新　幸二 (アタラシ　コウジ)

Atarashi, Koji

写真a

所属（所属キャンパス）

医学部 微生物学・免疫学教室 （信濃町）

職名

准教授

外部リンク
このページの先頭へ▲

経歴 【 表示 ／ 非表示 】

  • 2009年04月
    -
    2010年02月

    大阪大学大学院医学系研究科助教

  • 2010年03月
    -
    2012年06月

    東京大学大学院医学系研究科特任助教

  • 2011年10月
    -
    2013年03月

    独立行政法人科学技術振興機構さきがけ専任研究員

  • 2013年04月
    -
    2014年07月

    理化学研究所統合生命医科学研究センター上級研究員

  • 2014年08月
    -
    2015年03月

    慶應義塾大学医学部助教

全件表示 >>

このページの先頭へ▲

学歴 【 表示 ／ 非表示 】

  • 2000年04月
    -
    2004年03月

    九州大学, 理学部, 生物学科

    大学, 卒業

  • 2004年04月
    -
    2006年03月

    九州大学, 医学系学府, 医科学専攻

    大学院, 修了, 修士

  • 2006年04月
    -
    2009年03月

    大阪大学, 医学系研究科, 予防環境医学専攻

    大学院, 修了, 博士

このページの先頭へ▲

学位 【 表示 ／ 非表示 】

  • 博士（医学）, 大阪大学, 課程, 2009年03月

このページの先頭へ▲
 

研究分野 【 表示 ／ 非表示 】

  • ライフサイエンス / 細菌学

  • ライフサイエンス / 免疫学

このページの先頭へ▲

研究キーワード 【 表示 ／ 非表示 】

  • 粘膜免疫

  • 腸内細菌

このページの先頭へ▲
 

論文 【 表示 ／ 非表示 】

  • Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth

    Zagato E., Pozzi C., Bertocchi A., Schioppa T., Saccheri F., Guglietta S., Fosso B., Melocchi L., Nizzoli G., Troisi J., Marzano M., Oresta B., Spadoni I., Atarashi K., Carloni S., Arioli S., Fornasa G., Asnicar F., Segata N., Guglielmetti S., Honda K., Pesole G., Vermi W., Penna G., Rescigno M.

    Nature Microbiology （Nature Microbiology)  5 （ 3 ） 511 - 524 2020年03月

    　概要を見る

    © 2020, The Author(s), under exclusive licence to Springer Nature Limited. The microbiota has been shown to promote intestinal tumourigenesis, but a possible anti-tumourigenic effect has also been postulated. Here, we demonstrate that changes in the microbiota and mucus composition are concomitant with tumourigenesis. We identified two anti-tumourigenic strains of the microbiota—Faecalibaculum rodentium and its human homologue, Holdemanella biformis—that are strongly under-represented during tumourigenesis. Reconstitution of ApcMin/+ or azoxymethane- and dextran sulfate sodium-treated mice with an isolate of F. rodentium (F. PB1) or its metabolic products reduced tumour growth. Both F. PB1 and H. biformis produced short-chain fatty acids that contributed to control protein acetylation and tumour cell proliferation by inhibiting calcineurin and NFATc3 activation in mouse and human settings. We have thus identified endogenous anti-tumourigenic bacterial strains with strong diagnostic, therapeutic and translational potential.

  • TH1 cell-inducing Escherichia coli strain identified from the small intestinal mucosa of patients with Crohn’s disease

    Nagayama M., Yano T., Atarashi K., Tanoue T., Sekiya M., Kobayashi Y., Sakamoto H., Miura K., Sunada K., Kawaguchi T., Morita S., Sugita K., Narushima S., Barnich N., Isayama J., Kiridooshi Y., Shiota A., Suda W., Hattori M., Yamamoto H., Honda K.

    Gut Microbes （Gut Microbes)     1 - 14 2020年

    ISSN  19490976

    　概要を見る

    © 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. Dysbiotic microbiota contributes to the pathogenesis of Crohn’s disease (CD) by regulating the immune system. Although pro-inflammatory microbes are probably enriched in the small intestinal (SI) mucosa, most studies have focused on fecal microbiota. This study aimed to examine jejunal and ileal mucosal specimens from patients with CD via double-balloon enteroscopy. Comparative microbiome analysis revealed that the microbiota composition of CD SI mucosa differs from that of non-CD controls, with an increased population of several families, including Enterobacteriaceae, Ruminococcaceae, and Bacteroidaceae. Upon anaerobic culturing of the CD SI mucosa, 80 bacterial strains were isolated, from which 9 strains representing 9 distinct species (Escherichia coli, Ruminococcus gnavus, Klebsiella pneumoniae, Erysipelatoclostridium ramosum, Bacteroides dorei, B. fragilis, B. uniformis, Parabacteroides distasonis, and Streptococcus pasteurianus) were selected on the basis of their significant association with CD. The colonization of germ-free (GF) mice with the 9 strains enhanced the accumulation of TH1 cells and, to a lesser extent, TH17 cells in the intestine, among which an E. coli strain displayed high potential to induce TH1 cells and intestinal inflammation in a strain-specific manner. The present results indicate that the CD SI mucosa harbors unique pro-inflammatory microbiota, including TH1 cell-inducing E. coli, which could be a potential therapeutic target.

