Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver.
Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver.
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DOI：
10.1371/journal.pone.0134234
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yamazaki K
中科院分区：
文献类型：
--
作者：
Nakajima M;Arimatsu K;Kato T;Matsuda Y;Minagawa T;Takahashi N;Ohno H;Yamazaki K
虽然牙周炎已被认为是多种全身性疾病的危险因素，但牙周炎引起全身性疾病的确切机制仍有待阐明。我们先前已经揭示，牙龈卟啉单胞菌的重复口服给药通过回肠的肠道微生物群的变化引起内毒素血症，从而诱导全身性炎症和胰岛素抵抗。然而，尚不清楚单次施用牙龈卟啉单胞菌可以在多大程度上影响肠道微生物群组成、肠道屏障功能以及随后肠道微生物群流入肝脏。因此，在本研究中，C57 BL/6小鼠经口给予牙龈卟啉单胞菌（菌株W83）一次，并与假接种小鼠进行比较。通过对16 S核糖体RNA基因进行焦磷酸测序，分析了肠道和肝脏中微生物群落的系统发育结构和多样性。通过鲎试剂试验测定血清内毒素活性。通过定量聚合酶链反应检测肠道中的基因表达以及血液和肝脏中16 S rRNA基因的表达。施用牙龈卟啉单胞菌显著改变了肠道微生物群，其中拟杆菌门的比例增加，厚壁菌门的比例降低，并且血清内毒素水平增加。在肠组织中，与肠通透性相关的tjp-1和occludin基因表达下调。在感染小鼠的肝脏中检测到更高数量的细菌DNA。重要的是，肠道微生物群的变化先于全身炎症变化。这些结果进一步支持了口腔来源的牙周病细菌对肠道微生物群组成的干扰可能是牙周炎和全身性疾病联系的因果机制的观点。
Although periodontitis has been implicated as a risk factor for various systemic diseases, the precise mechanisms by which periodontitis induces systemic disease remain to be elucidated. We have previously revealed that repeated oral administration of Porphyromonas gingivalis elicits endotoxemia via changes in the gut microbiota of the ileum, and thereby induces systemic inflammation and insulin resistance. However, it is not clear to what extent a single administration of P. gingivalis could affect gut microbiota composition, gut barrier function, and subsequent influx of gut microbiota into the liver. Therefore, in the present study, C57BL/6 mice were orally administered P. gingivalis (strain W83) once and compared to sham-inoculated mice. The phylogenetic structure and diversity of microbial communities in the gut and liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined by a Limulus amebocyte lysate test. Gene expression in the intestine and expression of 16S rRNA genes in the blood and liver were examined by quantitative polymerase chain reaction. Administration of P. gingivalis significantly altered gut microbiota, with an increased proportion of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and increased serum endotoxin levels. In the intestinal tissues, gene expression of tjp-1 and occludin, which are involved in intestinal permeability, were downregulated. Higher amounts of bacterial DNA were detected in the liver of infected mice. Importantly, changes in gut microbiota preceded systemic inflammatory changes. These results further support the idea that disturbance of the gut microbiota composition by orally derived periodontopathic bacteria may be a causal mechanism linking periodontitis and systemic disease.