bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP31 Meta–omics reveals microbiome-driven proteolysis as a contributing factor to the severity of ulcerative colitis disease activity
Authors: Mills R , Dulai P , Vázquez-Baeza Y , Zhu Q , Humphrey G , DeRight Goldasich L , Quinn R , Gewirtz A , Chassaing B , Chu H , Sandborn W , Dorrestein P , Knight R , Gonzalez D 
Published: January 2020

Abstract

Background
Ulcerative colitis (UC) is characterised by an aberrant immune response directed towards the gut microbiota. It remains poorly understood which mechanisms govern pathogenic roles of the microbiome in UC.

Methods
A prospective cohort of 40 UC patients were phenotyped with clinical (partial Mayo), biochemical (faecal calprotectin), endoscopic (Mayo endoscopic sub-score and ulcerative colitis Endoscopic Index of Severity) and histologic (Geboes) disease activity indices. Individual patient-matched faecal samples collected within 24 h prior to the lower endoscopy underwent 16S, shotgut metagenomic, metabolomic, metaproteomic, and metapeptidomic sequencing in addition to proteomic sequencing of paired serum samples. Sequencing datasets were integrated and analysed for microbial determinants of UC disease severity. Confirmatory in-vivo and in-vitro experiments were performed in Caco-2 epithelial monolayers and IL10 knockout mice.

Results
All meta-omics displayed large-scale shifts related to disease severity, with the metabolome and metaproteome best predicting disease severity and the metapeptidome demonstrating an increase of peptide fragments in UC patients with high severity. Broad-scale analyses and taxonomic inferences identified Bacteroides proteases as a distinguishing feature of disease severity, with the Bacteroides association being driven by changes in protease protein expression. Using a Caco-2 model we confirmed that epithelial disruption by Bacteroides vulgatus was prevented by protease inhibition, without influencing growth rates. Guided by the metagenome and metaproteome we transplanted a high-severity UC faecal sample with an increased abundance of proteases related to Bacteroides vulgatus into an IL10−/− gnotobiotic mouse model, and observed that colitis induced by transplant of faeces was attenuated by oral administration of protease inhibitors.

Conclusion
Through an integrated multi-omics data analysis we demonstrate that certain members of the microbiome, such as Bacteroides vulgatus, may contribute to exacerbating disease activity in UC through protease activity. In-vivo and in-vitro experiments provide evidence that bacterial protease inhibition may be a novel therapeutic approach in UC.
DOP03 The impact of elemental diet on the human gut microbial structure and intestinal metabolites
Authors: Miyoshi J , Saito D , Nakamura M , Miura M , Mitsui T , Kudo T , Murakami S , Matsuura M , Hisamatsu T 
Published: January 2020

Abstract

Background
The incidence and prevalence of Crohn’s disease (CD) are increasing globally. The efficacy of elemental nutrition (EN) for CD has been reported for decades. Recent studies demonstrated that elemental diet (ED), one of the types of EN, which contains individual amino acids, sugars (mono- or polysaccharides), and low fat, improves the anti-TNFa antibody therapy outcome by reducing the loss of response and has the preventive effect against the postoperative recurrence. Given its excellent safety, ED can be a promising concomitant therapeutic option for CD. However, the underlying mechanisms of ED remain unclear. Imbalance of the gut microbiota, dysbiosis, is thought to be involved in CD pathogenesis. Meanwhile, diet influences gut microbiota. We hypothesised that ED exerts clinical efficacy by shifting the gut microbiota to the anti-inflammatory environment. We also believe that investigating human samples is crucial to obtain mechanistic insights into ED therapy, considering species-specific differences in interactions between the host and microbiota. In this study, we examined the impact of ED on the intestinal bacterial compositions as well as metabolites in human subjects.

Methods
Four healthy individuals participated in the study. The subjects continued their dietary habits for 2 weeks after the registration of the study and then replaced 900 kcal/day of their regular diet with 900 kcal/day of ED (time point 1, T1). ED was continued for 2 weeks (T2). After the withdrawal of ED, subjects resumed their original dietary habits for 2 weeks until the endpoint of this study (T3). Faecal samples were collected from all subjects at all time points, T1-3. Faecal DNA and metabolites were extracted and analysed with 16S rRNA gene amplicon sequencing and metabolomic analysis, respectively. This study was approved by the Institutional Review Board of Kyorin University School of Medicine (IRB No. 720) and performed in accordance with the principles of the Declaration of Helsinki.

