Dynamics of the fecal microbiome in patients with recurrent and nonrecurrent Clostridium difficile infection

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.

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

“…Indeed, recent studies of CDI in humans have found that decreased microbial diversity is associated with severe and recurrent CDI (51) and have also identified patterns of microbiota change associated with recovery from CDI (52). Antibiotic exposure is the primary risk factor for the development of symptomatic CDI because this treatment perturbs the gut microbiota and reduces colonization resistance (50).…”

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“…38 In addition, recently two studies have identified microbiome signatures that allow prediction of disease outcome allowing therapeutic stratification. 39, 40 An expansion of Proteobacteria in the setting of dysbiotic microbiota was described in patients with celiac disease with gastrointestinal symptoms compared to those with extra-intestinal manifestations of celiac disease. 41 In addition to diseases within gastrointestinal tract, it is interesting that several studies have described gut microbiome signatures in systemic disorders such as rheumatoid arthritis.…”

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“…Its excellent clinical efficacy is further upheld by the observation that host intestinal microbiota composition and diversity are intimately linked to CDI severity and recurrence risk [205]. …”