Updated on 2025/07/30

写真a

 
GOTOH Kazuyoshi
 
Organization
Faculty of Health Sciences Associate Professor
Position
Associate Professor
External link

Degree

  • 博士(医学)

Research Areas

  • Life Science / Bacteriology

Professional Memberships

 

Papers

  • Alteration of the intestinal microbiota associated with the development of nonalcoholic steatohepatitis and sarcopenia in SHRSP5/Dmcr. Reviewed International journal

    Taketo Fukuoka, Shusei Yamamoto, Koki Honma, Moe Fujii, Hinako Nakayama, Sora Kirihara, Kazuyoshi Gotoh, Shuma Tsuji, Yuki Kawai, Haruka Tago, Yuka Kono, Kunihiro Sonoda, Kazuya Kitamori, Shogo Watanabe

    Folia microbiologica   2025.6

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    Sarcopenia, characterized by skeletal muscle atrophy, was previously considered age-related; however, it is also associated with other diseases. Nonalcoholic fatty liver disease (NAFLD) is known to cause sarcopenia, and its complications have been reported to affect prognosis. The intestinal microbiota of patients with NAFLD or sarcopenia has been found to be altered compared to that of healthy individuals. However, the alterations that occur when both diseases coexist in humans or experimental animals remain unclear. Therefore, this study aimed to determine the intestinal microbiota changes associated with NAFLD with sarcopenia in SHRSP5/Dmcr rats at the time of concomitant disease. Fecal samples were collected from the rectum of SHRSP5/Dmcr rats fed a normal diet (non-NAFLD and non-Sarcopenia, n = 5) or a high-fat and high-cholesterol diet (NAFLD and Sarcopenia, n = 5) for 20 weeks, and subjected to 16S rRNA analysis. In the NAFLD and sarcopenia group, the diversity of the intestinal microbiota was reduced; further, the bacterial species reported in patients with NAFLD or sarcopenia were also changed. At the family level, the abundances of Akkermansiaceae, Bacteroidaceae, and Tannerellaceae were significantly higher whereas Ruminococcaceae and Lactobacillaceae were decreased in the NAFLD and sarcopenia group. At the genus level, the abundances of Akkermansia, Bacteroides, Ruminococcus, and Parabacteroides were significantly higher whereas the abundance of Lactobacillus was significantly decreased in the NAFLD and sarcopenia group. Overall, these findings help improve the existing understanding regarding the intestinal microbiota changes observed in conditions where NASH and sarcopenia co-occur.

    DOI: 10.1007/s12223-025-01283-3

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  • Quantification of Streptococcus salivarius using the digital polymerase chain reaction as a liver fibrosis marker. Reviewed International journal

    Shuichiro Iwasaki, Akira Také, Haruki Uojima, Kazue Horio, Yoshihiko Sakaguchi, Kazuyoshi Gotoh, Takashi Satoh, Hisashi Hidaka, Yasuhito Tanaka, Shunji Hayashi, Chika Kusano

    World journal of hepatology   17 ( 4 )   102027 - 102027   2025.4

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    BACKGROUND: The Streptococcus salivarius (S. salivarius) group, which produces the enzyme urease has been identified as a potential contributor to ammonia production in the gut. Researchers have reported that patients with minimal HE had an increased abundance of the S. salivarius group, which is a specific change in the gut microbiota that distinguishes them from healthy individuals. The correlation between the aggregation of specific bacterial species and fibrosis progression in chronic liver disease (CLD) is yet to be fully elucidated. AIM: To quantify S. salivarius using digital PCR (dPCR) as a liver fibrosis marker of CLD. METHODS: This study retrospectively analysed 52 patients with CLD. To quantify S. salivarius in patients with CLD using dPCR, we evaluated the specificity and sensitivity of S. salivarius bacterial load using dPCR for a type strain. Next, we evaluated the clinical usefulness of dPCR for S. salivarius load quantification for detecting liver fibrosis in patients with CLD. The liver fibrosis stage was categorized into mild and advanced fibrosis based on pathological findings. RESULTS: The dPCR assay revealed that S. salivarius was highly positive for the tnpA gene. The lower limit of quantification for dPCR using the tnpA gene with a 1 μL template comprising 1.28 × 102 CFU/mL was 4.3 copies. After considering the detection range in dPCR, we adjusted the extracted DNA concentration to 5.0 × 10-4 ng/μL from 200 mg stool samples. The median bacterial loads of S. salivarius in stool sample from patients with mild and advanced fibrosis were 1.9 and 7.4 copies/μL, respectively. The quantification of S. salivarius load was observed more frequently in patients with advanced fibrosis than in those with mild fibrosis (P = 0.032). CONCLUSION: Quantifying of S. salivarius load using digital PCR is a useful biomarker for liver fibrosis in patients with CLD.

    DOI: 10.4254/wjh.v17.i4.102027

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  • CCL19/MIP-3β as a key mediator in the production of anti-GPIIb/IIIa antibody-producing B cells in patients with chronic hepatitis C. Reviewed International journal

    Junki Iida, Haruki Uojima, Takashi Satoh, Masaya Sugiyama, Akira Take, Yoshihiko Sakaguchi, Kazuyoshi Gotoh, Hisashi Hidaka, Shunji Hayashi, Yasuhito Tanaka, Makoto Otsu, Chika Kusano

    Cytokine   190   156915 - 156915   2025.3

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    The roles of specific cytokines and chemokines in modulating the production of anti-GPIIb/IIIa antibody-producing B cells remain poorly understood. We aimed to assess key mediators that influence the number of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells in patients with hepatitis C virus (HCV). This study used a subset of a previously reported cohort in Japan. We first evaluated the number of anti-GPIIb/IIIa antibody-producing B cells using an enzyme-linked immunospot assay in samples from 22 patients who received direct-acting antivirals (DAA)-based therapy and achieved a sustained virological response (SVR). To identify the key mediators, we then analyzed levels of cytokines, chemokines, and inflammation markers in serum samples obtained from the same cohort using Bio-Plex Multiplex Immunoassays. The analysis revealed a significant correlation between the frequency of anti-GPIIb/IIIa antibody-producing B cells and CCL19/macrophage inflammatory protein-3 beta (MIP-3β) (r = 0.590, p = 0.006). After DAA treatment for HCV, both the frequency of these B cells and the levels of CCL19/MIP-3β significantly decreased. Furthermore, the frequency of anti-GPIIb/IIIa antibody-producing B cells and levels of CCL19/MIP-3β were significantly higher in the thrombocytopenia group compared to the non-thrombocytopenia group (p = 0.001 and p = 0.029, respectively). These results suggest that CCL19/MIP-3β may be a key mediator in the production of anti-GPIIb/IIIa antibody-producing B cells in patients with HCV.

    DOI: 10.1016/j.cyto.2025.156915

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  • Genetic variability in Neisseria meningitidis strains isolated in a Japanese hospital Reviewed

    Kazuyoshi Gotoh, Shinnosuke Fukushima, Hideharu Hagiya, Shuma Tsuji, Koji Iio, Osamu Matsushita

    IJID Regions   14   100511 - 100511   2025.3

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    DOI: 10.1016/j.ijregi.2024.100511

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  • Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease. Reviewed International journal

    Yui Kambara, Hideaki Fujiwara, Akira Yamamoto, Kazuyoshi Gotoh, Shuma Tsuji, Mari Kunihiro, Tadashi Oyama, Toshiki Terao, Ayame Sato, Takehiro Tanaka, Daniel Peltier, Keisuke Seike, Hisakazu Nishimori, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshihiko Soga, Pavan Reddy, Yoshinobu Maeda

    Blood   145 ( 8 )   881 - 896   2025.2

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    The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.

    DOI: 10.1182/blood.2024024540

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  • Clinical and microbiological characteristics of high-level daptomycin-resistant Corynebacterium species: A systematic scoping review. Reviewed International journal

    Shinnosuke Fukushima, Hideharu Hagiya, Kazuyoshi Gotoh, Shuma Tsuji, Koji Iio, Hidemasa Akazawa, Osamu Matsushita, Fumio Otsuka

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2024.12

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    INTRODUCTION: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections. METHODS: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including "Corynebacterium", "Daptomycin", and "Resistance", in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 μg/mL, were deemed eligible for this review. RESULTS: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8%), and prosthetic device-associated infections accounted for 66.7% of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71% to 100%) within 24 hours of incubation, compared to other Corynebacterium strains CONCLUSION: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen.

    DOI: 10.1016/j.jiac.2024.12.004

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  • 日本紅斑熱好発地域におけるヒト吸血をきたしたダニ種および保有病原体の検討

    福島 伸乃介, 後藤 和義, 辻 秀真, 角南 博, 中野 靖浩, 中本 健太, 萩谷 英大

    日本臨床微生物学会雑誌   35 ( Suppl.1 )   306 - 306   2024.12

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  • Phenotypic and Genetic Characteristics of Carbapenemase-Producing Enterobacterales Isolates at Okayama University Hospital. Reviewed

    Kazuyoshi Gotoh, Makoto Miyoshi, I Putu Bayu Mayura, Shuma Tsuji, Koji Iio, Shinnosuke Fukushima, Osamu Matsushita, Hideharu Hagiya

    Acta medica Okayama   78 ( 5 )   371 - 376   2024.10

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    Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 μg/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control.