Results
Interindividual differences were observed in the gut bacterial compositions (Figure 1) as well as metabolites (Figure 2) at all time points. Changes over time varied among subjects. On the other hand, some bacteria (e.g. [Ruminococcus] gnavus group and Parabacteroides) and metabolites including short-chain fatty acids and bile acids changed significantly between time points among the 4 subjects. The bacterial and metabolite profiles at T3 were different from those T1 in all subjects.

Conclusion
The alterations of the gut microbiota induced by ED vary with each individual. Some microbes and metabolites change commonly across the subjects. ED may have a lasting effect on the gut environment even after the withdrawal.
DOP05 Perioperative Dietary Therapy in inflammatory bowel disease
Authors: Adamina M , Gerasimidis K , Sigall-Boneh R , Zmora O , de Buck van Overstraeten A , Campmans-Kuijpers M , Ellul P , Katsanos K , Kotze P , Noor N , Schäfli-Thurnherr J , Vavricka S , Wall C , Wierdsma N , Yassin N , Lomer M 
Published: January 2020

Abstract

Background
The incidence of inflammatory bowel disease [IBD] is rising worldwide and no cure is available. Many patients require surgery and they often present with nutritional deficiencies. Although randomised controlled trials of dietary therapy are lacking, expert IBD centres have long-established interdisciplinary care, including tailored nutritional therapy, to optimise clinical outcomes and resource utilisation. This topical review aims to share expertise and offers current practice recommendations to optimise outcomes of IBD patients who undergo surgery.

Methods
A consensus expert panel consisting of dietitians, surgeons, and gastroenterologists, convened by the European Crohn’s and Colitis Organisation, performed a systematic literature review. Nutritional evaluation and dietary needs, perioperative optimisation, surgical complications, long-term needs, and special situations were critically appraised. Statements were developed using a Delphi methodology incorporating three successive rounds. Current practice positions were set when ≥80% of participants agreed on a recommendation.

Results
A total of 26 current practice positions were formulated which address the needs of IBD patients perioperatively and in the long term following surgery. Routine screening, perioperative optimisation by oral, enteral, or parenteral nutrition, dietary fibre, and supplements were reviewed. IBD-specific situations, including management of patients with a restorative proctocolectomy, an ostomy, strictures, or short-bowel syndrome, were addressed.

Conclusion
Perioperative dietary therapy improves the outcomes of IBD patients who undergo a surgical procedure. This topical review shares interdisciplinary expertise and provides guidance to optimise the outcomes of patients with Crohn’s disease and ulcerative colitis. taking advantage of contemporary nutrition science.
DOP10 Intestinal ultrasound response and transmural healing after ustekinumab induction in Crohn’s disease: Week 16 interim analysis of the STARDUST trial substudy
Authors: Kucharzik T , Wilkens R , Maconi G , D’Agostino M A , Le Bars M , Nazar M , Sloan S , Lahaye M , Ni L , Ercole E , Alloca M , Machková N , Maaser C 
Published: January 2020

Abstract

Background
Intestinal ultrasound (IUS) is a non-invasive tool for evaluating transmural disease activity in Crohn’s disease (CD) patients. We report interim Week (W)16 results from an IUS substudy of STARDUST, a phase 3B randomised trial of CD patients treated with ustekinumab (UST), comparing a treat-to-target (T2T) maintenance treatment strategy vs. standard of care (SoC). The aim of the substudy was to assess changes in IUS parameters, including transmural response to UST induction therapy.

