腸内細菌叢の構造と機能に関する研究
キーワード：腸内細菌叢
2010.04.
| 中山 二郎（なかやま じろう） | データ更新日：2023.11.27 |
主な研究テーマ
アジア人の食と腸内フローラと健康に関する調査研究
キーワード：腸内細菌叢
2010.04.
キーワード：腸内細菌叢
2010.04.
腸球菌の菌体外プロテアーゼの生産誘導フェロモンに関する基礎および応用研究
キーワード：クォーラムセンシング
1999.10.
キーワード：クォーラムセンシング
1999.10.
ヒト腸内細菌のCell-cellコミュニケーション
キーワード：クォーラムセンシング、プロバイオティクス、菌叢解析
1998.04.
キーワード：クォーラムセンシング、プロバイオティクス、菌叢解析
1998.04.
腸内細菌叢データを利用した乳幼児におけるアレルギー発症の早期診断法の確立
キーワード：腸内フローラ、アレルギー
2001.10.
キーワード：腸内フローラ、アレルギー
2001.10.
乳酸菌の生産するバクテリオシンに関する研究
キーワード：乳酸菌、バクテリオシン
2001.10.
キーワード：乳酸菌、バクテリオシン
2001.10.
醤油乳酸菌の分子シャペロンに関する研究
キーワード：シャペロン、耐塩性
2001.10～2007.12.
キーワード：シャペロン、耐塩性
2001.10～2007.12.
発酵食品の細菌叢の解析
キーワード：糠床、細菌叢、分子生態学
2001.10.
キーワード：糠床、細菌叢、分子生態学
2001.10.
従事しているプロジェクト研究
アジアにおける食と健康を繋ぐ腸内フローラの研究拠点の形成
2022.04～2025.03, 代表者：中山二郎, 九州大学農学研究院, 九州大学農学研究院（日本）
多様で固有なアジア食を、腸内フローラを起点とする健康維持に向けて次世代に継承することを目的に、アジア5か国の食健康医学と腸内細菌学の英知を結集した「アジア食と腸内フローラの研究拠点」をここに構築する。具体的には、腸内フローラ研究の先進国である日本にプロジェクトの拠点を構え、現代食侵襲の問題を抱えるインドネシア、タイ、フィリピン、モンゴルに各国の研究拠点を構える。日本側の拠点は、すでにAsian Microbiome Project（AMP）の拠点として豊富な研究実績を有し、腸内細菌・マイクロバイオームの解析技術が整備されている九州大学に構える。そこに栄養疫学（中村学園大学）、生活習慣病（九大医）、食とエピゲノム（早大）、アジア諸地域の生活環境変化の調査（明治大学）、海外微生物資源（東京農業大学）、の専門家が参加し、アジア諸国における調査をサポートする体制を整える。そして、日本とアジア各国との共同研究により各国のコホート調査を実施する。具体的には、まずマイクロバイオームの解析プロトコルを整備した上で(R1), 旧来の伝統的食習慣の残る地方と現代食の侵襲の激しい都市部の住民[成長期にある小学生児童(R2)と生活習慣病リスクの高い成人(R3)]を対象に、食と腸内フローラと健康の調査を行う。そして、我々が10年前に行った調査結果と比較し、また地域・国間でデータを比較し、伝統食から現代食への移行が、腸内フローラと健康に与えている影響を四次元軸で解析する。同時に、腸内フローラに有益なアジアの食と腸内菌を、未来に継承するためにデータベース化し、加えて、有益菌の菌株コレクションを整備する(R4)。以上の拠点事業には、日本と海外双方の若手研究者や大学院生を積極的に参加させ、この分野横断的な国際コホート調査のイロハを体験させ、当該分野の次世代のリーダーを数多く養成する。本年度は、以上の研究プロジェクト開始のために、まず、共同研究者の最も多いタイ国を訪問し、今後の研究計画について話し合いの機会を持つ。また9月に日本でキックオフミーティングを開催する。4か国からの各２名（できれば若手研究者や学生も含める）を招聘する。日本の参加者と本学の学生にも多く参加してもらい、情報と意見交換を十分に行う。.
2022.04～2025.03, 代表者：中山二郎, 九州大学農学研究院, 九州大学農学研究院（日本）
多様で固有なアジア食を、腸内フローラを起点とする健康維持に向けて次世代に継承することを目的に、アジア5か国の食健康医学と腸内細菌学の英知を結集した「アジア食と腸内フローラの研究拠点」をここに構築する。具体的には、腸内フローラ研究の先進国である日本にプロジェクトの拠点を構え、現代食侵襲の問題を抱えるインドネシア、タイ、フィリピン、モンゴルに各国の研究拠点を構える。日本側の拠点は、すでにAsian Microbiome Project（AMP）の拠点として豊富な研究実績を有し、腸内細菌・マイクロバイオームの解析技術が整備されている九州大学に構える。そこに栄養疫学（中村学園大学）、生活習慣病（九大医）、食とエピゲノム（早大）、アジア諸地域の生活環境変化の調査（明治大学）、海外微生物資源（東京農業大学）、の専門家が参加し、アジア諸国における調査をサポートする体制を整える。そして、日本とアジア各国との共同研究により各国のコホート調査を実施する。具体的には、まずマイクロバイオームの解析プロトコルを整備した上で(R1), 旧来の伝統的食習慣の残る地方と現代食の侵襲の激しい都市部の住民[成長期にある小学生児童(R2)と生活習慣病リスクの高い成人(R3)]を対象に、食と腸内フローラと健康の調査を行う。そして、我々が10年前に行った調査結果と比較し、また地域・国間でデータを比較し、伝統食から現代食への移行が、腸内フローラと健康に与えている影響を四次元軸で解析する。同時に、腸内フローラに有益なアジアの食と腸内菌を、未来に継承するためにデータベース化し、加えて、有益菌の菌株コレクションを整備する(R4)。以上の拠点事業には、日本と海外双方の若手研究者や大学院生を積極的に参加させ、この分野横断的な国際コホート調査のイロハを体験させ、当該分野の次世代のリーダーを数多く養成する。本年度は、以上の研究プロジェクト開始のために、まず、共同研究者の最も多いタイ国を訪問し、今後の研究計画について話し合いの機会を持つ。また9月に日本でキックオフミーティングを開催する。4か国からの各２名（できれば若手研究者や学生も含める）を招聘する。日本の参加者と本学の学生にも多く参加してもらい、情報と意見交換を十分に行う。.