  • IL-10 produced by macrophages regulates epithelial integrity in the small intestine

    Morhardt T.L., Hayashi A., Ochi T., Quirós M., Kitamoto S., Nagao-Kitamoto H., Kuffa P., Atarashi K., Honda K., Kao J.Y., Nusrat A., Kamada N.

    Scientific Reports （Scientific Reports)  9 （ 1 ）  2019年12月

    　概要を見る

    © 2019, The Author(s). Macrophages (Mϕs) are known to be major producers of the anti-inflammatory cytokine interleukin-10 (IL-10) in the intestine, thus playing an important role in maintaining gastrointestinal homeostasis. Mϕs that reside in the small intestine (SI) have been previously shown to be regulated by dietary antigens, while colonic Mϕs are regulated by the microbiota. However, the role which resident Mϕs play in SI homeostasis has not yet been fully elucidated. Here, we show that SI Mϕs regulate the integrity of the epithelial barrier via secretion of IL-10. We used an animal model of non-steroidal anti-inflammatory drug (NSAID)-induced SI epithelial injury to show that IL-10 is mainly produced by MHCII+ CD64+ Ly6Clow Mϕs early in injury and that it is involved in the restoration of the epithelial barrier. We found that a lack of IL-10, particularly its secretion by Mϕs, compromised the recovery of SI epithelial barrier. IL-10 production by MHCII+ CD64+ Ly6Clow Mϕs in the SI is not regulated by the gut microbiota, hence depletion of the microbiota did not influence epithelial regeneration in the SI. Collectively, these results highlight the critical role IL-10-producing Mϕs play in recovery from intestinal epithelial injury induced by NSAID.

  • Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis

    Nakamoto N., Sasaki N., Aoki R., Miyamoto K., Suda W., Teratani T., Suzuki T., Koda Y., Chu P.S., Taniki N., Yamaguchi A., Kanamori M., Kamada N., Hattori M., Ashida H., Sakamoto M., Atarashi K., Narushima S., Yoshimura A., Honda K., Sato T., Kanai T.

    Nature Microbiology （Nature Microbiology)  4 （ 3 ） 492 - 503 2019年03月

    　概要を見る

    © 2019, The Author(s), under exclusive licence to Springer Nature Limited. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and its frequent complication with ulcerative colitis highlights the pathogenic role of epithelial barrier dysfunction. Intestinal barrier dysfunction has been implicated in the pathogenesis of PSC, yet its underlying mechanism remains unknown. Here, we identify Klebsiella pneumonia in the microbiota of patients with PSC and demonstrate that K. pneumoniae disrupts the epithelial barrier to initiate bacterial translocation and liver inflammatory responses. Gnotobiotic mice inoculated with PSC-derived microbiota exhibited T helper 17 (T H 17) cell responses in the liver and increased susceptibility to hepatobiliary injuries. Bacterial culture of mesenteric lymph nodes in these mice isolated K. pneumoniae, Proteus mirabilis and Enterococcus gallinarum, which were prevalently detected in patients with PSC. A bacterial-organoid co-culture system visualized the epithelial-damaging effect of PSC-derived K. pneumoniae that was associated with bacterial translocation and susceptibility to T H 17-mediated hepatobiliary injuries. We also show that antibiotic treatment ameliorated the T H 17 immune response induced by PSC-derived microbiota. These results highlight the role of pathobionts in intestinal barrier dysfunction and liver inflammation, providing insights into therapeutic strategies for PSC.

  • A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

    Tanoue T., Morita S., Plichta D.R., Skelly A.N., Suda W., Sugiura Y., Narushima S., Vlamakis H., Motoo I., Sugita K., Shiota A., Takeshita K., Yasuma-Mitobe K., Riethmacher D., Kaisho T., Norman J.M., Mucida D., Suematsu M., Yaguchi T., Bucci V., Inoue T., Kawakami Y., Olle B., Roberts B., Hattori M., Xavier R.J., Atarashi K., Honda K.

    Nature （Nature)  565 （ 7741 ） 600 - 605 2019年01月

    ISSN  00280836

    　概要を見る

    © 2019, Springer Nature Limited. There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103 + dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.

全件表示 >>

このページの先頭へ▲

KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

このページの先頭へ▲

競争的研究費の研究課題 【 表示 ／ 非表示 】

  • クレブシエラ菌の腸内定着阻害に関わる腸内細菌の同定

    2019年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 新　幸二, 基盤研究（Ｃ）, 補助金,  研究代表者

  • 腸内細菌叢および腸管免疫系へ影響を及ぼす口腔内細菌の解析

    2016年04月
    -
    2019年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 新　幸二, 挑戦的萌芽研究, 補助金,  研究代表者

  • 腸内細菌による炎症性疾患の発症メカニズムの解明

    2015年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 新　幸二, 若手研究(A), 補助金,  研究代表者

このページの先頭へ▲
 

担当授業科目 【 表示 ／ 非表示 】

  • 微生物学

    2022年度

  • 微生物学

    2021年度

  • 微生物学

    2020年度

  • 微生物学

    2019年度

このページの先頭へ▲

担当経験のある授業科目 【 表示 ／ 非表示 】

  • 微生物学免疫学

    慶應義塾

    2015年04月
    -
    2016年03月
    , 

    春学期

このページの先頭へ▲