Faculty Profiles - NAKA Shuuhei

Papers - NAKA Shuuhei

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Birooted primary canines identified in 8-year-old Japanese girl – Case report Reviewed

Kazuma Kokomoto, Rena Okawa, Shuhei Naka, Ryota Nomura, Kazuhiko Nakano

Pediatric Dental Journal 29 ( 1 ) 48 - 51 2019.4

Relationship between Streptococcus mutans expressing Cnm in the oral cavity and non-alcoholic steatohepatitis: a pilot study. Reviewed International journal

Shuichi Tonomura, Shuhei Naka, Keiko Tabata, Tasuku Hara, Kojiro Mori, Saiyu Tanaka, Yoshio Sumida, Kazuyuki Kanemasa, Ryota Nomura, Michiyo Matsumoto-Nakano, Masafumi Ihara, Nobuyuki Takahashi, Kazuhiko Nakano

BMJ open gastroenterology 6 ( 1 ) e000329 2019

Language：English Publishing type：Research paper (scientific journal)

Background: Non-alcoholic steatohepatitis (NASH) is a severe state of non-alcoholic fatty liver disease (NAFLD), which is pathologically characterised by steatosis, hepatocyte ballooning, and lobular inflammation. Host-microbial interaction has gained attention as one of the risk factors for NASH. Recently, cnm-gene positive Streptococcus mutans expressing cell surface collagen-binding protein, Cnm (cnm-positive S. mutans), was shown to aggravate NASH in model mice. Here, we assessed the detection rate of cnm-positive S. mutans in oral samples from patients with NASH among NAFLD. Methods: This single hospital cohort study included 41 patients with NAFLD. NASH was diagnosed histologically or by clinical score. The prevalence of cnm-positive S. mutans, oral hygiene and blood tests, including liver enzymes, adipocytokines and inflammatory and fibrosis markers, were assessed in biopsy-proven or clinically suspected NASH among NAFLD. Results: Prevalence of cnm-positive S. mutans was significantly higher in patients with NASH than patients without NASH (OR 3.8; 95% CI 1.02 to 15.5). The cnm-positive S. mutans was related to decreased numbers of naturally remaining teeth and increased type IV collagen 7S level (median (IQR) 10.0 (5.0-17.5) vs 20.0 (5.0-25.0), p=0.06; 5.1 (4.0-7.9) vs 4.4 (3.7-5.3), p=0.13, respectively). Conclusions: Prevalence of cnm-positive S. mutans in the oral cavity could be related to fibrosis of NASH among NAFLD.

DOI： 10.1136/bmjgast-2019-000329

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Dental management of unilateral multiple impacted primary teeth

Yuki Matsumi, Yuko Morikawa, Eri Yoshida, Setsuyo Morimoto, Sho Yoshida, Tatsushi Matsumura, Seiji Iida, Yukiko Takashima, Shuhei Naka, Michiyo Matsumoto-Nakano

PEDIATRIC DENTAL JOURNAL 28 ( 3 ) 119 - 124 2018.12

A Potential New Risk Factor for Stroke: Streptococcus Mutans With Collagen-Binding Protein. Reviewed International journal

Chikanori Inenaga, Kazuya Hokamura, Kazuhiko Nakano, Ryota Nomura, Shuhei Naka, Toshihiko Ohashi, Takashi Ooshima, Nagato Kuriyama, Toshimitsu Hamasaki, Koichiro Wada, Kazuo Umemura, Tokutaro Tanaka

