The expression of collagen-binding activity by common oral bacteria suggests an important risk factor for cerebral microbleeds (CMBs) that often precede stroke, according to results of a multicenter study from Japan reported in Scientific Reports.1 Cerebral microbleeds have been reported in from 57% to 64% of patients diagnosed with intracranial hemorrhage (ICH) vs from 4% to 6% of healthy individuals and are, therefore, increasingly being used as markers for stroke.2,3
In an investigation of 279 participants (189 men, 90 women) in a community-based study conducted in Kyoto, Japan, the researchers found a significantly higher risk for Streptococcus mutans among those who had CMBs than among those who did not. Collagen-binding activity, measured by the presence of the cnm protein, cnm-positive S mutans, was closely related to CMBs in patients who also demonstrated cognitive impairment.
The cnm protein shows binding affinities both to fibrinogen and to collagen, which is found in dentin as well as in vascular endothelium and has been linked to the production of CMBs. The constant presence of cnm-positive S mutans, a type of oral bacteria commonly associated with dental caries, was reported in earlier studies by this group to be associated with a higher risk for stroke in mice.4
Dental evaluations from the Japan cohort showed that 86 (31%) of the participants had dental caries and 77 (28%) had community periodontal indices code 3 or higher. As the mean age of the participants was 70 years, most of them were missing teeth; the average number of remaining teeth for the group was 22.7 ± 7.5.
In the current clinical study, 94% of participants tested positive for S mutans and 33% for cnm-positive S mutans, and 25% showed collagen-binding activity associated with S mutans. Magnetic resonance imaging of the brain detected CMBs in 73 participants (26%).
Women in the study demonstrated a significantly higher frequency of S mutans compared with men, as 100% tested positive and 38% were positive for cnm-positive S mutans, whereas the frequencies among men were 91% and 30%, respectively. Men fared slightly better in the Mini-Mental State Examination, with mean scores of 28.6 ± 1.9 (SD) vs 27.9 ± 2.5 in women. This was despite a distinct pattern among the cohort favoring better overall health in the women: Men were more likely to have a history of smoking, drinking, diabetes, and higher body mass index. The percentage of men with dental caries was greater compared with women (37% vs 19%, respectively).
This investigation contributes to an increasing body of work that ties oral bacteria to stroke, cognitive decline, and the development of dementia. The authors suggest the need for greater collaboration between dental and medical research.
- Watanabe, I, Kuriyama N, Miyatan F, et al. Oral Cnm-positive streptococcus mutans expressing collagen binding activity is a risk factor for cerebral microbleeds and cognitive impairment [published online December 9, 2016]. Sci Rep. doi: 10.1038/srep38561
- Cordonnier C, Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain. 2007;130:1988-2003. doi: 10.1093/brain/awl387
- Bokura H, Saika R, Yamaguchi T, et al. Microbleeds are associated with subsequent hemorrhagic and ischemic stroke in healthy elderly individuals. Stroke. 2011;42:1867-1871. doi: 10.1161/STROKEAHA.110.601922
- Nakano K, Hokamura K, Taniguchi N, et al. The collagen-binding protein of Streptococcus mutans is involved in haemorrhagic stroke. Nat Commun. 2011;2:485. doi: 10.1038/ncomms1491