    DOI: 10.18926/AMO/67657

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  • Hepatic Mac2-BP expression depends on liver fibrosis and inflammation due to fat accumulation in patients with metabolic dysfunction-associated steatotic liver disease. Reviewed International journal

    Haruki Uojima, Hanako Tsujikawa, Ken Yamazaki, Masaya Sugiyama, Akira Take, Yoshihiko Sakaguchi, Kazuyoshi Gotoh, Takashi Satoh, Hisashi Hidaka, Shunji Hayashi, Chika Kusano, Michiie Sakamoto, Masashi Mizokami

    Hepatology research : the official journal of the Japan Society of Hepatology   2024.9

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    AIM: Data on the upregulation of Mac-2 binding protein (M2BP) expression associated with fat accumulation in the liver are limited. Therefore, we aimed to assess the relationship between hepatic M2BP expression and changes in the liver microenvironment due to fat accumulation in patients with metabolic dysfunction associated steatotic liver disease (MASLD). METHODS: Liver specimens obtained from 46 patients with MASLD were subjected to immunohistochemical staining to visualize M2BP expression in the liver. The staining intensity in the hepatocytes and sinusoidal cells was classified as high or low grade. First, the correlation between hepatic M2BP expression and microenvironmental changes caused by fat accumulation was examined. Then, the influence of hepatic M2BP expression on serum M2BP glycosylation isomer levels in patients with MASLD was evaluated. RESULTS: The staining grade of M2BP was higher in the sinusoidal cells than in the hepatocytes (p = 0.015). The patients with high staining grade in their hepatocytes had more severe lobular inflammation than those with low staining grade (p = 0.037). Additionally, the patients with high staining grade in their sinusoidal cells presented more severe fibrosis than those with low staining grade (p = 0.018). The staining grade in the hepatocytes correlated positively with serum M2BP glycosylation isomer levels (p = 0.023), whereas no correlation was observed between sinusoidal staining grade and serum M2BP glycosylation isomer levels (p = 0.393). CONCLUSIONS: Fat accumulation in patients with MASLD leads to M2BP expression in hepatocytes due to liver inflammation and that in sinusoidal cells due to fibrosis.

    DOI: 10.1111/hepr.14109

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  • Cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus clinical isolates Reviewed International journal

    Shuma Tsuji, Kazuyoshi Gotoh, Tadahiro Manabe, Koji Iio, Shinnosuke Fukushima, Osamu Matsushita, Hideharu Hagiya

    Diagnostic Microbiology and Infectious Disease   110 ( 1 )   116399 - 116399   2024.9

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    We investigated the prevalence and characteristics of Cefazolin inoculum effect (CInE) among clinical MSSA isolates in Japan. Although 35.5 % (39 isolates) were positive for the blaZ gene, none met the phenotypic criteria for CInE. Our findings suggested a very low prevalence of CInE among MSSA isolates in our clinical setting.

    DOI: 10.1016/j.diagmicrobio.2024.116399

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  • New Delhi Metallo-Beta-Lactamase Inhibitors: A Systematic Scoping Review. Reviewed International journal

    Lutfun Nahar, Hideharu Hagiya, Kazuyoshi Gotoh, Md Asaduzzaman, Fumio Otsuka

    Journal of clinical medicine   13 ( 14 )   2024.7

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    Background/Objectives: Among various carbapenemases, New Delhi metallo-beta-lactamases (NDMs) are recognized as the most powerful type capable of hydrolyzing all beta-lactam antibiotics, often conferring multi-drug resistance to the microorganism. The objective of this review is to synthesize current scientific data on NDM inhibitors to facilitate the development of future therapeutics for challenging-to-treat pathogens. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews, we conducted a MEDLINE search for articles with relevant keywords from the beginning of 2009 to December 2022. We employed various generic terms to encompass all the literature ever published on potential NDM inhibitors. Results: Out of the 1760 articles identified through the database search, 91 met the eligibility criteria and were included in our analysis. The fractional inhibitory concentration index was assessed using the checkerboard assay for 47 compounds in 37 articles, which included 8 compounds already approved by the Food and Drug Administration (FDA) of the United States. Time-killing curve assays (14 studies, 25%), kinetic assays (15 studies, 40.5%), molecular investigations (25 studies, 67.6%), in vivo studies (14 studies, 37.8%), and toxicity assays (13 studies, 35.1%) were also conducted to strengthen the laboratory-level evidence of the potential inhibitors. None of them appeared to have been applied to human infections. Conclusions: Ongoing research efforts have identified several potential NDM inhibitors; however, there are currently no clinically applicable drugs. To address this, we must foster interdisciplinary and multifaceted collaborations by broadening our own horizons.

    DOI: 10.3390/jcm13144199

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  • Complete Match of Streptococcus salivarius from Oral Saliva and Stool in a Patient with Hepatic Encephalopathy. Reviewed

    Nao Nomura, Akira Také, Haruki Uojima, Yoshihiko Sakaguchi, Kazuyoshi Gotoh, Takashi Satoh, Hisashi Hidaka, Kazue Horio, Masashi Mizokami, Shunji Hayashi, Chika Kusano

    Internal medicine (Tokyo, Japan)   64 ( 4 )   551 - 556   2024.7

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    We herein report a 67-year-old Japanese woman with liver cirrhosis caused by primary biliary cholangitis. The patient was admitted to the hospital with loss of consciousness. Hepatic encephalopathy (HE) was diagnosed after diagnostic imaging and symptom assessments. Molecular biology tests were performed on oral saliva and stool samples. The test results indicated sequence similarity between urease-positive S. salivarius in both oral saliva and stool, as revealed by the signals in the overlapping peaks. This bacterium can potentially increase ammonia production in the gut, leading to HE in patients with liver cirrhosis.

    DOI: 10.2169/internalmedicine.3989-24

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  • 胃癌患者の胃内より分離した硝酸塩還元菌のピロリ菌共感染マウスへの影響

    小松原 万里奈, 山本 由弥子, 内山 淳平, 松下 治, 後藤 和義, 渡辺 朱理, 横田 憲治

    日本細菌学雑誌   79 ( 2 )   140 - 140   2024.6

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  • 胃炎-胃癌患者の胃粘膜より分離された硝酸塩還元菌の性状

    桑木 星里香, 山本 由弥子, 内山 淳平, 松下 治, 後藤 和義, 渡辺 朱理, 横田 憲治

    日本細菌学雑誌   79 ( 2 )   152 - 152   2024.6

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  • Detection of imported clinical strain of blaNDM-1-harbouring ST147 Klebsiella pneumoniae from a Ukrainian immigrant. Reviewed International journal

    Shinnosuke Fukushima, Hideharu Hagiya, Kazuyoshi Gotoh, Shuma Tsuji, Koji Iio, Osamu Matsushita

    Journal of travel medicine   2024.1

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    DOI: 10.1093/jtm/taae011

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  • Metabolic dysfunction-associated fatty liver disease on distinct microbial communities at the bacterial phylum level. Reviewed

    Uojima H, Sakaguchi Y, Gotoh K, Satoh T, Hidaka H, Take A, Horio K, Hayashi S, Kusano C

    Dig Dis.   2023.9

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    DOI: 10.1159/000534284.

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  • Antimicrobial resistance and genotyping of Pseudomonas aeruginosa isolated from the ear canals of dogs in Japan Reviewed International journal

    Ahmed Elfadadny, Jumpei Uchiyama, Kazuyoshi Goto, Ichiro Imanishi, Rokaia F. Ragab, Wedad M. Nageeb, Keita Iyori, Yoichi Toyoda, Toshihiro Tsukui, Kaori Ide, Keiko Kawamoto, Koji Nishifuji

    Frontiers in Veterinary Science   10   1074127 - 1074127   2023.7

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    <jats:p>The strong bond between dogs and their owners creates a close association that could result in the transfer of antibiotic-resistant bacteria from canines to humans, potentially leading to the spread of antimicrobial resistance genes. <jats:italic>Pseudomonas aeruginosa</jats:italic>, a common causative agent of persistent ear infections in dogs, is often resistant to multiple antibiotics. Assessing the antimicrobial resistance profile and genotype of <jats:italic>P. aeruginosa</jats:italic> is crucial for the appropriate use of veterinary pharmaceuticals. However, in recent years, few studies have been conducted on this bacterium in Japan. We determined the antimicrobial resistance profile and genotype of <jats:italic>P. aeruginosa</jats:italic> isolated from the ear canal of dogs in Japan in 2020. Analysis of antimicrobial resistance using disk diffusion tests indicated a high frequency of resistance to most antimicrobial agents. Particularly, 29 isolates from the ear canals of the 29 affected dogs (100%) were resistant to cefovecin, cefpodoxime, and florfenicol; however, they were susceptible to cefepime and piperacillin/tazobactam. Only 3.4, 10.3, and 10.3% of the isolates were resistant to ceftazidime, tobramycin, and gentamicin, respectively. Furthermore, upon analyzing the population structure using multilocus sequence typing, a considerably large clonal complex was not observed in the tested isolates. Three isolates, namely ST3881, ST1646, and ST532, were clonally related to the clinically isolated sequence types in Japan (such as ST1831, ST1413, ST1812, and ST1849), which is indicative of dog-to-human transmission. Considering the variation in antibiotic resistance compared to that reported by previous studies and the potential risk of dog-to-human transmission, we believe that the survey for antimicrobial resistance profile and population structure should be continued regularly. However, the prevalence of multidrug-resistant <jats:italic>P. aeruginosa</jats:italic> in dogs in Japan is not a crisis.</jats:p>

