Dong Ling, Ji Zhaoxin, Sun Jing, Hu Jiangqi, Jiang Qingsong, Wei Wei
Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.
Department of Periodontology, Jinan Key Medical and Health Laboratory of Oral Diseases and Tissue Regeneration, Jinan Key Laboratory of Oral Diseases and Tissue Regeneration, Shandong Provincial Key Medical and Health Laboratory of Oral Diseases and Tissue Regeneration, Shandong Provincial Key Medical and Health Discipline of Oral Medicine, Jinan Stomatological Hospital, Jinan, Shandong, China.
mSystems. 2025 Feb 18;10(2):e0113624. doi: 10.1128/msystems.01136-24. Epub 2025 Jan 14.
Periodontitis is closely related to renal health, but the specific influence of (), a key pathogen in periodontitis, on the development of acute kidney injury (AKI) in mice has not been fully elucidated. In our study, AKI was induced in mice through ischemia-reperfusion injury while administering oral infection with . Comprehensive analyses were conducted, including 16S rRNA sequencing, liquid chromatography-mass spectrometry (LC-MS) metabolomics, and transcriptome sequencing. , the identified metabolite was used to stimulate mouse neutrophils. Subsequently, these modified neutrophils were co-cultured with mouse renal tubular epithelial cells. The results showed that oral infection with significantly exacerbated AKI in mice. 16S rRNA sequencing revealed notable shifts in gut microbiota composition. LC-MS metabolomics analysis identified significant metabolic alterations, particularly the upregulation of 3-indoleacrylic acid in the serum. Transcriptome sequencing showed an increased expression of neutrophilic granule protein (), which was closely associated with 3-indoleacrylic acid, and the presence of . Cellular experiments demonstrated that 3-indoleacrylic acid could activate neutrophils, leading to an elevation in NGP protein levels, a response that was associated with renal epithelial cell injury. Oral infection with exacerbated AKI through the gut-kidney axis, involving gut microbiota dysbiosis, metabolic disturbances, and increased renal expression of .
This study provides novel insights into the relationship between periodontal health and renal function. oral infection disrupted the balance of gut microbiota and was an important modifier determining the severity of acute kidney injury. Under the "gut-kidney axis," might cause an increase in the level of the gut microbial metabolite 3-indoleacrylic acid, interfering with kidney immunity and disrupting the maintenance of kidney epithelium.
牙周炎与肾脏健康密切相关，但牙周炎的关键病原体（）对小鼠急性肾损伤（AKI）发展的具体影响尚未完全阐明。在我们的研究中，通过缺血再灌注损伤诱导小鼠发生AKI，同时给予口腔感染（）。进行了综合分析，包括16S rRNA测序、液相色谱 - 质谱（LC - MS）代谢组学和转录组测序。鉴定出的代谢物用于刺激小鼠中性粒细胞。随后，将这些经过修饰的中性粒细胞与小鼠肾小管上皮细胞共培养。结果表明，口腔感染（）显著加重了小鼠的AKI。16S rRNA测序显示肠道微生物群组成发生显著变化。LC - MS代谢组学分析确定了显著的代谢改变，特别是血清中3 - 吲哚丙烯酸的上调。转录组测序显示嗜中性粒细胞颗粒蛋白（）表达增加，这与3 - 吲哚丙烯酸密切相关，并且存在（）。细胞实验表明，3 - 吲哚丙烯酸可激活中性粒细胞，导致NGP蛋白水平升高，这种反应与肾上皮细胞损伤有关。口腔感染（）通过肠 - 肾轴加重AKI，涉及肠道微生物群失调、代谢紊乱以及（）在肾脏中的表达增加。
本研究为牙周健康与肾功能之间的关系提供了新的见解。口腔感染（）破坏了肠道微生物群的平衡，是决定急性肾损伤严重程度的重要调节因素。在“肠 - 肾轴”下，（）可能导致肠道微生物代谢物3 - 吲哚丙烯酸水平升高，干扰肾脏免疫并破坏肾上皮的维持。