Asian Microbiome Project
2017.10～2024.03, 代表者：中山二郎, 九州大学, 明治大学、早稲田大学、カセサート大学（タイ）、マヒドン大学（タイ）、フィリピン大学マニラ校（フィリピン）、ガジャマダ大学（インドネシア）、モンゴル生命科学大学（モンゴル）、シンガポール国立大学（シンガポール）
アジアの多様で優良な食文化は我々アジア人の健康を支えてきた。しかし、アジア人の食習慣は近年の近代化とともに急速に変化し、それに伴い生活習慣病が急増するなど、アジア人の健康は変調をきたしている。その中で、我々はアジア人の腸内フローラを調査し、食と健康を仲介する腸内フローラが、この現代食の影響下にグローバルな変化、すなわちエンテロタイプのシフトを起こしていることを示してきた。ここでは、これまでの国際共同研究をさらに強化し、古来の食文化の直接的あるいは腸内フローラを介する保健効果を、科学的エビデンスをもって実証展開するための研究基盤を構築する。本研究基盤構築のアプトプットとして、アジア各国特有の食成分の作用を顕在化させるとともに、国を超えた共通のFood-Microbiome-Human axisを明らかにすることを目的とする。具体的には、インドネシア、タイ、フィリピン、モンゴル各国に特徴的な食品の、直接的あるいは腸内フローラを介する抗生活習慣病効果（特に抗２型糖尿病）について、オミックス解析にセルベースのエピゲノム解析を加えて網羅的に解析する。そして、各国の伝統的食文化の重要性を改めて認識し、食のグローバル化にアジア人の体をどのように適応させていくべきか、腸内フローラの観点から提言する。.
2017.10～2024.03, 代表者：中山二郎, 九州大学, 明治大学、早稲田大学、カセサート大学（タイ）、マヒドン大学（タイ）、フィリピン大学マニラ校（フィリピン）、ガジャマダ大学（インドネシア）、モンゴル生命科学大学（モンゴル）、シンガポール国立大学（シンガポール）
アジアの多様で優良な食文化は我々アジア人の健康を支えてきた。しかし、アジア人の食習慣は近年の近代化とともに急速に変化し、それに伴い生活習慣病が急増するなど、アジア人の健康は変調をきたしている。その中で、我々はアジア人の腸内フローラを調査し、食と健康を仲介する腸内フローラが、この現代食の影響下にグローバルな変化、すなわちエンテロタイプのシフトを起こしていることを示してきた。ここでは、これまでの国際共同研究をさらに強化し、古来の食文化の直接的あるいは腸内フローラを介する保健効果を、科学的エビデンスをもって実証展開するための研究基盤を構築する。本研究基盤構築のアプトプットとして、アジア各国特有の食成分の作用を顕在化させるとともに、国を超えた共通のFood-Microbiome-Human axisを明らかにすることを目的とする。具体的には、インドネシア、タイ、フィリピン、モンゴル各国に特徴的な食品の、直接的あるいは腸内フローラを介する抗生活習慣病効果（特に抗２型糖尿病）について、オミックス解析にセルベースのエピゲノム解析を加えて網羅的に解析する。そして、各国の伝統的食文化の重要性を改めて認識し、食のグローバル化にアジア人の体をどのように適応させていくべきか、腸内フローラの観点から提言する。.
世界の健康に貢献する日本食パターンの評価方法の確立とその応用に関する研究
2017.10～2020.03, 代表者：辻一郎, 東北大学, 東北大学、京都大学、岡山県立大学、理化学研究所、九州大学、慶應義塾大学、国立長寿医療研究センター
日本食は食事内容のスコア化による客観的な評価法の開発などの取組があまりなされておらず、科学的エビデンスの充実をはかり、日本食の健康有益性に関する情報を国際的に発信していく必要がある。本研究では、発表済みの日本食スコアをベースに、日本食の有益性や改善点を明らかにしたうえで、食材だけではなく、多様性、形式、調理法、調味料などに関しても盛り込むよう改良する。その日本食スコアに関して、健康増進効果の関連性について、動物試験やヒトデータで検証し、日本食スコアを完成させる。さらに、改良版日本食スコアを活用したヒト介入試験を行い、その有用性を証明する。また、改良日本食スコアを活用し、社会実装を促進する。.
2017.10～2020.03, 代表者：辻一郎, 東北大学, 東北大学、京都大学、岡山県立大学、理化学研究所、九州大学、慶應義塾大学、国立長寿医療研究センター
日本食は食事内容のスコア化による客観的な評価法の開発などの取組があまりなされておらず、科学的エビデンスの充実をはかり、日本食の健康有益性に関する情報を国際的に発信していく必要がある。本研究では、発表済みの日本食スコアをベースに、日本食の有益性や改善点を明らかにしたうえで、食材だけではなく、多様性、形式、調理法、調味料などに関しても盛り込むよう改良する。その日本食スコアに関して、健康増進効果の関連性について、動物試験やヒトデータで検証し、日本食スコアを完成させる。さらに、改良版日本食スコアを活用したヒト介入試験を行い、その有用性を証明する。また、改良日本食スコアを活用し、社会実装を促進する。.
食品機能性対応指標基づく階層的バイオプロセス制御の開発
2006.04～2008.03, 代表者：園元謙二, 九州大学大学院農学研究院, 九州大学大学院農学研究院.
2006.04～2008.03, 代表者：園元謙二, 九州大学大学院農学研究院, 九州大学大学院農学研究院.
乳酸菌バクテリオシンを利用した乳房炎予防・治療抗菌剤の開発
2006.04～2009.03, 代表者：園元謙二, 九州大学大学院農学研究院, 九州大学大学院農学研究院.
2006.04～2009.03, 代表者：園元謙二, 九州大学大学院農学研究院, 九州大学大学院農学研究院.
地域集団でのコホート研究による便中細菌診断妥当性の研究
2004.04～2006.03, 代表者：白川太郎, 京都大学大学院医学研究科, 厚生労働省
熊本県小国町にて出生する新生児を対象にビフィズス菌の経口投与の介入試験を行い、便中細菌叢とアレルギー発症を調査し、両者の間の関連性を実験疫学的に解析する。.
2004.04～2006.03, 代表者：白川太郎, 京都大学大学院医学研究科, 厚生労働省
熊本県小国町にて出生する新生児を対象にビフィズス菌の経口投与の介入試験を行い、便中細菌叢とアレルギー発症を調査し、両者の間の関連性を実験疫学的に解析する。.
