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基于多组学和Treg/Th17平衡对伴或不伴牙周炎的2型糖尿病患者龈下微生物的分析

Analysis of subgingival micro-organisms based on multi-omics and Treg/Th17 balance in type 2 diabetes with/without periodontitis.

作者信息

Jiang Lanlan, Zhang Jiaming, Fang Meifei, Qin Yingfen, Huang Yuxiao, Tao Renchuan

机构信息

Department of Periodontics and Oral Medicine, College of Stomatology, Guangxi Medical University, Nanning, China.

Guangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious Diseases, Nanning, China.

出版信息

Front Microbiol. 2022 Nov 28;13:939608. doi: 10.3389/fmicb.2022.939608. eCollection 2022.

Abstract

Type 2 diabetes mellitus (T2DM) and periodontitis are common and interrelated diseases, resulting in altered host response microbiota. The subgingival micro-organisms play a key role in periodontitis pathogenesis. To assess the shift of subgingival microbiome and metabolome in T2DM, we performed an analysis of the subgingival microbiome in patients with T2DM ( = 20) compared with non-diabetes (ND) subjects ( = 21). Furthermore, patients were subdivided into 10 T2DM with periodontitis (DP), 10 T2DM without periodontitis (DNP), 10 periodontitis (P), and 11 healthy control (H) groups. 16SrRNA gene sequencing combined with ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) based metabolomics was performed in all participants. T lymphocyte immunity was analyzed by flow cytometry. Furthermore, the network relationship among subgingival micro-organisms, metabolites, blood glucose level, and T lymphocyte immunity were analyzed. The results showed that the difference of the subgingival microbiome from healthy to periodontitis status was less prominent in T2DM compared with ND, though the clinical signs of disease were similar. The bacteria group, , , , and , amongst others, may be important in the pathopoiesia of periodontitis in the T2DM state. In addition, some dominant bacteria showed network relationships. The Treg/Th17 ratio was lower in the DP and DNP groups than in the P and H groups-though that of P was lower than for H. The percentage of CD4/CD8 PD1 and CD8 PDL1 was higher in the DP and DNP groups than in the H group; the percentage of CD8 PDL1 was higher in the DP than P groups. Subgingival micro-organisms in periodontitis had a significant metabolic shift in terms of their signature metabolites. Butyrate metabolism and phenylalanine metabolism may play a role in the pathogenesis of periodontitis with/without T2DM. Specifically, biphenyl degradation, tryptophan metabolism, and the two-component system may play important roles in periodontitis with T2DM. Lastly, the network relationship among subgingival micro-organisms, metabolites, blood glucose level, and T lymphocyte immunity were unbalanced. This study identified the changes in the subgingival microbiome associated with periodontitis in T2DM, as well as the associated network between bacterial flora, metabolism dysbiosis, and immune regulation.

摘要

2型糖尿病(T2DM)和牙周炎是常见的相关疾病,会导致宿主对微生物群的反应改变。龈下微生物在牙周炎发病机制中起关键作用。为了评估T2DM患者龈下微生物组和代谢组的变化,我们对20例T2DM患者和21例非糖尿病(ND)受试者的龈下微生物组进行了分析。此外,将患者分为10例伴牙周炎的T2DM(DP)、10例不伴牙周炎的T2DM(DNP)、10例牙周炎(P)和11例健康对照(H)组。对所有参与者进行了16SrRNA基因测序,并结合基于超高效液相色谱-质谱联用(UHPLC-MS)的代谢组学分析。通过流式细胞术分析T淋巴细胞免疫。此外,还分析了龈下微生物、代谢物、血糖水平和T淋巴细胞免疫之间的网络关系。结果显示,尽管疾病的临床症状相似,但与ND相比,T2DM患者从健康状态到牙周炎状态龈下微生物组的差异不那么明显。在T2DM状态下, 、 、 、 、 等菌群可能在牙周炎的发病机制中起重要作用。此外,一些优势菌呈现出网络关系。DP组和DNP组的Treg/Th17比值低于P组和H组,不过P组低于H组。DP组和DNP组中CD4/CD8 PD1和CD8 PDL1的百分比高于H组;DP组中CD8 PDL1的百分比高于P组。牙周炎患者的龈下微生物在标志性代谢物方面有显著的代谢变化。丁酸代谢和苯丙氨酸代谢可能在伴或不伴T2DM的牙周炎发病机制中起作用。具体而言,联苯降解、色氨酸代谢和双组分系统可能在伴T2DM的牙周炎中起重要作用。最后,龈下微生物、代谢物、血糖水平和T淋巴细胞免疫之间的网络关系失衡。本研究确定了T2DM中与牙周炎相关的龈下微生物组变化,以及菌群、代谢失调和免疫调节之间的相关网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3595/9743466/7ef6b5fe29de/fmicb-13-939608-g001.jpg

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