Early-Life Microbial Restitution Reduces Colitis Risk Promoted by Antibiotic-Induced Gut Dysbiosis in Interleukin 10–/– Mice

失调 归还 结肠炎 免疫学 生物 医学 肠道菌群 微生物学 抗生素 政治学 法学
作者
Jun Miyoshi,Sawako Miyoshi,Tom O. Delmont,Candace M. Cham,Sonny T. M. Lee,Aki Sakatani,Karen Yang,Yue Shan,Megan S. Kennedy,Evan Kiefl,Mahmoud Yousef,Sean Crosson,Mitchell L. Sogin,Dionysios A. Antonopoulos,A. Murat Eren,Vanessa Leone,Eugene B. Chang
出处
期刊:Gastroenterology [Elsevier BV]
卷期号:161 (3): 940-952.e15 被引量:25
标识
DOI:10.1053/j.gastro.2021.05.054
摘要

Background & AimsPerturbations in the early-life gut microbiome are associated with increased risk for complex immune disorders like inflammatory bowel diseases. We previously showed that maternal antibiotic-induced gut dysbiosis vertically transmitted to offspring increases experimental colitis risk in interleukin (IL) 10 gene deficient (IL10–/–) mice, a finding that may result from the loss/lack of essential microbes needed for appropriate immunologic education early in life. Here, we aimed to identify key microbes required for proper development of the early-life gut microbiome that decrease colitis risk in genetically susceptible animals.MethodsMetagenomic sequencing followed by reconstruction of metagenome-assembled genomes was performed on fecal samples of IL10–/– mice with and without antibiotic-induced dysbiosis to identify potential missing microbial members needed for immunologic education. One high-value target strain was then engrafted early and/or late into the gut microbiomes of IL10–/– mice with antibiotic-induced dysbiosis.ResultsEarly-, but not late-, life engraftment of a single dominant Bacteroides strain of non–antibiotic-treated IL10–/– mice was sufficient to restore the development of the gut microbiome, promote immune tolerance, and prevent colitis in IL10–/– mice that had antibiotic-induced dysbiosis.ConclusionsRestitution of a keystone microbial strain missing in the early-life antibiotic-induced gut dysbiosis results in recovery of the microbiome, proper development of immune tolerance, and reduced risk for colitis in genetically prone hosts. Perturbations in the early-life gut microbiome are associated with increased risk for complex immune disorders like inflammatory bowel diseases. We previously showed that maternal antibiotic-induced gut dysbiosis vertically transmitted to offspring increases experimental colitis risk in interleukin (IL) 10 gene deficient (IL10–/–) mice, a finding that may result from the loss/lack of essential microbes needed for appropriate immunologic education early in life. Here, we aimed to identify key microbes required for proper development of the early-life gut microbiome that decrease colitis risk in genetically susceptible animals. Metagenomic sequencing followed by reconstruction of metagenome-assembled genomes was performed on fecal samples of IL10–/– mice with and without antibiotic-induced dysbiosis to identify potential missing microbial members needed for immunologic education. One high-value target strain was then engrafted early and/or late into the gut microbiomes of IL10–/– mice with antibiotic-induced dysbiosis. Early-, but not late-, life engraftment of a single dominant Bacteroides strain of non–antibiotic-treated IL10–/– mice was sufficient to restore the development of the gut microbiome, promote immune tolerance, and prevent colitis in IL10–/– mice that had antibiotic-induced dysbiosis. Restitution of a keystone microbial strain missing in the early-life antibiotic-induced gut dysbiosis results in recovery of the microbiome, proper development of immune tolerance, and reduced risk for colitis in genetically prone hosts.
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