Association of Streptococcus mutans collagen binding genes with severe childhood caries

Lamba, Gurkaran S; Dufour, Delphine; Sm, Nainar; Cioffi, Iacopo; Lévesque, Christian; Gong, Siew‐Ging

doi:10.1007/s00784-020-03217-4

Cited by 9 publications

(7 citation statements)

References 47 publications

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“… 19 Experimental intravenous administration of cnm -positive S. mutans in stroke-prone spontaneously hypertensive rats and a mouse model of cerebral hemorrhage exacerbates cerebral bleeds. 19 Epidemiological studies from many countries have shown ≈20% to 30% of patients with ICH 15 , 22 and 7% to 20% of the general population 14 , 23 – 25 have cnm -positive S. mutans in their oral cavity. Clarifying the effects of cnm -positive S. mutans on the cerebral vasculature is, therefore, both necessary and urgent.…”

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confidence: 99%

Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds

Hosoki

Saitô

Tonomura

et al. 2020

Stroke

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Background and Purpose: Cerebral microbleeds (CMB) are associated with stroke and cognitive impairment. We previously reported a high prevalence of CMB in people with Streptococcus mutans expressing Cnm, a collagen-binding protein in the oral cavity. S. mutans is a major pathogen responsible for dental caries. Repeated challenge with S. mutans harboring the cnm gene encoding Cnm induced cerebral bleeding in stroke-prone spontaneously hypertensive rats. The purpose of this longitudinal study is to examine the relationship of cnm -positive S. mutans to the development of CMB. Methods: We retrospectively investigated patients with stroke receiving oral microbiological examination and head 3T magnetic resonance imaging evaluations twice in the period 2014 to 2019, allowing >180-day interval. Patients with cnm -positive S. mutans were compared with those without. Quasi-Poisson regression models were used to explore associations between cnm -positive S. mutans and the increase in number of CMB between the 2 magnetic resonance imaging scans. Results: A total of 111 patients were identified; 21 (19%) with cnm -positive S. mutans and 90 (81%) without. Clinical history, including blood pressure and the use of antithrombotic agents, were comparable between the 2 groups. New CMB were more commonly observed in patients with cnm -positive S. mutans (52% versus 23%; P =0.008). The incidence of CMB was significantly higher in the group with cnm -positive S. mutans , especially in deep areas, (incidence rate ratios [95% CI], 5.1 [1.9–13.6] for CMB in any brain region; 15.0 [5.4–42.0] for deep CMB), which persisted after adjusting for age, sex, hypertension, and renal impairment (4.7 [1.8–11.9] for CMB in any brain region; 13.9 [4.3–44.5] for deep CMB). Conclusions: This study demonstrates that cnm -positive S. mutans is associated with an increased incidence of CMB. Treatment for cnm -positive S. mutans infection may be a novel microbiota-based therapeutic approach for stroke and cognitive impairment.

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confidence: 99%

Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds

Hosoki

Saitô

Tonomura

et al. 2020

Stroke

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“…The sample size was determined by feasibility, but it was ensured to be substantial enough to perform the primary analysis. According to recent studies, the general prevalence rate of Cnm-positive S. mutans is 7–20% ( 19 , 25 – 27 ). Our previous retrospective study revealed that patients with Cnm-positive S. mutans has an incidence rate ratio (IRR) of 13.9 (4.3–44.5) when compared with patients without ( 20 ).…”

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confidence: 99%

Risk Assessment of Cnm-Positive Streptococcus mutans in Stroke Survivors (RAMESSES): Protocol for a Multicenter Prospective Cohort Study