World neurosurgery 113 e77-e81 2018.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Among human oral bacteria, particular kinds of Streptococcus mutans (SM) known as dental caries pathogens contain a collagen-binding protein, Cnm, and show platelet aggregation inhibition and matrix metalloproteinase-9 activation. We have previously reported that these strains may be a risk factor for intracerebral hemorrhage. As a major sample-providing hospital, we report the clinical details, including intracranial aneurysms and ischemic stroke. METHODS: After the study received approval from the Ethical Committee, 429 samples of whole saliva were obtained from patients who were admitted to or visited our hospital between February 16, 2010, and February 28, 2011. The study cohort comprised 48 patients with cardioembolic stroke (CES), 151 with non-CES infarct, 54 with intracerebral hemorrhage (ICH), 43 with ruptured intracranial aneurysm (RIA), and 97 with unruptured intracranial aneurysm (UIA). Cultured SM was identified as Cnm-positive when the corresponding gene was positive. The results were compared with those from 79 healthy volunteers. Relationships between Cnm-positive SM and known risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and alcohol consumption, were analyzed. RESULTS: A statistically significant high Cnm-positive rate was observed in patients with CES, non-CES infarct, ICH, and RIA (P = 0.002, 0.039, 0.013, and 0.009, respectively). There were no relationships between Cnm-positive SM and known risk factors. CONCLUSIONS: Specific types of oral SM can be a risk factor for cardioembolic infarct, intracerebral hemorrhage, and intracranial aneurysm rupture. Further study is needed.

DOI： 10.1016/j.wneu.2018.01.158

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Displacement of maxillary right second premolar caused by gutta percha filling in corresponding primary molar Reviewed

Shuhei Naka, Kazuma Kokomoto, Jumpei Ohata, Rena Okawa, Ryota Nomura, Kazuhiko Nakano

Pediatric Dental Journal 28 ( 1 ) 13 - 18 2018.4

Odontoma associated with unerupted primary tooth in primary dentition - Three cases

Yukiko Takashima, Yuko Morikawa, Atsushi Takagi, Yuki Matsumi, Tatsushi Matsumura, Seiji Iida, Shuhei Naka, Michiyo Matsumoto-Nakano

PEDIATRIC DENTAL JOURNAL 28 ( 1 ) 19 - 24 2018.4

Campylobacter rectus in the Oral Cavity Correlates with Proteinuria in Immunoglobulin A Nephropathy Patients. Reviewed International journal

Taro Misaki, Shuhei Naka, Kaoruko Wato, Rina Hatakeyama, Yasuyuki Nagasawa, Seigo Ito, Hiroaki Inaba, Ryota Nomura, Michiyo Matsumoto-Nakano, Kazuhiko Nakano

Nephron 139 ( 2 ) 143 - 149 2018

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Periodontitis-related pathogens, such as Campylobacter or Treponema species, have recently been shown to be associated with immunoglobulin A nephropathy (IgAN). Some strains of Streptococcus mutans, a major pathogen of dental caries, harbour the cnm gene that encodes a collagen-binding protein (Cnm). This has also been demonstrated to be associated with urinary protein levels in IgAN patients. OBJECTIVES: The purpose of the present study was to analyse the association of IgAN with C. rectus, Treponema denticola and cnm-positive S. mutans in the oral cavity of humans. METHODS: The presence of C. rectus, T. denticola and cnm-positive S. mutans strains in saliva samples of 117 IgAN patients and 56 healthy controls was evaluated by PCR, and the subjects' clinical parameters were analysed. RESULTS: C. rectus was significantly more prevalent in the IgAN group than in the control group (p < 0.05). The C. rectus-positive group was significantly associated with proteinuria in the IgAN group (p < 0.05). In addition, the C. rectus-positive and cnm-positive S. mutans group was shown to be more closely associated with urinary protein levels than the other groups (p < 0.0083). CONCLUSION: Our results suggest that harbouring C. rectus in the oral cavity could be associated with proteinuria in IgAN patients.

DOI： 10.1159/000487103

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Longitudinal comparison of Streptococcus mutans-induced aggravation of non-alcoholic steatohepatitis in mice. Reviewed International journal

Shuhei Naka, Kaoruko Wato, Rina Hatakeyama, Rena Okawa, Ryota Nomura, Kazuhiko Nakano

