Lea Ann Chen1, Suchitra K Hourigan2, Zoya Grigoryan1, Zhan Gao3, Jose C Clemente4, Jai Ram Rideout5, Sankar Chirumamilla6, Shervin Rabidazeh7, Shehzad Saeed8, Charles O Elson9, Maria Oliva-Hemker10, Martin J Blaser3, Cynthia L Sears11,12. 1. Department of Medicine, Division of Gastroenterology, New York University School of Medicine, New York, NY. 2. Johns Hopkins School of Medicine, Baltimore, MD. 3. Department of Medicine, New York University School of Medicine. 4. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY. 5. The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ. 6. Department of Physical Medicine and Rehabilitation, Pikeville Medical Center, Pikeville, KY. 7. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cedars-Sinai Hospital, Los Angeles, CA. 8. Division of Gastroenterology, Boonshoft School of Medicine, Wright State University, Dayton Children's Hospital, Dayton, OH. 9. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL. 10. Division of Pediatric Gastroenterology, Hepatology and Nutrition. 11. Department of Medicine, Johns Hopkins University School of Medicine. 12. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD.
Abstract
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.
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.
Authors: Alexander S F Berry; Brendan J Kelly; Denise Barnhart; Donna J Kelly; Daniel P Beiting; Robert N Baldassano; Laurel E Redding Journal: PLoS One Date: 2019-08-30 Impact factor: 3.240