bluuebunny/crossref_metadata_2025_split huggingface dataset:
P710 Evaluation of helminth extracellular vesicles as a novel therapeutic for inflammatory bowel disease in murine models of colitis
Authors: Bray G , Giacomin P 
Published: January 2022

Abstract

Background
With the increasing complexity of inflammatory bowel disease (IBD) new therapies are clearly required. Recent evidence is coming to light demonstrating beneficial effects of helminth proteins. We aim to assess the prophylactic and therapeutic effects of extracellular vesicles (EVs) from the nematode N. brasiliensis, which serves as a model organism for human hookworm infections, in an acute and chronic model of colitis.

Methods
Prophylactic and therapeutic effects of EVs were assessed in an acute model of colitis by the administration of 20µg intraperitoneally (i.p) of Nb EVs or grape EVs. Mice were sacrificed after 5 days. The therapeutic effects of Nb EVs were also assessed in a chronic model of colitis. Here, Rag1 knockout mice were treated twice weekly for three weeks with 20µg of either Nb EV, grape EV or aIL-12. Outcomes assessed for both experiments included weight loss, clinical disease, as well as macroscopic and histologic disease scores. Groups were statistically compared for significant differences.

Results
The prophylactic administration of Nb EVs significantly reduced weight loss, clinical disease, and histologic pathology compared to grape EV-treated negative controls. Therapeutic administration of Nb EVs significantly reduced weight loss and histologic pathology in the colon.

Conclusion
The current study provides important evidence that the anti-inflammatory effects of helminth EVs can be harnessed to prevent and reverse inflammation in an acute and chronic mouse model of colitis. With further characterization of helminth EVs, these compounds have the potential to generate much needed new anti-inflammatory therapies for IBD.
P711 Stool microbiome communities predict remission in pediatric Crohn’s disease patients even after start of treatment
Authors: Verburgt C , Dunn K A , Bielawski J P , Otley A R , Heyman M B , Sunseri W , Shouval D , Levine A , de Meij T , Hyams J S , Denson L A , Kugathasan S , Benninga M A , de Jonge W J , Van Limbergen J E 
Published: January 2022

Abstract

Background
Early relapse in children with Crohn’s Disease (CD) after reaching remission is associated with a more severe disease course that significantly impairs quality of life. We have previously shown that a Bayesian approach predicted clinical course in children with CD following the first year after diagnosis with high accuracy when ensuring samples were truly treatment-naïve. Here, we aimed to assess the impact on the accuracy when taking a broader timeframe of stool collection to baseline, in order to facilitate use in clinical trials and eventually daily practice.

Methods
We selected de novo paediatric CD patients with PCDAI&gt;10 from the RISK cohort with baseline stool samples within 14 days after start of induction treatment. We assessed if they sustained remission at 12 months (PCDAI≤10). Using QIIME2 sequences were demultiplexed, joined, and denoised (deblur) to obtain amplicon sequence variants (ASVs). The ASVs were classified (classify-sklearn) using a pre-trained SILVA database. We used hierarchical Bayesian model for microbial community structure (BioMiCo), previously trained on treatment-naïve stool samples to predict treatment outcomes at 6 months according to baseline gut microbiome differences.

Results
Patient metadata and 16S rRNA amplicon data were available from 197 stool samples of newly diagnosed paediatric CD patients as part of the RISK cohort. Previous analysis of 42 truly treatment-naïve samples lead to prediction of samples in patients maintaining remission without early treatment escalation and those that did not in 81% and 75% (AUC=0.79). In this analysis, we selected 13 samples of children with PCDAI that were taken within 14 days after start of induction therapy. PCDAI varied from 15–47.5 at baseline. Therapy regimens started within the first 14 days were EEN, 5ASA, corticosteroids, immunomodulators and antibiotics. The Bayesian model predicted 12-month outcome of patients that maintained remission with a positive predictive value of 75% and negative predictive value of 60% (AUC 0.76).