Journal of oral microbiology 10 ( 1 ) 1428005 - 1428005 2018

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Background: We previously reported that intravenous administration of Streptococcus mutans strain TW871 caused typical non-alcoholic steatohepatitis (NASH)-like findings in a high-fat diet (HFD) mouse model at 16 weeks after initiating the experiment. Objective: The purpose of the present study was to analyse mice administered S. mutans TW871 fed a HFD for various periods of time. Methods: First, 6-week-old C57BL/6J mice were fed an HFD for 4 weeks, then TW871 (1 × 107 CFU) or phosphate-buffered saline (PBS) were intravenously administered. Mice were euthanized 12, 16, 20, and 48 weeks after starting the experiment, and conventional clinical and histopathological evaluations were performed. Results: Typical NASH-like findings were not identified in the mice at 12 weeks, while they were observed in the TW871 group at 16 weeks, and the severity of NASH symptoms were increased at 20 weeks. Furthermore, signs of severe NASH were also observed at 48 weeks. In contrast, in the PBS-administered group, the NASH findings were identified only at 48 weeks and no typical NASH features were observed at 12, 16, or 20 weeks. Conclusion: These results suggest that intravenous administration of a specific S. mutans strain aggravates NASH in a time-dependent manner in the mice in contrast to mice without S. mutans exposure.

DOI： 10.1080/20002297.2018.1428005

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The in vivo Inhibition of Oral Biofilm Accumulation and Streptococcus mutans by Ceramic Water. Reviewed International journal

Ryota Nomura, Risa Yoneyama, Shuhei Naka, Masatoshi Otsugu, Yuko Ogaya, Rina Hatakeyama, Yumiko Morita, Jumpei Maruo, Michiyo Matsumoto-Nakano, Osamu Yamada, Kazuhiko Nakano

Caries research 51 ( 1 ) 58 - 67 2017

Language：English Publishing type：Research paper (scientific journal)

Combustion-synthesized titanium carbide ceramics uniformly disperse silver, producing silver ions and hydroxyl radicals in water. This generates antimicrobial activity against various bacteria. One such bacterium is Streptococcus mutans, a gram-positive anaerobic bacterium known as a major pathogen of dental caries. In this study, we analyzed the inhibition of oral biofilms and S. mutans by ceramic water in in vitro and human studies. S. mutans strains showed significantly lower antimicrobial and sucrose-dependent adhesion activity in the presence of ceramic powder compared with untreated culture medium. Confocal microscopy revealed that S. mutans biofilm structures with ceramic powder were thin and coarse. Twenty-seven volunteers (13 males, 14 females; 18-37 years old, mean 25.2 years) were enrolled for subsequent studies. After each meal, one group was asked to rinse with ceramic water while the other rinsed with untreated water for 1 week. After 1 week, the rinsing contents were switched between the groups and the same protocol was followed for an additional week. After rinsing with ceramic water, the average plaque score was 43.0 ± 3.7, which was significantly lower than the baseline value (74.1 ± 5.7, p < 0.001). However, no significant difference was observed when rinsing with untreated water. In addition, the total number of S. mutans in saliva was significantly reduced after rinsing with ceramic water compared with untreated water (p < 0.05). These results suggest that ceramic water possesses antimicrobial activity against S. mutans and inhibits biofilm formation. Rinsing with ceramic water can also inhibit dental plaque formation and S. mutans colonization in humans.

DOI： 10.1159/000452343

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Oral Cnm-positive Streptococcus Mutans Expressing Collagen Binding Activity is a Risk Factor for Cerebral Microbleeds and Cognitive Impairment. Reviewed International journal

Isao Watanabe, Nagato Kuriyama, Fumitaro Miyatani, Ryota Nomura, Shuhei Naka, Kazuhiko Nakano, Masafumi Ihara, Komei Iwai, Daisuke Matsui, Etsuko Ozaki, Teruhide Koyama, Masaru Nishigaki, Toshiro Yamamoto, Aiko Tamura, Toshiki Mizuno, Kentaro Akazawa, Akihiro Takada, Kazuo Takeda, Kei Yamada, Masanori Nakagawa, Tokutaro Tanaka, Narisato Kanamura, Robert P Friedland, Yoshiyuki Watanabe

Scientific reports 6 38561 - 38561 2016.12

Language：English Publishing type：Research paper (scientific journal)

