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

Author:

Fareed Shaaz12,Sarode Neha3,Stewart Frank J.4,Malik Aneeq2,Laghaie Elham2,Khizer Saadia5,Yan Fengxia6,Pratte Zoe4,Lewis Jeffery7,Immergluck Lilly Cheng12

Affiliation:

1. Department of Microbiology/Biochemistry/Immunology, Morehouse School of Medicine, Atlanta, GA, United States of America

2. Clinical Research Center, Morehouse School of Medicine, Atlanta, GA, United States of America

3. Department of Organismic & Evolutionary Biology, Harvard University, Boston, MA, United States of America

4. School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, United States of America

5. Clinical Research, Children’s Healthcare of Atlanta, Atlanta, GA, United States of America

6. Department of Community Health & Preventive Medicine, Morehouse School of Medicine, Atlanta, GA, United States of America

7. Pediatric Gastroenterology, Children’s Center for Digestive Health Care, LLC, Atlanta, GA, United States of America

Abstract

Background Fecal 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. Methods This 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. Results FMT 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. Conclusion The 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.

Funder

Children’s Healthcare of Atlanta, Friends’ Fund

National Center for Advancing Translational Sciences of the National Institutes of Health

K-08 Agency Healthcare Research Quality

Centers for Disease Control and Prevention Emerging Infections Program Grants

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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