Conclusion
Using treatment-naïve faecal samples only, a Bayesian approach predicted clinical course in treatment-naïve children with CD over the first year after diagnosis with high accuracy. When taking a broader timeframe of stool collection after start of treatment, the accuracy of the model decreased only slightly. Further exploration of microbiome signatures and potential use in practice should therefore emphasize the importance of treatment naivety of samples, but not necessarily rule them out for prediction of treatment outcome.
P712 Fungal microbiota composition in Inflammatory Bowel Disease patients in a Norwegian cohort: characterization of disease phenotypes and correlation with clinical activity and disease course
Authors: Catalàn-Serra x I , Thorsvik S , Beisvag V , Bruland T , Underhill D , Sandvik A K , Van Beelen Granlund A 
Published: January 2022

Abstract

Background
There is growing evidence of the role of the fungal microbiota in the pathogenesis of IBD, but a definite pattern defining the mycobiome in IBD is currently lacking.
In addition, the variations within the different phenotypes as well as the correlation between fungal composition and disease outcomes has been poorly characterized.
Our aim is to evaluate the fungal composition within the different IBD phenotypes, the changes with disease activity and the association with disease outcomes.

Methods
This prospective study presents sequencing of the faecal fungi of 111 individuals: 89 IBD (52 UC/37 CD) and 22 HC. Demographics,medication,Montreal Classification and disease history was collected. A fCalpro&gt;100 was considered active disease.
A subset of IBD patients was followed clinically (6±2 y) and classified as either “Complicated” or “Uncomplicated” based on the need of intensified medication and/or surgery.
Sequencing was done on amplicons targeting the ITS1 region of fungal DNA on a Illumina MiSeq sequencer. Chosen OTUs were compiled taxonomically.Data analysis was performed in R(phyloseq and deSeq2-packages).

Results
We found significant variations in the fungal microbiota composition in the different IBD phenotypes(Fig1)
In UC, Saccharomyces was predominant in pancolitis (E3), while Penicillium was more abundant in proctitis(E1) and Galactomyces in left-side UC (E2)(Pan.A). At species level, Rhodotorula mucilaginosa was significantly depleted in E3 (p≤0.05)(Pan.B)
In CD, Aspergillus was predominant in ileal affection(L1) while Candida and Rhodotorula genus were more abundant in L2-L3.Patients with structuring phenotype(B2) were depleted of Apergillus and Rodhotorula (Pan.A). At species level, ileal (L1) patients were depleted of Candida tropicalis and Penicillium kudriavzevii. B1 patients had a marked predominance of Candida albicans vs B2(p≤0.01)(Pan.B)
The mycobiome correlation with disease activity is depicted (Pan.C). Candida dublinensis was overrepresented in activity, while Saccharomyces pastorianus was depleted(p≤0.01)
The correlation of the mycobiome with disease outcomes is represented in Pan.D. Penicillium glabrum was significantly overrepresented in patients with a complicated course. The abundance of Candida tropicalis and D. nepalensis was correlated with the need for surgery.

Conclusion
This study shows important differences in the fungal microbiota composition in the different IBD phenotypes.
Some species are clearly correlated with the activity of the disease and worse clinical outcomes suggesting a potential deleterious role.Candida tropicalis was associated with the need of surgery in CD.
This in-depth characterization of the mycobiome serves as a significant addition to the understanding of the role of fungi in IBD.
P715 Selective enhancement of immune cell response to opportunistic microorganisms: An innovative proposal for Inflammatory Bowel Disease from an ancient grain
Authors: Pumarola Segura S 
Published: January 2022

Abstract

Background
Inflammatory Bowel Disease (IBD) results from an unbalanced immune response to the gut microbiome. There is a lack of proposals that integrate and may balance the multiple factors that together condition the onset and evolution of the disease: immunity, microbiome and diet.
D-fagomine is a small molecule, naturally present in buckwheat grain. It Is a monosaccharide mimetic showing glycosidase enzyme inhibition properties. Clinical studies have shown its efficacy to control postprandial glycemic response. Subsequent research “in vitro” had also shown D-fagomine to inhibit the fimbriae adhesion and biofilm formation of some proteobacteria, including ie E. coli or Salmonella.
The original aim of the study was to confirm the effects of D-fagomine on the adhesion to human gut mucosa using adherent-invasive E coli (AIEC) that is a microorganism usually linked to IBD.

