bluuebunny/crossref_metadata_2025_split huggingface dataset:
P050 Analysis of 61 exclusive enteral nutrition formulas used for induction of remission in Crohn’s disease: new insights on dietary disease triggers
Authors: Logan M , Gkikas K , Svolos V , Nichols B , Milling S , Ijaz U , Hansen R , Russell R K , Gerasimidis K 
Published: January 2020

Abstract

Background
Exclusive enteral nutrition (EEN) is an effective treatment of Crohn’s disease (CD). We hypothesise that food ingredients which are included in EEN formulas are less likely to initiate a disease flare and that their dietary elimination is not essential for disease amelioration.

Methods
We performed a compositional analysis of EEN formulas with evidence of clinical efficacy for the induction of remission in active CD. Macronutrient content was compared against the dietary reference values (DRVs), the UK National Diet and Nutrition Survey (NDNS) and children with CD. Food additives included with EEN formulas were cross-referenced against the FAO/WHO database.

Results
Sixty-one formulas were identified with variable composition [carbohydrates (23–89%), protein (8–30%), fat (0–50%)], Figure 1. Modified starches (e.g. maltodextrin), milk protein and vegetable/plant oils were the commonest sources of carbohydrate, protein and fat, respectively, Figure 2. The n-6:n-3 fatty acid ratio varied from 0.3 to 46.5. Fifty-six unique food additives were identified contained within EEN formulas (median per formula: 11), Figure 3. All formulas were lactose, gluten free. Eighty per cent lacked fibre. The five commonest food additive functional classes were emulsifiers, stabilisers, antioxidants, acidity regulators, and thickeners. Food additives, implicated in CD aetiology, were present in formulas [modified starches (100%), carrageenan (23%), carboxymethyl cellulose (14%) and polysorbate 80 (5%)]. EEN formulas derived 7.9% less energy from saturated fat than participants from the NDNS (p = 0.001). CD children consumed more sugars, total/saturated fat than the EEN content.

Conclusion
We provide a list of food ingredients which are unlikely, in the amount provided within EEN, to trigger CD activity. Current perceptions about the role of these ingredients in CD management are challenged.
P058 The lived experience of family planning of female patients diagnosed with inflammatory bowel disease and their partners during key reproductive stages: a qualitative study
Authors: Czuber-Dochan W , Homer R , Brookes M , Selinger C , Purewal S , Chapman S , Steed H 
Published: January 2020

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic illness affecting patients in their childbearing years. The physical effects of IBD on fertility and pregnancy in IBD in remission (e.g. disease is well controlled during conception and throughout pregnancy) are similar to the normal population. However, many women with IBD have high pregnancy-related anxieties and are more likely not to have children compared with women without IBD. The reasons cited for not having children include high levels of pregnancy-related anxieties have been insufficiently explored. The study aimed to explore the lived experience of family planning of women with inflammatory bowel disease (IBD) and their partners with or without IBD, during the reproductive stages of pre-conception, pregnancy and the postnatal period.

Methods
Descriptive phenomenology was used to conduct face-to-face in-depth individual interviews. Purposive sampling was used to select participants with a maximum variation of different demographic and clinical factors, e.g. age, sex, UC/CD diagnosis, disease duration, surgery and geographic location. The NVivo 12 software programme was used to manage the data and Colaizzi’s framework was utilised in thematic data analysis.

Results
Twenty-four participants (21 women 11CD/10UC and three partners) were recruited from out-patient clinics (22 participants) or through the Crohn’s and Colitis UK website (two participants). Women, average age 31 years old (range 27–38), were at different family planning stages: pre-conception six women (three actively planning family and three voluntarily childless); pregnant eight women and two partners; and postpartum seven women and one partner. Three women’s partners, age 32–39, were recruited allowing for additional perspective of the experience being captured. In total, 19 h of interviews data were collected. Six themes were identified: (1) being diagnosed and controlling IBD symptoms, (2) relationship and family planning, (3) sources of information,
(4) worries and concerns about pregnancy, (5) post pregnancy care and problems and (6) ways of improving care. Women in pre-pregnancy stage and pregnant expressed a need for more information around these themes: (1) their medication and the impact of IBD on the baby, (2) the genetic risk of passing the disease on. While pregnant and during post-partum stage, women identified a greater need for practical advice and support in relation to breastfeeding and looking after the baby.

