Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia.
Microb Pathog. 2020 Mar;140:103962. doi: 10.1016/j.micpath.2020.103962. Epub 2020 Jan 2.
Recent evidence suggests that oral bacteria can affect extra-oral diseases by modulating aspects of the gut environment such as the microbiome, metabolome, and immune profiles. However, differences in the effects of different types of oral bacteria, particularly periodontopathic and health-associated bacteria, remain elusive.
Five-week-old germ-free mice were orally administered with either periodontopathic bacteria as oral pathobionts (Porphyromonas gingivalis, Filifactor alocis, and Fusobacterium nucleatum) or bacteria associated with periodontal health (Actinomyces naeslundii, Streptococcus mitis, and Veillonella rogosae) twice a week for five weeks. The presence of all bacterial species in the feces and the livers of the mice was analyzed via polymerase chain reaction (PCR), using specific primers for 16S rRNA genes. Alveolar bone resorption was evaluated histologically. The expression profiles of various genes in the liver and small intestine were analyzed using real-time PCR. Sera were analyzed to determine the levels of antibodies and endotoxin. The proportions of T helper 17 (Th17) and regulatory T (Treg) cells in mesenteric lymph nodes and Peyer's patches were analyzed using flow cytometry.
Neither of the types of bacteria administered in this experiment induced alveolar bone resorption. All bacteria elicited some degree of systemic antibody response in the mice, although the response to S. mitis was not obvious. The response to P. gingivalis and V. rogosae was strongest. Generally, the health-associated bacteria but not the periodontitis-associated bacteria were detected in fecal samples. Interestingly, only Fusobacterium nucleatum DNA was detected in the liver, despite that live Fusobacterium nucleatum were not detected in the liver. The levels of interleukin-17 in the intestine and genes related to lipid accumulation in the liver were significantly higher in the mice that received periodontitis-associated bacteria. In addition, expression of the gene associated with endoplasmic reticulum stress was higher and that of the gene controlling circadian rhythm was lower in the periodontitis group. There was no difference in serum endotoxin, T-cell phenotypes in the lymphatic tissues, or genes related to the gut barrier.
Oral administration of periodontitis-associated bacteria can induce pathological changes in the liver and intestine that are implicated in the process of periodontitis. These findings further support the importance of the oral-gut connection.
最近的证据表明，口腔细菌可以通过调节肠道环境的微生物群、代谢组和免疫特征等方面来影响口腔外疾病。然而，不同类型的口腔细菌（尤其是牙周病相关细菌和与牙周健康相关的细菌）的影响差异仍不清楚。
5 周龄无菌小鼠每周两次口服牙周病相关细菌（牙龈卟啉单胞菌、颗粒拟杆菌和具核梭杆菌）或与牙周健康相关的细菌（奈瑟氏放线菌、口腔链球菌和罗氏普雷沃菌），共 5 周。使用针对 16S rRNA 基因的特定引物，通过聚合酶链反应（PCR）分析粪便和肝脏中所有细菌的存在情况。通过组织学评估牙槽骨吸收情况。使用实时 PCR 分析肝脏和小肠中各种基因的表达谱。分析血清以确定抗体和内毒素水平。使用流式细胞术分析肠系膜淋巴结和派伊尔斑中辅助性 T 细胞 17（Th17）和调节性 T（Treg）细胞的比例。
本实验中给予的两种细菌均未诱导牙槽骨吸收。所有细菌均在小鼠体内引起一定程度的全身性抗体反应，尽管口腔链球菌的反应不明显。牙龈卟啉单胞菌和罗氏普雷沃菌的反应最强。通常，健康相关细菌而不是牙周病相关细菌在粪便样本中被检测到。有趣的是，尽管肝脏中未检测到活的具核梭杆菌，但仅检测到具核梭杆菌的 DNA。接受牙周病相关细菌的小鼠肠道中白细胞介素 17 水平和肝脏中与脂质积累相关的基因显着升高。此外，与内质网应激相关的基因表达较高，与肠道屏障相关的基因表达较低。血清内毒素、淋巴组织中的 T 细胞表型或与肠道屏障相关的基因无差异。
口腔内给予牙周病相关细菌可诱导肝脏和肠道发生与牙周病过程相关的病理变化。这些发现进一步支持了口腔-肠道联系的重要性。
