Antibiotics promote inflammation through the translocation of native commensal colonic bacteria.
Antibiotics promote inflammation through the translocation of native commensal colonic bacteria.
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DOI：
10.1136/gutjnl-2014-309059
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发表时间：
2016-07
期刊：
影响因子：
24.5
通讯作者：
Newberry RD
中科院分区：
文献类型：
--
作者：
Knoop KA;McDonald KG;Kulkarni DH;Newberry RD
抗生素的使用与患多种炎症性疾病的风险增加有关，而炎症性疾病又与肠道微生物区系的改变有关。肠道微生物区系的这些变化如何转化为炎症反应风险的增加在很大程度上尚不清楚。在这里，我们调查了抗生素是否以及如何通过活的本地肠道共生细菌易位来促进炎症。给野生型和诱变型小鼠给予口服抗生素，并评估其对细菌易位、炎症反应和结肠炎易感性的影响。通过诱导突变小鼠菌株、16S rRNA测序鉴定微生物群落以及体内和体外成像技术，评估了细菌的来源和细菌易位所需的途径。口服抗生素诱导活的本地共生菌通过结肠上皮移位，促进炎症反应，并容易因同时发生的损伤而增加疾病。细菌易位是由传递给结肠杯细胞(GC)的微生物信号减少引起的，与结肠杯细胞相关抗原通道(GAP)的形成有关，当GCs耗尽时细菌易位被取消，需要CX3CR1+树突状细胞(DC)。大多数被测试的抗生素单次剂量后发生细菌移位，而炎症增加的易感性仅与抗生素诱导细菌移位有关。这些发现揭示了抗生素治疗的一个意想不到的结果，并表明肠道微生物群变化导致的细菌易位可能在抗生素使用量增加和炎症性疾病发病率增加之间提供了联系。
Antibiotic use is associated with an increased risk of developing multiple inflammatory disorders, which in turn are linked to alterations in the intestinal microbiota. How these alterations in the intestinal microbiota translate into an increased risk for inflammatory responses is largely unknown. Here we investigated if and how antibiotics promote inflammation via the translocation of live native gut commensal bacteria. Oral antibiotics were given to wildtype and induced mutant mouse strains and the effects on bacterial translocation, inflammatory responses, and the susceptibility to colitis were evaluated. The sources of the bacteria and the pathways required for bacterial translocation were evaluated using induced mutant mouse strains, 16s rRNA sequencing to characterize the microbial communities, and in vivo and ex vivo imaging techniques. Oral antibiotics induced the translocation of live native commensal bacteria across the colonic epithelium, promoting inflammatory responses, and predisposing to increased disease in response to coincident injury. Bacterial translocation resulted from decreased microbial signals delivered to colonic goblets cells (GCs), was associated with the formation of colonic goblet cell associated antigen passages (GAPs), was abolished when GCs were depleted, and required CX3CR1+ dendritic cells (DCs). Bacterial translocation occurred following a single dose of most antibiotics tested, and the predisposition for increased inflammation was only associated with antibiotics inducing bacterial translocation. These findings reveal an unexpected outcome of antibiotic therapy and suggest that bacterial translocation as a result of alterations in the intestinal microflora may provide a link between increasing antibiotic use and the increased incidence of inflammatory disorders.