Department of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical Discovery, Chicago, Illinois; Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan.
Department of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical Discovery, Chicago, Illinois; Department of General Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Gastroenterology. 2021 Sep;161(3):940-952.e15. doi: 10.1053/j.gastro.2021.05.054. Epub 2021 Jun 7.
BACKGROUND & AIMS: 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.
生命早期肠道微生物组的紊乱与复杂免疫疾病（如炎症性肠病）的风险增加有关。我们之前的研究表明，母亲抗生素诱导的肠道菌群失调垂直传递给后代，增加了白细胞介素 (IL) 10 基因缺陷 (IL10) 小鼠实验性结肠炎的风险，这一发现可能是由于生命早期缺乏适当免疫教育所需的必需微生物。在这里，我们旨在确定生命早期肠道微生物组正常发育所需的关键微生物，这些微生物可降低遗传易感动物的结肠炎风险。
对有和没有抗生素诱导的肠道菌群失调的 IL10 小鼠的粪便样本进行宏基因组测序和宏基因组组装基因组重建，以确定免疫教育所需的潜在缺失微生物成员。然后，将一种高价值的目标菌株早期和/或晚期定植到有抗生素诱导的肠道菌群失调的 IL10 小鼠的肠道微生物组中。
非抗生素处理的 IL10 小鼠的单一优势拟杆菌（Bacteroides）菌株的早期定植，而不是晚期定植，足以恢复肠道微生物组的发育，促进免疫耐受，并预防有抗生素诱导的肠道菌群失调的 IL10 小鼠的结肠炎。
在生命早期抗生素诱导的肠道菌群失调中缺失的关键微生物菌株的恢复导致了微生物组的恢复、免疫耐受的适当发育以及遗传易感宿主中结肠炎风险的降低。