Conclusion
Information specific to family planning stages need to be provided, to help women and their partners make the informed decision about family planning. Those who decided not to go down the family route also expressed a need for counselling and support.
P067 Proteins citrullination and Crohn’s disease: PAD4 but not PAD2 is a strong marker of ileal inflammation
Authors: Dragoni G , Creyns B , De Hertogh G , Verstockt B , Wollants W J , Ke B J , Marcellis L , Matteoli G , D’Hoore A , Galli A , Ferrante M , Vermeire S 
Published: January 2020

Abstract

Background
Citrullination is a post-translational modification of proteins, mediated by enzymes called PAD (peptidylarginine deiminases). The immune system can attack citrullinated proteins, leading to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and ulcerative colitis, and the activity of PAD2 and PAD4 in innate immune cells has been demonstrated for these disorders. Recently, high levels of PAD2 have been described in activated fibroblasts in the context of liver fibrosis. We therefore investigated the role of PAD2 and PAD4, both in inflammatory and fibrotic contexts of ileal Crohn’s disease (CD).

Methods
We obtained ileal transmural samples from patients operated for stricturing ileal CD. Three different macroscopic areas within each resection specimen (i.e. proximal normal ileum, inflamed ileum and fibrotic ileum) were selected and histologically confirmed by an expert pathologist. Patients undergoing ileocolic resection for other conditions (e.g. right colon cancer) and with healthy terminal ileum were used as controls. For each region (normal CD, inflamed CD, fibrotic CD and control), immunohistochemistry (IHC), RNA and protein evaluations for PAD2 and PAD4 were performed. Multiplex immunofluorescence (IF) for PAD2, PAD4, myeloperoxidase, neutrophil elastase, CD68, vimentin and α-smooth muscle actin were carried out to investigate the enzymes-expressing cells. Additional IF was performed to study citrullinated histone 3 (H3cit) expression, the product of PAD4 activity in neutrophils and component of neutrophil extracellular traps (NETs). Statistical analysis was carried out with Kruskal–Wallis test and post hoc Mann–Whitney test.

Results
Resection specimens from 13 CD and 11 controls were included. IHC and IF showed an increased expression of both PAD2 and PAD4 in the neutrophils of inflamed areas, in cytoplasm and nucleus, respectively (Figure 1). Activated fibroblasts (vimentin+ and α-smooth muscle actin+) were negative for both enzymes. PAD4 mRNA expression was increased in inflamed tissue (p = 0.001, p = 0.008 and p = 0.028 vs. normal CD, fibrotic CD and controls, respectively), and confirmed using Western Blot (Figure 2). H3cit was increased in the ileal inflammatory infiltrates too (Figure 3), confirming high PAD4 expression. For PAD2, no significant changes were observed at RNA and protein level, mainly due to its reduced expression in epithelial cells from normal to diseased tissue (Figure 4).

Conclusion
Both PAD2 and PAD4 are strongly expressed in neutrophils of CD ileal resection specimens, but only PAD4 shows a significantly higher expression in the inflammatory context which translates in the formation of NETs. No direct correlation was observed between PAD enzymes and intestinal fibroblasts.
P068 Erythrocyte and reticulocyte parameters in children with inflammatory bowel diseases
Authors: Semikina E , Potapov A , Tsvetkova V , Anoushenko A , Akulova S 
Published: January 2020

Abstract

Background
Anaemia is a frequent extraintestinal manifestation of inflammatory bowel diseases (IBD) and its severity leads to a deterioration in patient’s condition. Timely diagnosis and pathogenetic therapy are important for the effective treatment. The aim of this study was to evaluate the current cell indexes obtained from automatic blood analyser to identify the pathogenetic features of anaemia in children with IBD.

Methods
A total of 1400 blood samples were analysed in 420 children with IBD (177—Crohn’s disease (CD) and 243—ulcerative colitis (UC)) followed up in our centre in 2018–2019. A blood test was performed by flow hemocytometry on an automatic blood analyser Sysmex XN 1000. The evaluated parameters were: MCV, MCH, MCHC, RET, IFR and RET-He. Anaemia was established with haemoglobin level &lt;110 g/l. Clinical activity was evaluated according PUCAI (UC) and PCDAI (CD) scores.

