title: Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease.
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.
authors.affiliation: 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.
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Eric Z
authors.initials: EZ
authors.lastname: Chen
authors.affiliation: Department of Pediatric Gastroenterology Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.affiliation: Department of Pediatrics, IWK Health Centre, Halifax, NS B3K 6R8, Canada.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Otley
authors.affiliation: Division of Gastroenterology Hepatology and Nutrition, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Griffiths
authors.affiliation: 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.
authors.forename: Dale
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Bittinger
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Aubrey
authors.initials: A
authors.lastname: Bailey
authors.affiliation: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Friedman
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Hoffmann
authors.affiliation: Department of Pediatric Gastroenterology Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Albenberg
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Rohini
authors.initials: R
authors.lastname: Sinha
authors.affiliation: School of Nursing, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Charlene
authors.initials: C
authors.lastname: Compher
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Gilroy
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nessel
authors.affiliation: Department of Pediatrics, IWK Health Centre, Halifax, NS B3K 6R8, Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: Grant
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Christel
authors.initials: C
authors.lastname: Chehoud
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: gdwu@mail.med.upenn.edu.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bushman@mail.med.upenn.edu.
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Bushman
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001105:Archaea / Q000145:classification / Q000302:isolation & purification; D001419:Bacteria / Q000145:classification / Q000302:isolation & purification; D003424:Crohn Disease / Q000473:pathology* / Q000628:therapy*; D004032:Diet / Q000009:adverse effects / Q000379:methods*; D064806:Dysbiosis / Q000209:etiology*; D005658:Fungi / Q000145:classification / Q000302:isolation & purification; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D011446:Prospective Studies; D014780:Viruses / Q000145:classification / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents