Gut microbiome predictors of treatment response and recurrence in primary Clostridium difficile infection

S. Khanna, E. Montassier, B. Schmidt, R. Patel, D. Knights, D. S. Pardi, P. C. Kashyap

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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 nonresponders. A risk-index built from this panel of microbes differentiated responders (mean 0.07 ± 0.24) from nonresponders (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). Conclusion: Gut microbiota signatures predict treatment response and recurrence potentially, allowing identification of patients with Clostridium difficile infection that may benefit from early institution of alternate therapies.

Original languageEnglish (US)
Pages (from-to)715-727
Number of pages13
JournalAlimentary Pharmacology and Therapeutics
Volume44
Issue number7
DOIs
StatePublished - 2016

Bibliographical note

Funding Information:
Declaration of personal interests: Sahil Khanna has received research grant support from Merck Pharmaceuticals and has consulted with Rebiotix, Inc (consultation paid to Mayo Clinic) and Summit pharmaceuticals. Dr. Pardi has received funding from Seres therapeutics, Salix pharmaceuticals, Atlantic pharmaceuticals, Takeda pharmaceuticals, Merck pharmaceuticals, and Janssen pharmaceuticals. Dr. Pardi has also served as a Consultant to Merck pharmaceuticals and Otsuka pharmaceuticals. Dr. Patel reports grants from BioFire, Check-Points, Curetis, 3M, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company. Dr. Patel is a consultant to Curetis, Roche, Qvella, and Diaxonhit. In addition, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR with royalties paid by TIB, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. Dr. Patel serves on an Actelion data monitoring board. Dr. Patel receives travel reimbursement and an editor's stipend from ASM and IDSA, and honoraria from the USMLE, Up-to-Date and the Infectious Diseases Board Review Course. Declaration of funding interests: This research was made possible by support from NIH K08 DK100638 (PCK), Global Probiotic Council (PCK), Minnesota Partnership for Biotechnology and Genomics (PCK) and Center for Individualized Medicine, Mayo Clinic, Rochester and CTSA Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number P30 DK084567 (Clinical Core). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. EM was supported by the Robert Tournut award from the French National Society of Gastroenterology.

Publisher Copyright:
© 2016 John Wiley & Sons Ltd

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