研究業績
主要著書
主要原著論文
| 1. | Mai Watanabe, Abraham Sianoya, Riko Mishima, Phatthanaphong Therdtatha, Abigail Rodriguez, Donna Christene Ramos, Yuan Kun Lee, Leslie Michelle Dalmacio, Jiro Nakayama, Gut microbiome status of urban and rural Filipino adults in relation to diet and metabolic disorders., FEMS microbiology letters, 10.1093/femsle/fnab149, 368, 20, 2021.12, Here, we aim to understand the condition of the gut microbiome of Filipino adults in relation to their diet and metabolic status. Compared to rural Albay (n = 67), the gut microbiome of subjects living in urban Manila (n = 25) was more colonized by the order Clostridiales, which was negatively correlated with host carbohydrate consumption. Principal component analysis using the genus composition of the 92 total subjects indicated four microbiome types: one type driven by Prevotella, which was associated with high rice consumption and mainly consisted of healthy Albay subjects, one Clostridiales-driven group containing a number of type 2 diabetes mellitus (T2D) subjects from both Manila and Albay who showed lower butyrate levels in association with a decrease in Mediterraneibacter faecis, and the other two types showing dysbiosis-like microbiomes with Lactobacillus and Bifidobacterium overgrowth, with a high ratio of T2D and obese subjects. Multivariate logistic regression analysis suggested high dietary energy intake, and two Veillonellaeae genera, Dialister and Megasphaera, as T2D risk factors, while Prevotella and M. faecis as anti-T2D factors. In conclusion, low-carbohydrate diets restructured the Prevotella-driven gut microbiome, which may predispose Filipino people with high energy diet to T2D.. |
| 2. | Phatthanaphong Therdtatha, Yayi Song, Masaru Tanaka, Mariyatun Mariyatun, Maisaroh Almunifah, Nancy Eka Putri Manurung, Siska Indriarsih, Yi Lu, Koji Nagata, Katsuya Fukami, Tetsuo Ikeda, Yuan-Kun Lee, Endang Sutriswati Rahayu, Jiro Nakayama, Gut Microbiome of Indonesian Adults Associated with Obesity and Type 2 Diabetes: A Cross-Sectional Study in an Asian City, Yogyakarta., Microorganisms, 10.3390/microorganisms9050897, 9, 5, 2021.04, Indonesia is a developing country facing the national problem of the growing obesity and diabetes in its population due to recent drastic dietary and lifestyle changes. To understand the link between the gut microbiome, diet, and health of Indonesian people, fecal microbiomes and metabolomes of 75 Indonesian adults in Yogyakarta City, including obese people (n = 21), type 2 diabetes (T2D) patients (n = 25), and the controls (n = 29) were characterized together with their dietary and medical records. Variations of microbiomes showed a triangular distribution in the principal component analysis, driven by three dominant bacterial genera, namely Bacteroides, Prevotella, and Romboutsia. The Romboutsia-driven microbiome, characterized by low bacterial diversity and high primary bile acids, was associated with fat-driven obesity. The Bacteroides-driven microbiome, which counteracted Prevotella but was associated with Ruminococcaceae concomitantly increased with high-carbohydrate diets, showed positive correlation with T2D indices but negative correlation with body mass index. Notably, Bacteroides fragilis was increased in T2D patients with a decrease in fecal conjugated bile acids, particularly tauroursodeoxycholic acid (TUDCA), a farnesoid X receptor (FXR) antagonist with anti-diabetic activity, while these features disappeared in patients administered metformin. These results indicate that the gut microbiome status of Indonesian adults is differently associated with obesity and T2D under their varied dietary habits.. |
| 3. | Masaru Tanaka, Sakura Onizuka, Riko Mishima, Jiro Nakayama, Cultural isolation of spore-forming bacteria in human feces using bile acids., Scientific reports, 10.1038/s41598-020-71883-1, 10, 1, 15041-15041, 2020.09, Structurally-diversified bile acids (BAs) are involved in shaping of intestinal microbiota as well as absorption of dietary lipids. Taurocholic acid, a conjugated form of BA, has been reported to be a factor triggering germination of a wide range of spore-forming bacteria in intestine. To test a hypothesis that other BAs also promote germination of intestinal bacteria, we attempted culture of bacteria from ethanol-treated feces by using a series of BAs. It was found that conjugated-BAs, notably three glycine-conjugated BAs, glycodeoxycholic acid and glycochenodeoxycholic acid, significantly increased the number and the species variety of colonies formed on the agar plate. These colonized bacteria mostly belonged to class Clostridia, mainly consisting of families Lachnospiraceae, Clostridiaceae, and Peptostreptococcaceae. There were several types of bacteria associated with different sensitivity to each BA. Eventually, we isolated 72 bacterial species of which 61 are known and 11 novel. These results demonstrate that the culturable range of bacteria in intestine can be widened using the germination-inducing activity of BAs. This approach would advance the research on spore-forming Clostridia that contains important but difficult-to-cultured bacteria associate with host health and diseases.. |
| 4. | Masaru Tanaka, Masafumi Sanefuji, Seiichi Morokuma, Misako Yoden, Rie Momoda, Kenji Sonomoto, Masanobu Ogawa, Kiyoko Kato, Jiro Nakayama, The association between gut microbiota development and maturation of intestinal bile acid metabolism in the first 3 y of healthy Japanese infants, Gut Microbes, 10.1080/19490976.2019.1650997, 2, 11, 205-216, 2020.02, [URL], The gut microbial community greatly changes in early life, influencing infant health and subsequent host physiology, notably through its collective metabolism, including host–microbiota interplay of bile acid (BA) metabolism. However, little is known regarding how the development of the intestinal microbial community is associated with maturation of intestinal BA metabolism. To address this, we monitored the succession of gut bacterial community and its association with fecal BA profile in the first 3 y of ten healthy Japanese infants. The BA profiles were classified into four types, defined by high content of conjugated primary BA (Con type), unconjugated primary BA (chenodeoxycholic acid and cholic acid) (Pri type), ursodeoxycholic acid (Urs type), and deoxycholic and lithocholic acid (Sec type). Most subjects begun with Con type or Pri type profiles during lactation and eventually transited to Sec type through Urs type after the start of solid food intake. Con type and Pri type were associated with Enterobacteriaceae-dominant microbiota corresponding to the neonatal type or Bifidobacterium-dominant microbiota corresponding to lactation type, respectively. Urs type subjects were strongly associated with Ruminococcus gnavus colonization, mostly occurring between Pri type and Sec type. Sec type was associated with adult-type complex microbiota dominated by a variety of Firmicutes and Bacteroidetes species. Addressing the link of the common developmental passage of intestinal BA metabolism with infant’s health and subsequent host physiology requires further study.. |
