Microbiome profile and calprotectin levels as markers of risk of recurrent Clostridioides difficile infection

Abstract

IntroductionClostridioides difficile infection (CDI) is the main cause of nosocomial diarrhoea in developed countries. Recurrent CDI (R-CDI), which affects 20%-30% of patients and significantly increases hospital stay and associated costs, is a key challenge. The main objective of this study was to explore the role of the microbiome and calprotectin levels as predictive biomarkers of R-CDI.MethodsWe prospectively (2019-2021) included patients with a primary episode of CDI. Clinical data and faecal samples were collected. The microbiome was analysed by sequencing the hypervariable V4 region of the 16S rRNA gene on an Illumina Miseq platform.ResultsWe enrolled 200 patients with primary CDI, of whom 54 developed R-CDI and 146 did not. We analysed 200 primary samples and found that Fusobacterium increased in abundance, while Collinsella, Senegalimassilia, Prevotella and Ruminococcus decreased in patients with recurrent versus non-recurrent disease. Elevated calprotectin levels correlated significantly with R-CDI (p=0.01). We built a risk index for R-CDI, including as prognostic factors age, sex, immunosuppression, toxin B amplification cycle, creatinine levels and faecal calprotectin levels (overall accuracy of 79%).DiscussionCalprotectin levels and abundance of microbial genera such as Fusobacterium and Prevotella in primary episodes could be useful as early markers of R-CDI. We propose a readily available model for prediction of R-CDI that can be applied at the initial CDI episode. The use of this tool could help to better tailor treatments according to the risk of R-CDI.

Gut Microbiota–Gut Metabolites and Clostridioides difficile Infection: Approaching Sustainable Solutions for Therapy

“…[33] Patients with primary CDI are further divided into two groups based on recurrent CDI Calprotectin level combined with the gut microbiome composition provided better insight into the severity of the CDI. In patients with recurrent CDI, calprotectin level was higher, and it was accompanied by an increased proportion of Fusobacterium and a decreased proportion of Ruminococcus, Prevotella, and Collinsella [41] As well as bacteria, fungi also make a significant contribution to the gut microbiota. Minimal studies have been done on understanding their roles in CDI.…”

“…This information can then be used to determine the microbial signatures to help identify the patients at risk of getting CDI and recurrent CDI. Several studies have been done to understand the changes in the gut microbiota composition of patients with CDI [ 30 , 31 , 32 , 33 , 41 ]. The proteobacteria phylum was increased in the patients with CDI, where Enterobacteriaceae was a significant family contributing to that increase [ 28 , 31 , 42 ].…”

“…Similarly, another study found that patients with an increased abundance of Bacteroides , Ruminococcaceae , Clostridiacea , and Faecalibacterium had better responses to CDI treatments compared to the patients who had recurrent CDI, who had increased populations of Veillonella , Enterobacteriaceae , and Parabacteroides [ 42 ]. Several studies have shown that higher CDI severity is associated with an increased proportion of Enterobacteriaceae and Enterococcus and a decreased proportion of Lachnospiraceae and Bacteroidaceae [ 32 , 33 , 41 , 42 ].…”