bluuebunny/crossref_metadata_2025_split huggingface dataset:
P022 Development of a novel experimental model for studying creeping fat in Crohn's Disease
Authors: Clua L , Suau R , Guasch M , Monfort-Ferré D , Vañó I , Serena C , Domènech E , Bartolí R , Manyé J 
Published: January 2024

Abstract

Background
A characteristic feature of Crohn's disease (CD) is the transformation of mesenteric adipose tissue into creeping fat (CrF), which becomes inflamed and surrounds the transmural lesion. The occurrence of this condition has been associated with the severity of inflammation and post-surgical recurrence. In this study, we present a promising model of CD induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS) that exhibits experimental CrF. This model provides an innovative tool for the development of surgical techniques as well as the implementation of new therapeutic strategies, as it more accurately depicts the nature of the pathology.

Methods
Acute colitis was induced by intrarectal instillation of TNBS under conventional conditions. Five days after the administration, acute colitis developed (Fig. A). The variation in the percentage of weight compared to the initial weight was analyzed. Clinical activity was assessed through colonoscopy on the third and fifth days based on parameters such as hyperemia, the extension of ulcers, and presence of stenosis. Further, the weight-to-length ratio of the colon, as well as the area of the lesions, was also collected. All obtained data were analyzed in order to identify any possible differences between the sexes or between the groups that presented CrF or not.

Results
The frequency of CrF occurrence was approximately 50% in both sexes. Even though, females had smaller volume of CrF and a greater presence of fistulas. As compared to controls, the weight of the animals with CrF decreased (Fig. B) and their clinical activity index increased (Fig. C). Moreover, the area of the lesion was significantly increased in the group with CrF as compared with the group without CrF (Fig. D). The CrF group also demonstrated a significant increase in the weight-to-length ratio of the colon. There were no significant differences between the sexes in the aspects mentioned above.

Conclusion
The group presenting CrF showed a significant increase in all parameters of disease severity analyzed. We would like to emphasize that animals exhibiting severe symptoms by the fifth day were precisely those that manifested the development of CrF. Importantly, it is noteworthy that monitoring the disease through colonoscopy avoids the necessity for the sacrifice of animals, thereby facilitating a reduction in sample size.
P036 Microbiota Metabolite Butyrate Attenuates Intestinal Inflammation Through Autophagy Activation
Authors: Mao Q , Zhang W , Zhang Y , Lin B , Cao Q , Xu M 
Published: January 2024

Abstract

Background
Alteration of the microbiota metabolite short chain fatty acids (SCFAs) may contribute to the development of inflammatory bowel disease (IBD). Butyrate, one of the SCFAs produced by bacteria, is known to be beneficial in attenuating intestinal inflammation. However, the mechanisms underlying anti-inflammatory effects of butyrate have not yet been entirely investigated.

Methods
In vivo, wild-type C57BL/6J mice were given a gavage of sodium butyrate (SB) (0.12g/ml) for 5 days. The mice were then administered 2% dextran sodium sulfate to induce experimental colitis models. Fecal microbiota was analysed by 16S rDNA sequencing. In vitro, HCT116 cell line was used to investigate the protective roles of SB on lipopolysaccharide (LPS)-induced inflammatory response. The levels of inflammatory cytokines, intestinal tight junction and autophagy were detected by western blotting and quantitative polymerase chain reaction.

Results
We observed that SB treatment significantly attenuated colitis in rodent models with reduced tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β expression, and tended to restore intestinal barrier dysfunction. Mechanically, we identified that the inclusion of SB enhanced protein level of Atg16l1, which indicated enhanced autophagy function. In vitro cell experiments also proved that mRNA levels of IL-6 and TNF-α were decreased, while autophagy-related Beclin was enhanced. Furthermore, our results revealed a distinct alteration mediated by butyrate in the gut microbiota by restored ratio of Firmicutes/Bacteroides, increasing Erysipelotrichaceae and reduced Desulfovibrio abundance.