Cerebral microbleeds (CMBs) are an important risk factor for stroke and dementia. We have shown that the collagen binding surface Cnm protein expressed on cnm-positive Streptococcus mutans is involved in the development of CMBs. However, whether the collagen binding activity of cnm-positive S. mutans is related to the nature of the CMBs or to cognitive impairment is unclear. Two-hundred seventy nine community residents (70.0 years) were examined for the presence or absence of cnm-positive S. mutans in the saliva by PCR and collagen binding activity, CMBs, and cognitive function were evaluated. Cnm-positive S. mutans was detected more often among subjects with CMBs (p < 0.01) than those without. The risk of CMBs was significantly higher (odds ratio = 14.3) in the group with S. mutans expressing collagen binding activity, as compared to the group without that finding. Deep CMBs were more frequent (67%) and cognitive function was lower among subjects with cnm-positive S. mutans expressing collagen binding activity. This work supports the role of oral health in stroke and dementia and proposes a molecular mechanism for the interaction.

DOI： 10.1038/srep38561

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Contributions of Streptococcus mutans Cnm and PA antigens to aggravation of non-alcoholic steatohepatitis in mice. Reviewed International journal

Shuhei Naka, Rina Hatakeyama, Yukiko Takashima, Michiyo Matsumoto-Nakano, Ryota Nomura, Kazuhiko Nakano

Scientific reports 6 36886 - 36886 2016.11

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Streptococcus mutans, a major pathogen of dental caries, can cause infective endocarditis after invading the bloodstream. Recently, intravenous administration of specific S. mutans strains was shown to aggravate non-alcoholic steatohepatitis (NASH) in a mouse model fed a high-fat diet. Here, we investigated the mechanism of this aggravation in a NASH mouse model by focusing on the S. mutans cell surface collagen-binding protein (Cnm) and the 190-kDa protein antigen (PA). Mice that were intravenously administered a S. mutans strain with a defect in Cnm (TW871CND) or PA (TW871PD) did not show clinical or histopathological signs of NASH aggravation, in contrast to those administered the parent strain TW871. The immunochemical analyses demonstrated higher levels of interferon-γ and metallothionein expression in the TW871 group than in the TW871CND and TW871PD groups. Analysis of bacterial affinity to cultured hepatic cells in the presence of unsaturated fatty acids revealed that the incorporation rate of TW871 was significantly higher than those of TW871CND and TW871PD. Together, our results suggest that Cnm and PA are important cell surface proteins for the NASH aggravation caused by S. mutans adhesion and affinity for hepatic cells.

DOI： 10.1038/srep36886

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Presence of Streptococcus mutans strains harbouring the cnm gene correlates with dental caries status and IgA nephropathy conditions. International journal

Taro Misaki, Shuhei Naka, Rina Hatakeyama, Akiko Fukunaga, Ryota Nomura, Taisuke Isozaki, Kazuhiko Nakano

Scientific reports 6 36455 - 36455 2016.11

Language：English Publishing type：Research paper (scientific journal)

Streptococcus mutans is a major pathogen of human dental caries. Strains harbouring the cnm gene, which encodes Cnm, a collagen-binding protein, contribute to the development of several systemic diseases. In this study, we analysed S. mutans strains isolated from the oral cavity of immunoglobulin (Ig)A nephropathy (IgAN) patients to determine potential relationships between cnm and caries status as well as IgAN conditions. Saliva specimens were collected from 109 IgAN patients and the cnm status of isolated S. mutans strains was determined using PCR. In addition, the dental caries status (decayed, missing or filled teeth [DMFT] index) in patients who agreed to dental consultation (n = 49) was evaluated. The DMFT index and urinary protein levels in the cnm-positive group were significantly higher than those in the cnm-negative group (p < 0.05). Moreover, the urinary protein levels in the high DMFT (≥15) group were significantly higher than those in the low DMFT (<15) group (p < 0.05). Our results show that isolation of cnm-positive S. mutans strains from the oral cavity may be associated with urinary protein levels in IgAN patients, especially those with a high dental caries status.

