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

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

来源：Inflammatory Bowel Diseases, 2016, 22(10): 2328-2340.

DOI：10.1097/MIB.0000000000000914

• antibiotics
• colitis
• microbiome
• immunity

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.

• 出版日期2016-10