P920 Gut microbiota at diagnosis is associated with clinical features and future disease course in Inflammatory Bowel Disease: Data from IBSEN III, a new large Norwegian population-based inception cohort
Hyll Hansen, S.(1,2,3)*;Gjerstad Maseng, M.(3,4,5);Björkqvist, O.(6);Halfvarsson, J.(7);Bang, C.(8);Detlie, T.E.(9,10);Huppertz-Hauss, G.(11);Kristensen, V.(5,12);Opheim, R.(5,13);Perminow, G.(14);Asak, Ø.(15);Bengtson, M.B.(10);Boyar Cetinkaya, R.(16);Henriksen, M.(17);Hovde, Ø.(3,18);Medhus, A.W.(3,5);Pallenschat, J.(19);Strande, V.(3,20,21);Valeur, J.(21);Svendsen Vatn, S.(10);Bergene Aabrekk, T.(22);Høivik, M.L.(5);Hov, J.R.(1,2,3,23);
(1)Oslo University Hospital, Norwegian PSC Research Center- Department of Transplantation Medicine- Division of Surgery- Inflammatory Diseases and Transplantation, Oslo, Norway;(2)Oslo University Hospital, Research Institute of Internal Medicine- Division of Surgery- Inflammatory Diseases and Transplantation, Oslo, Norway;(3)University of Oslo, Institute of Clinical Medicine- Faculty of Medicine, Oslo, Norway;(4)Bio-Me, Bio-Me, Oslo, Norway;(5)Oslo University Hospital, Department of Gastroenterology, Oslo, Norway;(6)Örebro University, School of Medical Sciences, Örebro, Sweden;(7)Örebro University, Department of Gastroenterology- Faculty of Medicine and Health, Örebro, Sweden;(8)Christian-Albrechts-University of Kiel, Institute of Clinical Molecular Biology, Kiel, Germany;(9)University of Oslo, University of Oslo, Oslo, Norway;(10)Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway;(11)Telemark Hospital, Department of Gastroenterology, Skien, Norway;(12)Lovisenberg Diaconal Hospital, Unger-Vetlesen Insitute, Oslo, Norway;(13)University of Oslo, Department of Public Health- Institute of Health and Society, Oslo, Norway;(14)Oslo University Hospital, Pediatric Department, Oslo, Norway;(15)Innlandet Hospital Trust, Medical Department, Oslo, Norway;(16)Diakonhjemmet Hospital, Department of Medicine, Oslo, Norway;(17)Østfold Hospital Trust, Department of Gastroenterology, Grålum, Norway;(18)Innlandet Hospital Trust, Department of Medicine, Gjøvik, Norway;(19)Sørlandet Hospital Flekkefjord, Department of Medicine, Flekkefjord, Norway;(20)Lovisenberg Diaconal Hospital, Department of Medicine/Gastroenterology, Oslo, Norway;(21)Lovisenberg Diaconal Hospital, Unger-Vetlesen Institute, Oslo, Norway;(22)Vestfold Hospital Trust, Medical Department, Tønsberg, Norway;(23)Oslo University Hospital, Section of Gastroenterology- Department of Transplantation Medicine- Division of Surgery- Inflammatory Diseases and Transplantation, Oslo, Norway;
Background
Inflammatory bowel disease (IBD) in South-Eastern Norway (IBSEN) III is a population-based inception cohort including patients with suspected IBD between 2017 and 2019. The present study aimed to evaluate the diagnostic and prognostic properties of baseline microbiota profiling, particularly regarding future disease course within the first year from diagnosis.
Methods
Stool samples were collected in preservative before index colonoscopy or as close after as possible. Patients with suspected IBD but no evidence of inflammation were categorized as symptomatic controls. Patients <18 years and patients treated with antibiotics the previous three months were excluded. A severe disease course was defined as the need for one or more of the following within one year of diagnosis: IBD-related surgery, hospitalizations due to IBD, exposure to ≥2 biologics, exposure to >2 steroid courses, or development of complicated disease behaviour. The V3-V4 region of the 16S rRNA gene was amplified and sequenced on an Illumina platform. Statistics were performed in R version 4.2.0, using MaAsLin2 with confounder correction to test for differential abundance of bacteria. XGBoost with 5-fold cross validation was used with area under the curve (AUC) analysis to produce predictive machine learning (ML) models.
Results
970 patients were included: n=569 Ulcerative colitis (UC, 53% male), n=287 Crohn’s disease (CD, 41% male), n=114 symptomatic controls (51% male). Baseline microbiota was associated with a severe disease course in UC-patients when compared to those with an indolent disease course, characterized by a reduced α-diversity at baseline (Shannon diversity index, p = 0.0001, beta = -1.42 [-1.79, -1.05]) and a distinct microbial profile identified by differential abundance analyses (q < 0.05, 42 taxa). UC and CD had unique microbial profiles compared to each other (q < 0.05, 35 taxa), and both presented with decreased α-diversity when baseline disease severity increased. Further, UC and CD were different from symptomatic controls (q < 0.05, 12 and 4 taxa respectively), but only UC had a reduced α-diversity compared to systematic controls. Using ML-models and AUC analyses, microbial profiles were better prognostic markers than calprotectin and CRP for predicting both IBD subtype, i.e. UC vs CD, and a severe disease course in UC (p < 0.00001, Table).
Conclusion
In this large IBD inception cohort followed for one year, baseline microbial profiles show potential as both a prognostic and diagnostic tool. The microbial profile outperformed traditional biochemical markers in predicting diagnosis as well as a severe disease course, which may have clinical implications.