , Turnbull J , Robertson H , Fitzgerald A , Sebastian S 
Published: January 2024

Abstract

Background
The need for directed self-are is fundamental to the safe management of relapsing and remitting course in IBD and access to timely assessment and modification of treatment is essential during IBD flares to avoid the need for hospitalisation. Similarly, scheduled care models may cause significant disruption to activities of daily living for patients
IBD Home is a whole system model is comprehensive, integrated, and holistic approach to value-based care to provide `multidisciplinary ring` of supported care around the needs of patients in their own homes. Electronic- and virtual-based platforms have been developed to routinely monitor IBD patients and guide appropriate interventions. We incorporated a patient-facing app called MyIBD Care® and CalproSmart™ self-calprotectin test in two cohorts of patients participating in IBD Home in our IBD unit

Methods
Eligible IBD patients were invited to participate in the project. We piloted two cohorts of patients in this phase – cohort 1: patients in long-term remission on no therapies /and or mezalazine . Cohort 2: Patients on self-administered biologics or immunomodulatory agents. Following consent to digital data sharing and training, home FC results and patient reported measures entered by patient in portal of My IBD Care App. The interval of PROMS and frequency of home calprotectin tests were personalised to the cohort. IBD care navigator reviewed the information and those with raised calprotectin was reviewed virtually by IBD nurse in the clinician portal with a bidirectional record of the contact.

Results
1382 patients were eligible and invited to participate the two cohorts (29.5% of the entire Hull IBD cohort). 594 patients (43%) joined cohort (284 in cohort 1 and 310 in cohort 2). 550 patients (total number of PROMS 2309, mean 4.25) completed PROM. PROM engagement is depicted in figure 1. One hundred and forty seven patients had an intermediate or high calprotectin results among whom 94 had symptoms suggestive of flare on PROMs. In patients with elevated home calprotectin test 42 needed in person appointment and 24 others had change in therapy. One hundred and eleven patients in cohort 1 did not require an annual clinic review because of PROM result and low calprotectin levels. At 12 months, 41 patients (6.9%) were withdrawn from the cohorts.

Conclusion
Patient initiated follow up using My IBD care app along with self-monitoring of calprotectin is feasible in IBD patients in long-term remission and may reduce in person appointment. In those who join, the engagement to the PROM completion and continuation in pathway remains high at 12 months .Identification of suitability and studying patient preferences is important to increase uptake rates in digital pathways.
N25 "I Felt So Alone” Exploration of experience of being newly diagnosed with inflammatory bowel disease: a phenomenological study
Authors: Chaudhary A , Norton C , Watson N , Czuber-Dochan W 
Published: January 2024

Abstract

Background
Individuals recently diagnosed with Inflammatory bowel Disease (IBD) often have unmet informational and psychological needs, leading to distress and anxiety. This lack of support negatively affects their quality of life, mental health, social functioning, and physical outcomes. Additionally, the absence of counselling and peer support isolates many people and places an emotional burden on them. Delayed diagnosis or misdiagnoses due to symptoms being dismissed by health professionals exacerbate the problem. Acknowledging these unmet needs and adverse outcomes, this study aims to shed light on patients' experiences to inform improvements in clinical practice, support services, and workplace policies, particularly during the immediate diagnosis phase.

Aim
The aim of this study is to explore the experience of people newly diagnosed with IBD and their need for support.

Methods
The study employed interpretive phenomenology semi-structured interviews following a topic guide and analysed the data using Braun & Clark's (2023) thematic analysis method and Nvivo software. Crohn's and Colitis UK (CCUK) charity acted as the gatekeeper for access to participants. Participants were purposively selected on specific criteria: IBD diagnosis ≤1 year, aged 16 or older, English language proficiency and diversity of demographic and clinical variables.

Results
Of 49 volunteers who responded to the research advertisement, 15 were selected based on eligibility criteria. Participant characteristics are shown in Table 1. Four themes emerged (Fig 1), with 12 subthemes. Participants expressed extreme dissatisfaction, either due to misdiagnosis or diagnostic delays, indicating the need for timely streamlined diagnosis. Additionally, IBD diagnosis itself triggered distress and anxiety. Participants reported the need for continuous psychological counselling and peer support. Due to symptoms like blood loss and diarrhoea, IBD profoundly affects physical health, emotional wellbeing, social interactions, and work-life balance, hence challenging patients' sense of normalcy. However, patients demonstrated resilience via lifestyle adjustments, social support networks, and coping strategies.

Conclusion
This qualitative study sheds light on the profound impact of an IBD diagnosis. It reveals emotional struggles and the need for streamlined diagnosis and psychological support. Lifestyle disruptions affect physical and mental health, but participants adapt through support and coping. These insights have practical implications for improving care, mental health services, workplace adjustments, social support, and coping resources for the newly diagnosed IBD population. Future research should expand to larger, diverse patient samples.
Table 1: