Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children.

Shaaz Fareed,Saadia Khizer,Zoe Pratte,Neha Sarode,Aneeq Malik,Fengxia Yan,Elham Laghaie,Frank J Stewart,Jeffery Lewis,Lilly Cheng Immergluck

doi:10.7717/peerj.4663

Abstract

BackgroundFecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT.MethodsThis is a prospective, observational, pilot study of 15 children ≤18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors’ and the patients’ pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing.ResultsFMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles.ConclusionThe low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome.

Highlights

Childhood infections by the anaerobic gram-positive bacterium Clostridium difficile pose a significant health challenge, with limited viable treatment options for recurrent infections
Risks associated with Clostridium difficile infections (CDI) include prior antibiotic use (Schutze et al, 2013) and gut motility dysfunction, with higher incidence observed in children with inflammatory bowel disease (IBD) (Pascarella et al, 2009)
Though fecal microbiota transplantation (FMT) has showed promising results in adults (Rao & Safdar, 2016), this treatment option has been applied sparingly in children (Russell et al, 2010), and even fewer studies have analyzed the efficacy of FMT to treat pediatric recurrent Clostridium difficile infection (rCDI) and the impact of the procedure on pediatric gut microbiomes (Hourigan & Oliva-Hemker, 2016)

Summary

INTRODUCTION

Childhood infections by the anaerobic gram-positive bacterium Clostridium difficile pose a significant health challenge, with limited viable treatment options for recurrent infections. An estimated 17,000 CDI cases involve children ages 1 to 17 years (Center for Disease Control and Prevention, 2015), the majority of studies exploring treatment efficacy focus on adults (Lees et al, 2016). Though FMT has showed promising results in adults (Rao & Safdar, 2016), this treatment option has been applied sparingly in children (Russell et al, 2010), and even fewer studies have analyzed the efficacy of FMT to treat pediatric rCDI and the impact of the procedure on pediatric gut microbiomes (Hourigan & Oliva-Hemker, 2016). Ours is the largest FMT study to be conducted among pediatric patients with rCDI, which involves children both with and without underlying inflammatory bowel disease

MATERIALS & METHODS

RESULTS

DISCUSSION