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

By James D. Lewis, Eric Z. Chen, R. Baldassano, A. Otley, A. Griffiths, Dale Lee, Kyle Bittinger, Aubrey Bailey, E. Friedman, Christian Hoffmann and 10 more. Cell Host and Microbe, 2015

735 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8872588da2b9a4470a5978c406fc95eaa68d63b2

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In Epidemiology

1. Ashwin N. Ananthakrishnan
2. Curtis Huttenhower
3. Eric G. Pamer
4. Ramnik J. Xavier

In Genetics

1. Ashwin N. Ananthakrishnan
2. Xianyang Zhang
3. Curtis Huttenhower
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In Molecular Biology

1. Curtis Huttenhower
2. Eric G. Pamer
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5. Y. Taur
6. Ashwin N. Ananthakrishnan
7. Jun Chen
8. Xianyang Zhang

Citations in the corpus

• A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients (2017, methodology): “(n = 368) [13], and HMP (n = 80) [15] cohorts.”
• Gut Microbiome: Profound Implications for Diet and Disease (2019, background): “Treatment with antibiotics in the last six months was strongly associated with microbial dysbiosis [22], consistent with earlier findings that oral antibiotics for acne are a risk factor for new onset Crohn’s disease [23].”
• Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. (2016, background): “This finding demonstrates that multiple variables can influence gut microbiota composition in disease [63].”
• LinDA: linear models for differential abundance analysis of microbiome compositional data (2021, background): “Secondly, ANCOM-BC is not applicable to correlated/clustered microbiome datasets such as those from family/longitudinal microbiome studies or studies with paired and repeated measurements [27, 28].”