Results
Anaemia was detected in 31.7% of patients with UC and in 26.8% of patients with CD. Decreasing of Hb level was observed in both diseases with an increasing in the clinical activity. The average Hb levels in CD in remission, moderate and severe activity were 132.15 ± 17.07, 120.51 ± 18.28 and 105.06 ± 12.46 g/l, respectively; in children with UC with remission, minimal, moderate and severe activity 124.86 ± 16.01; 114.53 ± 15.56; 109.71 ± 20.34 and 96.09 ± 16.52 g/l, respectively. In patients with CD, anaemia was predominantly hypochromic: the average values of MCV, MCH and RET-He indicates a leading role the bioavailable iron deficiency and corresponded to those in CD remission: 82.8 ± 7.0 fl, 27.35 ± 3.02 pg and 31.28 ± 3.82 pg; in low/moderate CD activity: 78.93 ± 7.49 fl, 25.29 ± 3.51 pg, 28.62 ± 5.1 pg; in high CD activity: 74.7 ± 6.74 fl, 22.99 ± 2.69 pg, 27.14 ± 4.99 pg, respectively. RET count in CD was moderate and equal 58–68 cell/ml. With an increase in the UC process activity, hypochromia was not enhanced: MCV in the range 79–82 fl, MCH—25–26 pg. RET-He in remission of UC were 30.22 ± 3.95 pg; in minimal activity—28.93 ± 4.96 pg; in moderate activity—27.99 ± 4.62 pg and only with high activity of UC there was a decreasement to 25.21 ± 4.99 pg. In UC the level of RET and IFR increases with increasing severity of the disease: 57.75 ± 17.48‰, 63.31 ± 31.12‰, 77.29 ± 41.81‰, 111.29 ± 78,9‰ and IFR 11.62 ± 5.235%, 15.69 ± 8.065%, 18.97 ± 8.385%, 26.97 ± 9.785%, respectively. This suggests that anaemia in UC is mainly associated with blood loss.

Conclusion
Anaemia in different forms of IBD in children has different pathogenetic mechanisms. Evaluation of current parameters of red blood cells by modern automatic blood count analyser is cheap and informative for the differential diagnosis of anaemic syndrome in children with IBD.
P070 Machine learning approaches to identify IBD biomarkers from longitudinal microbiome data
Authors: Madgwick M , Sudhakar P , Tabib N S , Norvaisas P , Creed P , Verstockt B , Vermeire S , Korcsmáros T 
Published: January 2020

Abstract

Background
Inflammatory bowel disease (IBD) has been shown to be associated with alterations in the intestinal microbiome. However, the precise nature of these microbial changes remains unclear. With billions of microbes present within the gut, novel and powerful computational techniques are required to identify the relevant shifts in microbiota contributing to the disease. Machine learning (ML) allows a data-driven approach to identify these discrete dynamic changes, while the findings of the ML algorithms can be interpreted using systems biology (SB) techniques. By combining ML and SB approaches, we aim to characterise key microbial factors in IBD pathogenesis, distinct patterns of variability in a diverse patient cohort and provide a method for patient stratification.

Methods
The causal relationship between the changes in the gut microbiome and IBD is difficult to establish. Data from cross-sectional studies are plagued by confounding factors and inconsistencies between cohorts. To overcome this, the authors used rich longitudinal datasets and integrated metagenomic, multi-omic and clinical patient data. This workflow has been validated using large longitudinal IBD databases, including data from IBDMDB. We assessed the performance of the ML models using well-documented performance metrics to ensure the outcomes were robust.

Results
As a baseline, we used multiple ML models to predict disease type (UC, CD and non-IBD) from integrated multi-omics profiles. We analysed multiple ML techniques, including linear (e.g. linear mixed model), non-linear (e.g. Random Forest), time-series models (e.g. Rotation Forest) and deep learning models (e.g. long short-term memory network model). The authors identified the models which would allow flexibility to analyse the dynamic nature of the microbiome and allow integration of the microbiome data with clinical patient data. The payoff of greater flexibility was a reduction in the model performance in terms of identifying specific features from the metagenomics that could be used as biomarkers. However, we were able to identify connections between microbial and host proteins relevant to IBD and were able to stratify these by the patient’s metagenomic data.