| 5. | Miki Fujiwara, Daichi Kuwahara, Masahiro Hayashi, Takeshi Zendo, Masao Sato, Jiro Nakayama, Kenji Sonomoto, Lowering effect of viable Pediococcus pentosaceus QU 19 on the rise in postprandial glucose, Bioscience of Microbiota, Food and Health, 10.12938/BMFH.19-041, 39, 2, 57-64, 2020.01, [URL], In the present study, we investigated the glucose-decreasing action of lactic acid bacteria (LAB). The finding of this study could be helpful for people in controlling their blood sugar levels. The LAB candidate was isolated from a Japanese fermented food and identified as Pediococcus pentosaceus by an analysis of its genome sequence. Postprandial blood glucose elevation was investigated using oral starch tolerance tests in mice. Normal mice were fed starch and lyophilized cells of P. pentosaceus QU 19 at the same time. Even without pre-administration of P. pentosaceus QU 19, elevation of the blood glucose level was significantly suppressed by the intake of P. pentosaceus QU 19 at the same time as oral administration of starch. According to the results for its survival in simulated digestive juice and the reduction of blood glucose level in mice, P. pentosaceus QU 19 has potential hypoglycemic activity. In vitro measurements revealed that the glucose-decreasing action of P. pentosaceus QU 19 is probably caused by the glucose assimilation of the strain, not the inhibition of carbohydrate-splitting enzymes which has been reported for other LABs previously. These findings indicate that specific strains of LAB, especially P. pentosaceus QU 19, and foods fermented by LAB may be beneficial for people who must manage glucose ingestion.. |
| 6. | Mugihito Oshiro, Rie Momoda, Masaru Tanaka, Takeshi Zendo, Jiro Nakayama, Dense tracking of the dynamics of the microbial community and chemicals constituents in spontaneous wheat sourdough during two months of backslopping., Journal of bioscience and bioengineering, 10.1016/j.jbiosc.2019.02.006, 128, 2, 170-176, 2019.08, [URL], Wheat sourdough is a common traditional fermented food that is produced worldwide. However, product quality of spontaneous sourdough is not easy to control because it depends on natural fermentation and backslopping, about which little is known, notably after ten backslopping steps. To this end, we tracked the spontaneous fermentation of three sourdoughs made from wheat flours during 32 backslopping steps for 60 days. At 24 time points, the microbial community was analyzed by both culture-dependent and culture-independent methods and its chemical constituents were assessed. Dynamic changes were observed in the microbial community, which showed a common succession pattern among the three sourdoughs at the bacterial family level and differences at the species level. The bacterial communities evolved through three phases that were driven by different groups of lactic acid bacteria (LAB) species. The dynamism among the metabolites also differed, depending on the species composition of the LAB and yeast communities. In one sourdough, the growth of Saccharomyces cerevisiae was detected along with a concentration of increased ethanol, while in the other two sourdoughs, Wickerhamomyces anomalus was detected without ethanol production. Regarding the LAB communities, two sourdoughs were eventually co-dominated by Lactobacillus plantarum and L. brevis, while the other sourdough was eventually dominated solely by the heterolactic fermentative bacterium Lactobacillus fermentum, and ethanol was produced at the same level as lactic acid. Further research is needed to determine the bacterial and yeast species involved in the fermentation of sourdough, to help improve the design and quality control of the final product.. |
| 7. | Juma M. Kisuse, Orawan La-ongkham, Massalin Nakphaichit, Phatthanaphong Therdtatha, Rie Momoda, Masaru Tanaka, Shinji Fukuda, Siam Popluechai, Kongkiat Kespechara, Kenji Sonomoto, Yuan-Kun Lee, Sunee Nitisinprasert and Jiro Nakayama, Urban Diets Linked to Gut Microbiome and Metabolome Alterations in Children: A Comparative Cross-sectional Study in Thailand, Front. Microbiol., 10.3389/fmicb.2018.01345, 2018.08. |
| 8. | Keika Adachi, Kaori Ohtani, Michio Kawano, Ravindra Pal Singh, Basit Yousuf, Kenji Sonomoto, Tohru Shimizu, Jiro Nakayama, Metabolic dependent and independent pH-drop shuts down VirSR quorum sensing in Clostridium perfringens., Journal of bioscience and bioengineering, 10.1016/j.jbiosc.2017.12.019, 125, 5, 525-531, 2018.05, [URL], Clostridium perfringens produces various exotoxins and enzymes that cause food poisoning and gas gangrene. The genes involved in virulence are regulated by the agr-like quorum sensing (QS) system, which consists of a QS signal synthesis system and a VirSR two-component regulatory system (VirSR TCS) which is a global regulatory system composed of signal sensor kinase (VirS) and response regulator (VirR). We found that the perfringolysin O gene (pfoA) was transiently expressed during mid-log phase of bacterial growth; its expression was rapidly shut down thereafter, suggesting the existence of a self-quorum quenching (sQQ) system. The sQQ system was induced by the addition of stationary phase culture supernatant (SPCS). Activity of the sQQ system was heat stable, and was present following filtration through the ultrafiltration membrane, suggesting that small molecules acted as sQQ agents. In addition, sQQ was also induced by pure acetic and butyric acids at concentrations equivalent to those in the stationary phase culture, suggesting that organic acids produced by C. perfringens were involved in sQQ. In pH-controlled batch culture, sQQ was greatly diminished; expression level of pfoA extended to late-log growth phase, and was eventually increased by one order of magnitude. Furthermore, hydrochloric acid induced sQQ at the same pH as was used in organic acids. SPCS also suppressed the expression of genes regulated by VirSR TCS. Overall, the expression of virulence factors of C. perfringens was downregulated by the sQQ system, which was mediated by primary acidic metabolites and acidic environments. This suggested the possibility of pH-controlled anti-virulence strategies.. |