et al. 2022

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IntroductionThe role of commensal microbiota in systemic diseases, including brain diseases, has attracted increasing attention. Oral infectious diseases, such as dental caries and periodontitis, are also involved in cerebrovascular diseases and cognitive impairment. Cerebral microbleeds (CMBs) and intracerebral hemorrhage due to small vessel disease (SVD), are presumably associated with a high risk of vascular cognitive impairment and stroke. We previously reported that Streptococcus mutans (S. mutans, the main pathogen of dental caries), harboring the cnm gene that encodes the collagen-binding protein Cnm, is associated with the development of hypertensive intracerebral hemorrhage and aggravation of CMBs. We also proposed a mechanism by which the circulating Cnm-expressing S. mutans causes intracerebral hemorrhage or CMBs; it binds to denuded basement membranes mainly composed of collagen IV through damaged tight junctions or it directly invades endothelial cells, resulting in blood-brain barrier injury. In November 2018, we initiated a multicenter, prospective cohort study (RAMESSES: Risk Assessment of Cnm-positive S. mutans in Stroke Survivors; UMIN Clinical Trials Registry: UMIN000045559) to explore the longitudinal association between Cnm-positive S. mutans and CMBs with comprehensive dental findings, which should determine the effect of Cnm-positive S. mutans in the oral cavity on the risk of CMB development and cognitive decline.MethodsFifteen domestic institutes will be enlisted to enroll 230 patients who have at least one CMB in the deep brain area and develop a stroke within the past year. The prevalence of Cnm-positive S. mutans based on oral specimens and dental hygiene will be examined. The primary outcome is the number of newly developed deep CMBs. The secondary outcomes include the new development of lobar, subtentorial, or any type of CMBs; symptomatic intracerebral hemorrhage or ischemic stroke; changes in cognitive function or frailty; major bleeding; all-cause mortality; and antibody titers against periodontal pathogens. The observation period will be 2 years.DiscussionThe 2-year longitudinal prospective cohort study is expected to establish the role of Cnm-positive S. mutans in SVD including CMBs and intracerebral hemorrhage from the perspective of the “brain-oral axis” and provide guidance for novel prophylactic strategies against Cnm-positive S. mutans-induced SVD.

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“…Eventually, these conditions may lead to root canal treatment or extraction of the affected tooth, i.e., tooth loss. Certain S. mutans strains like the Cnm and Cbm possess proteins capable of binding collagen and are linked to aggressive form of caries [12]. S. mutans expressing collagen-binding protein (CBP) has been previously shown to be more prevalent in oral samples of cerebral hemorrhage patients [13] and the persons affected by aSAH or other forms of intracranial hemorrhage [8].…”

Section: Introductionmentioning

confidence: 99%

Unlike severe periodontitis, caries does not associate with intracranial aneurysms or aneurysmal subarachnoid hemorrhage

et al. 2022

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Purpose Periodontal diseases and caries are common oral diseases that predispose to tooth loss if untreated. In this study, we investigated whether loss of teeth or caries associate with intracranial aneurysm (IA) pathology similar to periodontal diseases. Methods A total of 166 patients with either IA or aneurysmal subarachnoid hemorrhage (aSAH) underwent oral examination in Kuopio University Hospital and Tampere University Hospital. Findings were compared to geographically matched controls acquired from cross-sectional Health2000 survey. This study consisted of three sequential steps. First, we compared the number of missing teeth and prevalence of caries in IA and aSAH patients and geographically matched control population, second step was a multivariate analysis including other risk factors, and third step was a 13-year follow-up of the Health2000 survey participants with missing teeth or caries at baseline. Results Loss of teeth did not significantly differ between IA patients and controls. In logistic regression model adjusted for known risk factors and demographic data, 1–4 caries lesions (OR: 0.40 95%Cl 0.2–0.9, p = 0.031) was associated with lack of IAs, while age (OR: 1.03 95%Cl 1.01.1 p = 0.024), current smoking (OR: 2.7 95%Cl 1.4–5.1, p = 0.003), and severe periodontitis (OR: 5.99 95%Cl 2.6–13.8, p < 0.001) associated to IA formation. In the cox-regression, severe periodontitis at baseline increased the risk of aSAH (HR: 14.3, 95%Cl 1.5–135.9, p = 0.020) during a 13-year follow-up, while caries or missing teeth did not. Conclusion Unlike severe periodontitis, caries does not increase the risk of IAs and aSAHs. However, cariogenic bacteria may participate to IA pathology by disseminating to circulation via inflamed gingival tissue.

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Association of Streptococcus mutans collagen binding genes with severe childhood caries

Cited by 9 publications

References 47 publications

Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds

Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds

Risk Assessment of Cnm-Positive Streptococcus mutans in Stroke Survivors (RAMESSES): Protocol for a Multicenter Prospective Cohort Study

Unlike severe periodontitis, caries does not associate with intracranial aneurysms or aneurysmal subarachnoid hemorrhage

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