LMM researchers identify biomarkers predictive of Clostridioides difficile infection (CDI)

Berkell  M, Mysara M, Xavier BB, Werkhoven CH van, Monsieurs P, Lammens C, Ducher A, Vehreschild MJGT, Goossens H, de Gunzburg J, Bonten MJM, Malhotra-Kumar S.

Microbiota-based markers predictive of development of Clostridioides difficile infection. Nature Communications 2021: https://doi.org/10.1038/s41467-021-22302-0

The bacterial composition in the colon can be used to recognize patients at increased risk of infection with the bacterium Clostridium difficile after a course of antibiotics. This was the result of gut microbiota research led by LMM, UAntwerp in collaboration with UMC Utrecht, University of Cologne and the French company, Da Volterra.

Clostridioides difficile is the most common cause of infectious antibiotic-associated diarrhea (AAD) and is the pathogen responsible for the largest number of healthcare-associated infections world-wide. The biggest risk factor for this disease is treatment with broad-spectrum antibiotics, and particularly affects elderly and hospitalized people. Therefore, identification of markers predictive of Clostridioides difficile infection (CDI) could substantially contribute to guiding therapy and decreasing the infection burden.


The Assessment of the Incidence of C. difficile Infections in hospitalized Patients on Antibiotic TrEatment (ANTICIPATE) study is an international, multicenter, prospective, observational cohort study conducted in 2016 and 2017 in 34 hospitals (21 university medical centers and 13 general hospitals) in Germany, France, Greece, the Netherlands, Romania and Spain. The aim of the study was to determine the incidence of infections with C. difficile and to better predict the risk of acquiring this infection. The ANTICIPATE study was conducted by the COMBACTE research consortium in close collaboration with Da Volterra (https://doi.org/10.1038/s41467-021-22269-y).

Analyzing the gut microbiota composition

In this part of the study, led by LMM, University of Antwerp, high-resolution 16S ribosomal RNA gene profiling (and shotgun metagenomics) was utilized to study the composition of the gut microbiota of high-risk patients enrolled in the ANTICIPATE study before and after antibiotic treatment and at diarrheal onset. Patients that eventually developed CDI already exhibited significantly lower diversity of their intestinal microbiota prior to antibiotic treatment and a distinct composition enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to patients that did not develop CDI. Importantly, further validation of the identified markers in an independent cohort of CDI patients demonstrated that these prevailed over confounders that commonly limit the wider applicability of microbiota-based markers. Study lead Surbhi Malhotra-Kumar, professor of medical microbiology at the University of Antwerp  says: “This study is an example of truly translational research wherein analysis of patient samples from a multi-national clinical trial led to the successful identification of robust microbiota-based markers that can be exploited to enrich for high-risk patients in prospective clinical trials, and to develop predictive, microbiota-based diagnostics for clinical management of patients at risk of CDI.”

Read the blogpost by M. Berkell for Nature Communications.