九州大学 研究者情報
総説一覧
中山 二郎(なかやま じろう) データ更新日:2023.11.27

教授 /  農学研究院 生命機能科学部門 システム生物工学講座


総説, 論評, 解説, 書評, 報告書等
1. 中山 二郎, 変わりゆくアジア食とアジア人の腸内細菌叢, Microbiome Science, 2, 6-12, 2023.02.
2. Phatthanaphong Therdtatha, Akari Shinoda, Jiro Nakayama, Crisis of the Asian gut: associations among diet, microbiota, and metabolic diseases, Bioscience of microbiota, food and health, 10.12938/bmfh.2021-085, 41(3), 83-93, 2022.04.
3. 田中 優, 中山 二郎, 腸管機能と腸内細菌の関係を読み解く(2)"胆汁酸"を介した腸内細菌と宿主のクロストーク : 胆汁酸が宿主と腸内細菌の関係を紐解く鍵になる, 化学と生物, Vol.60, No.2, pp.79-88, 2022.02.
4. Mugihito Oshiro, Takeshi Zendo, Jiro Nakayama , Diversity and dynamics of sourdough lactic acid bacteriota created by a slow food fermentation system, Journal of Bioscience and Bioengineering, https://doi.org/10.1016/j.jbiosc.2020.11.007, 131(4), 333-340, 2021.04, Sourdough is a naturally fermented dough that is used worldwide to produce a variety of baked foods. Various lactic acid bacteria (LAB), which can determine the quality of sourdough baked foods by producing metabolites, have been found in the sourdough ecosystem. However, spontaneous fermentation of sourdough leads to unpredictable growth of various micro-organisms, which result in unstable product quality. From an ecological perspective, many researchers have recently studied sourdough LAB diversity, particularly the elucidation of LAB community interactions and the dynamic mechanisms during the fermentation process, in response to requests for the control and design of a desired sourdough microbial community. This article reviews recent advances in the study of sourdough LAB diversity and its dynamics in association with unique characteristics of the fermentation system; it also discusses future perspectives for better understanding of the complex sourdough microbial ecosystem, which can be attained efficiently by both in vitro and in situ experimental approaches.
5. 篠田 あかり, 渡邉 麻衣, Therdtatha Phatthanaphong, 中山 二郎, 【個人差の理解へ向かう肥満症研究 GWAS、エピゲノム、腸内細菌、栄養学的知見から多様な病態を解明し、Precision Medicineをめざす】(第4章)肥満症の個人差 アジア人の食習慣と腸内細菌叢の変化と現代生活習慣病リスク向上の関連性について, 実験医学, Vol.39, No.5, pp.787-794, 2021.03, アジア諸国における肥満や2型糖尿病などの生活習慣病の増加は顕著で深刻である。その背景には食習慣の変化が関係する。一方、数十兆個の細菌が宿るとされる腸内細菌叢が、食と健康のインターフェースとして重要な働きを有し、生活習慣病の増加にも関与していることがわかってきた。われわれは、Asian Microbiome Project(AMP)を設立し、アジアの老若男女の細菌叢を網羅的に調査している。本稿では、そのなかから、各国の食事情を如実に反映していると捉えられる小学児童の調査結果と、成人の肥満と2型糖尿病患者の腸内細菌叢について解説する。(著者抄録).
6. 井上 貴子, 中山 二郎, 田中 靖人, C型肝炎ウイルス感染によるDysbiosis(腸内フローラ異常)と病態進展へのインパクト, Nagoya Medical Journal, Vol.56, No.4, pp.273-278, 2020.12, 病期の異なるC型慢性肝炎(CHC)患者と健常人の腸内フローラを比較することで、HCV感染と腸内フローラの変化・病態進展との関連について検討した。CHC患者166例と健常人23例を対象とした。CHC患者では、健常人の腸内フローラ主構成菌種であるラクノスピラ科やルミノコッカス科が減少し、レンサ球菌科やラクトバシラス科、腸内細菌科の細菌が増加していた。HCV感染者では病初期の段階から腸内フローラが変化し、病期の進行につれてdysbiosisが進行することが証明された。便中アンモニア産生菌の量に比例して便pHが上昇していることから、dysbiosisが高アンモニア血症の原因となる可能性を間接的に示すことができた。.