Conclusion
This study provides the first data demonstrating that butyrate supplementation attenuates intestinal inflammation probably via promoting autophagy and regulating intestinal microbiota. Our findings provide new insights into butyrate-mediated remission of IBD and butyrate as a potential modulator for autophagy to prevent and treat IBD.
P044 Evaluation of the CO2 Footprint of Laparoscopic Ileocecal Resection for Terminal Ileitis in Crohn's Disease
Authors: Munster L , van der Zwet B M , de Groof E J , Mundt M W , D'Haens G R A M , Bemelman W A , Buskens C J , Stobernack T , van der Bilt J D W 
Published: January 2024

Abstract

Background
Each year, huge amounts of carbon dioxide (CO2/equivalents) are generated and healthcare systems play a major role in the production of those so called greenhouse gases (GHG). The aim of this study is to assess the environmental impact, in particular the CO2 footprint, of laparoscopic ileocecal resection (ICR) for terminal ileitis in Crohn’s disease (CD) patients.

Methods
This is a prospective, multicentre evaluation of the carbon dioxide (CO2) emission caused by the care of CD patients undergoing laparoscopic ICR for terminal ileitis. All processes and products used during laparoscopic ICR for terminal ileitis in adult CD patients (≥16 years) between March and May 2023 were collected by one monitor. A Life Cycle Assessment (LCA) was conducted, including midpoint and endpoint analysis, to evaluate and compare the environmental impact, mainly focussing on CO2 (-equivalents), of all products and processes.

Results
The total CO2 footprint of a laparoscopic ICR for terminal ileitis in one CD patient (including transport of staff and patients) was 139 kg CO2eq, which equals a one way trip by car from Amsterdam to Berlin. Major contributors to CO2 emissions (“hotspots”) were transport of employees, transport of patients, medication, laparoscopic tools, electricity in theatre and a combination of standard surgery items. In addition to the carbon footprint, a significant impact on ozone formation, human carcinogenic and ecotoxicity, water consumption and mineral resource scarcity was found. The amount of disability-adjusted life years (DALY’s) as a result of the environmental impact of one laparoscopic ICR are equal to approximately 2.5 hours of health damage per laparoscopic ICR.

Conclusion
The “5 R principle” (refuse, reduce, reuse, repurpose, recycle) is an import aspect in reduction of the CO2 footprint and in current medical guidelines, which should be taken into account by all employees (e.g. consider traveling by train/carpooling). The total CO2 footprint of a laparoscopic ICR for terminal ileitis in one CD patient is 139 kg CO2eq. In addition to quality of life (QoL) and overall costs, the carbon footprint and overall the environmental impact of all medical procedures, should be taken into consideration and should be optimized if possible in the multimodal treatment of patients with CD terminal ileitis. Therefore, further research into the environmental impact of (medical/surgical) treatment of CD patients is warranted and more process data should become available.
P046 Real-world data on the treatment with Mirikizumab in a mostly biological-experienced Ulcerative colitis cohort
Authors: Lande R , Kubesch A , Farrag K , Dienethal A , Sprinzl K , Zeuzem S , Blumenstein I 
Published: January 2024

Abstract

Background
Mirikizumab was approved for treating Ulcerative colitis (UC) in May 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Mirikizumab in mostly treatment-experienced UC patients.

Methods
All patients treated for UC in the Inflammatory Bowel Disease (IBD) outpatient clinic of the University Hospital Frankfurt from 07/23-11/23 were analyzed retrospectively. Data on clinical (Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (fecal calprotectin (FC)), as well as patient history, were collected. Patients were followed up for at least 12 weeks.

