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Cell Host Microbe. 2015 Oct 14;18(4):489-500. doi: 10.1016/j.chom.2015.09.008.

Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease.

Author information

1
Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2
Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Department of Pediatric Gastroenterology Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
4
Department of Pediatrics, IWK Health Centre, Halifax, NS B3K 6R8, Canada.
5
Division of Gastroenterology Hepatology and Nutrition, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
6
Department of Pediatric Gastroenterology Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Pediatric Gastroenterology Hepatology and Nutrition, Seattle Children's Hospital, University of Washington, Seattle, WA 98105, USA.
7
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
8
Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
9
School of Nursing, University of Pennsylvania, Philadelphia, PA 19104, USA.
10
Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: gdwu@mail.med.upenn.edu.
11
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bushman@mail.med.upenn.edu.

Abstract

Abnormal composition of intestinal bacteria--"dysbiosis"-is characteristic of Crohn's disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn's disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments.

PMID:
26468751
PMCID:
PMC4633303
DOI:
10.1016/j.chom.2015.09.008
[Indexed for MEDLINE]
Free PMC Article

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