Fecal Transplant in Children With Clostridioides difficile Gives Sustained Reduction in Antimicrobial Resistance and Potential Pathogen Burden

Suchitra K Hourigan; Michelle Ahn; Keylie M Gibson; Marcos Pérez-Losada; Grace Felix; Melissa Weidner; Ian Leibowitz; John E Niederhuber; Cynthia L Sears; Keith A Crandall; Maria Oliva-Hemker

doi:10.1093/ofid/ofz379

Fecal Transplant in Children With Clostridioides difficile Gives Sustained Reduction in Antimicrobial Resistance and Potential Pathogen Burden

Open Forum Infect Dis. 2019 Aug 26;6(10):ofz379. doi: 10.1093/ofid/ofz379. eCollection 2019 Oct.

Authors

Suchitra K Hourigan^{1

2

3

4}, Michelle Ahn⁵, Keylie M Gibson⁵, Marcos Pérez-Losada^{5

6

7}, Grace Felix^{3

4}, Melissa Weidner⁴, Ian Leibowitz³, John E Niederhuber^{1

4

8}, Cynthia L Sears⁴, Keith A Crandall^{5

6}, Maria Oliva-Hemker⁴

Affiliations

¹ Inova Translational Medicine Institute, Falls Church, Virginia.
² Inova Children's Hospital, Falls Church, Virginia.
³ Pediatric Specialists of Virginia, Fairfax, Virginia.
⁴ Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁵ Computational Biology Institute and, Washington, DC.
⁶ Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, DC.
⁷ CIBIO-InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, Vairão, Portugal.
⁸ Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, Virginia.

Abstract

Background: Fecal microbiota transplantation (FMT) treats Clostridioides difficile infection (CDI). Little is known regarding the changes in antimicrobial resistance (AMR) genes and potential pathogen burden that occur in pediatric recipients of FMT. The aim of this study was to investigate changes in AMR genes, potential pathogens, species, and functional pathways with FMT in children.

Methods: Nine children with recurrent CDI underwent FMT. Stool was collected from donor and recipient pre-FMT and longitudinally post-FMT for up to 24 weeks. Shotgun metagenomic sequencing was performed. Reads were analyzed using PathoScope 2.0.

Results: All children had resolution of CDI. AMR genes decreased post-FMT (P < .001), with a sustained decrease in multidrug resistance genes (P < .001). Tetracycline resistance genes increased post-FMT (P < .001). Very low levels of potential pathogens were identified in donors and recipients, with an overall decrease post-FMT (P < .001). Prevotella sp. 109 expanded in all recipients post-FMT, and no recipients had any clinical infection. Alpha diversity was lower in recipients vs donors pre-FMT (P < .001), with an increase post-FMT (P ≤ .002) that was sustained. Beta diversity differed significantly in pre- vs post-FMT recipient samples (P < .001). Bacterial species Faecalibacterium prausnitzii and Bacteroides ovatus showed higher abundance in donors than recipients (P = .008 and P = .040, respectively), with expansion post-FMT. Biosynthetic pathways predominated in the donor and increased in the recipient post-FMT.

Conclusions: FMT for CDI in children decreases AMR genes and potential pathogens and changes microbiota composition and function. However, acquisition of certain AMR genes post-FMT combined with low levels of potential pathogens found in donors suggests that further study is warranted regarding screening donors using metagenomics sequencing before FMT.

Keywords: Clostridioides difficile; Clostridium difficile; antimicrobial resistance; children; fecal transplant; pathogen.

Abstract

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