Abstract
BackgroundRecurrent Clostridium difficile infection (CDI) remains problematic, with up to 30 % of individuals diagnosed with primary CDI experiencing at least one episode of recurrence. The success of microbial-based therapeutics, such as fecal microbiota transplantation, for the treatment of recurrent CDI underscores the importance of restoring the microbiota. However, few studies have looked at the microbial factors that contribute to the development of recurrent disease. Here we compare microbial changes over time in patients with or without recurrence to identify microbial signatures associated with the development of recurrence.MethodsWe used 16S rRNA-encoding gene sequence analysis to compare the fecal microbiota of 93 patients with recurrent and nonrecurrent CDI, sampled longitudinally. Cross-group and intra-individual differences in microbial community diversity and similarity were compared prior to the development of recurrent disease and over time.ResultsSamples from these patient groups exhibited variable community profiles, clustering into four distinct community groups. Cross-group comparison of the index sample collected from patients that did or did not develop recurrence revealed differences in diversity and community structure (analysis of molecular variance, p < 0.05). Intra-individual comparisons of the microbiota were more informative and samples from recurrent patients were less likely to recover in diversity (Chi-square test, p < 0.005), exhibiting less community similarity overall (Kruskal–Wallis test, p < 0.05). Interestingly, patients with severe disease harbored a significantly less diverse community, a trend that was observed across both nonrecurrent and recurrent patient groups (Wilcoxon test, p < 0.05).ConclusionsTo date, this study represents one of the largest studies focused on the relationship between predictive signals from the gut microbiota and the development of recurrent CDI. Our data demonstrate that specific microbiota-derived characteristics associate with disease severity and recurrence and that future studies could incorporate these characteristics into predictive models.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0298-8) contains supplementary material, which is available to authorized users.
Highlights
Recurrent Clostridium difficile infection (CDI) remains problematic, with up to 30 % of individuals diagnosed with primary CDI experiencing at least one episode of recurrence
Distinct microbial community features are present in the feces of patients with severe C. difficile infection but are not with recurrent infection Following an initial diagnosis of CDI, longitudinal fecal samples were collected from patients with nonrecurrent and recurrent disease and patients who were reinfected with C. difficile past the 56-day window of the recurrence definition, as described in “Methods” (Fig. 1, Table 1)
Clustering (mean S(i) = 0.26) of all samples resulted in four major community clusters (Fig. 2): a high-diversity cluster defined by a high relative abundance of one of two Proteobacteria members; a cluster of samples rich in Bacteroidetes; and two low-diversity clusters characterized by Enterococcus or an Enterobacteriaceae operational taxonomic unit (OTU)
Summary
Recurrent Clostridium difficile infection (CDI) remains problematic, with up to 30 % of individuals diagnosed with primary CDI experiencing at least one episode of recurrence. The success of microbial-based therapeutics, such as fecal microbiota transplantation, for the treatment of recurrent CDI underscores the importance of restoring the microbiota. Few studies have looked at the microbial factors that contribute to the development of recurrent disease. Fecal microbiota transplantation (FMT) is one of the most effective therapies for recurrent CDI, with an over 90 % success rate [6,7,8]. Several studies have observed a significant recovery in the diversity of the microbial community following FMT, the specific microbes that contribute to recovery are variable between patients [9,10,11]. Studies have not followed CDI patients over time to compare those that do or do not develop recurrent disease
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