Methods
A) Ex vivo human resected colonic mucosa was cultured (4 h) with AIEC inoculum and D-fagomine at different range of doses (0-5000 ppm). The amount of E. coli in tissue and supernatant was quantified, measuring also TNF-alfa and LDH.
B) Ex vivo human blood was cultured with D-fagomine (50 ppm) and the correspondent inoculum of different microorganism models able to evade the human immune system: bacteria = E. coli (AIEC) and fungus = Blastomyces sp. TNF-alfa was quantified.

Results
It was confirmed the inhibition of AIEC adhesion to the colonic mucosa in a direct dose-response relationship. Totally unexpected, D-fagomine was found to modulate TNF-alfa in an apparent double sigmoid curve with the max activity in the range of 50 ppm (Fig 1). This curve corresponds to an activator of the innate immune cells with mechanism related to complement activation, (ie mannose, betaglucan). Finally D-fagomine was helping the mucosa to detect and overcome the evasion mechanism of AIEC at the range of 50 ppm.
Additional studies (method B) were carried out with the result that D-fagomine, at 50 ppm, stimulates TNF-alfa response of human immune cells against AIEC and also Blastomyces (Fig 2). Both models give coherent results, and confirm that D-fagomine at the range of 50 ppm improves the capacity of the innate immune cells to detect human opportunistic microorganisms.

Conclusion
Our results have shown for the first time D-fagomine helping human immune cells to develop a more efficient immune response to better control the presence of opportunistic microorganisms. This is of great interest in IBD and is also synergistic with the other known properties of D-fagomine, which overall could finally help reduce some of the negative effects of the Western diet on humans and also their microbiome.
P716 Exclusive Enteral Nutrition refurbishes beneficial gut microbiota in patients with Acute Severe Ulcerative Colitis
Authors: Bajaj A , Markandey M , Sahu P , Vuyyuru S K , Kante B , Kumar P , Singh N , Gupta A , Singh M , Verma M , Makharia G , Kedia S , Ahuja V 
Published: January 2022

Abstract

Background
Exclusive enteral nutrition (EEN) acts as an adjunctive therapy to intravenous corticosteroids in patients with ASUC. Recently reported by Sahu et.al., patients with ASUC undergoing EEN showed reduced corticosteroid failure rates compared with standard-of-care (SOC) group1. While the mechanism of action of EEN is unclear, EEN is known to cause marked alterations in the gut microbiome. The present study extending the findings of Sahu et.al., aims to decipher the compositional changes in gut microbiome accompanying the EEN-augmented steroid responsiveness

Methods
In an open-label RCT, patients with ASUC were randomized 1:1 to EEN and SOC groups. Patients on EEN received a semi-elemental formula for 7 days along with SOC. The primary outcome was steroid failure, defined by the need for salvage medical intervention. Faecal microbial analysis was performed on day-0 and day-7 by 16S-rRNA gene sequencing. Processing of raw reads, ASV tables, diversity, and core microbiome analysis was done using QIIME2-2021.4. Differential abundance analysis (DAA) was performed using Deseq2.

Results
The α and β diversity indices showed deviation neither in EEN nor in SOC groups. EEN caused a shift in core microbiota of patients with ASUC, adding Streptococcus and Faecalibacterium prausnitzii, while SOC could not change the core microbiota. DAA on the pre- and post-treatment samples showed that EEN resulted in diminished Ruminococcus gnavus, Escherichia sp., Bifidobacterium longum and Enterococcus sp., while the SOC led to reduction in beneficial F. prausnitziiand enhanced Escherichia.
DAA between steroid responders and steroid non-responders in the EEN group, showed significant enhancement of Veillonella, Ligilactobacillus, Limosilactobacillus, Gamella, Enterococcus and Eggerthella in the SR group, while Schaalia, R.gnavus, Lactobacillus, Bifidobacterium, Haemophilus were elevated in SNR group.

Conclusion
ASUC accompanies gut dysbiosis. EEN refurbishes certain beneficial gut microbial genera, which may account for its augmentation of the steroid responsiveness in patients with ASUC.