7. 北垣 浩志, 浜島 弘史, 中山 二郎, 永尾 晃治, 麹由来グリコシルセラミドによるコレステロール代謝改善, バイオサイエンスとインダストリー, Vol.78, No.5, pp.410-411, 2020.09.
8. 北崎 宏平, 古賀 祥子, 桑野 剛一, 善藤 威史, 園元 謙二, 片本 宏, 永利 浩平, 中山 二郎, セファゾリンとナイシンAの乳房炎原因菌に対する相乗的殺菌効果, 日本獣医師会雑誌, Vol.72, No.11, pp.709-710, 2019.11.
9. 山本 裕貴, 浜島 弘史, 田中 優, 藤丸 裕貴, 阪本 真由子, 宮川 幸, 西向 めぐみ, 柳田 晃良, 中村 強, 光武 進, 永尾 晃治, 中山 二郎, 北垣 浩志, 【発酵食品の機能性と関連領域】麹に含まれるグリコシルセラミドの健康効果, 生物工学会誌, Vol.97, No.4, pp.182-184, 2019.04.
10. 田中 優, 中山 二郎, 【アレルギー疾患とマイクロバイオーム】ヒト常在マイクロバイオーム研究の技術の進歩, アレルギーの臨床, Vol.39, No.2, pp.75-78, 2019.02, 近年の次世代シークエンサー、質量分析計、バイオインフォマティクスの著しい技術進歩により、腸内フローラなどの非常に複雑なヒト常在マイクロバイオームの研究が加速している。これらのオミックス研究分野の技術革新により、マイクロバイオームを構成する微生物群の分類学的および機能的特徴やバイオマーカーの探索のような細部にわたるデータ収集から俯瞰的な考察までが可能となった。そして得られた知見を実証する動物実験の技術も成熟してきている。マイクロバイオームのコミュニティーをインビトロに再現し、その組成や機能変化をリアルタイムでモニタリングするヒト腸管モデルもまた注目される。(著者抄録).
11. 中山二郎, 腸内フローラ研究からみた日本人とアジア人の健康, 日本食生活学会誌, 29, 137-140, 2018.12.
12. 安達桂香、中山二郎, 腸内細菌叢におけるケミカルコミュニケーション, 腎臓内科・泌尿器科, 7,599-606, 2018.06.
13. Masaru Tanaka, Jiro Nakayama, Development of the gut microbiota in infancy and its impact on health in later life
, Allergology International, 66, 515-522, 2017.07.
14. 内川彩夏、田中優、中山二郎, ヒト腸内細菌叢のダイナミズムとダイバーシティ, 日本乳酸菌学会誌, 28, 74-83, 2017.07.
15. 余田美沙子、中山二郎, Asian Microbiome Project:アジア人腸内細菌叢の実態調査
, バイオサイエンスとバイオインダストリー, 75,299-303, 2017.06.
16. Jiro Nakayama, Heping Zhang, Yuan Kun Lee, Asian gut microbiome, Science Bulletin, 10.1016/j.scib.2017.04.001, 62(12), 816-817, 2017.06, [URL].
17. 田中優、中山二郎, アジア人の食習慣と腸内細菌叢, Helicobacter Research, 21,31-37, 2017.04.
18. Juma Kisuse, Jiro Nakayama, 16S rRNA Metagenomics of Asian Gut Microbiota, Understanding Host-Microbiome Interactions - An Omics Approach, 10.1007/978-981-10-5050-3, 1, 71-81, 2017.01.
19. Jiro Nakayama, Ravindra Pal Singh, Quorum quenching strategy targeting Gram-positive pathogenic bacteria, Advances in Microbiology and Infectious Diseases and Public Health, 910, 109-130, 2016.05.