Results
Seventeen patients with UC were included. Sixteen patients had already received at least one biological agent before starting Mirikizumab. Twelve patients were exposed to ≥ 2 biological agents, and four patients to ≥ 4 biological agents before starting Mirikizumab. One patient received Mirikizumab as a first-line treatment. 4 patients were treated with Ustekinumab before the therapy with Mirikizumab. Nine patients received oral steroids as a concomitant treatment. The median SCCAI at the time of the first infusion/start of induction was 7. We report a reduction in clinical disease activity from 7 to 5 based on the preliminary data of the SCCAI. Biochemical disease activity was assessed with FC levels. The median FC level at the start of the induction was 557.5. At week 8, the median FC level was 513 based on 7 out of 17 patients reached week eight until November 2023. Intravenous induction therapy was extended in 2 of 17 patients.
There was no report of adverse events.

Conclusion
We report preliminary real-world data on the evidence and efficacy of Mirikizumab. In our interim analysis, Mirikizumab is an effective and safe treatment in biological-experienced UC patients.
P047 Deconditioning in quiescent Crohn’s Disease patients with heightened fatigue perception
Authors: McGing J J , Nicholas R , Serres S , Gupta A , Radford S J , Bradley C , Bawden S , Francis S T , Greenhaff P L , Moran G 
Published: January 2024

Abstract

Background
Heightened fatigue perception and premature exercise fatigue are common in inflammatory bowel disease (IBD). Physical deconditioning is greater in patients with increased fatigue perception relative to patients with a lower perception of fatigue, implicating deconditioning as an aetiological factor.
This study used physiology and multiparametric Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) during exercise to comprehensively phenotype quiescent IBD fatigue.

Methods
Participant body mass and regional body composition was assessed by DEXA, and tknee extensor strength and fatiguability using isokinetic dynamometry (Cybex, USA). A supine CPET was performed using an MR-compatible Ergometer (Cardiostepper, Ergospect) to standardize relative exercise intensity for in-bore 1H MRI measures. 1H MRI data were collected on a Philips 3T Ingenia wide bore scanner using a Philips Head/Neck coil and in-built posterior coil. Across rest, steady-state exercise (50% VO2 peak) and recovery, Phase Contrast-MRI was used to compute cardiac output and cerebral blood flow (CBF), and T2 Relaxation under spin tagging (TRUST-MRI) to measure brain oxygen extraction fraction (OEF).
31P MRS data was collected on a 3T Philips Achieva using a 14cm 31P coil over the medial gastrocnemius. Ischaemic plantar flexion exercise was performed at 50% maximum voluntary contraction (MVC) using an MR-compatible ergometer (Trispect, Ergospect) during non-localized pulse-acquire 31P-MRS. 31P spectra were analysed using the AMARES function in jMRUI Beta 6.0. In vivo muscle mitochondrial flux during post-exercise PCr recovery (VPCr = kPCr * ΔPCr) where ΔPCr is PCrendrecovery –PCrendex) was quantified after reinstating limb blood flow and fitting PCr recovery to a mono-exponential function in GraphPad prism (PCr(t) = PCrinitial+(PCrend – PCrinitial)(1-exp(-k.t) where t is time from start of non-ischaemic recovery).

Results
16 quiescent CD patients and 12 age and BMI matched HV’s completed the study. General fatigue score was greater in CD relative to HV (P = 0.001, Table 1). Body composition, isometric strength, fatigue development were not different between groups (Table 1). CBF response to steady-state exercise was less in CD (P = 0.003) alongside the maintenance of cardiac output and brain OEF in HV (Figure 1). VPCr following ischemic plantar flexion exercise was less in CD than HV (P = 0.02, Figure 1) (Figure 1).

Conclusion
Greater fatigue perception in CD was accompanied by lower CBF on exercise and blunted post-exercise PCr resynthesis, but no differences in body composition, strength and fatiguability relative to HV. These finding point to greater deconditioning in CD, corroborated by their lower daily step count relative to HV.
P055 GPR43 and GPR84 play a crucial role in supporting perianal fistula formation and disease progression in Crohn’s Disease
Authors: Rubbino F , Di Cristofaro A , Wozny M , Rizzo G , Pineda Chavez S E , Converso G , Heijink M , Giera M , Maroli A , Bezzio C , Loy L , Carvello M , Spinelli A , Laghi L , Repici A , Armuzzi A , Vetrano S 
Published: January 2024

