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, ANTICIPATE study group, Annemarie Engbers, Marieke de Regt, Lena M Biehl, Oliver A Cornely, Nathalie Jazmati, Marie-Noelle Bouverne, Frederique Sablier-Gallis, France Mentré, Uta Merle, Andreas Stallmach, Jan Rupp, Johannes Bogner, Christoph Lübbert, Gerda Silling, Oliver Witzke, Achilleas Gikas, Sofia Maraki, George Daikos, Sotirios Tsiodras, Athanasios Skoutelis, Helen Sambatakou, Miquel Pujol, M Angeles Dominguez-Luzon, Jose M Aguado, Emilio Bouza, Javier Cobo, Jesús Rodríguez-Baño, Benito Almirante, Julian de la Torre Cisneros, Simin A Florescu, Maria Nica, Andrei Vata, Adriana Hristea, Mihaela Lupse, Delia Herghea, Deborah Postil, Olivier Barraud, Jean-Michel Molina, Victoire De Lastours, Thomas Guimard, Jean-Philippe Talarmin, Xavier Duval, Louis Bernard, Odile Launay, 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, ANTICIPATE study group, Annemarie Engbers, Marieke de Regt, Lena M Biehl, Oliver A Cornely, Nathalie Jazmati, Marie-Noelle Bouverne, Frederique Sablier-Gallis, France Mentré, Uta Merle, Andreas Stallmach, Jan Rupp, Johannes Bogner, Christoph Lübbert, Gerda Silling, Oliver Witzke, Achilleas Gikas, Sofia Maraki, George Daikos, Sotirios Tsiodras, Athanasios Skoutelis, Helen Sambatakou, Miquel Pujol, M Angeles Dominguez-Luzon, Jose M Aguado, Emilio Bouza, Javier Cobo, Jesús Rodríguez-Baño, Benito Almirante, Julian de la Torre Cisneros, Simin A Florescu, Maria Nica, Andrei Vata, Adriana Hristea, Mihaela Lupse, Delia Herghea, Deborah 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.
Conflict of interest statement
C.H.v.W. received speaker fees from Pfizer and Merck/MSD, and non-financial research support from bioMérieux. A.D. is an employee and shareholder of Da Volterra. J.d.G. is a consultant and shareholder of Da Volterra. M.J.G.T.V. has received research grants from 3M, Astellas Pharma, Da Volterra, Gilead Sciences, Glycom, MaaT Pharma, Merck/MSD, Organobalance, Seres Therapeutics; speaker fees from Astellas Pharma, Basilea, Gilead Sciences, Merck/MSD, Organobalance, Pfizer and has been a consultant to Alb Fils Kliniken GmbH, Astellas Pharma, Da Volterra, Ferring, MaaT Pharma, Merck/MSD and Summit Therapeutics. M.B., M.M., B.B.X., C.L., P.M., M.J.M.B., H.G., S.M.-K. report no competing interests.
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