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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.
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•Inflammation, antibiotics, and diet independently affect microbiota in Crohn’s disease•Antibiotics are associated with bacterial dysbiosis and increased fungi•Dysbiosis decreases with reduction in intestinal inflammation•Diet has an independent and rapid effect on gut microbiota composition
Intestinal microbiota dysbiosis is characteristic of Crohn’s disease, but the contributing factors remain unclear. By examining pediatric Crohn’s disease patients, Lewis et al. show that dysbiosis is independently associated with antibiotics, inflammation, and diet and decreases with reduced intestinal inflammation. These results may facilitate biomarker discovery and therapeutic interventions.