| 9. | Inoue T, Nakayama J, Moriya K, Kawaratani H, Momoda R, Ito K, Iio E, Nojiri S, Fujiwara K, Yoneda M, Yoshiji H, Tanaka Y, Gut dysbiosis associated with hepatitis C virus infection, Clin Infect Dis, 10.1093/cid/ciy205, 67, 6, 869-877, 2018.05, Background：Little is known about the effect of hepatitis C virus (HCV) infection on gut microbiota and the relationship between alteration of gut microbiota and chronic hepatitis C (CHC) progression. We performed a comparative study of gut microbiota composition between CHC patients and healthy individuals. Methods：Fecal samples from 166 CHC patients were compared with those from 23 healthy individuals; the gut microbiota community was analyzed using 16S ribosomal RNA gene sequencing. CHC patients were diagnosed with persistently normal serum alanine aminotransferase without evidence of liver cirrhosis (LC) (PNALT, n = 18), chronic hepatitis (CH, n = 84), LC (n = 40), and hepatocellular carcinoma in LC (n = 24). Results：Compared with healthy individuals, bacterial diversity was lower in persons with HCV infection, with a decrease in the order Clostridiales and an increase in Streptococcus and Lactobacillus. Microbiota dysbiosis already appeared in the PNALT stage with the transient increase in Bacteroides and Enterobacteriaceae. Predicted metagenomics of microbial communities showed an increase in the urease gene mainly encoded by viridans streptococci during CHC progression, consistent with a significantly higher fecal pH in CH and LC patients than in healthy individuals or those in the PNALT stage. Conclusions：HCV infection is associated with gut dysbiosis, even in patients with mild liver disease. Additionally, overgrowth of viridans streptococci can account for hyperammonemia in CH and LC. Further studies would help to propose a novel treatment strategy because the gut microbiome can be therapeutically altered, potentially reducing the complications of chronic liver disease.. |
| 10. | Masaru Tanaka, Jiro Nakayama, Development of the gut microbiota in infancy and its impact on health in later life., Allergology international : official journal of the Japanese Society of Allergology, 10.1016/j.alit.2017.07.010, 66, 4, 515-522, 2017.10, [URL], Gut microbial ecology and function are dynamic in infancy, but are stabilized in childhood. The 'new friends' have a great impact on the development of the digestive tract and host immune system. In the first year of life, especially, the gut microbiota dramatically changes through interactions with the developing immune system in the gut. The process of establishing the gut microbiota is affected by various environmental factors, with the potential to be a main determinant of life-long health. In this review, we summarize recent findings regarding gut microbiota establishment, including the importance of various factors related to the development of the immune system and allergic diseases later in life.. |
| 11. | Masaru Tanaka, Yuki Korenori, Masakazu Washio, Takako Kobayashi, Rie Momoda, Chikako Kiyohara, Aki Kuroda, Yuka Saito, Kenji Sonomoto, Jiro Nakayama, Signatures in the gut microbiota of Japanese infants who developed food allergies in early childhood., FEMS microbiology ecology, 10.1093/femsec/fix099, 93, 8, 1-11, 2017.08, [URL], Bacterial colonization in infancy is considered crucial for the development of the immune system. Recently, there has been a drastic increase in childhood allergies in Japan. Therefore, we conducted a prospective study with 56 infants on the relationship between gut microbiota in the first year of life and the development of allergies during the first 3 years. In the lactation period, organic acid producers such as Leuconostoc, Weissella and Veillonella tended to be underrepresented in subjects who developed food allergies (FA, n = 14) within the first two years. In the weaning period, children in the FA group were highly colonized by unclassified Enterobacteriaceae and two Clostridium species closely related to Clostridium paraputrificum and C. tertium, and the whole tree phylogenetic diversity index was significantly lower in the FA group. All of these differences in the weaning period were statistically significant, even after adjusting for potential confounding factors. A higher abundance of unclassified Enterobacteriaceae was also found in the other allergic group (n = 15), whereas the two Clostridium species were highly specific to the FA group. The mode of action of these Clostridium species in childhood food allergies remains unknown, warranting further investigation.. |
| 12. | Jiro Nakayama, Azusa Yamamoto, Ladie A. Palermo-Conde, Kanako Higashi, Kenji Sonomoto, Julie Tan, Yuan Kun Lee, Impact of westernized diet on gut microbiota in children on Leyte island, Frontiers in Microbiology, 10.3389/fmicb.2017.00197, 8, FEB, 2017.02, [URL], Urbanization has changed life styles of the children in some towns and cities on Leyte island in the Philippines. To evaluate the impact of modernization in dietary habits on gut microbiota, we compared fecal microbiota of 7 to 9-year-old children from rural Baybay city (n = 24) and urban Ormoc city (n = 19), and assessed the correlation between bacterial composition and diet. A dietary survey indicated that Ormoc children consumed fast food frequently and more meat and confectionary than Baybay children, suggesting modernization/westernization of dietary habits. Fat intake accounted for 27.2% of the total energy intake in Ormoc children; this was remarkably higher than in their Baybay counterparts (18.1%) and close to the upper limit (30%) recommended by the World Health Organization. Their fecal microbiota were analyzed by high-throughput 16S rRNA gene sequencing in conjunction with a dataset from five other Asian countries. Their microbiota were classified into two enterotype-like clusters with the other countries' children, each defined by high abundance of either Prevotellaceae (P-type) or Bacteroidaceae (BB-type), respectively. Baybay and Ormoc children mainly harbored P-type and BB-type, respectively. Redundancy analysis showed that P-type favored carbohydrates whereas BB-type preferred fats. Fat intake correlated positively with the Firmicutes-to-Bacteroidetes (F/B) ratio and negatively with the relative abundance of the family Prevotellaceae/genus Prevotella. A species-level analysis suggested that dietary fat positively correlated with an Oscillibacter species as well as a series of Bacteroides/Parabacteroides species, whereas dietary carbohydrate positively correlated with Dialister succinatiphilus known as succinate-utilizing bacteria and some succinate-producing species of family Prevotellaceae, Veillonellaceae, and Erysipelotrichaceae. We also found that a Succinivibrio species was overrepresented in the P-type community, suggesting the syntroph via hydrogen and succinate. Predicted metagenomics suggests that BB-type microbiota is well nourished and metabolically more active with simple sugars, amino acids, and lipids, while P-type community is more involved in digestion of complex carbohydrates. Overweight and obese children living in Ormoc, who consumed a high-fat diet, harbored microbiota with higher F/B ratio and low abundance of Prevotella. The altered gut microbiota may be a sign of a modern diet-associated obesity among children in developing areas.. |