20. 中山 二郎, 本田倫子, アジア人の食・健康・腸内細菌叢, 化学療法の領域, 32(2),253-260, 2016.02.
21. 東 佳那子, 中山 二郎, 進化する次世代シーケンサーによる腸内細菌叢の解析, 腸内細菌学雑誌, 29(3), 135-144, 2015.06.
22. 東 佳那子, 中山 二郎, グローバル化する腸内フローラ研究とAsian Microbiome Project, ソフト・どリング技術資料, 175, 49-70., 2015.05.
23. 小野浩, 中山 二郎, 次世代シーケンサーを用いた発酵食品の細菌叢解析ー見えてきた複雑系の深部ー, 日本乳酸菌学会誌, 25(1), 3-12, 2014.03.
24. 中山 二郎, 腸内細菌と健康:ゆりかごから墓場まで, 日本醸造協会, 108(10), 724-733, 2013.09.
25. 中山 二郎, 次世代シークェンサーによるヒト腸内フローラの解析, 九州大学中央分析センター報告, 2012.12.
26. 是則有希、Jiahui Jiang、中山二郎, 16S rRNA遺伝子の大量シークェンシングによる菌叢解析の現状と問題点、日本乳酸菌学会誌、Vol.23, pp.24-33(2012)., 日本乳酸菌学会誌, 23(1), 24-34, 2012.03.
27. 阪本直茂, 中山二郎, 糠床のミクロフローラと乳酸菌の共生, 生物工学会誌, 89(8), 482-485, 2011.08.
28. 中山二郎, 細菌の世界における細胞間ケミカルコミュニケーションとその分子メカニズム, 腸内細菌学雑誌, 25, 221-234, 2011.04.
29. 中山二郎, 赤ちゃんの腸内フローラと過剰衛生仮説, 科学, 3, 246-250, 2011.03.
30. 中山二郎, 乳児期の腸内フローラの偏倚と後のアレルギー疾患発症の関連性について, アレルギー・免疫, 17(7), 1194-1205, 2010.07.
31. 佐藤まみ、中山二郎, グラム陽性細菌のクオラムセンシング研究の最前線, 日本乳酸菌学会誌, 21(2), 95-106, 2010.04.
32. Jiro Nakayama, Pyrosequence-based 16S rRNA profiling of gastro-intestinal microbiota, Bioscience & Microflora, 29(2), 83-96, 2010.04.
33. 辻村晃, 山本圭介, 福原慎一郎, 平井利明, 植田知博, 中山二郎, 木内寛, 高尾徹也, 宮川康, 奥山明彦, 松下正輝, 性的領域への関心が低い男性人格に関する検討, 日本泌尿器科学会雑誌, Vol.100, No.2, p.190, 2009.02.
34. 辻村晃, 山本圭介, 福原慎一郎, 平井利明, 植田知博, 中山二郎, 木内寛, 高尾徹也, 宮川康, 松下正輝, 奥山明彦, AVSS時にヒト男性の人格が影響をおよぼす視覚関心領域に関する検討, 日本性機能学会雑誌, Vol.23, No.2, pp.217-218, 2008.08.
35. 辻村晃, 山本圭介, 福原慎一郎, 平井利明, 植田知博, 中山二郎, 木内寛, 小森和彦, 松岡庸洋, 高尾徹也, 宮川康, 奥山明彦, 松下正輝, 視線追跡装置と人格評価による性的関心度に対する性差解析, 日本泌尿器科学会雑誌, Vol.99, No.2, p.268, 2008.02.
