Gut microbiota dysbiosis links chronic apical periodontitis to liver fibrosis in nonalcoholic fatty liver disease: Insights from a mouse model

IF 5.4 1区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International endodontic journal Pub Date : 2024-07-03 DOI:10.1111/iej.14119

Guowu Gan, Yufang Luo, Yu Zeng, Shihan Lin, Beibei Lu, Ren Zhang, Shuai Chen, Huaxiang Lei, Zhiyu Cai, Xiaojing Huang

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Abstract

Aim

In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis.

Methodology

Sixteen 7-week-old male apolipoprotein E knockout (apoE^−/−) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first- and second-maxillary molars with bacterium-containing cotton balls. Apical lesions were evaluated by micro-CT. Histological evaluations of NAFLD were performed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography–mass spectrometry (LC–MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues.

Results

Micro-CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D-galactosamine, were enriched and that 16-hydroxyhexadecanoic acid and 3-methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin-1 expression in the CAP group.

Conclusion

This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism.

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肠道微生物群失调将慢性根尖牙周炎与非酒精性脂肪肝的肝纤维化联系起来：小鼠模型的启示

目的：在这项研究中，我们探讨了慢性根尖牙周炎（CAP）的系统性影响。CAP可能通过肠道微生物群及其代谢产物导致非酒精性脂肪肝（NAFLD）的进展，而肠道微生物群及其代谢产物与纤维化程度有关：16只7周大的雄性载脂蛋白E基因敲除（apoE-/-）小鼠被随机分为两组：CAP组和Con组。通过用含菌棉球封闭第一和第二颌磨牙，建立 CAP 模型。通过显微 CT 对根尖病变进行评估。使用二次谐波发生/双光子激发荧光（SHG/TPEF）检测法对非酒精性脂肪肝进行组织学评估。此外，我们还利用 16S rRNA 基因测序对肠道微生物群进行了全面分析，并利用液相色谱-质谱法（LC-MS）对代谢谱进行了研究。免疫荧光分析用于研究 CAP 对紧密连接蛋白和粘蛋白表达的影响。转录组测定阐明了肝组织中基因表达的改变：结果：显微 CT 扫描显示，CAP 组根尖周骨质明显流失，总胶原蛋白百分比增加（Con，0.0361 ± 0.00510%；CAP，0.0589 ± 0.00731%，p 结论：该研究全面证实了 CAP 对全身骨质疏松症的影响：本研究通过阐明肠道微生物群组成和代谢的改变，为 CAP 对非酒精性脂肪肝患者肝纤维化的全身影响提供了全面的证据。

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来源期刊

International endodontic journal 医学-牙科与口腔外科

CiteScore

10.20

自引率

28.00%

发文量

195

审稿时长

4-8 weeks

期刊介绍： The International Endodontic Journal is published monthly and strives to publish original articles of the highest quality to disseminate scientific and clinical knowledge; all manuscripts are subjected to peer review. Original scientific articles are published in the areas of biomedical science, applied materials science, bioengineering, epidemiology and social science relevant to endodontic disease and its management, and to the restoration of root-treated teeth. In addition, review articles, reports of clinical cases, book reviews, summaries and abstracts of scientific meetings and news items are accepted. The International Endodontic Journal is essential reading for general dental practitioners, specialist endodontists, research, scientists and dental teachers.