| 13. | Yuhzo Fujita, Haruo Tsuno, Jiro Nakayama, Fermented papaya preparation restores age- related reductions in peripheral blood mononuclear cell cytolytic activity in tube- fed patients, PLoS One, 10.1371/journal.pone.0169240, 12, 1, 2017.01, [URL], Tube-fed elderly patients are generally supplied with the same type of nutrition over long periods, resulting in an increased risk for micronutrient deficiencies. Dietary polyphenols promote immunity and have anti-inflammatory, anti-carcinogenic, and anti-oxidative properties. Carica papaya Linn. is rich in several polyphenols; however, these polyphenols are poorly absorbed from the digestive tract in their original polymerized form. Therefore, we determined the molecular components of a fermented Carica papaya Linn. preparation, as well as its effects on immunity and the composition of gut microbiota in tube-fed patients. Different doses of the fermented C. papaya L. preparation were administered to three groups of tube-fed patients for 30 days. Its effects on fecal microbiota composition and immunity were assessed by 16S rRNA gene sequencing and immune-marker analysis, respectively. The chemical composition of the fermented C. papaya L. preparation was analyzed by capillary electrophoresisand liquid chromatography- time of flight mass spectrometry. The fermented C. papaya L. preparation restored peripheral blood mononuclear cell (PBMC) cytolytic activity; however, no other biomarkers of immunity were observed. Treatment with the preparation (9 g/day) significantly reduced the abundance of Firmicutes in the fecal microbiota. In particular, treatment reduced Clostridium scindens and Eggerthella lenta in most patients receiving 9 g/day. Chemical analysis identified low-molecular-weight phenolic acids as polyphenol metabolites; however, no polymerized, large-molecular-weight molecules were detected. Our study indicates that elderly patients who are tube-fed over the long-term have decreased PBMC cytolytic activity. In addition, low-molecular-weight polyphenol metabolites fermented from polymerized polyphenols restore PBMC cytolytic activity and modulate the composition of gut microbiota in tube-fed patients.. |
| 14. | Supatjaree Ruengsomwong, Orawan La-Ongkham, Jiahui Jiang, Bhusita Wannissorn, Jiro Nakayama, Sunee Nitisinprasert, Microbial Community of Healthy Thai Vegetarians and Non-Vegetarians, Their Core Gut Microbiota, and Pathogen Risk., Journal of microbiology and biotechnology, 10.4014/jmb.1603.03057, 26, 10, 1723-1735, 2016.10, [URL], Pyrosequencing analysis of intestinal microflora from healthy Thai vegetarians and non-vegetarians exhibited 893 OTUs covering 189 species. The strong species indicators of vegetarians and non-vegetarians were Prevotella copri and Bacteroides vulgatus as well as bacteria close to Escherichia hermanii with % relative abundance of 16.9 and 4.5-4.7, respectively. Core gut microbiota of the vegetarian and non-vegetarian groups consisted of 11 and 20 different bacterial species, respectively, belonging to Actinobacteria, Firmicutes, and Proteobacteria commonly found in both groups. Two species, Faecalibacterium prausnitzii and Gemmiger formicilis, had a prevalence of 100% in both groups. Three species, Clostridium nexile, Eubacterium eligens, and P. copri, showed up in most vegetarians, whereas more diversity of Collinsella aerofaciens, Ruminococcus torques, various species of Bacteroides, Parabacteroides, Escherichia, and different species of Clostridium and Eubacterium were found in most non-vegetarians. Considering the correlation of personal characters, consumption behavior, and microbial groups, the age of non-vegetarians showed a strong positive correlation coefficient of 0.54 (p = 0.001) to Bacteroides uniformis but exhibited a moderate one to Alistipes finegoldii and B. vulgatus. Only a positive moderate correlation of body mass index and Parabacteroides distasonis appeared. Based on the significant abundance of potential pathogens, the microbiota of the non-vegetarian group showed an abundance of potential pathogen varieties of Bilophila wadsworthia, Escherichia coli, and E. hermannii, whereas that of the vegetarian group served for only Klebsiella pneumoniae. These results implied that the microbiota of vegetarians with high abundance of P. copri and low potential pathogen variety would be a way to maintain good health in Thais.. |
| 15. | Yasuhiro Igarashi, Fumiya Gohda, Taito Kadoshima, Takao Fukuda, Tomoaki Hanafusa, Akane Shojima, Jiro Nakayama, Gerald F Bills, Stephen Peterson, Avellanin C, an inhibitor of quorum-sensing signaling in Staphylococcus aureus, from Hamigera ingelheimensis., The Journal of antibiotics, 10.1038/ja.2015.50, 68, 11, 707-710, 2015.11, [URL]. |
| 16. | Jiro Nakayama, Koichi Watanabe, Jiahui Jiang, Kazunori Matsuda, Shiou-Huei Chao, Pri Haryono, Orawan La-Ongkham, Martinus-Agus Sarwoko, I Nengah Sujaya, Liang Zhao, Kang-Ting Chen, Yen-Po Chen, Hsueh-Hui Chiu, Tomoko Hidaka, Ning-Xin Huang, Chikako Kiyohara, Takashi Kurakawa, Naoshige Sakamoto, Kenji Sonomoto, Kousuke Tashiro, Hirokazu Tsuji, Ming-Ju Chen, Vichai Leelavatcharamas, Chii-Cherng Liao, Sunee Nitisinprasert, Endang S Rahayu, Fa-Zheng Ren, Ying-Chieh Tsai, Yuan-Kun Lee, Diversity in gut bacterial community of school-age children in Asia., Scientific reports, 10.1038/srep08397, 5, 8397-8397, 2015.02, [URL], Asia differs substantially among and within its regions populated by diverse ethnic groups, which maintain their own respective cultures and dietary habits. To address the diversity in their gut microbiota, we characterized the bacterial community in fecal samples obtained from 303 school-age children living in urban or rural regions in five countries spanning temperate and tropical areas of Asia. The microbiota profiled for the 303 subjects were classified into two enterotype-like clusters, each driven by Prevotella (P-type) or Bifidobacterium/Bacteroides (BB-type), respectively. Majority in China, Japan and Taiwan harbored BB-type, whereas those from Indonesia and Khon Kaen in Thailand mainly harbored P-type. The P-type microbiota was characterized by a more conserved bacterial community sharing a greater number of type-specific phylotypes. Predictive metagenomics suggests higher and lower activity of carbohydrate digestion and bile acid biosynthesis, respectively, in P-type subjects, reflecting their high intake of diets rich in resistant starch. Random-forest analysis classified their fecal species community as mirroring location of resident country, suggesting eco-geographical factors shaping gut microbiota. In particular, children living in Japan harbored a less diversified microbiota with high abundance of Bifidobacterium and less number of potentially pathogenic bacteria, which may reflect their living environment and unique diet.. |
