Maria G. Maseng, Simen H. Hansen, Corina Bang, Trond Espen Detlie, Gert Huppertz-Hauss, Vendel A. Kristensen, Randi Opheim, Gøri Perminow, Øyvind Asak, May-Bente Bengtson, Raziye Boyar, Øistein Hovde, Vibeke Strande, Jørgen Valeur, Simen Vatn, Tone B. Aabrekk, Marte L. Høivik#*, Johannes R. Hov# *Presenter

Affiliates

Maria G. Maseng [1,2,3], Simen H. Hansen [1,4,5], Corina Bang [6], Trond Espen Detlie [1,7], Gert Huppertz-Hauss [8], Vendel A. Kristensen [1,2], Randi Opheim [2,9], Gøri Perminow [10], Øyvind Asak [11], May-Bente Bengtson [12], Raziye Boyar [13], Øistein Hovde [1,14], Vibeke Strande [1,8, 15], Jørgen Valeur [1,8], Simen Vatn [1, 7], Tone B. Aabrekk [1, 12], Marte L. Høivik [1,2]#*, Johannes R. Hov [1, 4, 5, 16]# 1 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 2 Dep. of Gastroenterology, Oslo University Hospital, Oslo, Norway; 3 Bio-Me, Oslo, Norway; 4 Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway; 5 Norwegian PSC Research Center, Dep. of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway; 6 Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; 7 Dep. of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; 8 Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway; 9 Dep. of Public Health, Institute of Health and Society, University of Oslo, Norway; 10 Pediatric Dep., Oslo University Hospital, Oslo; 11 Medical Dep., Innlandet Hospital Trust, Lillehammer; 12 Medical Dep., Vestfold Hospital Trust, Tønsberg, Norway; 13 Dep. of Medicine, Diakonhjemmet Hospital, Oslo, Norway 14 Dep. of Medicine, Sørlandet Hospital Flekkefjord, Flekkefjord, Norway; 15 Dep. of Medicine/Gastroenterology, Lovisenberg Diaconal Hospital, Oslo, Norway; 16 Section of Gastroenterology, Dep. of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital

Abstract

Background & Aim
Despite the well-established involvement of the gut microbiota in inflammatory bowel disease (IBD), lesser is known about how the gut microbiota changes over time or these changes correlate with clinical disease activity and fecal calprotectin. To address this gap, we utilized the population-based inception cohort IBSEN III.
Methods
Stool samples from IBD patients and symptomatic controls (SC) were collected at diagnosis and after 3, 6, and 12 months. Comprehensive data collection was performed at baseline and at the 12-month follow-up, while faecal calprotectin (F-calprotectin) and patient reported clinical disease activity indices (mPRO2) data were also gathered at 3 and 6 months. Microbiota profiling of stool was performed targeting the V3-V4 region of the 16S rRNA gene, and a consensus-based approach utilizing mixed models was employed for the microbiota analysis.
Results
We included 761 patients with ulcerative colitis (UC) (median age 37, 48% female) and 448 with Crohn’s disease (CD) (median age 33, 55% female), each contributing at least one fecal sample. A subset of 79 UC and 58 CD patients provided samples at all four time points. Patient-reported symptoms decreased over the year for both UC and CD, and CD subtypes. F-calprotectin levels generally decreased over the first year, but subtype analyses revealed differences: patients with colon-affected CD showed persistently higher F-calprotectin levels, while levels remained stable over time in those with ileal-affected CD.
Distinct changes in gut microbiota of IBD subjects were observed throughout the first year, such as increased alpha diversity and significant taxonomic changes over time (figure). The degree of variability in microbiota composition varied significantly between CD, UC and symptomatic controls. Furthermore, there was significant overlap with microbial patterns associated with F-calprotectin and mPRO2 score, and the changes in these scores were reflected in the microbial changes over time.
Conclusion
The gut microbiota during the first year after IBD diagnosis showed changes that paralleled inflammation and clinical disease activity.

Figure: Through a consensus-based differential abundance analysis we identified significant changes (q-value < 0.05) in the abundance of several gut bacterial genera over the first year in subjects with CD (left) and UC (right).