36. Jun Ichi Nagao, Yuji Aso, Kouki Shioya, Jiro Nakayama, Kenji Sonomoto, Lantibiotic engineering
Molecular characterization and exploitation of lantibiotic-synthesizing enzymes for peptide engineering
, Journal of Molecular Microbiology and Biotechnology, 10.1159/000104749, 13(4),235-242, 2007.09, [URL], Lanthionine-containing peptide antibiotics called lantibiotics are produced by a large number of Gram-positive bacteria. Nukacin ISK-1 produced by Staphylococcus warneri ISK-1 is type-A(II) lantibiotic. Ribosomally synthesized nukacin ISK-1 prepeptide (NukA) consists of an N-terminal leader peptide followed by a C-terminal propeptide moiety that undergoes several post-translational modification events including unusual amino acid formation by the modification enzyme NukM, cleavage of leader peptide and export by the dual functional ABC transporter NukT, finally yielding a biologically active peptide. Unusual amino acids in lantibiotics contribute to biological activity and also structural stability against proteases. Thus, lantibiotic-synthesizing enzymes have a high potentiality for peptide engineering by introduction of unusual amino acids into desired peptides with altering biological and physicochemical properties, e.g., activity and stability, termed lantibiotic engineering. We report the establishment of a heterologous expression of nukacin ISK-1 biosynthetic gene cluster by the nisin-controlled expression system and discuss our recent progress in understanding of the biosynthetic enzymes for nukacin ISK-1 such as localization, molecular interaction in biophysical and biochemical aspects. Substrate specificity of the lantibiotic-synthesizing enzymes was evaluated by complementation of the biosynthetic enzymes (LctM and LctT) of closely related lantibiotic lacticin 481 for nukacin ISK-1 biosynthesis. We further explored a rapid and powerful tool for introduction of unusual amino acids by co-expression of hexa-histidine-tagged NukA and NukM in Escherichia coli..
37. 辻村晃, 福原慎一郎, 平井利明, 植田知博, 中山二郎, 木内寛, 小森和彦, 松岡庸洋, 高尾徹也, 宮川康, 高田晋吾, 奥山明彦, 松下正輝, 視線追跡装置を用いたヒト男性の性的興味とMMPIによる人格評価との関連性, 日本性機能学会雑誌, Vol.22, No.2, pp.228-229, 2007.08.
38. 中山二郎、田中重光、Prapa Songjinda、立山敦、坪内美樹、清原千香子、白川太郎、園元謙二, 各種分子生物学的手法による乳幼児腸内細菌叢の解析-幼児アレルギー発症ハイリスク原因究明の大規模疫学調査にむけて-, 腸内細菌学雑誌, 2007.05.
39. Jun ichi Nagao, Sikder M. Asaduzzaman, Yuji Aso, Ken ichi Okuda, Jiro Nakayama, Kenji Sonomoto, Lantibiotics
Insight and foresight for new paradigm
, Journal of Bioscience and Bioengineering, 10.1263/jbb.102.139, 102(3),139-149, 2006.09, [URL], Lantibiotics are a unique type of antimicrobial peptide produced by a large number of gram-positive bacteria that contain unusual amino acids, such as lanthionine and dehydrated amino acids. Ribosomally synthesized lantibiotic prepeptide consists of an N-terminal leader peptide followed by a C-terminal propeptide moiety that undergoes several post-translational modification events to yield a biologically active lantibiotic. Research on lantibiotics has drawn much attention in recent years and has undergone extensive progress as a step forward to the next paradigm. Unusual amino acids in lantibiotics solely contribute to their biological activity and also enhance their structural stability. Thus, enzymes involved in lantibiotic biosynthesis would have a high potential for peptide engineering by introducing unusual amino acids into desired peptides, which may establish a universal approach to advance the structural design of novel peptides, termed lantibiotic engineering. In this review, we focus on recent development with contemporary innovations and perspective of lantibiotic research..
40. 奥田 賢一, 麻生 祐司, 中山 二郎, 抗菌性ペプチドであるバクテリオシンとその耐性メカニズム, ニューフードインダストリー, Vol.48, No.3, pp.37-46, 2006.03.