    DOI: 10.3389/fvets.2023.1074127

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  • Impact of liver fibrosis on the relative abundance of urease-positive Streptococcus salivarius group from saliva in patients with chronic liver disease. Reviewed International journal

    Akira Také, Haruki Uojima, Yoshihiko Sakaguchi, Kazuyoshi Gotoh, Takashi Satoh, Hisashi Hidaka, Kazue Horio, Masashi Mizokami, Shunji Hayashi, Chika Kusano

    Hepatology research : the official journal of the Japan Society of Hepatology   2023.6

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    AIM: We performed genomic analysis to study the relative abundance of a urease-positive Streptococcus salivarius group isolated from the saliva of patients with chronic liver disease (CLD). METHODS: Male and female patients with CLD aged over 20 years were included. First, we assessed the frequency and type of the S. salivarius group isolated from oral saliva using molecular biology techniques based on 16S rRNA and coaE gene sequencing. Next, we assessed the correlation between the urease positivity rate in S. salivarius group isolated from oral saliva and liver fibrosis based on CLD. Urease-positive strains were identified by the urease test using urea broth (Difco). Liver fibrosis was evaluated by the liver stiffness measurement value based on Magnetic resonance elastography. RESULTS: Forty-five patients identified using the multiplex PCR for the 16S rRNA gene were tested using the multiplex PCR for the coaE gene. Confirming the strains detected in each of the 45 patients, urease-positive S.salivarius was detected in 28 patients (62%), urease-negative S. salivarius in 25 patients (56%), and urease-positive Streptococcus vestibularis in 12 patients (27%). There was no patient with urease-negative S. vestibularis. The urease-positive rate of the S. salivarius group in the cirrhosis and non-cirrhosis groups were 82.2% and 39.2%, respectively. The liver cirrhosis group had a higher urease positivity rate than the non-cirrhotic group. (P<0.001) CONCLUSIONS: Liver fibrosis influences the frequency of a urease-positive S.salivarius group isolated from oral saliva. This article is protected by copyright. All rights reserved.

    DOI: 10.1111/hepr.13930

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  • Current Prevalence of Antimicrobial Resistance in Okayama from a National Database between 2018 and 2021. Reviewed

    Shinnosuke Fukushima, Hideharu Hagiya, Kazuhiro Uda, Kazuyoshi Gotoh, Fumio Otsuka

    Acta medica Okayama   77 ( 3 )   255 - 262   2023.6

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    Antimicrobial resistance is an emerging global threat that must be addressed using a multidisciplinary approach. This study aimed to raise awareness of high-level antimicrobial-resistant (AMR) pathogens in Japan by comparing their recent prevalences among prefectures, particularly Okayama. Data for the isolation proportions of meropenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae, and levofloxacin-resistant E. coli and K. pneumoniae were collected from the Japan Nosocomial Infections Surveillance, a national database sponsored by the Japanese Ministry of Health, Labour, and Welfare, between 2018 and 2021. The average isolated proportions of the seven AMR pathogens were higher in Okayama compared to other prefectures: the worst (19.9%) was meropenem-resistant P. aeruginosa, the sixth worst (57.2%) was methicillin-resistant S. aureus, the eighth worst (3.3%) was vancomycin-resistant E. faecium, the second (37.8%) and fifth worst (17.6%) were cefotaxime-resistant E. coli and K. pneumoniae, respectively, and the fourth (49.9%) and third worst (8.7%) were levofloxacin-resistant E. coli and K. pneumoniae, respectively. Our study highlights the notably high prevalences of representative AMR pathogens in Okayama, suggesting the need for fundamental infection prevention and control by healthcare professionals, promoting antimicrobial stewardship, and educating undergraduates and postgraduates in Okayama.

    DOI: 10.18926/AMO/65490

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  • Prevalence of Inducible Macrolide, Lincosamide, and Streptogramin B (inducible MLSB) Resistance in Clindamycin-Susceptible Staphylococcus aureus at Okayama University Hospital Reviewed

    Nahar L, Hagiya H, Nada T, Iio K, Gotoh K, Matsushita O, Otsuka F

    Acta Med Okayama   77 ( 1 )   1 - 9   2023.2

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    DOI: 10.18926/AMO/64355.

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  • 海外渡航歴のない患者から検出されたNDM-5産生Escherichia coli Reviewed

    馬生 良則, 崎田 彩弥加, 横山 恵三, 小坂 紀子, 矢野 朋文, 後藤 和義, 萩谷 英大

    岡山医学検査   60 ( 1 )   13 - 13   2023.2

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  • 臨床検査室におけるナノポアシーケンシング技術を用いた新型コロナウイルス感染症の疫学的解析実用化に向けての取り組み Reviewed

    飯尾 耕治, 後藤 和義, 萩谷 英大, 小川 寛人, 三好 諒, 大塚 文男, 東影 明人

    医学検査   72 ( 2 )   248 - 255   2023.2

  • RNA editing is a valuable biomarker for predicting carcinogenesis in ulcerative colitis. Reviewed International journal

    Kazutaka Takahashi, Kunitoshi Shigeyasu, Yoshitaka Kondo, Kazuyoshi Gotoh, Shuya Yano, Yuzo Umeda, Toshihiro Inokuchi, Caiming Xu, Kazuhiro Yoshida, Hibiki Umeda, Toshiaki Takahashi, Sho Takeda, Ryuichi Yoshida, Fuminori Teraishi, Hiroyuki Kishimoto, Yoshiko Mori, Kazuhiro Noma, Yoshinaga Okugawa, Sakiko Hiraoka, Hiroyuki Michiue, Hiroshi Tazawa, Osamu Matsushita, Ajay Goel, Toshiyoshi Fujiwara

    Journal of Crohn's & colitis   17 ( 5 )   754 - 766   2022.12

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    BACKGROUND AND AIMS: Ulcerative colitis (UC) can develop colitis-associated colorectal neoplasm (CAN). Adenine-to-inosine RNA editing, which is regulated by adenosine deaminase acting on RNA (ADAR), induces the posttranscriptional modification of critical oncogenes, including antizyme inhibitor 1 (AZIN1), leading to colorectal carcinogenesis. Therefore, we hypothesized that ADAR1 might be involved in the development of CAN in UC. METHODS: We systematically analyzed a cohort of 139 UC cases (40 acute phase, 73 remission phase, 26 CAN). The degree of inflammation was evaluated using the Mayo endoscopic score (MES). RESULTS: The type 1 IFN-related inflammation pathway was upregulated in the rectum of active UC, rectum of UC-CAN, and tumor site of UC-CAN patients. ADAR1 expression was upregulated in the entire colon of CAN cases, while it was down-regulated in non-CAN MES0 cases. ADAR1 expression in the rectum predicted the development of CAN better than p53 or β-catenin, with an area under the curve of 0.93. The high expression of ADAR1 and high AZIN1 RNA editing in UC was triggered by type 1 IFN stimulation from UC-specific microbiomes, such as Fusobacterium in vitro analyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted by Fusobacterium, may induce carcinogenesis in UC. CONCLUSIONS: The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC.

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  • Effects of Helicobacter pylori and Nitrate-Reducing Bacteria Coculture on Cells. Reviewed International journal

    Hinako Ojima, Sakiko Kuraoka, Shyoutarou Okanoue, Hiroyuki Okada, Kazuyoshi Gotoh, Osamu Matsushita, Akari Watanabe, Kenji Yokota

    Microorganisms   10 ( 12 )   2022.12

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    Helicobacter pylori infection is an important risk factor for developing gastric cancer. However, only a few H. pylori-infected people develop gastric cancer. Thus, other risk factors aside from H. pylori infection may be involved in gastric cancer development. This study aimed to investigate whether the nitrate-reducing bacteria isolated from patients with atrophic gastritis caused by H. pylori infection are risk factors for developing atrophic gastritis and gastric neoplasia. Nitrate-reducing bacteria were isolated from patients with atrophic gastritis caused by H. pylori infection. Among the isolated bacteria, Actinomyces oris, Actinomyces odontolyticus, Rothia dentocariosa, and Rothia mucilaginosa were used in the subsequent experiments. Cytokine inducibility was evaluated in monocytic cells, and mitogen-activated protein kinase (MAPK) activity and cell cycle were assessed in the gastric epithelial cells. The cytotoxicities and neutrophil-inducing abilities of the Actinomyces and Rothia species were enhanced when cocultured with H. pylori. Th1/Th2-related cytokines were also expressed, but their expression levels differed depending on the bacterial species. Moreover, H. pylori and Actinomyces activated MAPK (ERK and p38) and affected cell cycle progression. Some nitrate-reducing bacteria cocultured with H. pylori may promote inflammation and atrophy by inducing cytokine production. In addition, the MAPK activation and cell cycle progression caused by these bacteria can contribute to gastric cancer development.

