OP30: Lyophilised orally administered faecal microbiota transplantation for Active Ulcerative Colitis (LOTUS study)Year: 2021
Source: ECCO'21 Virtual
Authors: Craig Haifer
Created: Friday, 1 October 2021, 12:41 PM
BackgroundFaecal microbiota transplantation (FMT) administered via the lower GI tract effectively induces remission in ulcerative colitis (UC). Orally administered FMT capsules may improve patient tolerability and facilitate maintenance therapy while it is unclear if pre-FMT antibiotics enhance therapeutic efficacy.
MethodsWe performed a dual-centre randomised, double blind, placebo-controlled trial of oral lyophilised FMT in adults with mild-moderately active UC (total Mayo 4-10). All subjects received 2-weeks of pre-FMT antibiotics (amoxycillin, metronidazole and doxycycline) before 1:1 randomisation to either oral FMT (0.35g stool content per capsule from 1 of 2 healthy donors) or identical placebo for 8 weeks. Enforced tapering and cessation of corticosteroids was mandated. The primary endpoint was week 8 steroid-free clinical remission with endoscopic remission or response (total Mayo score ≤2 with subscores ≤ 1 for rectal bleeding, stool frequency and endoscopic appearance, and ≥1-point reduction from baseline in endoscopy subscore). Responders to FMT induction were re-randomised to either continue maintenance FMT or withdrawal of FMT with final outcomes assessed at week 56.
ResultsRecruitment was paused due to the COVID-19 pandemic. 37 patients were randomised. Baseline patient and disease characteristics were balanced between the randomised groups. The primary outcome was achieved in 8/16 (50%) receiving FMT versus 3/19 (16%) receiving placebo (OR: 4.63; 95%CI: 1.74-12.30; P=0.002). Steroid-free clinical remission rates and endoscopic remission rates were 69% vs 26% (P=0.012) and 44% vs 16% (P=0.074) in the FMT and placebo arms, respectively. Reported SAE were worsening colitis (2 FMT, 1 placebo) and PR bleeding relating to previous anal surgery (placebo). Ten patients entered the maintenance withdrawal study. Steroid-free clinical, endoscopic and histologic remission was achieved in 4/4 patients who continued daily oral FMT, with all 6 patients randomised to FMT withdrawal having a flare of disease with a median time to relapse of 6 months.
ConclusionOral lyophilised FMT following antibiotic pre-treatment for mild-moderately active ulcerative colitis was associated with a significant increased rate of clinical remission with endoscopic remission or response versus antibiotic treatment alone at week 8. Pre-treatment antibiotics had an additive impact upon treatment efficacy compared with previous studies utilising FMT. Maintenance FMT therapy was associated with sustained clinical, endoscopic and histologic remission at week 56. Treatment was well tolerated and there were no new safety signals related to FMT therapy.
OP30: Upadacitinib modulates inflammatory pathways in gut tissue in patients with Ulcerative Colitis: Transcriptomic profiling from the Phase 2b study, U-ACHIEVEYear: 2022
Source: ECCO'22
Authors: Verstockt, B.(1);Blink Polakow, S.(2);Mahi, N.(2);Lee, J.(2);Wang, J.(3);Guay, H.(4);Salas, A.(5);Panés, J.(5);Ungaro, R.C.(6);Vermeire, S.(1);
Created: Friday, 11 February 2022, 3:52 PM
OP31 Meta–omics reveals microbiome-driven proteolysis as a contributing factor to the severity of ulcerative colitis disease activityYear: 2020
Authors: R. Mills1, P. Dulai2, Y. Vázquez-Baeza3, Q. Zhu3, G. Humphrey3, L. DeRight Goldasich3, R. Quinn4, A. Gewirtz5, B. Chassaing5, H. Chu6, W. Sandborn2, P. Dorrestein1, R. Knight3, D. Gonzalez1
Created: Thursday, 30 January 2020, 10:12 AM
OP31: Dietary and Multi-Omic characterization of new onset treatment naive Crohn Disease identifies factors that may contribute to disease pathogenesisYear: 2022
Source: ECCO'22
Authors: Haberman Ziv, Y.(1);Braun, T.(1);Amir, A.(1);Levhar , N.(1);Malik, A.(1);Neuman, S.(1);Picard, O.(1);Yavzuri, M.(1);Efroni, G.(1);Hadar, R.(1);Ben-Horin, S.(1);
Created: Friday, 11 February 2022, 3:52 PM