41. 善藤威史, Eungruttanagorn, N, 藤岡澄江, 田代幸寛, 野村久美, 世良芳子, 小林元太, 中山二郎, 石崎文彬, 園元謙二, Identification and production of a bacteriocin from Enterococcus mundtii QU2 isolated from soybean, Journal of Applied Microbiology, 10.1111/j.1365-2672.2005.02704.x, Vol.99, No.5, pp.1181-1190, 2005.11, Aims: Identification of the bacteriocin produced by Enterococcus mundtii QU 2 newly isolated from soybean and fermentative production of the bacteriocin. Methods and Results: The bacteriocin produced by Ent. mundtii QU 2 inhibited the growth of various indicator strains, including Enterococcus, Lactobacillus, Leuconostoc, Pediococcus and Listeria. The bacteriocin activity was stable at wide pH range and against heat treatment, but completely abolished by proteolytic enzymes. The bacteriocin was purified from the culture supernatant by the three-step chromatographic procedure. Mass spectrometry, amino acid sequencing and DNA sequencing revealed that the bacteriocin was similar to class IIa bacteriocins produced by other Ent. mundtii strains. The bacteriocin production decreased in the absence of glucose, nitrogen sources, or Tween 80 in MRS medium. Additionally, it was strongly suppressed by addition of Ca2+(CaCO3or CaCl2). In pH-controlled fermentations, the highest bacteriocin production was achieved at pH 6.0 whereas the highest cell growth was obtained at pH 7.0. Conclusions: Ent. mundtii QU 2 produced a class IIa bacteriocin. Some growth factors (e.g. Ca2+and pH) influenced the bacteriocin production. Significance and Impact of the Study: A new soybean isolate, Ent. mundtii QU 2 was found to be a class IIa bacteriocin producer. Factors influencing the bacteriocin production described herein are valuable for applications of the bacteriocins from Ent. mundtii strains. © 2005 The Society for Applied Microbiology..
42. J Nagao, Y Harada, K Shloya, Y Aso, T Zendo, J Nakayama, K Sonomoto, Lanthionine introduction into nukacin ISK-1 prepeptide by co-expression. with modification enzyme NAM in Escherichia coli, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 10.1016/j.bbrc.2005.08.125, Vol.336, No.2, pp.507-513, 2005.10, We demonstrated lanthionine introduction into hexa-histidine-tagged (His-tagged) nukacin ISK-1 prepeptide NukA by modification enzyme NukM in Escherichia coli. Co-expression of nukA and nukM, purification of the resulting His-tagged prepeptide by affinity chromatography, and subsequent mass spectrometry analysis showed that the prepeptide was converted into a postulated peptide with decrease in mass of 72 Da which resulted from dehydration of four amino acids. Characterization of the resultant prepeptide indicated the presence of unusual amino acids, such as dehydrated amino acid, lanthionine or 3-methyllanthionine, in its C-terminal propeptide moiety. The modified prepeptide encompassing the leader peptide attached to the post-translation ally modified propeptide moiety was readily obtained by one-step purification. Our findings will thus be a powerful tool for introducing unusual amino acids aimed at peptide engineering and also helpful to provide new insight for further understanding of lanthionine-forming enzymes for lantibiotics. (c) 2005 Elsevier Inc. All rights reserved..
