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Decreased Fecal Bacterial Diversity and Altered Microbiome in Children Colonized With Clostridium difficile

Chen, Lea Ann*; Hourigan, Suchitra K.; Grigoryan, Zoya*; Gao, Zhan; Clemente, Jose C.§; Rideout, Jai Ram||; Chirumamilla, Sankar; Rabidazeh, Shervin#; Saeed, Shehzad**; Elson, Charles O.††; Oliva-Hemker, Maria‡‡; Blaser, Martin J.; Sears, Cynthia L.§§,||||

Journal of Pediatric Gastroenterology and Nutrition: April 2019 - Volume 68 - Issue 4 - p 502–508
doi: 10.1097/MPG.0000000000002210
Original Articles: Gastroenterology
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Objectives: The gut microbiome is believed to play a role in the susceptibility to and treatment of Clostridium difficile infections (CDIs). It is, however, unknown whether the gut microbiome is also affected by asymptomatic C difficile colonization. Our study aimed to evaluate the fecal microbiome of children based on C difficile colonization, and CDI risk factors, including antibiotic use and comorbid inflammatory bowel disease (IBD).

Methods: Subjects with IBD and non-IBD controls were prospectively enrolled from pediatric clinics for a biobanking project (n = 113). A fecal sample was collected from each subject for research purposes only and was evaluated for asymptomatic toxigenic C difficile colonization. Fecal microbiome composition was determined by 16S rRNA sequencing.

Results: We found reduced bacterial diversity and altered microbiome composition in subjects with C difficile colonization, concurrent antibiotic use, and/or concomitant IBD (all P < 0.05). Accounting for antibiotic use and IBD status, children colonized with C difficile had significant enrichment in taxa from the genera Ruminococcus, Eggerthella, and Clostridium. Children without C difficile had increased relative abundances of Faecalibacterium and Rikenellaceae. Imputed metagenomic functions of those colonized were enriched for genes in oxidative phosphorylation and beta-lactam resistance, whereas in the subjects without C difficile, several functions in translation and metabolism were over-represented.

Conclusions: In children, C difficile colonization, or factors that predispose to colonization such as antibiotic use and IBD status were associated with decreased gut bacterial diversity and altered microbiome composition. Averting such microbiome alterations may be a method to prevent or treat CDI.

*Department of Medicine, Division of Gastroenterology, New York University School of Medicine, New York, NY

Johns Hopkins School of Medicine, Baltimore, MD

Department of Medicine, New York University School of Medicine

§Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY

||The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ

Department of Physical Medicine and Rehabilitation, Pikeville Medical Center, Pikeville, KY

#Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cedars-Sinai Hospital, Los Angeles, CA

**Division of Gastroenterology, Boonshoft School of Medicine, Wright State University, Dayton Children's Hospital, Dayton, OH

††Department of Medicine, University of Alabama at Birmingham, Birmingham, AL

‡‡Division of Pediatric Gastroenterology, Hepatology and Nutrition

§§Department of Medicine, Johns Hopkins University School of Medicine

||||Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD.

Address correspondence and reprint requests to Lea Ann Chen, MD, Division of Gastroenterology, NYU Langone Medical Center, 462 1st Ave 10E1, New York, NY 10016 (e-mail: leaann.chen@nyumc.org).

Received 19 June, 2018

Accepted 1 October, 2018

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).

This study was funded in part by UL1 TR000038, R01 DK090989, and U01AI122285 from the National Institutes of Health, as well as the Colton Family Scholar Award and the Crohn's and Colitis Foundation. The NYUMC Genome Technology Center is partially supported by the Cancer Center Support Grant (P30CA016087) at the Laura and Isaac Perlmutter Cancer Center.

The authors report no conflicts of interest

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,