| 17. | Ravindra Pal Singh, Ken Ichi Okubo, Kaori Ohtani, Keika Adachi, Kenji Sonomoto, Jiro Nakayama, Rationale design of quorum-quenching peptides that target the VirSR system of Clostridium perfringens, FEMS Microbiology Letters, 10.1093/femsle/fnv188, 362, 22, 2015.01, [URL], In Clostridium perfringens, a 5-membered thiolactone peptide acts as an autoinducing peptide (AIPCp) to activate the VirSR two-component signal transduction system, which in turn controls the expression of genes encoding multiple toxins, including α, θ and κ. To develop anti-pathogenic agents against virulent C. perfringens, quorum-quenching peptides were rationally designed based on the structure-activity relationship (SAR) data on AIPCp. Alanine scanning study of AIPCp suggested that Trp3 and Phe4 are involved in receptor binding and activation, respectively. On the basis of the SAR, we designed two quorum-quenching peptides with different modes of action: Z-AIPCp-L2A/T5A (partial agonist) and Z-AIPCp-F4A/T5S (partial antagonist). Both peptides significantly attenuated transcription of θ toxin gene (pfoA) in a virulent strain of C. perfringens with IC50 = 0.32 and 0.72 μM, respectively.. |
| 18. | Said E. Desouky, Akane Shojima, Ravindra Pal Singh, Takahisa Matsufuji, Yasuhiro Igarashi, Takashi Suzuki, Tohru Yamagaki, Ken Ichi Okubo, Kaori Ohtani, Kenji Sonomoto, Jiro Nakayama, Cyclodepsipeptides produced by actinomycetes inhibit cyclic-peptide-mediated quorum sensing in Gram-positive bacteria, FEMS Microbiology Letters, 10.1093/femsle/fnv109, 362, 14, 2015.01, [URL], Cyclic peptides are commonly used as quorum-sensing autoinducers in Gram-positive Firmicutes bacteria. Well-studied examples of such molecules are thiolactone and lactone, used to regulate the expression of a series of virulence genes in the agr system of Staphylococcus aureus and the fsr system of Enterococcus faecalis, respectively. Three cyclodepsipeptides WS9326A,WS9326B and cochinmicin II/III were identified as a result of screening actinomycetes culture extracts for activity against the agr/fsr system. These molecules are already known as receptor antagonists, the first two for tachykinin and the last one for endothelin. WS9326A also inhibited the transcription of pfoA regulated by the VirSR two-component system in Clostridium perfringens. Receptor-binding assays using a fluorescence-labeled autoinducer (FITC-GBAP) showed that WS9326A and WS9326B act as receptor antagonists in this system. In addition, an ex vivo assay showed that WS9326B substantially attenuated the toxicity of S. aureus for human corneal epithelial cells. These results suggest that these three natural cyclodepsipeptides have therapeutic potential for targeting the cyclic peptide-mediated quorum sensing of Gram-positive pathogens.. |
| 19. | Akane Shojima, Jiro Nakayama, Quorum sensing in gram-positive bacteria Assay protocols for staphylococcal agr and enterococcal fsr systems, Methods in Molecular Biology, 10.1007/978-1-4939-0467-9_3, 1147, 33-41, 2014.01, [URL], A thiolactone/lactone peptide-mediated quorum sensing (QS) system is commonly employed in gram- positive bacteria to control the expression of a variety of phenotypes, including the production of virulence factors and biofilm formation. Here, we describe assay protocols for the well-studied QS systems (agr and fsr) of two representative gram-positive pathogens, Staphylococcus aureus and Enterococcus faecalis . These convenient assay systems are useful for the screening of QS inhibitors as well as for basic research to address the mechanism of these QS systems.. |
| 20. | Hiroshi Ono, Shoko Nishio, Jun Tsurii, Tetsuhiro Kawamoto, Kenji Sonomoto, Jiro Nakayama, Monitoring of the microbiota profile in nukadoko, a naturally fermented rice bran bed for pickling vegetables, Journal of Bioscience and Bioengineering, 10.1016/j.jbiosc.2014.04.017, 118, 5, 520-525, 2014.01, [URL], Nukadoko is a fermented rice bran mash traditionally used for pickling vegetables in Japan. To date, the production of both homemade and commercial nukadoko depends on natural fermentation without using starter cultures. Here, we monitored chemical and microbiological changes in the initial batch fermentation of nukadoko. Nukadoko samples were prepared by spontaneous fermentation of four different brands of rice bran, and microbiome dynamics were analyzed for 2 months. In the first week, non-Lactobacillales lactic acid bacteria (LAB) species, which differed among the samples, grew proportionally to pH decrease and lactate increase. Thereafter, Lactobacillus plantarum started growing and consumed residual sugars, causing further lactate increase in nukadoko. Finally, microbial communities in all tested nukadoko samples were dominated by L.plantarum. Taken together, our results suggest that the mixture of the fast-growing LAB species and slow-growing L.plantarum may be used as a suitable starter culture to promote the initial fermentation of nukadoko.. |
| 21. | Said E. Desouky, Kenzo Nishiguchi, Takeshi Zendo, Yasuhiro Igarashi, Paul Williams, Kenji Sonomoto, Jiro Nakayama, High-throughput screening of inhibitors targeting Agr/Fsr quorum sensing in staphylococcus aureus and enterococcus faecalis, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb.120769, 77, 5, 923-927, 2013.06, [URL], Staphylococcus aureus and Enterococcus faecalis employ cyclic peptide-mediated quorum sensing (QS) systems, termed agr and fsr respectively, to regulate the expression of a series of virulence genes. To identify quorum sensing inhibitors (QSIs) that target agr/fsr systems, an efficient screening system was established. In addition to the gelatinase-induction assay to examine E. faecalis fsr QS, the use of an S. aureus agr reporter strain that carries luciferase and green fluorescence protein genes under the agr P3 promoter facilitated the development of a high-throughput screen (HTS) for QSIs. As a result of screening of 906 actinomycetes culture extracts, four showed QSI activity against the agr and fsr systems without growth inhibitory activity. The extracts were purified on a small scale, and three HPLC peaks were obtained with obvious QSI activity. In sum, the established HTS system is a promising strategy for the discovery of anti-pathogenic agents targeting cyclic peptide-mediated QS in Gram-positive pathogens.. |