Reference
1. Sahu P, Kedia S, Vuyyuru SK, Bajaj A, Markandey M, Singh N, Singh M, Kante B, Kumar P, Ranjan M, et al. Randomised clinical trial: exclusive enteral nutrition versus standard of care for acute severe ulcerative colitis. Aliment Pharmacol Ther 2021.
P718 Characterization of microbiota and metabolomic profile in human colonic surgical resections of UC patients
Authors: Bauset C , Carda-Diéguez M , Buetas E , Lis-López L , Navarro F , Ortiz-Masiá D , Calatayud S , Barrachina M D , Mira Á , Cosín-Roger J 
Published: January 2022

Abstract

Background
Ulcerative colitis (UC) is characterized by a diffuse, continuous, and chronic inflammation of mucosa and submucosa layers in the colon whose etiology is still unknown. Intestinal microbiota dysbiosis and alterations in the metabolomic profile have been reported in mucosal biopsies from Inflammatory Bowel Disease (IBD) patients. We aim to characterize the microbiota composition and metabolomic profile in colonic resections of UC patients.

Methods
Colonic resections from UC (n=18) and non-IBD (n=20) patients were obtained. Microbiota identification, composition and classification was performed by 16S rRNA gene Illumina Miseq sequencing. The bioinformatic analysis of sequencing data was performed using constrained correspondence analysis (CCA) and non-parametric Wilcoxon test to compare species and genera proportions. Bacterial load was estimated by qPCR. Metabolomic analysis was performed using Nuclear Magnetic Resonance (NMR) to study polar metabolites and Gas-Chromatography or Liquid-Chromatography Mass-Spectrometry to study non-polar metabolites.

Results
Microbiota analysis revealed differences at genus and species level between UC and non-IBD patients. Cellulosimicrobium was found at 10-fold higher levels in UC samples while Escherichia genus was 3.88 times more abundant in controls. A reduction in bacterial load was seen in UC samples. Levels of short-chain fatty acids (FA), medium-chain FA, long-chain FA, carboxylic acids and amino acids were obtained from the metabolomics analysis and a positive correlation between propionic, aspartic and hydroxybutyric acids and Cellulosimicrobium and Pseudomonas was found (Fig1B). Gut commensals such as unclassified Agathobacter, Blautia faecis, Oscillospiraceae or Faecalibacterium prausnitzii positively correlated with the abundance of butyric acid, acetic acid and succinic acid; meanwhile Subdoligranulum, Lachnospireace or unclassified Blautia negatively correlated with some medium or long chain fatty acids (Fig1B).

Fig1. Correlations between bacterial species and metabolites in (A) controls and (B) UC patients. Performed with mixOmics library in R.

Conclusion
Significant differences in microbiota composition and abundance are found in UC patients, which undergo a clear gut dysbiosis in colonic tissue. Correlation analysis suggests Cellulosimicrobium and Pseudomonas as sources of propionic, aspartic and hydroxybutyric acid. These results point at Cellulosimicrobium as a potential candidate in UC pathology.
N13 Clinical service delivery implications of the Covid-19 pandemic on people with inflammatory bowel disease: a qualitative study
Authors: Kemp K , Avery P , Bryant R , Cross A , Danter K , Kneebone A , Morris D , Walker A , Whitley L , Dibley L 
Published: January 2022

Abstract

Background
As part of a qualitative study exploring the experiences of IBD patients during three UK lockdowns, we identified specific clinical service implications of the pandemic on IBD care.

Methods
Participants aged 18 years+ with a confirmed diagnosis of Crohn’s disease, Ulcerative Colitis or IBD-Unclassified, who had shielded or not during any lockdown period were recruited from Crohn’s and Colitis UK. Semi-structured online or phone interviews (captured February-May 2021) were audio-recorded, transcribed professionally, and analysed using thematic analysis.

Results
Forty-three people took part; median age 38 years (19–63 years); 27 (62.7%) females; diagnosed with Crohn’s Colitis (n=2), Crohn’s disease (n=21), Ulcerative colitis (n=18) and IBD-Unclassified (n=2). Median disease duration 13 years (0.6–36 years). Four clinically focussed themes emerged: The Risk of Attending Hospital; Missing Routine Monitoring; Accessing Care as Needed and Remote Access and The Future.

The Risk of Attending Hospital
Against the prevailing media messages to avoid going to hospital, staying at home to avoid burdening the healthcare system and the rising numbers of Covid patients in hospitals, participants felt anxious about the dilemma of needing treatment for their IBD but putting themselves at risk to receive it.

