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

Highlights

• We examined the relationship between the relative rates of periodontal pathogens in the oral cavity and cerebral small vessel disease (CSVD).

• The relative rates of Fusobacterium nucleatum in the oral cavity were strongly associated with CSVD in patients with ischemic stroke.

• Oral care targeting Fusobacterium nucleatum may aid in impeding CSVD progression.

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

  1. Fusobacterium nucleatum
  2. Cerebral small vessel disease
  3. Ischemic stroke
  4. Periodontal pathogen

Introduction

Periodontal disease, which is a persistent bacterial infection causing chronic inflammation in the periodontal tissues, is characterized by the loss of connective tissue and alveolar bone support, resulting in tooth loss.1 Several cohort studies have demonstrated periodontal disease to be associated with an increased risk of stroke.2-5 A meta-analysis of two cohort studies found that periodontal disease increased the risk of ischemic stroke by 1.6-fold.6 The Atherosclerosis Risk in Communities (ARIC) cohort study of 10362 stroke-free participants over a 15-year follow-up period demonstrated periodontal disease to be significantly associated with the incidence of cardioembolic and thrombotic stroke and that regular dental care was related to a lower adjusted stroke risk.7 Periodontal disease is an established risk factor for ischemic stroke.

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