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. 2025 Jan;34(1):108183.
doi: 10.1016/j.jstrokecerebrovasdis.2024.108183. Epub 2024 Dec 6.

Fusobacterium nucleatum in the oral cavity is associated with cerebral small vessel disease in patients with ischemic stroke

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Free article

Fusobacterium nucleatum in the oral cavity is associated with cerebral small vessel disease in patients with ischemic stroke

Shiro Aoki et al. J Stroke Cerebrovasc Dis. 2025 Jan.
Free article

Abstract

Objectives: Periodontal disease is reportedly associated with an increased risk of stroke. Recent evidence suggests that periodontal disease aggravates cerebral small vessel disease (CSVD), including lacunar stroke. However, the periodontal pathogens associated with CSVD remain unclear. Thus, we examined the relationship between the relative rates of periodontal pathogens in the oral cavity and CSVD, to elucidate the effects of different types of periodontal pathogens on small cerebral vessels.

Materials and methods: Consecutive patients with acute ischemic stroke were prospectively enrolled. The associations between the relative rates of periodontal pathogens on tongue coating, background factors, and CSVD imaging findings were statistically analyzed. The relative rates of periodontal pathogens were calculated using quantitative polymerase chain reaction for six species of periodontal pathogens. Positivity for each periodontal pathogen was defined as the presence of more than the third quartile of the amount of each periodontal pathogen relative to the total amount of tongue-coating bacteria.

Results: A total of 347 patients with acute ischemic stroke (149 [42.9%] females, mean age 75.2±13.1 y) were registered. Positivity for Fusobacterium nucleatum was independently associated with high-grade white matter hyperintensities (odds ratio, 1.84; 95% confidence interval [CI], 1.10-3.08; p=0.021) and high-grade total CSVD score (odds ratio, 1.76; 95% CI, 1.04-2.96; p=0.035); however, the other five species did not show any association.

Conclusions: The qualitative positivity for Fusobacterium nucleatum in the oral cavity was independently associated with high-grade white matter hyperintensities and high-grade total CSVD score in patients with ischemic stroke. Thus, oral care targeting Fusobacterium nucleatum may aid in impeding CSVD progression.

Keywords: Cerebral small vessel disease; Fusobacterium nucleatum; Ischemic stroke; Periodontal pathogen.

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Conflict of interest statement

Declaration of competing interest Shiro Aoki received Grants-in-Aid for Scientific Research (21K10210). Tomohisa Nezu received Grants-in-Aid for Scientific Research (20K16579). Hirofumi Maruyama received Grants-in-Aid for Scientific Research (23H02827) and research support from Eisai, Takeda Pharmaceutical, Otsuka Pharmaceutical, Shionogi, Teijin Pharma, PDRadiopharma, Sumitomo Pharma, Daiichi Sankyo, Kyowa Kirin, Japan Blood Products Organization, Chugai Pharmaceutical, and Mitsubishi Tanabe Pharma, which are unrelated to the submitted work. All other authors declare that they have no conflicts of interest.

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