Missing Routine Monitoring
Routine appointments and monitoring, which participants relied on for ‘keeping on top of’ their condition, stopped for some. Many could not access their IBD team or GP services at all, so routine blood tests for therapeutic levels were missed; in some cases, disease activity increased.

Accessing Care as Needed
Many were able to get clinical help as needed, even if the method of contact, and source of help, was different to usual. For others, the pandemic had caused considerable delay in getting diagnosed, and they felt overwhelmed and unsupported. Most understood the disruption to services due to staff redeployment, but some coped with the changes better than others.

Remote Access and The Future
the shifting focus away from face to face and towards remote appointments received mixed opinions. Many were happy with remote (phone, email) contact during the pandemic, out of necessity, but there were concerns from others that this would become normal in the future. It was suggested that first appointments should always be face to face.

Conclusion
Maintenance of IBD services in some form is essential throughout crisis periods; newly diagnosed patients needed additional support; dependence on IBD services could be reduced in the future through use of treatment/self-management plans. Mode of appointment needs to suit the patient.
N17 Co Design of young person’s IBD clinic for 16–24 year olds
Authors: Hamzawi M , Brannick S , Hickey Y , Cullen G , Sheridan J 
Published: January 2022

Abstract

Background
In Ireland,young people with Inflammatory Bowel Disease (IBD), diagnosed in a paediatric hospital transition to adult services at 16 years of age. Transition is an essential milestone for adolescents with IBD as critical functioning skills necessary for self-management are not fully developed and adolescents often find it difficult to engage with health care professionals about their disease. To date an ideal transition model has not been defined. The aim of this pilot study was to seek input from a transition group to aid the development of future transition and young person clinics.

Methods
During 2019, 8 patients transitioning into our adult IBD service were assigned to the pilot structured multidisciplinary (MDT) pathway for 12 months. This involved meeting with Consultant, CNS, psychologist and dietitian at each clinic appointment. Patient experience measures were given after each visit and on completion of the pathway participants rated their experience on Likert scales and free text responses. Findings would be useful to steer service development.

Results
At the end of 1 year excellent satisfaction rates were reported by those attending clinics with MDT input. Nonetheless 50% preferred consultant only clinics. 37.5% opted for full MDT review and 12.5% requested psychology input plus consultant at clinic.

Conclusion
The project highlights the importance of patient focused studies when designing young patient’s transition clinics. 50% of young IBD patients did not request full MDT on a regular basis. This study is being expanded to review patient experiences from a larger cohort aged 18–24 years and a Randomised Control Trial will be conducted to guide future a transition pathway
The Frequency of Focal Cortical Dysplasia-Like Histologic Features Near Adult-Type Diffuse Gliomas
Authors: Bitar Mireille , Chornenkyy Yevgen , Flanagan Margaret E , Steffens Alicia , McCortney Kathleen , Horbinski Craig 
Published: January 2022

Abstract
While the coexistence of focal cortical dysplasia (FCD) and grade 1 noninfiltrative gliomas has been described, to date, only rare case reports have described FCD adjacent to infiltrating gliomas. We therefore sought to determine how often FCD-like findings occur near adult-type diffuse gliomas. This was a retrospective survey of 186 consecutive, newly diagnosed, en bloc glioma resections. Fifty-nine (31.7%) had sufficient adjacent cortex to evaluate for FCD-like features. Among IDH mutant (“IDHmut”) gliomas, 40/77 (52%) had adjacent evaluable cortex, whereas only 19/109 (17%) of IDH wild-type (“IDHwt”) gliomas did (p &lt; 0.0001). Among cases with evaluable cortex, 15 (25.4%) contained features suggestive of FCD, including radial/tangential dyslamination and/or maloriented neurons. In a multivariable analysis, increasing glioma grade (OR = 4.0, 95% CI = 1.2–13.5, p = 0.027) and IDHmut (OR = 6.5, 95% CI = 1.3–32.2, p = 0.022) emerged as independently positive correlates with the appearance of FCD-like findings. However, FCD-like features were also found in 13/32 (40.6%) cortical samples from adult brains without any neoplastic disease or seizure histories (p = 0.16). Together, these data suggest that, while FCD-like histologic features can be incidentally found in at least a subset of diffusely infiltrative gliomas, the frequencies are not significantly different from that seen in otherwise non-neoplastic brains, and are therefore most likely nonpathologic.