Conclusion
We have developed an integrated ml-based microbiome analysis pipeline to identify biomarkers for IBD from longitudinal metagenomic data. Furthermore, using a variety of SB approaches, we were able to interpret the predicted key microbial features and communities by inferring connections between microbial and host proteins. This pipeline will enable us to analyse vast amounts of patient microbiome data in the context of clinical and metagenomic data, to allow identification of biomarkers for disease subtypes.
P075 Muc5ac expression protects the colonic barrier in experimental colitis
Authors: O’Connell L , Olli K , Rapp C , Collins C , McNamee E , Jensen O , Jedlicka P , Allison K , Goldberg M , Gerich M , Evans C , AHERNE C 
Published: January 2020

Abstract

Background
The mucus gel layer (MGL) lining the colon is integral to exclusion of bacteria and maintaining intestinal homeostasis in health and disease. MGL defects allowing bacteria to directly contact the colonic surface are commonly observed in ulcerative colitis (UC). The major macromolecular component of the colonic MGL is the secreted gel-forming mucin, MUC2, whose expression is essential for homeostasis in health. In UC, another gel-forming mucin, MUC5AC is induced. In mice, Muc5ac is protective during intestinal helminth infection. Here, we tested the expression and functional role of MUC5AC/Muc5ac in colitis patient biopsies and murine colitis.

Methods
We measured MUC5AC/Muc5ac expression in UC patient biopsies and during acute dextran sulphate sodium (DSS) colitis. We performed DSS-colitis in mice deficient in Muc5ac (Muc5ac−/−) to model the potential functional role of Muc5ac in colitis. To assess MGL integrity, we quantified bacterial–epithelial interaction and translocation to mesenteric lymph nodes (MLNs). Antibiotic treatment was performed to directly investigate the role of colonic bacteria in our murine colitis studies.

Results
Colonic MUC5AC/Muc5ac mRNA expression increased significantly in active UC and murine colitis. Muc5ac−/− mice experienced worsened injury and inflammation in DSS-colitis compared with controls. This was associated with increased bacterial–epithelial contact and translocation to the MLN. Antibiotic treatment normalised colitis severity in Muc5ac−/− mice to that of antibiotic treated controls.

Conclusion
We demonstrate for the first time that MUC5AC/Muc5ac induction in acute colitis controls injury by reducing bacterial breach of the MGL. Therefore, developing strategies to induce MUC5AC expression may protect the intestinal barrier in UC.
P080 Therapeutical effect of urine-derived stem cells on DSS-induced chronic model of mice
Authors: Wu X R , Zhou C , Liu H S , Xuan-hui L , Hu T , Zheng X B , Liang Z X , Wu X J , Gao X , He X S , Ke J , Chen Y F , He X W , Hu J C , Zou Y , Lan P 
Published: January 2020

Abstract

Background
The application of stem cell therapy in the treatment of inflammatory bowel diseases (IBD) is limited because of the invasive approaches of stem cells. Urine-derived stem cells (USCs) were recently shown to have regenerative properties, which can be harvested in a safe, low-cost and non-invasive way.

Methods
Human USC were isolated and expanded from the urine of healthy male adult volunteers (n = 3, age arrange 24–30 years old). USC were characterised by cell surface marker expression profile and multipotent differentiation. In vivo therapeutic value of USC was assessed using murine colitis chronic model induced by dextran sulphate sodium (DSS).

Results
USC were positive for mesenchymal stem cell markers but were negative for hematopoietic stem cell markers. These cells differentiated into osteo-, adipo- and chondro-genic cell lineages. Systemic administration of USC significantly ameliorated the clinical and histopathological severity of colitis and increased the survival rate in chronic murine colitis model.

Conclusion
This study demonstrated that implantation of USC reduces inflammation in IBD rodent model, indicating that USC therapy serves as a potential cell-based therapeutic candidate for IBD.
P087 Biomarkers of elastin degradation differentiate between clinically inactive and active disease in ulcerative colitis patients
Authors: Pehrsson M , Domislović V , Karsdal M A , Brinar M , Barisic A , Krznaric Z , Manon-Jensen T , Mortensen J H 
Published: January 2020

Abstract

Background
In ulcerative colitis (UC), the state of chronic inflammation results in increased matrix metalloprotease (MMP) and serine protease activity, which effectively leads to a higher degree of intestinal tissue remodelling, including components of the extracellular matrix (ECM). One of these components is elastin a matrix protein of the interstitial matrix in the lamina propria and submucosa, providing tissue resilience and elasticity. As such, we investigated whether elastin degradation in UC patients was associated with disease activity and severity, potentially enabling patient differentiation based on elastin degradation.

