TY - JOUR
T1 - Antibiotic Treatment Induces Long-lasting Changes in the Fecal Microbiota that Protect Against Colitis
AU - Ward, Naomi L.
AU - Phillips, Caleb D.
AU - Nguyen, Deanna D.
AU - Shanmugam, Nanda Kumar N.
AU - Song, Yan
AU - Hodin, Richard
AU - Shi, Hai Ning
AU - Cherayil, Bobby J.
AU - Goldstein, Allan M.
N1 - Publisher Copyright:
Copyright © 2016 Crohn's & Colitis Foundation of America, Inc.
PY - 2016/8/26
Y1 - 2016/8/26
N2 - 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.
AB - 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.
KW - antibiotics
KW - colitis
KW - immunity
KW - microbiome
UR - http://www.scopus.com/inward/record.url?scp=84988643285&partnerID=8YFLogxK
U2 - 10.1097/MIB.0000000000000914
DO - 10.1097/MIB.0000000000000914
M3 - Article
C2 - 27607336
AN - SCOPUS:84988643285
SN - 1078-0998
VL - 22
SP - 2328
EP - 2340
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 10
ER -