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: James D Lewis, Eric Z Chen, Robert N Baldassano, Anthony R Otley, Anne M Griffiths, Dale Lee, Kyle Bittinger, Aubrey Bailey, Elliot S Friedman, Christian Hoffmann, Lindsey Albenberg, Rohini Sinha, Charlene Compher, Erin Gilroy, Lisa Nessel, Amy Grant, Christel Chehoud, Hongzhe Li, Gary D Wu, Frederic D Bushman
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 18 Issue 4 Pg. 489-500 (Oct 14 2015) ISSN: 1934-6069 [Electronic] United States
• PMID: 26468751 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Bacterial Agents

Topics

• Anti-Bacterial Agents (administration & dosage, adverse effects)
• Archaea (classification, isolation & purification)
• Bacteria (classification, isolation & purification)
• Crohn Disease (pathology, therapy)
• Diet (adverse effects, methods)
• Dysbiosis (etiology)
• Fungi (classification, isolation & purification)
• Gastrointestinal Microbiome (drug effects)
• Humans
• Inflammation (pathology)
• Prospective Studies
• Viruses (classification, isolation & purification)