Antibiotic Treatment Induces Long-lasting Changes in the Fecal Microbiota that Protect Against Colitis

Naomi L. Ward, Caleb D. Phillips, Deanna D. Nguyen, Nanda Kumar N. Shanmugam, Yan Song, Richard Hodin, Hai Ning Shi, Bobby J. Cherayil, Allan M. Goldstein

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9 Scopus citations

Abstract

Background: The interplay between host genetics, immunity, and microbiota is central to the pathogenesis of inflammatory bowel disease. Previous population-based studies suggested a link between antibiotic use and increased inflammatory bowel disease risk, but the mechanisms are unknown. The purpose of this study was to determine the long-term effects of antibiotic administration on microbiota composition, innate immunity, and susceptibility to colitis, as well as the mechanism by which antibiotics alter host colitogenicity. Methods: Wild-type mice were given broad-spectrum antibiotics or no antibiotics for 2 weeks, and subsequent immunophenotyping and 16S rRNA gene sequencing-based analysis of the fecal microbiome were performed 6 weeks later. In a separate experiment, control and antibiotic-treated mice were given 7 days of dextran sulfate sodium, 6 weeks after completing antibiotic treatment, and the severity of colitis scored histologically. Fecal transfer was performed from control or antibiotic-treated mice to recipient mice whose endogenous microbiota had been cleared with antibiotics, and the susceptibility of the recipients to dextran sulfate sodium-induced colitis was analyzed. Naive CD4 + T cells were transferred from control and antibiotic-treated mice to immunodeficient Rag-1 -/- recipients and the severity of colitis compared. Results: Antibiotics led to sustained dysbiosis and changes in T-cell subpopulations, including reductions in colonic lamina propria total T cells and CD4 + T cells. Antibiotics conferred protection against dextran sulfate sodium colitis, and this effect was transferable by fecal transplant but not by naive T cells. Conclusions: Antibiotic exposure protects against colitis, and this effect is transferable with fecal microbiota from antibiotic-treated mice, supporting a protective effect of the microbial community.

Original languageEnglish
Pages (from-to)2328-2340
Number of pages13
JournalInflammatory Bowel Diseases
Volume22
Issue number10
DOIs
StatePublished - Aug 26 2016

Keywords

  • antibiotics
  • colitis
  • immunity
  • microbiome

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    Ward, N. L., Phillips, C. D., Nguyen, D. D., Shanmugam, N. K. N., Song, Y., Hodin, R., Shi, H. N., Cherayil, B. J., & Goldstein, A. M. (2016). Antibiotic Treatment Induces Long-lasting Changes in the Fecal Microbiota that Protect Against Colitis. Inflammatory Bowel Diseases, 22(10), 2328-2340. https://doi.org/10.1097/MIB.0000000000000914