Methods
Patients (≥18 years) with moderate–severe active CD (CD Activity Index [CDAI] 220–450 and simple endoscopic index for CD [SES-CD] ≥3) who failed conventional therapy and/or 1 biologic, received weight-based IV UST dosing of ~6mg/kg at Week 0, then SC UST 90mg at W8. At Week 16, patients with CDAI reduction ≥70 points were randomised (1:1) to T2T or SoC treatment arms. Exclusion criteria: characteristics precluding IUS visualisation of affected bowel segments and normal bowel wall thickness (BWT) (≤2.0mm terminal ileum; ≤3.0mm colon) for all segments at baseline (BL). Key IUS endpoints assessed at W4, W8 and W16 (central reading): IUS response ≥25% BWT reduction from BL; BWT change from BL (mm); IUS remission (transmural healing) ‒ BWT normalisation, colour Doppler signal ≤1, normal echo stratification, and absence of inflammatory fat. The most affected bowel segment at BL was used for all IUS parameters. Correlations/% agreement between IUS response/remission and clinical (CDAI70, clinical response/remission), biomarker (CRP/FCal levels) and endoscopy outcomes (SES-CD scores) were assessed.

Results
The analysis included 82/94 patients enrolled in the IUS substudy; n = 76 patients had BL and ≥1 post-BL IUS assessment. BL characteristics were similar to those of the main STARDUST population. Overall IUS response and remission (transmural healing) rates at W16 were 33.8% and 11.3%, respectively (Table 1). The most affected segments were ileum in 66% and colon in 34% of patients, with better outcomes found in the colon (Table 2). BWT and Doppler’s signal started to normalise at W8, inflammatory fat and echo stratification at W16 (Table 2). Mean BWT improvement from BL was statistically significant as early as W4 (p = 0.0002; Table 3). Moderate agreement was observed between earlier IUS responses and later biomarkers/endoscopic improvements.

Conclusion
This was the first international, interventional, multicentre study using IUS in CD. IUS response to UST was detected as early as Week 4, and a clinically meaningful % of patients achieved transmural healing, primarily in the colon, at W16. IUS could be a valuable tool to detect early response to treatment in CD. Future studies need to confirm whether early IUS response is predictive of long-term outcomes for CD patients.
DOP20 Can lifestyle and psychosocial factors predict flares of IBD; an exploratory study using telemedicine
Authors: Lalisang R C A , Adriaans G , de Jong M , van der Meulen-de Jong A , Romberg-Camps M , Mahmmod N , Markus-de Kwaadsteniet T , Dijkstra G , Haans J , Stamm C , Vanwersch R , Jonkers D , Almeida R J , Pierik M J 
Published: January 2020

Abstract

Background
Tight control of mucosal inflammation and prevention of disease flares are emerging treatment goals to prevent disease progression in inflammatory bowel disease (IBD). The state of the art clinical classification only marginally predict flare occurrence. Mounting evidence shows that psychosocial and lifestyle factors are associated with flares. Longitudinal monitoring of these factors has been made possible by implementing a web-based telemedicine tool, called myIBDcoach. This study is an exploration on the potential additive predictive value of data captured in a telemedicine system to predict flares.

Methods
Consecutive IBD patients (n = 393) were recruited from the prospective myIBDcoach telemedicine study cohort (ClinicalTrials.gov, NCT02173002). During a one-year follow-up, every 1–3 months, participants reported information on all variables displayed in Figure 1 via myIBDcoach. Variables were subdivided into two main categories; Baseline and myIBDcoach. The myIBDcoach variables were once again subdivided (Figure 1). The outcome of interest, a flare during follow-up, was defined as having clinical symptoms of disease activity (using the Monitor IBD At Home questionnaire) combined with either a faecal calprotectin &gt; 250g/g, disease activity on endoscopy, MRI or CT. Stepwise group-Lasso logistic regression (G-LASSO) was used to estimate associations between flares and individual variables, as well as between flares and the different variable categories (Figure 1). G-LASSO performs variable selection, resulting in models that contain only the most relevant explanatory variables.

Results
Seven G-LASSO regressions were estimated and evaluated using the Akaike information criteria (AIC), the area under the curve (AUC) and stepwise importance using 10-fold cross-validated penalty parameter. Figure 2 shows that the overall model performance increased when consecutively adding extra variable categories, the largest increase occurred for psychosocial and lifestyle factors. All telemedicine variable categories were found to be more important compared with the baseline variable category, as shown in Figure 3. Results shown in Figure 4 indicate that the information from myIBDcoach was found to be more important than the baseline variables.