DOI： 10.1038/srep36455

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Lowe syndrome oral findings: Case report Reviewed

Rena Okawa, Shuhei Naka, Kanae Saga, Kazuhiko Nakano

Pediatric Dental Journal 26 ( 1 ) 34 - 37 2016.4

Distribution of Streptococcus mutans strains with collagen-binding proteins in the oral cavity of IgA nephropathy patients.

Taro Misaki, Shuhei Naka, Keiko Kuroda, Ryota Nomura, Tempei Shiooka, Yoshitaka Naito, Yumiko Suzuki, Hideo Yasuda, Taisuke Isozaki, Kazuhiko Nakano

Clinical and experimental nephrology 19 ( 5 ) 844 - 50 2015.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: IgA nephropathy (IgAN) is the most common primary chronic glomerulonephritis; however, its precise initiating pathogenesis remains unclear. Streptococcus mutans is a major pathogen of human dental caries. S. mutans strains with the cnm gene encoding Cnm, a collagen-binding protein, have been reported to contribute to the development of systemic diseases. However, the contribution of S. mutans with Cnm in the development of IgAN has not been reported. The aim of this study was to investigate the prevalence of cnm-positive S. mutans in IgAN patients and clarify the effects of cnm-positive S. mutans on the histological pathology of IgAN. METHODS: We identified the cnm gene in S. mutans isolated in saliva specimens, which were collected from IgAN patients (n = 53) and control subjects (n = 50). We evaluated the collagen-binding properties of S. mutans in IgAN patients and controls. The clinical parameters and histological scores were also assessed in IgAN patients. RESULTS: The rates of S. mutans isolation in IgAN and control groups were 84.0 and 84.9 %, respectively, not significantly dfferent. cnm-positive strains were significantly more prevalent in the IgAN group than in controls (32.1 vs. 14.0 %, p < 0.05). With regard to collagen-binding assays, the binding rates of cnm-positive strains were significantly higher in the IgAN group than in controls (96.6 vs. 30.0, p < 0.05). In addition, the segmental glomerulosclerosis scores were significantly higher in cnm-positive patients with IgAN than in cnm-negative patients with IgAN (0.94 vs. 0.57, p < 0.05). CONCLUSION: cnm-positive S. mutans strains are potentially associated with the pathogenesis of IgAN.

DOI： 10.1007/s10157-014-1072-0

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Epulis appeared after exfoliation of natal tooth in infant Japanese boy Reviewed

Rena Okawa, Kazuyo Fujita, Shuhei Naka, Ryota Nomura, Kazuhiko Nakano

Pediatric Dental Journal 24 ( 3 ) 189 - 191 2014.12

Contribution of the interaction of Streptococcus mutans serotype k strains with fibrinogen to the pathogenicity of infective endocarditis. Reviewed International journal

Ryota Nomura, Masatoshi Otsugu, Shuhei Naka, Noboru Teramoto, Ayuchi Kojima, Yoshinori Muranaka, Michiyo Matsumoto-Nakano, Takashi Ooshima, Kazuhiko Nakano

Infection and immunity 82 ( 12 ) 5223 - 34 2014.12

Language：English Publishing type：Research paper (scientific journal)

Streptococcus mutans, a pathogen responsible for dental caries, is occasionally isolated from the blood of patients with bacteremia and infective endocarditis (IE). Our previous study demonstrated that serotype k-specific bacterial DNA is frequently detected in S. mutans-positive heart valve specimens extirpated from IE patients. However, the reason for this frequent detection remains unknown. In the present study, we analyzed the virulence of IE from S. mutans strains, focusing on the characterization of serotype k strains, most of which are positive for the 120-kDa cell surface collagen-binding protein Cbm and negative for the 190-kDa protein antigen (PA) known as SpaP, P1, antigen I/II, and other designations. Fibrinogen-binding assays were performed with 85 clinical strains classified by Cbm and PA expression levels. The Cbm(+)/PA(-) group strains had significantly higher fibrinogen-binding rates than the other groups. Analysis of platelet aggregation revealed that SA31, a Cbm(+)/PA(-) strain, induced an increased level of aggregation in the presence of fibrinogen, while negligible aggregation was induced by the Cbm-defective isogenic mutant SA31CBD. A rat IE model with an artificial impairment of the aortic valve created using a catheter showed that extirpated heart valves in the SA31 group displayed a prominent vegetation mass not seen in those in the SA31CBD group. These findings could explain why Cbm(+)/PA(-) strains are highly virulent and are related to the development of IE, and the findings could also explain the frequent detection of serotype k DNA in S. mutans-positive heart valve clinical specimens.