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  • Detection of Enterobacter cloacae complex strain with a blaNDM-1-harboring plasmid from an elderly resident at a long-term care facility in Okayama, Japan. Reviewed International journal

    Kazuyoshi Gotoh, Hideharu Hagiya, Koji Iio, Haruto Yamada, Osamu Matsushita, Fumio Otsuka

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   28 ( 12 )   1697 - 1699   2022.12

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    Amidst the global spread of antimicrobial resistance, New Delhi metallo-β-lactamase (NDM)-type carbapenemase-producing Enterobacterales (CPE) remain uncommon in Japan, and the detection of such highly drug-resistant organisms is limited to inbound cases. There is little evidence regarding the prevalence of NDM β-lactamase gene (blaNDM)-harboring CPE in the domestic community, especially in the provincial cities of Japan. Herein, we report the isolation of a blaNDM-1-harboring plasmid in Enterobacter cloacae complex strain isolated from an elderly woman without a history of traveling abroad who had resided in a long-term care facility in Okayama, Japan. The multidrug-resistant blaNDM-harboring CPE isolate was detected in a stool sample of the patient during routine screening at admission. We performed whole-genome sequencing analysis of the isolate using MiSeq (Illumina) and MinION (Oxford Nanopore Technologies) platforms. The isolate was identified as sequence type 171, which has predominantly been reported in the United States and China. The blaNDM-1 gene was encoded on the 46,161 bp IncX3 plasmid, with sequence similarity to plasmids of similar size isolated from individuals in China. Collectively, the genomic data suggest that an imported CPE isolate may have spread among healthy individuals in the regional area of Japan.

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  • Phylogenic analysis of new viral cluster of large phages with unusual DNA genomes containing uracil in place of thymine in gene-sharing network, using phages S6 and PBS1 and relevant uncultured phages derived from sewage metagenomics Reviewed International journal

    Jumpei Uchiyama, Iyo Takemura-Uchiyama, Kazuyoshi Gotoh, Shin-ichiro Kato, Yoshihiko Sakaguchi, Hironobu Murakami, Tomoki Fukuyama, Mao Kaneki, Osamu Matsushita, Shigenobu Matsuzaki

    Virus Research   319   198881 - 198881   2022.10

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    Bacteriophages (phages) are the most diverse and abundant life-form on Earth. Jumbophages are phages with double-stranded DNA genomes longer than 200 kbp. Among these, some jumbophages with uracil in place of thymine as a nucleic acid base, which we have tentatively termed "dU jumbophages" in this study, have been reported. Because the dU jumbophages are considered to be a living fossil from the RNA world, the evolutionary traits of dU jumbophages are of interest. In this study, we examined the phylogeny of dU jumbophages. First, tBLASTx analysis of newly sequenced dU jumbophages such as Bacillus phage PBS1 and previously isolated Staphylococcus phage S6 showed similarity to the other dU jumbophages. Second, we detected the two partial genome sequences of uncultured phages possibly relevant to dU jumbophages, scaffold_002 and scaffold_007, from wastewater metagenomics. Third, according to the gene-sharing network analysis, the dU jumbophages, including phages PBS1 and S6, and uncultured phage scaffold_002 formed a cluster, which suggested a new viral subfamily/family. Finally, analyses of the phylogenetic relationship with other phages showed that the dU jumbophage cluster, which had two clades of phages infecting Gram-negative and Gram-positive bacteria, diverged from the single ancestral phage. These findings together with previous reports may imply that dU jumbophages evolved from the same origin before divergence of Gram-negative and Gram-positive bacteria.

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  • 若年者におけるヘリコバクターピロリ除菌治療による腸内細菌叢の変化についての検討

    岡上 昇太郎, 後藤 和義, 倉岡 紗樹子, 稲生 祥子, 里見 拓也, 濱田 健太, 河野 吉泰, 神崎 洋光, 岩室 雅也, 川野 誠司, 河原 祥朗, 横田 憲治, 岡田 裕之

    日本ヘリコバクター学会学術集会プログラム・抄録集   28回   103 - 103   2022.6

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  • Fecal microbiota transplantation as therapy for recurrent Clostridioides difficile infection is associated with amelioration of delirium and accompanied by changes in fecal microbiota and the metabolome. Reviewed International journal

    Gotoh K, Sakaguchi Y, Kato H, Osaki H, Jodai Y, Wakuda M, Také A, Hayashi S, Morita E, Sugie T, Ito Y, Ohmiya N

    Anaerobe   73   102502 - 102502   2021.12

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    Recurrent Clostridioides difficile infection (rCDI) is a frustrating condition that may affect a person's quality of life for months. Microbiome-based therapy such as fecal microbiota transplantation (FMT) has been effective for the treatment of rCDI by correcting the imbalance of the gut microbiota. Appropriate antibiotic treatment is recommended for at least two recurrences before offering FMT. Here, we report the case of a 92-year-old woman who experienced five recurrences of Clostridioides difficile infection (CDI) (six episodes in total) complicated by dementia and delirium, both of which were dramatically improved by FMT, which was associated with alterations in fecal microbiota and the metabolome. Analyses of whole microbial communities and metabolomic analyses were performed on stool specimens collected from the patient on the first episode, the third episode, the day of FMT (before FMT), and 2, 8, and 23 weeks after the FMT and from the donor. The patient had various fecal dysbioses on the first and third episodes and on the day of FMT. Two weeks after FMT, diversity of the gut bacteriome as well as the virome increased dramatically and was reflected in a positive clinical outcome for this patient. Metabolomic analysis revealed that short-chain fatty acids, which have been reported to be associated with improved memory function, were increased after FMT.

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  • Detection of in-frame mutation by IS30-family insertion sequence in the phospholipid phosphatidylglycerol synthase gene (pgsA2) of high-level daptomycin-resistant Corynebacterium striatum Reviewed International journal

    Kazuyoshi Gotoh, I. Putu Bayu Mayura, Yusaku Enomoto, Koji Iio, Osamu Matsushita, Fumio Otsuka, Hideharu Hagiya

    European Journal of Clinical Microbiology & Infectious Diseases   41 ( 2 )   331 - 333   2021.10

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    The emergence of high-level daptomycin (DAP)-resistant (HLDR) Corynebacterium striatum has been reported as a result of loss-of-function point mutations or premature stop codon mutations in a responsible gene, pgsA2. We herein describe the novel detection of an HLDR C. striatum clinical isolate, in which IS30-insertion was corroborated to cause destruction of pgsA2 gene. We isolated an HLDR C. striatum from a critically ill patient with underlying mycosis fungoides who had been treated with DAP for 10 days. With a sequence investigation, IS30-insertion was discovered to split pgsA2 in the HLDR C. striatum strain, which may cause disrupted phospholipid phosphatidylglycerol (PG) production. Future studies should survey the prevalence of IS-mediated gene inactivation among HLDR C. striatum clinical isolates.

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    Other Link: https://link.springer.com/article/10.1007/s10096-021-04369-1/fulltext.html

  • In vitro effectiveness of biapenem against IMP-producing Enterobacteriaceae Reviewed International coauthorship

    Kazuyoshi Gotoh, Makoto Miyoshi, I Putu Bayu Mayura, Koji Iio, Osamu Matsushita, Fumio Otsuka, Hideharu Hagiya

    Journal of Medical Microbiology   70 ( 10 )   2021.10

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    The options available for treating infections with carbapenemase-producing <italic>
    <named-content content-type="family">
    <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.3091" xlink:type="simple">Enterobacteriaceae</ext-link>
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    </italic> (CPE) are limited; with the increasing threat of these infections, new treatments are urgently needed. Biapenem (BIPM) is a carbapenem, and limited data confirming its <italic>in vitro</italic> killing effect against CPE are available. In this study, we examined the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of BIPM for 14 IMP-1-producing <italic>
    <named-content content-type="family">
    <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.3091" xlink:type="simple">Enterobacteriaceae</ext-link>
    </named-content>
    </italic> strains isolated from the Okayama region in Japan. The MICs against almost all the isolates were lower than 0.5 µg ml−1, indicating susceptibility to BIPM, while approximately half of the isolates were confirmed to be bacteriostatic to BIPM. However, initial killing to a 99.9 % reduction was observed in seven out of eight strains in a time–kill assay. Despite the small data set, we concluded that the <italic>in vitro</italic> efficacy of BIPM suggests that the drug could be a new therapeutic option against infection with IMP-producing CPE.

