Naomi L Ward1, Caleb D Phillips, Deanna D Nguyen, Nanda Kumar N Shanmugam, Yan Song, Richard Hodin, Hai Ning Shi, Bobby J Cherayil, Allan M Goldstein. 1. *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.
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.
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 immunodeficientRag-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 sodiumcolitis, 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.
Authors: Ben P Willing; Johan Dicksved; Jonas Halfvarson; Anders F Andersson; Marianna Lucio; Zongli Zheng; Gunnar Järnerot; Curt Tysk; Janet K Jansson; Lars Engstrand Journal: Gastroenterology Date: 2010-10-08 Impact factor: 22.682
Authors: Deanna D Nguyen; Marc-Andre Wurbel; Jeremy A Goettel; Michelle A Eston; Osub S Ahmed; Romela Marin; Elisa K Boden; Eduardo J Villablanca; Helena Paidassi; Vineet Ahuja; Hans-Christian Reinecker; Edda Fiebiger; Adam Lacy-Hulbert; Bruce H Horwitz; J Rodrigo Mora; Scott B Snapper Journal: Gastroenterology Date: 2012-06-15 Impact factor: 22.682
Authors: Dionysios A Antonopoulos; Susan M Huse; Hilary G Morrison; Thomas M Schmidt; Mitchell L Sogin; Vincent B Young Journal: Infect Immun Date: 2009-03-23 Impact factor: 3.441
Authors: Maria Ennamorati; Chithirachelvi Vasudevan; Kara Clerkin; Stefan Halvorsen; Smriti Verma; Samira Ibrahim; Shaniah Prosper; Caryn Porter; Vladimir Yeliseyev; Margot Kim; Joseph Gardecki; Slim Sassi; Guillermo Tearney; Bobby J Cherayil; Lynn Bry; Brian Seed; Nitya Jain Journal: Proc Natl Acad Sci U S A Date: 2020-01-21 Impact factor: 11.205
Authors: Ceren Ozkul; Victoria E Ruiz; Thomas Battaglia; Joseph Xu; Claire Roubaud-Baudron; Ken Cadwell; Guillermo I Perez-Perez; Martin J Blaser Journal: Genome Med Date: 2020-07-25 Impact factor: 11.117
Authors: Cassandra E Gheorghe; Nathaniel L Ritz; Jason A Martin; Hannah R Wardill; John F Cryan; Gerard Clarke Journal: Gut Microbes Date: 2021 Jan-Dec