Conclusion
In this exploratory study, psychosocial and lifestyle factors monitored via telemedicine are of superior value to predict flares in IBD patients compared with clinical stratification. Holistic monitoring, including psychosocial and lifestyle factors, and targeted interventions are of interest for future trials and are a promising strategy to prevent flares and improve the outcome of IBD.
DOP23 Endoscopic evaluation at 1 month after ileocolic resection for Crohn’s disease predicts postoperative recurrence and is safe
Authors: Guo Z , Zhu Y , Cao L , Li Y , Wang Z , Zhu W 
Published: January 2020

Abstract

Background
Endoscopic surveillance remains the gold standard for evaluating postoperative recurrence in Crohn’ disease (CD). However, the optimal timing of the first postoperative endoscopic evaluation is unclear. The commonly used strategy, first endoscopy at 3, 6, or 12 months, demonstrates high rates of endoscopic recurrence, which means this strategy may delay the detection and treatment. The aim of this study was to determine the clinical value and safety of the endoscopy at 1 month after surgery, and define the related factors.

Methods
This was a prospective cohort study of CD patients undergoing an ileocolic resection between 2015 and 2018, with a postoperative colonoscopy at 4–5 week after surgery. The primary outcome was endoscopic recurrence at 12 months, or clinical recurrence, or surgical recurrence within 12 months after surgery. Univariate and multivariate analyses were performed to identify related factors.

Results
Eighty-four eligible CD patients were included. Among 84 colonoscopies at 4–5 week, no endoscopic complication occurred. The main endoscopic findings at the first evaluation were anastomotic ulcers (45 [10 circumferential ulcers and 35 scattered ulcers], 53.6%), ulcers in the neoterminal ileum (16, 19.0%), oedema in anastomosis (50, 59.5%), mild narrowing in anastomosis (7, 8.3%), and mild narrowing in neoterminal ileum (3, 3.6%). On univariate and multivariable analysis, anastomotic scattered ulcers were associated with forward postoperative recurrence (HR, 2.532; 95% CI, 1.019–6.318; p = 0.046). We then used the modified Rutgeerts score to define endoscopic findings: i0, 26(44.0%); i1, 4(4.8%); i2a (circumferential anastomotic ulcers were not included), 40(34.5%); i2b, 11(13.1%); i3, 0; i4, 3(7.1%). Univariate and multivariable analysis showed ≥i2a were associated with forward postoperative recurrence (HR, 3.174; 95% CI, 1.218–8.273; p = 0.018). No factor was associated with ≥i2a at the first endoscopy.

Conclusion
Endoscopic evaluation at 4–5 weeks after surgery in CD was safe, and endoscopic findings were associated with postoperative recurrence. Earlier endoscopic examination after surgery may be useful for the adjustment of medication.
DOP27 Transanal minimally invasive surgery (TAMIS): A novel approach for treatment of pouch failure
Authors: Van Praag E , Hompes R , Buskens C , Tanis P , Duijvestein M , Bemelman W 
Published: January 2020

Abstract

Background
Many different pouch failure (PF) indications and procedures are known. In literature, different types of PF are randomly classified and often stacked together due to complexity. Transanal minimally invasive surgery (TAMIS) is becoming increasingly popular for redo-surgery due to greater accessibility and visibility in complex pelvic surgery compared with the conventional abdominal approach. We aimed to evaluate the efficacy of TAMIS in patients with PF.

Methods
This retrospective study includes all consecutive patients over 18-year old with an ileal pouch-anal anastomosis (IPAA) and PF that were managed with TAMIS between July 2014 and July 2019. Patient characteristics, operative indications, perioperative outcomes and short-term follow-up (FU) are described using a suggested subclassification for surgical-related PF (Figure 1).

