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



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.



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.



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.
*Department of Molecular Biology, University of Wyoming, Laramie, Wyoming; †Research and Testing Laboratory, Lubbock, Texas; ‡Department of Biological Sciences, Texas Tech University, Lubbock, Texas; §Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; ‖Mucosal Immunology and Biology Research Center, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Departments of ¶Surgery, and **Pediatric Surgery, Massachusetts General Hospital, Boston, Massachusetts.
Naomi L
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Ward
Caleb D
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Phillips
Deanna D
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Nguyen
Nanda Kumar N
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Shanmugam
Yan
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Song
Richard
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Hodin
Hai Ning
HN
Shi
Bobby J
BJ
Cherayil
Allan M
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Goldstein
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology* / Q000517:prevention & control; D016264:Dextran Sulfate; D064806:Dysbiosis / Q000382:microbiology; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000382:microbiology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects / Q000382:microbiology
D000900:Anti-Bacterial Agents; D016264:Dextran Sulfate