Identifying predictive features of Clostridium difficile infection recurrence before, during, and after primary antibiotic treatment

Abstract

BackgroundColonization by the pathogen Clostridium difficile often occurs in the background of a disrupted microbial community. Identifying specific organisms conferring resistance to invasion by C. difficile is desirable because diagnostic and therapeutic strategies based on the human microbiota have the potential to provide more precision to the management and treatment of Clostridium difficile infection (CDI) and its recurrence.MethodsWe conducted a longitudinal study of adult patients diagnosed with their first CDI. We investigated the dynamics of the gut microbiota during antibiotic treatment, and we used microbial or demographic features at the time of diagnosis, or after treatment, to predict CDI recurrence. To check the validity of the predictions, a meta-analysis using a previously published dataset was performed.ResultsWe observed that patients’ microbiota “before” antibiotic treatment was predictive of disease relapse, but surprisingly, post-antibiotic microbial community is indistinguishable between patients that recur or not. At the individual OTU level, we identified Veillonella dispar as a candidate organism for preventing CDI recurrence; however, we did not detect a corresponding signal in the conducted meta-analysis.ConclusionAlthough in our patient population, a candidate organism was identified for negatively predicting CDI recurrence, results suggest the need for larger cohort studies that include patients with diverse demographic characteristics to generalize species that robustly confer colonization resistance against C. difficile and accurately predict disease relapse.Electronic supplementary materialThe online version of this article (10.1186/s40168-017-0368-1) contains supplementary material, which is available to authorized users.

Microbiota diversity following antibiotic treatment of Clostridium difficile infection

“…Examination of intestinal bacterial populations of CDI patients and their correlation with previous antibiotic treatment, showed that there was no phylum-and family-level composition common to all CDI patients, as has been described in other studies [21][22][23]. In their study comparing the gut microbiome pro le of CDI versus non-CDI patients, Manges et al found an increase in Firmicutes, Proteobacteria and Actinobacteria phyla, as well as a decrease in Bacteroidetes [24].…”

Stronger connectivity of the resident gut microbiome lends resistance to invading bacteria

“…Thus, weak connectivity of the patient gut bacterial community after FMT was an indicator that the patient was more likely to relapse. Prior efforts to predict C. difficile relapse from the microbiome did not find post-FMT indicators of relapse, although connectivity was not previously considered (Pakpour et al 2017).…”

Temporal Gut Microbial Changes Predict RecurrentClostridium difficilein Patients with and without Ulcerative Colitis

“…identified decreased Shannon diversity, depletion of Bacteroidetes and reduced abundance of Veillonella dispar by random forest models as being predictive of rCDI. 38 However, the predictive capability of their model was poor (AuROC=0.68). Although there were differences in the microbial characteristics identified, this was likely related to differences in patient populations between our studies.…”