经口灌胃牙周病原体和菌斑生物膜对小鼠肠道微生物群生态和肠道组织结构的影响：一项机制研究

Effects of oral gavage with periodontal pathogens and plaque biofilm on gut microbiota ecology and intestinal tissue architecture in mice: a mechanistic study.

作者信息

Huang Lan, Ge Song, Yang Kun, Duan Lian, Gao Li, Li Yu Zhen, Yi Yu Shi

机构信息

Periodontal Department, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China.

出版信息

Front Cell Infect Microbiol. 2025 Aug 8;15:1589055. doi: 10.3389/fcimb.2025.1589055. eCollection 2025.

DOI:10.3389/fcimb.2025.1589055

PMID:40861490

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12370644/

Abstract

OBJECTIVE

This study aimed to establish an model simulating periodontal biofilm architecture with three representative periodontal pathogens and evaluate its systemic impact through oral gavage administration in C57BL/6 mice. The findings provide mechanistic insights into the oral-gut axis dysbiosis, elucidating potential pathways linking periodontal inflammation to gastrointestinal pathophysiology.

METHODS

Fifty 7-week-old male C57BL/6 mice were randomized into five groups(n=10/group): control (H), (F), (P), (S) and biofilm (BF, + + ) groups. Mice were gavaged twice weekly for 6 weeks with 1×10 CFU (F, P, BF groups) and 1×10 CFU (S group) of bacterial suspensions or PBS (H group). Post-intervention, fecal and colon tissues were collected for 16S rRNA sequencing, H&E staining, immunohistochemistry (Occludin expression), and qRT-PCR analysis of inflammatory markers(IL18, TNF-α, IL-1β, B220, F4/80, NOS2, ARG1).

RESULTS

A stable three-species biofilm model was successfully established to mimic the ecology of periodontal plaque. Gavage with , or the biofilm consortium (BF group) induced intestinal barrier disruption and elevated pro-inflammatory cytokines levels. PCR indicated a significant increase in the expression of IL-1β, TNF-α, B220, F4/80, and NOS2 in the P group ( < 0.001), while Arg-1 expression exhibited a significant decrease < 0.01). In the BF group, only TNF-α expression demonstrated a significant increase ( < 0.01). The expression of occludin is significantly reduced in the F/P/BF group, with the most pronounced decrease observed in the P group ( 0.01). Gut microbiota alterations occurred in all groups. At the phylum level, the (F/B) ratio increased in all three groups (F/P/BF group). abundance rose substantially in the P group, while increased and decreased in the F/P/BF and F/S groups, respectively. Genus-level analysis showed reduced in the F/P/BF group, alongside elevated pro-inflammatory bacteria (e.g., , ) and diminished beneficial bacteria (e.g., , ).

CONCLUSION

These findings demonstrate that periodontal pathogens induce gut barrier compromise through microbiome-driven immunomodulation, with exhibiting predominant pro-inflammatory effects.

摘要

目的

本研究旨在建立一个模拟牙周生物膜结构的模型，该模型包含三种具有代表性的牙周病原体，并通过对C57BL/6小鼠进行灌胃给药来评估其对全身的影响。这些发现为口腔-肠道轴的生态失调提供了机制性见解，阐明了将牙周炎症与胃肠道病理生理学联系起来的潜在途径。

方法

将50只7周龄雄性C57BL/6小鼠随机分为五组（每组n = 10）：对照组（H）、（F）组、（P）组、（S）组和生物膜组（BF，++）。小鼠每周接受两次灌胃，持续6周，分别给予1×10 CFU（F、P、BF组）和1×10 CFU（S组）的细菌悬液或PBS（H组）。干预后，收集粪便和结肠组织进行16S rRNA测序、苏木精-伊红（H&E）染色、免疫组织化学（紧密连接蛋白Occludin表达）以及炎症标志物（IL18、TNF-α、IL-1β、B220、F4/80、NOS2、ARG1）的定量逆转录聚合酶链反应（qRT-PCR）分析。

结果

成功建立了一个稳定的三种菌生物膜模型，以模拟牙周菌斑的生态。用、或生物膜联合体（BF组）灌胃可导致肠道屏障破坏并升高促炎细胞因子水平。PCR结果表明，P组中IL-1β、TNF-α、B220、F4/80和NOS2的表达显著增加（<0.001），而精氨酸酶-1（Arg-1）表达显著降低（<0.01）。在BF组中，只有TNF-α表达显著增加（<0.01）。紧密连接蛋白Occludin在F/P/BF组中的表达显著降低，其中P组下降最为明显（<0.01）。所有组均出现肠道微生物群改变。在门水平上，所有三组（F/P/BF组）中的厚壁菌门/拟杆菌门（F/B）比值均升高。P组中放线菌门丰度大幅上升，而在F/P/BF组和F/S组中，变形菌门分别增加和减少。属水平分析显示，F/P/BF组中双歧杆菌属减少，同时促炎细菌（如、）增加，有益细菌（如、）减少。