DOI： 10.1128/IAI.02164-14

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A specific Streptococcus mutans strain aggravates non-alcoholic fatty liver disease. Reviewed International journal

S Naka, R Nomura, Y Takashima, R Okawa, T Ooshima, K Nakano

Oral diseases 20 ( 7 ) 700 - 6 2014.10

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Streptococcus mutans, a major dental caries pathogen, has shown to be associated with the aggravation of cerebral hemorrhage and inflammatory bowel diseases. In this study, we evaluated the effects ofS. mutans on the development of non-alcoholic steatohepatitis (NASH) in a mouse model. MATERIALS AND METHODS: Streptococcus mutans oral strain MT8148 (serotype c) and a blood isolate TW871 (k) were used. C57BL/6J mice (6 weeks old)were fed a high-fat diet for 4 weeks; the test strains or phosphate-buffered saline was then intravenously administered. Mice were euthanized after 8 or 12 weeks. Whole body, extirpated liver, and visceral fat weights were determined, and histopathological evaluations of the liver specimens were performed. RESULTS: Mice infected with TW871 showed significantly greater body and liver weights than those administered MT8148 or phosphate-buffered saline. Histopathological analyses revealed prominent infiltration of inflammatory cells and adipocellular deposition in livers extirpated 8 weeks after an infection with TW871; fibrosis was also observed in livers extirpated after 12 weeks. CONCLUSION: These results suggest that a specific strain of S. mutans could induce NASH.

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Delayed eruption of mandibular primary central incisors in a child with severe lingual inclination and their spontaneous movement to appropriate positions Reviewed

Rena Okawa, Shuhei Naka, Miharu Higashino, Ryota Nomura, Kazuhiko Nakano

Pediatric Dental Journal 24 ( 2 ) 120 - 123 2014.8

Hypoplasia in crown of primary mandibular left lateral incisor identified in infant Japanese girl Reviewed

Rena Okawa, Shuhei Naka, Kanae Saga, Ryota Nomura, Kazuhiko Nakano

Pediatric Dental Journal 24 ( 2 ) 129 - 131 2014.8

Aggravation of inflammatory bowel diseases by oral streptococci. Reviewed International journal

A Kojima, R Nomura, S Naka, R Okawa, T Ooshima, K Nakano

Oral diseases 20 ( 4 ) 359 - 66 2014.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Streptococcus mutans can aggravate colitis in mice. We evaluated the virulence of colitis using type strains as well as blood isolates of several oral streptococcal species. MATERIALS AND METHODS: We investigated the susceptibility of blood isolates of several oral streptococci to phagocytosis, adhesion to and invasion of hepatic cells and interferon-γ secretion. A mouse model of dextran sodium sulphate-induced colitis was used to evaluate bacterial aggravation of colitis. In addition, interferon-γ antibody was administered to mice with prominent aggravation of colitis. RESULTS: In vitro analyses showed that Streptococcus sanguinis ATCC 10556 was a possible virulent strain among type strains of several oral streptococci, and that analysis of blood isolates of S. sanguinis TW289 revealed a potential virulent strain. Intravenous administration of ATCC 10556 and TW289 caused prominent aggravation of dextran sodium sulphate-induced colitis, and histopathological examinations showed that interferon-γ secretion due to infection of hepatic cells caused colitis aggravation. Administration of interferon-γ antibody suppressed TW289-induced colitis. CONCLUSION: These results suggest that some virulent oral streptococcal strains are associated with the aggravation of colitis induced by enhanced secretion of interferon-γ when they invade the bloodstream.

DOI： 10.1111/odi.12125

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