43. MHJ Sturme, J Nakayama, D Molenaar, Y Murakami, R Kunugi, T Fujii, EE Vaughan, M Kleerebezem, WM de Vos, An agr-like two-component regulatory system in Lactobacillus plantarum is involved in production of a novel cyclic peptide and regulation of adherence, JOURNAL OF BACTERIOLOGY, 10.1128/JB.187.15.5224-5235.2005, Vol.187, No.15, pp.5224-5235, 2005.08, We have analyzed a locus on the annotated Lactobacillus plantarum WCFS1 genome that showed homology to the staphylococcal agr quorum-sensing system and designated it lam for Lactobacillus agr-like module. Production of the lamBDCA transcript was shown to be growth phase dependent. Analysis of a response regulator-defective mutant (Delta lamA) in an adherence assay showed that lam regulates adherence of L. plantarum to a glass surface. Global transcription analysis of the wild-type and Delta lamA strains in early, mid-, and late log phase of growth was performed using a clone-based microarray. Remarkably, only a small set of genes showed significant differences in transcription profiles between the wild-type and lamA mutant strains. The microarray analysis confirmed that lamBDCA is autoregulatory and showed that lamA is involved in regulation of expression of genes encoding surface polysaccharides, cell membrane proteins, and sugar utilization proteins. The lamBD genes encoding the putative autoinducing peptide precursor (LamD) and its processing protein (LamB) were overexpressed using the nisin-controlled expression system, and culture supernatants were analyzed by liquid chromatography/mass spectrometry (LC/MS) to identify overproduced Lam-derived peptides. In this way, a cyclic thiolactone pentapeptide that possesses a ring structure similar to those of autoinducing peptides of the staphylococcal agr system was identified. The peptide was designated LamD558, and its sequence (CVGIW) matched the annotated precursor peptide sequence. Time course analysis of wild-type culture supernatants by LC/MS indicated that LamD558 production was increased markedly from mid-log to late log growth phase. This is the first example of an agr-like system in nonpathogenic bacteria that encodes a cyclic thiolactone autoinducing peptide and is involved in regulation of adherence..
44. 中山二郎,善藤威史,園元謙二, 乳酸菌の機能制御とクォーラムセンシング, バイオサイエンスインダストリー, 62(10), 663-667, 2004.10.
45. Y Aso, T Sashihara, J Nagao, Y Kanemasa, H Koga, T Hashimoto, T Higuchi, A Adachi, H Nomiyama, A Ishizaki, J Nakayama, K Sonomoto, Characterization of a gene cluster of Staphylococcus warneri ISK-1 encoding the biosynthesis of and immunity to the lantibiotic, nukacin ISK-1, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 10.1271/bbb.68.1663, Vol.68, No.8, pp.1663-1671, 2004.08, We characterized a gene cluster in a plasmid designated pPI-1 of Staphylococcus warneri ISK-1 encoding the biosynthesis of and immunity to the lacticin-481 type lantibiotic, nukacin ISK-1. The DNA sequence suggested that the nukacin ISK-1 gene cluster consists of at least six genes, nukA (a structural gene), -M, -T, -F, -E, -G, and two open reading frames, ORF1 and ORF7. NukM and NukT were predicted to be involved in post-translational modification and secretion of nukacin ISK-1 respectively. NukF, -E, and -G were predicted to form a membrane complex which contributes to self-protection from nukacin ISK-1. Transcriptional analyses revealed that nukM through ORF7 comprises an operon, and that ORF1 is transcribed independently from downstream of nukA. The transcriptional levels of the nukA and nukM genes were enhanced by osmotic stress. The expression level of the nukA transcript was scarcely enhanced by nukacin ISK-1, suggesting that expression is not under the control of the autoregulatory circuit..
46. 中山 二郎, 福井 学, SONJINDA Prapa, 田中 重光, 久貫 良子, 園元 謙二, 腸内フローラの構造解析 : DGGE/TGGE法による腸内細菌叢解析, 腸内細菌学雑誌 = Journal of intestinal microbiology, Vol.18, No.2, pp.147-153, 2004.07.
47. 中山二郎,田中笑美,西口賢三,園元謙二, ブドウ球菌および腸球菌のクオラムセンシング—環状ペプチドにより制御される病原因子の発現—., 臨床と微生物, 31(3), 251-259, 2004.03.
48. 冨士田浩二,善藤威史,中山二郎,園元謙二, 乳酸菌バクテリオシンとその応用, 防菌防黴誌, 32(3), 127-134, 2004.03.
49. 善藤威史,中山二郎,園元謙二, 新しい乳酸菌バクテリオシンの探索と利用, バイオサイエンスとインダストリー, 61(9), 11-16, 2003.09.
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