Microbiota-based markers predictive of development of Clostridioides difficile infection
Matilda Berkell, Mohamed Mysara, Basil Britto Xavier, Cornelis H. van Werkhoven, Pieter Monsieurs, Christine Lammens, Annie Ducher, Maria J. G. T. Vehreschild, Herman Goossens, Jean de Gunzburg, Marc J. M. Bonten, Surbhi Malhotra‐Kumar, the ANTICIPATE study group, Annemarie M. S. Engbers, Marieke de Regt, Lena M. Biehl, Oliver A. Cornely, Nathalie Jazmati, Marie-Noëlle Bouverne, Frédérique Sablier-Gallis, France Mentré, Uta Merle, Andreas Stallmach, Jan Rupp, Johannes R. Bogner, Christoph Lübbert, Gerda Silling, Oliver Witzke, Achilleas Gikas, Sofia Maraki, G. K. Daikos, Sotirios Tsiodras, Athanasios Skoutelis, Helen Sambatakou, Miquel Pujol, M.Á. Domínguez, J. M. Aguado, Emilio Bouza, Javier Cobo, Jesús Rodríguez‐Baño, Benito Almirante, Julián de la Torre Cisneros, Simin Aysel Florescu, Maria Nica, A Vâţă, Adriana Hristea, Mihaela Lupșe, Delia Herghea, D. Postil, Olivier Barraud, Jean‐Michel Molina, Victoire de Lastours, Thomas Guimard, Jean‐Philippe Talarmin, Xavier Duval, Louis Bernard, Odile Launay
Abstract
Antibiotic-induced modulation of the intestinal microbiota can lead to Clostridioides difficile infection (CDI), which is associated with considerable morbidity, mortality, and healthcare-costs globally. Therefore, identification of markers predictive of CDI could substantially contribute to guiding therapy and decreasing the infection burden. Here, we analyze the intestinal microbiota of hospitalized patients at increased CDI risk in a prospective, 90-day cohort-study before and after antibiotic treatment and at diarrhea onset. We show that patients developing CDI already exhibit significantly lower diversity before antibiotic treatment and a distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients. We find that antibiotic treatment-induced dysbiosis is class-specific with beta-lactams further increasing enterococcal abundance. Our findings, validated in an independent prospective patient cohort developing CDI, can be exploited to enrich for high-risk patients in prospective clinical trials, and to develop predictive microbiota-based diagnostics for management of patients at risk for CDI.