Gut Microbiome Predictors of Treatment Response and Recurrence in Primary Clostridium difficile Infection

Abstract

Background

Clostridium difficile infection (CDI) may not respond to initial therapy and frequently recurs but predictors of response and recurrence are inconsistent. The impact of specific alterations in the gut microbiota determining treatment response and recurrence in patients with CDI is unknown.

Aim

To assess microbial signatures as predictors of treatment response and recurrence in CDI.

Methods

Pre-treatment stool samples and clinical metadata including outcomes were collected prospectively from patients with their first CDI episode. Next generation 16s rRNA sequencing using MiSeq Illumina platform was performed and changes in microbial community structure were correlated with CDI outcomes.

Results

Eighty-eight patients (median age 52.7 years, 60.2% female) were included. Treatment failure occurred in 12.5% and recurrence after response in 28.5%. Patients who responded to treatment had an increase in Ruminococcaceae, Rikenellaceae, Clostridiaceae, Bacteroides, Faecalibacterium and Rothia compared to non-responders. A risk-index built from this panel of microbes differentiated responders (mean 0.07±0.24) from non-responders (0.52±0.42; p=0.0002). Receiver operating characteristic (ROC) curve demonstrated that risk-index was a strong predictor of treatment response with an area under the curve (AUC) of 0.85. Among clinical parameters tested, only proton-pump inhibitor use predicted recurrent CDI (OR 3.75, 95%CI 1.27-11.1, p=0.01). Patients with recurrent CDI had statistically significant increases in Veillonella, Enterobacteriaceae, Streptococci, Parabacteroides and Lachnospiraceae compared to patients without recurrence and a risk index was able to predict recurrence (AUC=0.78).

Conclusions

Gut microbiota signatures predict treatment response and recurrence potentially allowing identification of CDI patients that may benefit from early institution of alternate therapies.