Abstract

Background
Fistula complication represents one of the most disabling manifestations of Crohn’s Disease and a risk factor for more aggressive disease progression and mucinous adenocarcinoma . However, molecular mechanisms behind this transformation are completely unknown. Growing evidence supported epithelial-to-mesenchymal transition (EMT) as a critical process to replace impaired intestinal fibroblasts in repairing mucosal membrane damage. However, EMT drivers during fistula formation and progression are still not completely known. Here, we investigated whether G-protein coupled receptors serve as new drivers of EMT and fistula disease progression.

Methods
Surgical specimens (N=9) collected from perianal fistula and non-involved areas of CD patients were analyzed by bulk RNA-sequencing and Lipidomics analysis. Gene set enrichment analysis (GSEA) was used to detect the levels of differentially expressed pathways. GPR43 and GPR84 analysis was performed on perianal fistula; adenocarcinoma; and mucinous adenocarcinoma-associated (MA) CD fistula FFPE tissue section. Caco-2 cell line was stimulated for 24 h with agonists and antagonists of GPRs. Genes associated to EMT were evaluated by RT-PCR and WB.

Results
Gene sets related to the signatures of epithelial-to-mesenchymal transition, G-protein coupled receptors (GPRs), immune response, lipid oxidation were significantly enriched in the fistula compared to non-involved tissue. Among differentially GPRs expressed genes FFAR2 encoding for GPR43, sensor for Small Chain Fatty Acids (SCFAs), and GPR84 sensor for Medium Chain Fatty Acids (MCFAs), predominantly expressed in immune cells, reported to be upregulated in the context of acute inflammation. Upregulation of GPRs expression correlated positively with enzymes associated to lipid oxidation gen set including PLA2G2D, ALOX5, NR4A3, PLA2G7, ACOXL and negatively with their lipids substrates. Caco2 cells stimulated with SCFAs and MCFAs upregulated not only the expression of GPR43 and GPR84, but also of EMT-transcription factor Twist1 and PLA2G2D, all effects reverted in the presence of their antagonists. An increase expression of GPR43 and GPR84 in association with Twist1 was found in MA-CD tissue section.

Conclusion
Our results highlighted GPR43 and GPR84 as new potential factors of fistula formation that support the EMT process through increased fatty acid oxidation, which in turn fuels the activation of GPRs. However, the increase expression of both receptors in the fistula oncogenic disease progression suggests that strategies regulating lipid metabolism or targeting GPRs could pave the way for novel therapeutic approaches to prevent fistula complication in CD patients.
P088 Single-cell transcriptomic analysis identifies early immune disturbances in preclinical Crohn's disease
Authors: Kioroglou D , Egia-Mendikute L , Palazon A , Barreiro-de Acosta M , Rodríguez-Lago I , Martinez Marigorta U 
Published: January 2024

Abstract

Background
Despite the increasing incidence of Crohn’s disease (CD), its early immune disturbances have not been described yet. The preclinical period provides an opportunity to gain insight into the initial processes involved in the pathogenesis of the disease. The main aim of our study was to describe how the subclinical inflammatory process is modifying the individual’s immunologic environment while the patient is still on preclinical period.

Methods
We analysed scRNASeq data from peripheral blood mononuclear cells (PBMC) of patients with incidentally-diagnosed CD according to ECCO criteria during the colorectal cancer screening programme, after histologic confirmation. Their gene expression profile was compared to healthy individuals acquired from publicly available datasets. The analytical pipeline included merging of the datasets followed by batch correction concerning integration from different studies, quality control and filtering, and finally cell-type annotation and differential gene expression analysis.