| 22. | Jiro Nakayama, Ryoji Yokohata, Mami Sato, Takashi Suzuki, Takahisa Matsufuji, Kenzo Nishiguchi, Takeshi Kawai, Yosuke Yamanaka, Koji Nagata, Masaru Tanokura, Kenji Sonomoto, Development of a peptide antagonist against fsr quorum sensing of Enterococcus faecalis., ACS chemical biology, 10.1021/cb300717f, 8, 4, 804-811, 2013.04, [URL], Enterococcus faecalis fsr quorum sensing (QS) involves an 11-residue cyclic peptide named gelatinase biosynthesis-activating pheromone (GBAP) that autoinduces two pathogenicity-related extracellular proteases in a cell density-dependent fashion. To identify anti-pathogenic agents that target fsr QS signaling, peptide antagonists of GBAP were created by our unique drug design approach based on reverse alanine scanning. First of all, a receptor-binding scaffold (RBS), [Ala(4,5,6,8,9,11)]Z-GBAP, was created, in which all amino acids within the ring region of GBAP, except for two essential aromatic residues, were substituted to alanine. Next, the substituted alanine residues were changed back to the original amino acid one by one, permitting selection of those peptide combinations exhibiting increased antagonist activity. After three cycles of this reverse alanine scan, [Ala(5,9,11)]Z-GBAP was obtained as a maximally reverted peptide (MRP) holding the strongest antagonist activity. Then, the fifth residue in MRP, which is one of the critical residues to determine agonist/antagonist activity, was further modified by substituting with different types of amino acids including unnatural amino acids. As a result, [Tyr(Bzl)(5), Ala(9,11)]Z-GBAP, named ZBzl-YAA5911, showed the strongest antagonist activity [IC(50) = 26.2 nM and Kd against GBAP receptor (FsrC) = 39.4 nM]. In vivo efficacy of this peptide was assessed with an aphakic rabbit endophthalmitis model. ZBzl-YAA5911 suppressed the translocation of E. faecalis from the aqueous humor into the vitreous cavity by more than 1 order of magnitude and significantly reduced retinal damage. We propose that ZBzl-YAA5911 or its derivatives would be useful as anti-infective agents to attenuate virulence expression in this opportunistic pathogen.. |
| 23. | Jiro Nakayama, Takako Kobayashi, Shigemitsu Tanaka, Yuki Korenori, Atsushi Tateyama, Naoshige Sakamoto, Chikako Kiyohara, Taro Shirakawa, Kenji Sonomoto, Aberrant structures of fecal bacterial community in allergic infants profiled by 16S rRNA gene pyrosequencing., FEMS immunology and medical microbiology, 10.1111/j.1574-695X.2011.00872.x, 63, 3, 397-406, 2011.12, [URL], We investigated the correlation between fecal bacteria composition in early infancy and the prevalence of allergic diseases in late infancy. The fecal microbiota in the first 2 months was profiled using the 16S rRNA V6 short-tag sequences in the community and statistically compared between two groups of subjects who did and did not show allergic symptoms in the first 2 years (n = 11 vs. 11). In the allergic group, genus Bacteroides at 1 month and genera Propionibacterium and Klebsiella at 2 months were more abundant, and genera Acinetobacter and Clostridium at 1 month were less abundant than in the nonallergic group. Allergic infants who showed high colonization of Bacteroides and/or Klebsiella showed less colonization of Clostridium perfringens/butyricum, suggesting antagonism between these bacterial groups in the gastrointestinal tract. It was also remarkable that the relative abundance of total Proteobacteria, excluding genus Klebsiella, was significantly lower in the allergic than in the nonallergic group at the age of 1 month. These results indicate that pyrosequence-based 16S rRNA gene profiling is valid to find the intestinal microbiotal disorder that correlates with allergy development in later life.. |
| 24. | Naoshige Sakamoto, Shigemitsu Tanaka, Kenji Sonomoto, Jiro Nakayama, 16S rRNA pyrosequencing-based investigation of the bacterial community in nukadoko, a pickling bed of fermented rice bran., International journal of food microbiology, 10.1016/j.ijfoodmicro.2010.10.017, 144, 3, 352-359, 2011.01, [URL], Nukadoko is a naturally fermented rice bran mash traditionally used for pickling vegetables in Japan; its refreshment and fermentation cycles sometimes continue for many years. Here, we investigated the structure and dynamics of the bacterial community in nukadoko by conducting pyrosequencing and quantitative polymerase chain reaction (PCR) analyses of 16S ribosomal RNA genes (rDNA). Of the 16 different samples studied, 13 showed Lactobacillus-dominated microbiota, suggesting that aged nukadoko samples tend to realize a niche, favorable Lactobacillus species. The lactic acid bacterial community of each of the 16 samples was classified into 3 types according to the presence or absence of 2 predominant species, Lactobacillus namurensis and Lactobacillus acetotolerans. The dynamics of the bacterial community during fermentation and the subsequent ripening process were examined using a laboratory model of nukadoko inoculated with an aged nukadoko sample (inoculated model). Lb. namurensis grew rapidly in the first 2 days, accompanied with a rapid decrease in pH and an increase in lactate levels, while Lb. acetotolerans grew with a longer doubling time and slow acidification during the 20 days after inoculation. On the other hand, spontaneous fermentation of the nukadoko model prepared from fresh rice bran without the nukadoko inoculation (inoculant-free model), showed the growth of some non-Lactobacillus species such as staphylococci and bacilli within the first 10 days; thereafter, Lb. namurensis was dominant, while Lb. acetotolerans was not detected during the 20-day experimental period. These results suggest that the naturally established Lactobacillus community in aged nukadoko is effectively involved in the biocontrol of the microbial community of nukadoko during the refreshment and fermentation cycles.. |
| 25. | Jiro Nakayama, Yumi Uemura, Kenzo Nishiguchi, Norito Yoshimura, Yasuhiro Igarashi, Kenji Sonomoto, Ambuic acid inhibits the biosynthesis of cyclic peptide quormones in gram-positive bacteria., Antimicrobial agents and chemotherapy, 10.1128/AAC.00995-08, 53, 2, 580-586, 2009.02, [URL], Quorum sensing is a cell-density-dependent regulatory system in gram-positive bacteria and is often regulated by cyclic peptides called "quormones," which function as extracellular communication signals. With an aim to discover an antipathogenic agent targeting quorum sensing in gram-positive bacteria, we screened 153 samples of fungal butanol extracts with the guidance of the inhibition of quorum-sensing-mediated gelatinase production in Enterococcus faecalis. Following the screenings, we found that ambuic acid, a known secondary fungal metabolite, inhibited the quorum-sensing-mediated gelatinase production without influencing the growth of E. faecalis. We further demonstrated that ambuic acid targeted the biosynthesis of a cyclic peptide quormone called gelatinase biosynthesis-activating pheromone. Furthermore, ambuic acid also inhibited the biosynthesis of the cyclic peptide quormones of Staphylococcus aureus and Listeria innocua. These results suggest the potential use of ambuic acid as a lead compound of antipathogenic drugs that target the quorum-sensing-mediated virulence expression of gram-positive bacteria.. |
| 26. | