Prediction of Response to Systemic Corticosteroids in Active UC by Microbial Composition—A Prospective Multicenter Study
Andreas Blesl, Philipp Wurm, Silvio Waschina, Hans Peter Gröchenig, Gottfried Novacek, Christian Primas, Walter Reinisch, Maximilian Kutschera, Constanze Illiasch, Barbara Hennlich, P Steiner, Robert Koch, W Tillinger, Thomas Haas, G Reicht, Andreas Mayer, Othmar Ludwiczek, Wolfgang Miehsler, K Steidl, Lukas Binder, Simon Reider, Christina Watschinger, Stefan Fürst, Patrizia Kump, Alexander R. Moschen, Konrad Aden, Gregor Gorkiewicz, Christoph Högenauer
Abstract
BACKGROUND: Corticosteroids are used for induction of remission in patients with moderately to severely active ulcerative colitis. However, up to one-third of patients fail to this therapy. We investigated if fecal microbial composition or its metabolic capacity are associated with response to systemic corticosteroids. METHODS: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥4) receiving systemic corticosteroids were eligible. Data were assessed and fecal samples collected before and after 4 weeks of treatment. Patients were divided into responders (decrease of Lichtiger Score ≥50%) and nonresponders. The fecal microbiome was assessed by the 16S rRNA gene marker and analyzed with QIIME 2. Microbial metabolic pathways were predicted using parsimonious flux balance analysis. RESULTS: Among 93 included patients, 69 (74%) patients responded to corticosteroids after 4 weeks. At baseline, responders could not be distinguished from nonresponders by microbial diversity and composition, except for a subgroup of biologic-naïve patients. Within 4 weeks of treatment, responders experienced changes in beta diversity with enrichment of ascribed beneficial taxa, including Blautia, Anaerostipes, and Bifidobacterium, as well as an increase in predicted butyrate synthesis. Nonresponders had only minor longitudinal taxonomic changes with a significant increase of Streptococcus salivarius and a microbial composition shifting away from responders. CONCLUSION: Baseline microbial diversity and composition seem to be of limited use to predict response to systemic corticosteroids in active ulcerative colitis. Response is longitudinally associated with restoration of microbial composition and its metabolic capacity.