Results
Forty-six procedures were completed in 42 patients, predominantly male (66.7%) with a median age of 44.6 (range 22.0–70.8) years. Initial IPAA indications were familial adenomatous polyposis (n = 11), medical refractory ulcerative colitis (UC) (n = 29) or other (n = 2). Seven (24.1%) UC patients turned out to have Crohn’s disease (CD). Reasons for PF were septic complications (n = 18), retained rectum (n = 3), outlet problems (n = 8) (with megapouch: n = 5), inlet problems (n = 6), cuff problems (n = 8) and refractory pouchitis with unknown aetiology (n = 3). Twenty-three pouch redo’s (16 remodelling, 7 new pouches), 5 sleeve advancements, 4 cuff excisions, 1 posterior pouchpexy, and 13 pouch excisions were recorded. Five pouch excisions were performed in CD patients. Five procedures were fully completed transanally, and 41 were a combined transabdominal (with 32 open and 9 laparoscopic) and TAMIS approach. None were converted to an open procedure. Apart from the patients with a pouch excision, 9 ended up with a permanent ileostomy, although technical success was achieved in 4 of those. Six permanent ileostomies were in patients with a redo-pouch (3 remodelling, 3 new pouches), 2 after sleeve advancement and 1 after cuff excision. Major morbidity (Clavien-Dindo ≥3) occurred after 17 procedures (37.0%), 14 within 1 month after surgery with a median FU of 17.9 (0.9–41.6) months. There was no peri-operative mortality.

Conclusion
TAMIS for PF after IPAA is technically feasible with acceptable short-term outcomes. Peri-operative morbidity is high and reflects the complexity of these procedures. Success after PF procedures is difficult to interpret due to a wide range of possible outcomes such as technical success, conversion rate and number of patients with a permanent stoma. The PF subclassification makes the complex problem and surgical management of PF comprehensible.
DOP29 Elevation of a novel blood-based gene signature in a severe Crohn’s disease (CD) subtype preceding surgery defines and predicts a post-surgical decrease in pro-inflammatory pathway activation
Authors: Gonsky R , Fleshner P , Botwin G , Biener-Ramanujan E , McGovern D , Targan S 
Published: January 2020

Abstract

Background
CD is defined by transmural inflammation leading to inflammatory, stricturing and/or penetrating phenotypes. Identifying underlying molecular pathways and distinct disease subsets is critical for improved prognostics, therapeutics and biomarker discovery.

Methods
CD3+ T cells were purified from paired blood and mucosal tissue from 101 CD and 17 non-IBD subjects requiring surgery. Longitudinal samples (n = 30) were collected 4–13 mo. post-surgery. Expression profiles were generated by RNAseq, T-cell subset deconvolution by xCell and transcriptome-wide associations (TWAS) using TWAS-hub.

Results
Unsupervised clustering of peripheral T-cell gene expression at surgery revealed 2 CD profiles: Expression from cluster1, labelled CD-PBT (63%), clustered tightly with the non-IBD group. In cluster2, expression shifted from a peripheral toward a mucosal profile, labelled CD-PBmu(cosal) (37%). CD-PBmu was defined by differentially expressed genes (DEG) (1944 DEG, p &lt; 0.001) regulating cell migration and adhesion pathways and a distinct T-cell subset composition associated with stricturing disease (p = 0.03), increased resected bowel length (p = 0.036) and post-op recurrence (p = 0.01). There were no significant differences in disease location/behaviour. Independent validation (5 public datasets) confirmed the CD-PBmu signature in data from whole blood (CD patients failing anti-TNF therapy, n = 204) and the mucosal-like expression profile in data from ileal tissue (paediatric CD patients, studies n = 751). A defining feature of CD-PBmu, validated in a separate CD cohort (n = 19), was decreased pro-inflammatory cytokine/chemokine and adhesion molecule expression following surgery (900 DEG, p &lt; 0.001). No post-surgery change in expression was detected in CD-PBT. A 44-gene classifier was identified to enable clinical application. The classifier accurately detected the CD-PBmu patient subtype, correlated with the altered composition of peripheral T-cell subsets and overlapped with IBD associated TWAS signals (&gt;60%). Recently, another group posed a blood-based 17 gene panel as predictive for aggressive IBD. These genes were not predictive for either the CD-PBmu or CD-PBT subtype (&lt;50% DEG).

Conclusion
Severe CD can be stratified into 2 subtypes based on peripheral T-cell gene expression. Circulating T cells from CD-PBmu exhibit a mucosal-like gene signature, altered T-cell subset composition, clinical features of severity and decreased pro-inflammatory gene expression post-surgery. These findings hold potential to identify targets for CD subtype-specific therapeutic development. The 44-gene classifier overlapped with multiple paediatric CD datasets, suggesting the potential application of these findings for treatment stratification early in the disease process.