Methods
Twenty-nine UC patients and 29 healthy donors were included in the study. Disease activity was determined according to the partial Mayo score (pMayo &gt;1) and the Mayo Endoscopic Score (MES). Disease severity and extension was assessed using the Montreal classification. Disease severity was additionally assessed using the Trulove and Witt’s (TW) clinical score. The biomarkers of elastin degradation included: MMP-7 (ELM-7) cathepsin-G (EL-CG) and proteinase-3 (ELP-3), measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) correcting for the false discovery rate were applied for the statistical analysis.

Results
TW: ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison with HD (p &lt; 0.001). Partial Mayo: EL-CG levels in patients with active UC were significantly elevated in comparison with HD (p &lt; 0.01), and UC patients in remission (p &lt; 0.01). ELP-3 levels were likewise significantly elevated in active UC patients compared with HD (p &lt; 0.001), and UC patients in remission (p &lt; 0.01). Montreal classification: ELM-7 was significantly elevated in active UC compared with HD (p &lt; 0.05), and UC patients in remission (p &lt; 0.05). EL-CG were also significantly elevated in active UC compared with HD (p &lt; 0.05), and UC patients in remission (p &lt; 0.05). ELP-3 was significantly elevated in active UC compared with HD (p &lt; 0.01). According to the MES score, ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison to HD (p &lt; 0.01).

Conclusion
The data presented in this study demonstrate an association between biomarkers of proteolytic elastin degradation and disease activity in UC patients especially the protease-3-derived biomarker, ELP-3, showed significant association with active UC in all the clinical scoring systems as well as the MES score. Utilising these minimally invasive elastin degradation biomarkers could serve as surrogate markers for monitoring of disease activity and potentially aid the differentiation of patients with an active disease from patients in remission or with a lower disease activity for UC.
P088 TLR3 ameliorates colitis-associated colon tumourigenesis in mice
Authors: Jun Y K , Koh S J , Gang H W , Chung K Y , Han J M , Kim J W , Kim B G , Lee K L , Im J P , Kim J S 
Published: January 2020

Abstract

Background
Toll-like receptor 3 (TLR3) signalling regulates innate and adaptive immune systems by the recognition of dsRNA. Activation of TLR3 signalling by poly(I:C) attenuates dextran sodium sulphate (DSS)-induced murine colitis. However, little information is available on the role of TLR3 signalling in the development of colitis-associated colon tumourigenesis.

Methods
Wild-type (WT) and TLR3-deficient (TLR3−/−) mice were intraperitoneally injected azoxymethane (AOM) 12.5 mg/kg on day 0 followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. Clinical indices such as weight change, colon length, the number of tumours, and the histologic severity of colitis were evaluated in each experiment. Immunohistochemical or immunofluorescence analyses for phospho-IκB kinase (IKK) and β-catenin were performed in colon tissues. To elucidate the antitumourigenic mechanism by colon inflammation, poly(I:C) or PBS was intraperitoneally injected in the AOM/DSS-induced tumourigenesis model in WT mice. To evaluate direct antitumor effect on tumourigenesis, as first experimental model, both WT and TLR3−/− mice were intraperitoneally injected AOM weekly for 12 weeks without DSS treatment. As the second experimental model, WT and TLR3−/− mice were received 2% DSS mixed with drinking water three times for 5 days every 2 weeks after one intraperitoneal AOM injection.

Results
TLR3−/− mice exhibited a higher tumour burden compared with wild-type mice. Body weight loss was greater in TLR3−/− mice than in WT mice. However, here was no significant difference in colon length and the severity of colitis between the two groups. Immunoreactivity for β-catenin was markedly increased in TLR3−/− mice. However, there was no difference in IKK expression. Activation of TLR3 by poly(I:C) was not associated with the reduced tumour development in WT mice. However, repeated AOM injections without DSS resulted in greater body weight loss in TLR3−/− mice than in WT mice, which was associated with the increased tumour development in TLR3−/−mice.

Conclusion
TLR3 signalling attenuated colitis-associated colon cancer development. Based on our experiments, TLR3 signalling inhibits colon tumourigenesis by direct antitumor activity rather than anti-inflammatory effect of colitis.