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  • Elizabethkingia anophelis, an emerging pathogen, inhibits RAW 264.7 macrophage function Reviewed

    I. Putu Bayu Mayura, Kazuyoshi Gotoh, Hayato Nishimura, Erina Nakai, Takehiko Mima, Yumiko Yamamoto, Kenji Yokota, Osamu Matsushita

    Microbiology and Immunology   65 ( 8 )   317 - 324   2021.8

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    DOI: 10.1111/1348-0421.12888

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  • Serodiagnosis and bacterial genome of helicobacter pylori infection Reviewed

    Aina Ichihara, Hinako Ojima, Kazuyoshi Gotoh, Osamu Matsushita, Susumu Take, Hiroyuki Okada, Akari Watanabe, Kenji Yokota

    Toxins   13 ( 7 )   2021.7

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  • Septic pulmonary emboli caused by Tsukamurella inchonensis: A case report Reviewed

    Kazuyoshi Gotoh, I. Putu Bayu Mayura, Hideharu Hagiya, Kyoichi Obata, Tatsuo Ogawa, Koji Iio, Takumi Fujimori, Fumio Otsuka, Osamu Matsushita

    Journal of Infection and Chemotherapy   27 ( 2 )   369 - 372   2021.2

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    DOI: 10.1016/j.jiac.2020.09.024

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  • Antibacterial effects of disulfiram in helicobacter pylori Reviewed

    Tomomi Kobatake, Keiki Ogino, Hiroyuki Sakae, Kazuyoshi Gotoh, Akari Watanabe, Osamu Matsushita, Hiroyuki Okada, Kenji Yokota

    Infection and Drug Resistance   14   1757 - 1764   2021

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  • Enhancement of intestinal epithelial barrier function by Weissella confusa F213 and Lactobacillus rhamnosus FBB81 probiotic candidates in an in vitro model of hydrogen peroxide-induced inflammatory bowel disease Reviewed

    Ni Nengah Dwi Fatmawati, Kazuyoshi Gotoh, I. Putu Bayu Mayura, Komang Ayu Nocianitri, Gede Ngurah Rsi Suwardana, Ni Luh Gede Yoni Komalasari, Yan Ramona, Masakiyo Sakaguchi, Osamu Matsushita, I. Nengah Sujaya

    BMC Research Notes   13 ( 1 )   2020.12

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    DOI: 10.1186/s13104-020-05338-1

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  • Analysis of a plasmid encoding botulinum neurotoxin type G gene in Clostridium argentinense Reviewed

    Yoshihiko Sakaguchi, Jumpei Uchiyama, Akira Také, Kazuyoshi Gotoh, Masakiyo Sakaguchi, Tomonori Suzuki, Yumiko Yamamoto, Koji Hosomi, Tomoko Kohda, Masafumi Mukamoto, Shunji Kozaki, Shunji Hayashi, Keiji Oguma

    Anaerobe   66   2020.12

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    DOI: 10.1016/j.anaerobe.2020.102281

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  • Caco-2 cells monolayer as an in-vitro model for probiotic strain translocation Reviewed

    Ni Nengah Dwi Fatmawati, Kazuyoshi Goto, I. Putu Bayu Mayura, Komang Ayu Nocianitri, Yan Ramona, Masakiyo Sakaguchi, Osamu Matsushita, I. Nengah Sujaya

    Bali Medical Journal   9 ( 1 )   137 - 142   2020

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  • Expression of Collagenase is Regulated by the VarS/VarA Two-Component Regulatory System in Vibrio alginolyticus Reviewed

    Takehiko Mima, Kazuyoshi Gotoh, Yumiko Yamamoto, Keiko Maeda, Taku Shirakawa, Shunsuke Matsui, Yumi Murata, Takaki Koide, Hiroshi Tokumitsu, Osamu Matsushita

    Journal of Membrane Biology   251 ( 1 )   51 - 63   2018.2

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    DOI: 10.1007/s00232-017-9991-9

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  • DEC205 mediates local and systemic immune responses to Helicobacter pylori infection in humans Reviewed

    Masahide Kita, Kenji Yokota, Chihiro Kageyama, Susumu Take, Kazuyoshi Goto, Yoshiro Kawahara, Osamu Matsushita, Hiroyuki Okada

    Oncotarget   9 ( 22 )   15828 - 15835   2018

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    DOI: 10.18632/oncotarget.24574

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  • Vibrio alginolyticus VepA induces lysosomal membrane permeability and cathepsin-independent cell death Reviewed

    Agus Eka Darwinata, Kazuyoshi Gotoh, Takehiko Mima, Yumiko Yamamoto, Kenji Yokota, Osamu Matsushita

    Acta Medica Okayama   72 ( 3 )   231 - 239   2018

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  • Fungal ITS1 deep-sequencing strategies to reconstruct the composition of a 26-species community and evaluation of the gut mycobiota of healthy Japanese individuals Reviewed

    Daisuke Motooka, Kosuke Fujimoto, Reiko Tanaka, Takashi Yaguchi, Kazuyoshi Gotoh, Yuichi Maeda, Yoki Furuta, Takashi Kurakawa, Naohisa Goto, Teruo Yasunaga, Masashi Narazaki, Atsushi Kumanogoh, Toshihiro Horii, Tetsuya Iida, Kiyoshi Takeda, Shota Nakamura

    Frontiers in Microbiology   8 ( FEB )   2017.2

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  • Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine Reviewed

    Yuichi Maeda, Takashi Kurakawa, Eiji Umemoto, Daisuke Motooka, Yoshinaga Ito, Kazuyoshi Gotoh, Keiji Hirota, Masato Matsushita, Yoki Furuta, Masashi Narazaki, Noriko Sakaguchi, Hisako Kayama, Shota Nakamura, Tetsuya Iida, Yukihiko Saeki, Atsushi Kumanogoh, Shimon Sakaguchi, Kiyoshi Takeda

    Arthritis and Rheumatology   68 ( 11 )   2646 - 2661   2016.11

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  • Temporal dynamics of bacterial microbiota in the human oral cavity determined using an in situ model of dental biofilms Reviewed

    Nanako Wake, Yoko Asahi, Yuichiro Noiri, Mikako Hayashi, Daisuke Motooka, Shota Nakamura, Kazuyoshi Gotoh, Jiro Miura, Hiroyuki Machi, Tetsuya Iida, Shigeyuki Ebisu

    npj Biofilms and Microbiomes   2   2016.8

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  • Metagenomic Analysis Reveals Dynamic Changes of Whole Gut Microbiota in the Acute Phase of Intensive Care Unit Patients Reviewed

    Masahiro Ojima, Daisuke Motooka, Kentaro Shimizu, Kazuyoshi Gotoh, Ayumi Shintani, Kazuhisa Yoshiya, Shota Nakamura, Hiroshi Ogura, Tetsuya Iida, Takeshi Shimazu

    Digestive Diseases and Sciences   61 ( 6 )   1628 - 1634   2016.6

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  • Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia Reviewed

    Ryu Okumura, Takashi Kurakawa, Takashi Nakano, Hisako Kayama, Makoto Kinoshita, Daisuke Motooka, Kazuyoshi Gotoh, Taishi Kimura, Naganori Kamiyama, Takashi Kusu, Yoshiyasu Ueda, Hong Wu, Hideki Iijima, Soumik Barman, Hideki Osawa, Hiroshi Matsuno, Junichi Nishimura, Yusuke Ohba, Shota Nakamura, Tetsuya Iida, Masahiro Yamamoto, Eiji Umemoto, Koichi Sano, Kiyoshi Takeda

    Nature   532 ( 7597 )   117 - 121   2016.4

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  • Functional specialization in regulation and quality control in thermal adaptive evolution Reviewed

    Kazuma Yama, Yuki Matsumoto, Yoshie Murakami, Shigeto Seno, Hideo Matsuda, Kazuyoshi Gotoh, Daisuke Motooka, Shota Nakamura, Bei Wen Ying, Tetsuya Yomo

    Genes to Cells   20 ( 11 )   943 - 955   2015.11

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  • Post-Golgi anterograde transport requires GARP-dependent endosome-to-TGN retrograde transport Reviewed

    Tetsuya Hirata, Morihisa Fujita, Shota Nakamura, Kazuyoshi Gotoh, Daisuke Motooka, Yoshiko Murakami, Yusuke Maeda, Taroh Kinoshita

    Molecular Biology of the Cell   26 ( 17 )   3071 - 3084   2015.9

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  • Baseline assessment of mesophotic reefs of the Vitória-Trindade Seamount Chain based on water quality, microbial diversity, benthic cover and fish biomass data Reviewed

    Pedro M. Meirelles, Gilberto M. Amado-Filho, Guilherme H. Pereira-Filho, Hudson T. Pinheiro, Rodrigo L. De Moura, Jean Christophe Joyeux, Eric F. Mazzei, Alex C. Bastos, Robert A. Edwards, Elizabeth Dinsdale, Rodolfo Paranhos, Eidy O. Santos, Tetsuya Iida, Kazuyoshi Gotoh, Shota Nakamura, Tomoo Sawabe, Carlos E. Rezende, Luiz M.R. Gadelha, Ronaldo B. Francini-Filho, Cristiane Thompson, Fabiano L. Thompson

    PLoS ONE   10 ( 6 )   2015.6

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  • Interaction between the Type III Effector VopO and GEF-H1 Activates the RhoA-ROCK Pathway Reviewed

    Hirotaka Hiyoshi, Ryu Okada, Shigeaki Matsuda, Kazuyoshi Gotoh, Yukihiro Akeda, Tetsuya Iida, Toshio Kodama

    PLoS Pathogens   11 ( 3 )   1 - 19   2015.3

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  • Complete nucleotide sequence of a plasmid containing the botulinum neurotoxin gene in Clostridium botulinum type B strain 111 isolated from an infant patient in Japan Reviewed

    Koji Hosomi, Yoshihiko Sakaguchi, Tomoko Kohda, Kazuyoshi Gotoh, Daisuke Motooka, Shota Nakamura, Kaoru Umeda, Tetsuya Iida, Shunji Kozaki, Masafumi Mukamoto

    Molecular Genetics and Genomics   289 ( 6 )   1267 - 1274   2014.11

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  • Endosomes-to-TGN retrograde transport mediated by GARP is required for post-Golgi anterograde transport and glycosylation Reviewed