Results
Two patients with CD (mean age 53,5 years) and 2 healthy controls were included. We observed distinct transcriptomic profile in preclinical patients compared to controls, with small intragroup differences. The cell-type annotation identified B cells (B), CD4+ and CD8+ T-cells (CD4T, CD8T), dendritic cells (DC), monocytes (Mono) and natural killer cells (NK). The analytical pipeline included 17,021 cells (B:3,274, CD4T:5,798, CD8T:3,476, DC:315, 2, Mono:928, NK:3,230) and 3000 quantified genes. Considering each cell type individually, we identified 49 differentially expressed genes (DEG) between CD patients and controls (B:39, CD4T:37, CD8T:41, DC:42, Mono:37, NK:37), from which 30 were DEGs in all cell types.
Building on the list of 49 detected DEGs, we report three insights into the preclinical period of the disease. First, pathway analysis revealed significant enrichment of the pathway that is related to immunoregulatory interactions between lymphoid and non-lymphoid cells, and functional annotation analysis identified gene products that are related to immunological defense. Second, we identified significant transcriptomic alterations in genes that have previously been related to the symptomatic phase of IBD, or reported as potential biomarkers. Third, after performing principal component analysis we observed greater separation between the patients groups in the CD8T cells compared to the other cell-types.

Conclusion
This study reveals the initial transcriptomic profiles and the main pathways that precede the onset of symptomatic inflammatory bowel disease. Our findings may help in identifying potential targets for early disease intervention.
P103 Natural compounds in Ulcerative Colitis and Irritable Bowel Syndrome: Insights from immune-metabolic profiles
Authors: McShane C , O'Connell F , Pigott M , Obaidi I , Sheridan H , Kevans D , O'Sullivan J 
Published: January 2024

Abstract

Background
Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) represent chronic and occasionally disabling conditions, necessitating innovative treatment strategies. Covering 14% of Ireland's landscape, bogland ecosystems house unique plant biodiversity, yielding biologically active secondary metabolites. Informed by traditional medicinal knowledge and in vitro screening for immunomodulatory potential, three plant extracts (NTP0226A, NTP0127B, NTP0206EA) were selected for exploration of their potential to treat IBD and IBS within the "Unlocking Nature’s Pharmacy from Bogland Species" project.

Methods
Patients undergoing colonoscopy were prospectively recruited in three cohorts: healthy controls, IBS, and ulcerative colitis (UC). Recto-sigmoid biopsies were collected and cultured for 24 h with treatments (Infliximab, NTP0226A, NTP0127B, NTP0206EA). Colonic tissue explants underwent real-time energy metabolism profiling and quantification of 10 inflammatory mediators using Seahorse Xfe24 analyser and multiplex ELISA, respectively. P values &lt;0.05 were considered significant in analyses.

Results
Twenty-seven patients were recruited (6 healthy controls, 6 IBS, and 15 UC). UC patient explants exhibited elevated glycolytic metabolism and increased IL-4, IL-6, and IL-12p70 secretion compared to non-UC patients. No differences were observed between healthy controls and IBS patients. Linear regression did not show correlation between age and mitochondrial bioenergetics. There was no change in metabolism profiles of any cohort following treatment with Infliximab or the 3 novel extracts. In the UC tissue, treatment with Infliximab reduced IL-12p70 secretion (p=0.0098), this reduction was not seen in the other 2 cohorts. NTP0206EA reduced IL-10 secretion in the UC cohort (p=0.0255). In the IBS cohort; NTP0127B reduced IL-10 secretion (p=0.0048) and NTP0226A reduced IL-4 (p=0.004) and IL-6 (p=0.0219) secretion. Principal component analysis demonstrated reduced separation between the immune-metabolic profiles of UC patients and healthy controls following treatment with NTP0226A (Figure 1).

Conclusion
Using an explant model, we have shown that UC patients have a distinct immune-metabolic profile modifiable by a standard IBD therapy and novel plant extracts. Blockade of IL-6 trans-signalling has recently shown promise as an effective treatment target in IBD. Our natural extract NTP0226A reduced IL-6 secretion in IBS patients and is a promising candidate for therapeutic exploration. These findings contribute to our understanding of the complex interplay in the colonic microenvironment and highlight potential avenues for novel therapeutic interventions.