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 and Surbhi Malhotra-Kumar ()
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Matilda Berkell: University of Antwerp
Mohamed Mysara: University of Antwerp
Basil Britto Xavier: University of Antwerp
Cornelis H. van Werkhoven: Utrecht University
Pieter Monsieurs: SCK–CEN
Christine Lammens: University of Antwerp
Annie Ducher: Da Volterra
Maria J. G. T. Vehreschild: University of Cologne
Herman Goossens: University of Antwerp
Jean de Gunzburg: Da Volterra
Marc J. M. Bonten: Utrecht University
Surbhi Malhotra-Kumar: University of Antwerp

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22302-0

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