    Tetsuya Hirata, Morihisa Fujita, Shota Nakamura, Kazuyoshi Gotoh, Daisuke Motooka, Yoshiko Murakami, Yusuke Maeda, Taroh Kinoshita

    GLYCOBIOLOGY   24 ( 11 )   1188 - 1189   2014.11

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  • Performance comparison of second- and third-generation sequencers using a bacterial genome with two chromosomes Reviewed

    Mari Miyamoto, Daisuke Motooka, Kazuyoshi Gotoh, Takamasa Imai, Kazutoshi Yoshitake, Naohisa Goto, Tetsuya Iida, Teruo Yasunaga, Toshihiro Horii, Kazuharu Arakawa, Masahiro Kasahara, Shota Nakamura

    BMC Genomics   15 ( 1 )   2014.8

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  • BEC, a Novel Enterotoxin of Clostridium perfringens Found in Human Clinical Isolates from Acute Gastroenteritis Outbreaks Reviewed

    Shinya Yonogi, Shigeaki Matsuda, Takao Kawai, Tomoko Yoda, Tetsuya Harada, Yuko Kumeda, Kazuyoshi Gotoh, Hirotaka Hiyoshi, Shota Nakamura, Toshio Kodama, Tetsuya Iida

    INFECTION AND IMMUNITY   82 ( 6 )   2390 - 2399   2014.6

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  • Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota Reviewed

    Kei Arimatsu, Hitomi Yamada, Haruna Miyazawa, Takayoshi Minagawa, Mayuka Nakajima, Mark I. Ryder, Kazuyoshi Gotoh, Daisuke Motooka, Shota Nakamura, Tetsuya Iida, Kazuhisa Yamazaki

    Scientific Reports   4   2014.5

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  • Peyerʼs Patches Play a Protective Role in Nonsteroidal Anti-inflammatory Drug-induced Enteropathy in Mice Reviewed

    Satoshi Hiyama, Hideki Iijima, Shinichiro Shinzaki, Takahiro Inoue, Eri Shiraishi, Shoichiro Kawai, Manabu Araki, Motohiko Kato, Yoshito Hayashi, Tsutomu Nishida, Hironobu Fujii, Akira Mukai, Naoko Shibata, Shintaro Sato, Hiroshi Kiyono, Kazuyoshi Gotoh, Daisuke Motooka, Shota Nakamura, Tetsuya Iida, Masahiko Tsujii, Tetsuo Takehara

    Inflammatory Bowel Diseases   20 ( 5 )   790 - 799   2014.5

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  • Comprehensive metagenomic approach for detecting causative microorganisms in culture-negative infective endocarditis Reviewed

    Atsuko Imai, Kazuyoshi Gotoh, Yoshihiro Asano, Noriaki Yamada, Daisuke Motooka, Masaki Fukushima, Machiko Kanzaki, Tomohito Ohtani, Yasushi Sakata, Hiroyuki Nishi, Koichi Toda, Yoshiki Sawa, Issei Komuro, Toshihiro Horii, Tetsuya Iida, Shota Nakamura, Seiji Takashima

    International Journal of Cardiology   172 ( 2 )   2014.3

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    DOI: 10.1016/j.ijcard.2013.12.197

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  • Allergic bronchopulmonary mycosis due to co-infection with Aspergillus fumigatus and Schizophyllum commune Reviewed

    Masafumi Seki, Hideaki Ohno, Kazuyoshi Gotoh, Daisuke Motooka, Shota Nakamura, Tetsuya Iida, Yoshitsugu Miyazaki, Kazunori Tomono

    ID Cases   1 ( 1 )   5 - 8   2014.2

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    DOI: 10.1016/j.idcr.2014.01.001

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  • Physiologic and metagenomic attributes of the rhodoliths forming the largest CaCO<inf>3</inf> bed in the South Atlantic Ocean Reviewed

    Giselle S. Cavalcanti, Gustavo B. Gregoracci, Eidy O. Dos Santos, Cynthia B. Silveira, Pedro M. Meirelles, Leila Longo, Kazuyoshi Gotoh, Shota Nakamura, Tetsuya Iida, Tomoo Sawabe, Carlos E. Rezende, Ronaldo B. Francini-Filho, Rodrigo L. Moura, Gilberto M. Amado-Filho, Fabiano L. Thompson

    ISME Journal   8 ( 1 )   52 - 62   2014.1

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    DOI: 10.1038/ismej.2013.133

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  • Allergic bronchopulmonary mycosis due to co-infection with Aspergillus fumigatus and Schizophyllum commune. Reviewed International journal

    Masafumi Seki, Hideaki Ohno, Kazuyoshi Gotoh, Daisuke Motooka, Shota Nakamura, Tetsuya Iida, Yoshitsugu Miyazaki, Kazunori Tomono

    IDCases   1 ( 1 )   5 - 8   2014

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    A 61-year-old female presented with eosinophilic pneumonia accompanied by bronchial asthma. She was finally diagnosed with allergic bronchopulmonary mycosis (ABPM) due to co-infection with Aspergillus fumigatus and Schizophyllum commune detected by genetic analysis of the plug and from cultures.

    DOI: 10.1016/j.idcr.2014.01.001

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  • Mutation accumulation in bacteria exposed to UV radiation Reviewed

    Atsushi Shibai, Saburo Tsuru, Bei Wen Ying, Daisuke Motooka, Kazuyoshi Gotoh, Shota Nakamura, Tetsuya Yomo

    Artificial Life 14 - Proceedings of the 14th International Conference on the Synthesis and Simulation of Living Systems, ALIFE 2014   757 - 758   2014

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  • Severe respiratory failure due to co-infection with human metapneumovirus and Streptococcus pneumoniae. Reviewed International journal

    Masafumi Seki, Hisao Yoshida, Kazuyoshi Gotoh, Nobuyuki Hamada, Daisuke Motooka, Shota Nakamura, Norihisa Yamamoto, Shigeto Hamaguchi, Yukihiro Akeda, Hiroshi Watanabe, Tetsuya Iida, Kazunori Tomono

    Respiratory medicine case reports   12   13 - 5   2014

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    A 64-year-old male patient was admitted with respiratory failure, although chest X-rays revealed only mild bronchiolitis. Streptococcus pneumoniae, which usually presents as massive lobular pneumonia, was isolated from sputum, however, pan-pathogen screening using a next-generation sequencer also detected human metapneumovirus genome fragments.

    DOI: 10.1016/j.rmcr.2013.12.007

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  • Generation of colonic IgA-secreting cells in the caecal patch Reviewed

    Kazunori Masahata, Eiji Umemoto, Hisako Kayama, Manato Kotani, Shota Nakamura, Takashi Kurakawa, Junichi Kikuta, Kazuyoshi Gotoh, Daisuke Motooka, Shintaro Sato, Tomonori Higuchi, Yoshihiro Baba, Tomohiro Kurosaki, Makoto Kinoshita, Yosuke Shimada, Taishi Kimura, Ryu Okumura, Akira Takeda, Masaru Tajima, Osamu Yoshie, Masahiro Fukuzawa, Hiroshi Kiyono, Sidonia Fagarasan, Tetsuya Iida, Masaru Ishii, Kiyoshi Takeda

    Nature communications   5   3704   2014

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    DOI: 10.1038/ncomms4704

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  • Mode of binding of RNA polymerase alpha subunit to the phased A-tracts upstream of the phospholipase C gene promoter of Clostridium perfringens Reviewed

    Seiichi Katayama, Kotaro Ishibashi, Kazuyoshi Gotoh, Daisuke Nakamura

    ANAEROBE   23   62 - 69   2013.10

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    DOI: 10.1016/j.anaerobe.2013.06.007

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  • Metagenomic Analysis of Healthy and White Plague-Affected Mussismilia braziliensis Corals Reviewed

    Gizele D. Garcia, Gustavo B. Gregoracci, Eidy de O. Santos, Pedro M. Meirelles, Genivaldo G.Z. Silva, Rob Edwards, Tomoo Sawabe, Kazuyoshi Gotoh, Shota Nakamura, Tetsuya Iida, Rodrigo L. de Moura, Fabiano L. Thompson

    Microbial Ecology   65 ( 4 )   1076 - 1086   2013.5

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    DOI: 10.1007/s00248-012-0161-4

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  • Fatal sepsis caused by an unusual Klebsiella species that was misidentified by an automated identification system. Reviewed International journal

    Masafumi Seki, Kazuyoshi Gotoh, Shota Nakamura, Yukihiro Akeda, Tadashi Yoshii, Shinichi Miyaguchi, Hidenori Inohara, Toshihiro Horii, Kazunori Oishi, Tetsuya Iida, Kazunori Tomono

    Journal of medical microbiology   62 ( Pt 5 )   801 - 803   2013.5

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    This is a description of fatal sepsis caused by infection with Klebsiella variicola, which is an isolate genetically related to Klebsiella pneumoniae. The patient's condition was incorrectly diagnosed as common sepsis caused by K. pneumoniae, which was identified using an automated identification system, but next-generation sequencing and the non-fermentation of adonitol finally identified the cause of sepsis as K. variicola.

    DOI: 10.1099/jmm.0.051334-0

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  • Metagenomic profile of gut microbiota in children during cholera and recovery Reviewed

    Shirajum Monira, Shota Nakamura, Kazuyoshi Gotoh, Kaori Izutsu, Haruo Watanabe, Nur Haque Alam, Takaaki Nakaya, Toshihiro Horii, Sk Imran Ali, Tetsuya Iida, Munirul Alam

    Gut Pathogens   5 ( 1 )   2013

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    DOI: 10.1186/1757-4749-5-1

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  • VopV, an F-actin-binding type III secretion effector, is required for vibrio parahaemolyticus-induced enterotoxicity Reviewed

    Hirotaka Hiyoshi, Toshio Kodama, Kazunobu Saito, Kazuyoshi Gotoh, Shigeaki Matsuda, Yukihiro Akeda, Takeshi Honda, Tetsuya Iida

    Cell Host and Microbe   10 ( 4 )   401 - 409   2011.10

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    DOI: 10.1016/j.chom.2011.08.014

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  • Gut microbiota of healthy and malnourished children in Bangladesh Reviewed

    Shirajum Monira, Shota Nakamura, Kazuyoshi Gotoh, Kaori Izutsu, Haruo Watanabe, Nur Haque Alam, Hubert Ph Endtz, Alejandro Cravioto, Sk Imran Ali, Takaaki Nakaya, Toshihiro Horii, Tetsuya Iida, Munirul Alam

    Frontiers in Microbiology   2 ( NOV )   2011

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    DOI: 10.3389/fmicb.2011.00228

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  • Two Regulators of Vibrio parahaemolyticus Play Important Roles in Enterotoxicity by Controlling the Expression of Genes in the Vp-PAI Region Reviewed

    Toshio Kodama, Kazuyoshi Gotoh, Hirotaka Hiyoshi, Mikiharu Morita, Kaori Izutsu, Yukihiro Akeda, Kwon-Sam Park, Vlademir V. Cantarelli, Rikard Dryselius, Tetsuya Iida, Takeshi Honda

    PLOS ONE   5 ( 1 )   e8678   2010.1

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    DOI: 10.1371/journal.pone.0008678

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  • Identification of two translocon proteins of Vibrio parahaemolyticus type III secretion system 2 Reviewed

    Toshio Kodama, Hirotaka Hiyoshi, Kazuyoshi Gotoh, Yukihiro Akeda, Shigeaki Matsuda, Kwon-Sam Park, Vlademir V. Cantarelli, Tetsuya Iida, Takeshi Honda

    INFECTION AND IMMUNITY   76 ( 9 )   4282 - 4289   2008.9

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    DOI: 10.1128/IAI.01738-07

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MISC

  • In vitro evaluation of bioactivities of the intestine-inhabitant actinomycetes that are isolated from a therapeutically beneficial fecal microbiota for recurrent CDI

    阪口義彦, 武晃, 後藤和義, 友信奈保子, 山本健一, 竹原正也, 塩見慎也, 吉田昌裕, 久保美和, 野路征昭, 和久田光毅, 阪口政清, 加藤はる, 大宮直木, 永浜政博

    日本薬学会年会要旨集(Web)   144th   2024

  • Effects of nitrate-reducing bacteria from the gastric cancer patients in H. pylori co-infected mice

    小松原万里奈, 山本由弥子, 内山淳平, 松下治, 後藤和義, 渡辺朱理, 横田憲治

    日本細菌学雑誌(Web)   79 ( 2 )   2024

  • Characteristics of nitrate-reducing bacteria from patients with gastritis and gastric cancer

    桑木星里香, 山本由弥子, 内山淳平, 松下治, 後藤和義, 渡辺朱理, 横田憲治

    日本細菌学雑誌(Web)   79 ( 2 )   2024

  • 当院におけるメチシリン感受性黄色ブドウ球菌のイノキュラムエフェクト陽性率

    福島 伸乃介, 後藤 和義, 萩谷 英大, 飯尾 耕治, 松下 治

    日本臨床微生物学会雑誌   34 ( Suppl.1 )   280 - 280   2023.12

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  • 糞便微生物移植から見出した高齢者における難治性疾患に対する新規治療および予防戦略

    阪口 義彦, 武 晃, 後藤 和義, 大宮 直木

    大和証券ヘルス財団研究業績集   ( 46 )   76 - 81   2023.3

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  • ファージvs細菌 その仁義なき?戦い ウラシル含有DNAゲノムを有する巨大ファージの細菌進化への影響

    内山 淳平, 内山 伊代, 後藤 和義, 山本 由弥子, 松崎 茂展, 松下 治

    日本細菌学雑誌   78 ( 1 )   19 - 19   2023.2

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  • 細菌性コラゲナーゼの構造活性相関の解析(Structure-function analysis of Clostridial collagenases)

    Asaduzzaman Md, 美間 健彦, 後藤 和義, 山本 由弥子, 内山 淳平, Sakon Joshua, 松下 治

    日本細菌学雑誌   78 ( 1 )   136 - 136   2023.2

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  • ヒト糞便検体からの放線菌の分離とその生物活性評価

    武 晃, 阪口 義彦, 菊池 雄太, 稲橋 佑起, 後藤 和義, 林 俊治, 坂本 光央, 大宮 直木

    日本細菌学雑誌   78 ( 1 )   148 - 148   2023.2

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  • Isolation of actinomycetes from human feces and evaluation of their biological activities

    武晃, 阪口義彦, 菊池雄太, 稲橋佑起, 後藤和義, 林俊治, 坂本光央, 大宮直木

    日本細菌学雑誌(Web)   78 ( 1 )   2023

  • Genomic analysis of neurotoxin-converting phages of Clostridium botulinum types C and D

    阪口義彦, 武晃, 後藤和義, 山本由弥子, 幸田知子, 向本雅郁, 小崎俊司, 林俊治, 林哲也, 小熊惠二

    日本細菌学雑誌(Web)   78 ( 1 )   2023

  • Isolation and taxonomic study of actinomycetes from agricultural products and fertilizers

    武晃, 阪口義彦, 稲橋佑起, 稲橋佑起, 後藤和義, 林俊治

    日本放線菌学会大会講演要旨集   37th   2023

  • In vitro evaluation of bioactivities of the intestine-inhabitant actinomycetes that are isolated from a therapeutically beneficial fecal microbiota

    阪口義彦, 武晃, 後藤和義, 竹原正也, 友信奈保子, 山本健一, 菊池雄太, 坂本光央, 加藤はる, 大宮直木, 阪口政清, 永浜政博

    組織培養研究(Web)   41 ( 2 )   2023

  • Analysis of pseudolysogenic lifecycle of Clostridium botulinum types C and D phages

    阪口義彦, 武晃, 後藤和義, 山本由弥子, 幸田知子, 向本雅郁, 小崎俊司, 林俊治, 林哲也, 小熊惠二

    日本細菌学雑誌(Web)   77 ( 1 )   2022

  • Isolation of actinomycetes from human fecal specimens and analyses of their metabolites

    武晃, 武晃, 阪口義彦, 菊池雄太, 稲橋佑起, 稲橋佑起, 後藤和義, 坂本光央, 林俊治

    日本放線菌学会大会講演要旨集   36th   2022

  • Survival of Actinomycetes Isolated from Food and Human Feces in Artificial Digestive Media

    武晃, 阪口義彦, 稲橋佑起, 後藤和義, 林俊治, 加藤はる, 大宮直木

    日本細菌学雑誌(Web)   77 ( 1 )   2022

  • 糞便微生物移植治療から見出した腸内放線菌の役割~高齢者における難治性疾患の治療および予防に向けて~

    阪口義彦, 武晃, 後藤和義, 大宮直木

    アサヒグループ財団研究紀要(Web)   2022   2022

  • Omics analysis in fecal transplantation therapy for Clostridioides difficile infection

    阪口義彦, 後藤和義, 武晃, 尾崎隼人, 城代康貴, 和久田光毅, 林俊治, 大宮直木, 加藤はる

    日本細菌学雑誌(Web)   76 ( 1 )   2021

  • Evaluation of intestinal environmental viability of actinomycetes isolated from food

    武晃, 阪口義彦, 稲橋佑起, 後藤和義, 林俊治, 大宮直木, 加藤はる

    日本細菌学雑誌(Web)   76 ( 1 )   2021

  • 根野菜からの放線菌の分離とその腸内環境生存能の評価

    武晃, 武晃, 阪口義彦, 稲橋佑起, 稲橋佑起, 後藤和義, 林俊治, 加藤はる, 大宮直木

    日本放線菌学会大会講演要旨集   35th (CD-ROM)   2021

  • Multi-omics analysis of gut contents in a case of fecal microbiota transplantation therapy for Clostridioides difficile infection

    阪口義彦, 後藤和義, 武晃, 尾崎隼人, 城代康貴, 和久田光毅, 林俊治, 加藤はる, 大宮直木

    日本薬学会年会要旨集(Web)   141st   2021

  • C型とD型ボツリヌス毒素変換ファージの解析(Analysis of botulinum neurotoxin-converting phages in Clostridium botulinum types C and D)

    阪口 義彦, 内山 淳平, 小椋 義俊, 後藤 和義, 山本 由弥子, 松崎 茂展, 山口 明日美, 林 哲也, 小熊 惠二, 林 俊治

    日本細菌学雑誌   73 ( 1 )   94 - 94   2018.2

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  • Vibrio alginolyticusのコラゲナーゼ発現はHapRにより調節される(Expression of colA is regulated by HapR in Vibrio alginolyticus)

