Gut microbiota-dependent trimethylamine n-oxide pathway contributes to the bidirectional relationship between intestinal inflammation and periodontitis

Qiqi Wang; Yue Sun; Tianyu Zhou; Cong Jiang; Lan A; Wenzhou Xu

doi:10.3389/fcimb.2022.1125463

Gut microbiota-dependent trimethylamine n-oxide pathway contributes to the bidirectional relationship between intestinal inflammation and periodontitis

Front Cell Infect Microbiol. 2023 Jan 13:12:1125463. doi: 10.3389/fcimb.2022.1125463. eCollection 2022.

Authors

Qiqi Wang¹, Yue Sun^{2

3}, Tianyu Zhou², Cong Jiang², Lan A^{2

3}, Wenzhou Xu^{1

3}

Affiliations

¹ Department of Periodontology, School and Hospital of Stomatology, Jilin University, Changchun, China.
² Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, China.
³ Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, Changchun, China.

Abstract

Background: Intestinal inflammation and periodontitis influence the development of each other through the bidirectional relationship. As the intestinal microbiome metabolite, trimethylamine-N-oxide (TMAO) could contribute to chronic inflammation in the gut by influencing the gut microbial composition and intestinal immunity. Increased circulating TMAO levels often accompany clinical findings in patients with experimental periodontitis. However, the role of TMAO in the bidirectional relationship between intestinal inflammation and periodontitis remains unclear. Thus, we explored whether TMAO influences the periodontitis process by affecting intestinal immunity and microbial composition in this article.

Methods: Periodontitis was induced by unilateral ligation of the first molar in mice, and 3,3-dimethyl-1-butanol (DMB) was used as an inhibitor to reduce TMAO circulating. Twenty-five BALB/c mice were randomly assigned to five study sets (n = 5/group): no periodontitis with DMB (Control group), periodontitis (P) group, periodontitis with TMAO (P+TMAO) group, periodontitis with TMAO and DMB (P+TMAO+DMB) group, and periodontitis with DMB (P+DMB) group. The effect of TMAO was determined by assessing changes in intestinal histology, intestinal flora composition, periodontal tissue, and periodontal pro-inflammatory factors at ten days.

Results: The outcomes indicated a marked improvement in the intestinal inflammation severity, and intestinal flora diversity was reduced. Firmicutes number and the ratio of Firmicutes/Bacteroidetes were improved in the P+TMAO group. In addition, the alveolar bone resorption and the degree of periodontal tissue inflammation were more severe in the P+TMAO group than in other groups. Immunohistochemistry showed higher levels of TGF-β and IL-1β expression in the periodontal tissues of P+TMAO.

Conclusions: Our data suggest that TMAO could influence periodontal immunity and promote periodontal inflammation by affecting the intestinal microenvironment, revealing TMAO may affect the development of periodontitis through the bidirectional relationship of the oral-gut axis.

Keywords: gut microbiota; inflammation; intestinal-oral axis; periodontitis; trimethylamine N-oxide (TMAO).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Gastrointestinal Microbiome*
Inflammation / metabolism
Methylamines
Mice
Periodontitis* / complications

Substances

trimethyloxamine
Methylamines

Grants and funding

This work was supported by the Bethune Project of Jilin University (2020B44), National Natural Science Foundation of China (82201102), the General program of Natural Science of Jilin Province (YDZJ202201ZYTS017), the Science and Technology Project of Jilin Province Financial Department (JCSZ2021893-21), Science and Technology Project of Jilin Province (20220201121GX), Education Science and Technology Research Project of Jilin Province Department (JJKH20221098KJ).