OP31: RESTORE: Interim analysis of a Phase 2 study of QBECO SSI for the induction and maintenance of clinical and endoscopic remission in subjects with Moderate to Severe Crohn’s DiseaseYear: 2021
Source: ECCO'21 Virtual
Authors: Bressler, B.(1);Marshall, J.K.(2);Atkinson, K.(3);Sutcliffe, S.(4);Pankovich, J.(4);Jones, M.(4);Kalyan, S.(4);Gunn, H.(4)
Created: Wednesday, 2 June 2021, 4:12 PM
OP31: TP53 mutation in human colonic organoids acquires resistance to in vitro long-term inflammationYear: 2019
Source: ECCO '19 Copenhagen
Authors: K. Tsuchiya*1, S. Watanabe1, T. Shirasaki1, R. Nishimura1, N. Katsukura1, S. Hibiya1, R. Okamoto1, T. Nakamura1, M. Watanabe1
Created: Friday, 22 February 2019, 9:41 AM
OP32: Stool microbiome communities predict remission in treatment-naïve Pediatric Crohn’s Disease patientsYear: 2021
Source: ECCO'21 Virtual
Authors: Verburgt, C.(1,2);Dunn, K.(3);Bielawski, J.(3,4);Otley, A.(5);Heyman, M.(6);Sunseri, W.(7);Shouval, D.(8);Levine, A.(9);de Meij, T.(1);Hyams, J.(10);Denson, L.(11);Kugathasan, S.(12);Benninga, M.(1);de Jonge, W.(2,13);Van Limbergen, J.(1,2,5)
Created: Wednesday, 2 June 2021, 4:12 PM
OP32: Stool microbiome communities predict remission in treatment-naïve Pediatric Crohn’s Disease patientsYear: 2021
Source: ECCO'21 Virtual
Authors: Charlotte Verburgt
Created: Friday, 1 October 2021, 12:41 PM
BackgroundEarly relapse in paediatric Crohn’s Disease (CD) is associated with severe disease course that heavily impairs quality of life. Changes in gut microbiome composition have been linked to active CD and disease course. This has led to development of microbiome-based prediction models for diagnosis and response to treatment. Our aim was to identify community-level microbiome signatures of treatment-naïve children with mild-to-moderate CD who did not require anti-TNF or surgery at diagnosis, with the goal of predicting need for re-induction or treatment escalation within the first year after diagnosis.
MethodsWe selected de novo, treatment-naïve paediatric CD patients from the RISK cohort(Gevers 2014). Taxonomic labels were assigned to the 16s rRNA amplicon data using QIIME and closed OTU-picking. A hierarchical Bayesian model for microbial community structure was used to learn how baseline gut microbiomes differed according to treatment outcome. Model predictions were assessed using a leave-one-out analysis. We compared 16S rRNA sequences of CD patients with non-IBD controls(Gevers 2014) and healthy siblings of CD patients(Turpin 2016).
ResultsMetadata and 16S rRNA amplicon data were available from 197 stool samples of de novo paediatric CD patients from the RISK cohort. We selected 44 out of 197 samples of patients that were treatment-naïve. Prior to treatment, PCDAI scores were similar between patients reaching remission and those that did not at 6 months. Bayesian analysis characterized 4 assemblages that accounted for 93% of the posterior probability distribution. The Bayesian model on pre-treatment stool microbiomes was able to predict 6-month outcome of patients that maintained remission and those that did not from the pre-treatment microbiome in 81% and 75% of samples (AUC=0.79). When comparing CD samples to 28 non-IBD controls (many with GI symptoms but negative for IBD during endoscopy, e.g. Irritable Bowel Syndrome), 6 assemblages were characterized with 44% of distributions shared between groups (AUC=0.61). In contrast, in CD samples compared to 728 healthy sibling samples (with increased genetic susceptibility), shared distribution within 4 characterized assemblages was less than 1% (AUC=1).
ConclusionA Bayesian approach predicted clinical course in treatment-naïve children with CD in the first year after diagnosis with high accuracy, when ensuring only treatment-naïve faecal samples in the analysis. This classification level is comparable to previous findings using mucosal samples. Further study is needed to validate these pre-treatment microbiome signatures of newly diagnosed paediatric CD patients to allow identification of patients with mild-to-moderate disease who are most likely to require treatment escalation.