    美間 健彦, 西川 裕太郎, 中田 悠介, 波多野 直哉, 後藤 和義, 山本 由弥子, 横田 憲治, 松下 治

    日本細菌学雑誌   72 ( 1 )   106 - 106   2017.2

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  • Vibrio alginolyticusのコラゲナーゼ発現はHapRにより調節される(Expression of colA is regulated by HapR in Vibrio alginolyticus)

    美間 健彦, 西川 裕太郎, 中田 悠介, 波多野 直哉, 後藤 和義, 山本 由弥子, 横田 憲治, 松下 治

    日本細菌学雑誌   72 ( 1 )   106 - 106   2017.2

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  • Vibrio alginolyticus I.029のコラゲナーゼ発現はHapRにより調節される

    西川 裕太郎, 美間 健彦, 中田 悠介, 後藤 和義, 山本 由弥子, 横田 憲治, 松下 治

    日本細菌学雑誌   71 ( 1 )   127 - 127   2016.2

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Research Projects

  • 新興病原体エリザベスキンギア菌によるマクロファージ成熟抑制現象の解明

    Grant number:22K07069  2022.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    後藤 和義, 横田 憲治, 中山 真彰

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

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  • 高齢者の低栄養における腸内細菌叢の役割解明と新規シンバイオティクス療法の開発

    Grant number:22K10057  2022.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    小山 絵理, 後藤 和義, 大野 彩, 窪木 拓男, 大森 江, 大野 充昭

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

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  • Study for the host recognition mechanism of bacteriophage tail adsorption molecules in Clostridioides difficile

    Grant number:22K07074  2022.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    阪口 義彦, 後藤 和義, 武 晃, 大宮 直木

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

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  • Study for a molecular machinery of the host recognition by Clostridioides difficile phage to develop the advanced therapy

    Grant number:19K07560  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Sakaguchi Yoshihiko

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    Clostridioides difficile infection (CDI), which is caused by excessive proliferation of C. difficile, is one of the antibacterial drug-related diarrhea and enteritis. Therefore, it is important to develop a new and specific treatment method for C. difficile disinfection. The current study was focused on bacteriophage (phage) as a potential treatment. Phage binds specifically to the host bacterium and generates a bactericidal activity. In this study, the recombinant phage proteins were expressed and purified and the bindings between these proteins and C. difficile were examined using enzyme-linked immunosorbent assay (ELISA) and western blot analysis. The results of the study showed a dose- and a time-dependent binding.

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  • ピロリ菌除菌療法における腸内エコシステム破綻のメカニズムと制御

    Grant number:19K08395  2019.04 - 2022.03

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    岡田 裕之, 後藤 和義, 横田 憲治, 松下 治, 田中 健大, 岡上 昇太郎

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    大学新入生において標準的なピロリ菌除菌レジメンの下で下痢・軟便を主とした副作用を起こす患者の腸内細菌叢に共通するファクターを見出すことを目的とする。さらにはメタゲノムデータと常在細菌叢の抗菌薬感受性を融合させることで、なぜ特定の菌叢を持つ(または持たない)ことでDysbiosisが起こるのか、そのメカニズムを説明する。さらに内視鏡的な胃炎、組織学的胃炎評価も行い、最終的に腸内細菌叢解析データと融合する。平成31年度(2019年度)から3年間にわたり岡山大学医学部・歯学部新入生(医学科・保健学科・歯学部)に対してピロリ菌検診を例年通り実施し、H.pylori-IgG抗体陽性例を本研究の対象とする。
    2019年度は新入生314人中17人が抗体陽性であった。抗体陽性者14人に内視鏡検査を行い、内視鏡的胃炎、組織学的胃炎の評価および菌株培養を行った。組織学的陽性例は現感染と診断した。組織学的胃炎、菌株培養陰性例に対しては、さらに尿素呼気試験も行い、それら3検査とも陰性の場合は抗体検査が偽陽性と判断し、未感染と診断した。その結果、現感染11名、未感染3名であった。現感染者には除菌治療を行い、除菌前、除菌1週後、2ケ月後の糞便採取を行うとともに、除菌前後2週間の排便回数も含めた消化管症状についてアンケートを実施した。未感染者に対しても1回糞便採取とアンケートを実施した。
    得られた糞便の核酸抽出を実施した。
    2020年度、2021年度新入生に対しても同様に進めていく予定である。

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  • Mechanism of ferroptosis-like cell death induced by Vibrio

    Grant number:18K15147  2018.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

    Gotoh Kazuyoshi

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    Grant amount:\4030000 ( Direct expense: \3100000 、 Indirect expense:\930000 )

    Opportunistic pathogen, Vibrio alginolticus induce cell death via effector VepA in type III secretion system. I found this cell death depends on intracellular ferrous ion, calling this type of cell death ferroptosis. When I transfected recombinant VepA into HeLa cell, I observed cell death that is similar with that by V. alginolyticus infection. In this condition, I treated the cell with ferrous chelater in the cell death induction by VepA-transfection. Unlike the infection experiment, that cell death didn't inhibit by ferrous chelataing. Hence, I deny correlation between VepA-dependent cell death and intracellular ferrous ion. I also examined other possible mechanism of the cell death such as cathepsin, calcium ion, proton and ER stress. However, these factor didn't relate to this cell death. I concluded that novel mechanism hides in VepA-dependent cell death.

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  • The mechanism of periodontal tissue destruction by proteases from periodontal bacteria Porpyromonas gingivalis.

    Grant number:17K11668  2017.04 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Nakayama Masaaki

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

    The purpose of this study is to reveal the molecular mechanism of infection between periodontal pathogenic bacteria and host cells using cellular and molecular biological approaches, and to analyze the function of pathogenic proteases produced by periodontal pathogenic bacteria to clarify the pathogenesis of periodontal disease. In this study, we focused on gingipains, which are cysteine proteases, produced by Porphyromonas gingivalis (P. gingivalis), to elucidate the pathogenesis of periodontal disease infected with P. gingivalis. We examined the host cell response to the molecular mechanism of COX-2 expression by gingipains and showed that activation of two signaling pathways, ERK and IKK, and found that intracellular calcium is required for COX-2 expression and PGE2 production as the upstream factors.

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  • Posttranscriptional regulation and mutual regulation of small RNA

    Grant number:17K08830  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Mima Takehiko

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    Grant amount:\4680000 ( Direct expense: \3600000 、 Indirect expense:\1080000 )

    VarS/VarA two-component system controls the expression of target genes thorough regulating the expression of small RNAs (sRNAs). In other bacteria, the expression of sRNAs is considered to be regulated only by VarS/VarA system. Vibrio alginolyticus has four sRNAs. In this study, we found that different proteins bound to the promoter region of each sRNA. We also revealed that ArcA, a response regulator of ArcB/ArcA two-component regulatory system, bound only to the promoter region of sRNA1, but not to those of other sRNAs. Furthermore, we revealed that ArcB/ArcA system regulates the expression of sRNA1 when cells were grown under anaerobic conditions. It seems likely that expression of VarS/VarA-controlled sRNAs were controlled not only by VarS/VarA, but also by multiple regulators. From these results, we propose that sRNAs is the arithmetic system to optimize the expression of many target genes by integrating multiple environmental signals.

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  • Expression mechanism of three CsrB family regulatory RNA in Vibrio alginolyticus

    Grant number:15K19093  2015.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    Gotoh Kazuyoshi

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    Grant amount:\3510000 ( Direct expense: \2700000 、 Indirect expense:\810000 )

    Vibrio alginolyticus posses three CsrB family regulatory RNA. In this study, we investigated the mechanism of these RNAs expression system in transcriptional and post-transcriptional level. First, we checked stability among these RNAs using rifampicin RNA-chase assay. As a result, no any difference of RNA stability in three RNAs was shown. Next, we analyzed the possibility that ORF regions affect transcriptional activity. However, reporter assay indicated that the no difference of the activity was shown in ORF containing promoter. These resultu indicated that unknown mechanism produce the non-redundancy among three CsrB family regulatory RNAs.

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  • Development of new enteropathogen detection system target at IgA

    Grant number:25670272  2013.04 - 2015.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    GOTOH Kazuyoshi

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    Grant amount:\3380000 ( Direct expense: \2600000 、 Indirect expense:\780000 )

    When we detect nucleic acids of enteric pathogens from diarrheal stool normal gut microbiota, a dominant in fecal DNA pools, masks the low abundance of pathogens. To solve this problem we employed IgA-coated bacterial sorting technologies. First, we examined that IgA-coated cells were separated by a cell sorter from healthy human stool. DNA was extracted from sorting fraction. However, undetectable level DNA by PCR was obtained from low sorted cell count with our equipment. Because it was difficult to find other optimal conditions, I tried magnetic beads-based separation against IgA. Analysis of 16S rDNA deep sequencing using beads bound showed that no any significant differences was revealed between total and IgA-positive fractions despite the direct observation of IgA-positive bacteria by fluorescent microscopy.
    We proposed that IgA-targeted separation should be carefully validated using microscopy although that technique has been published as successful experiences.

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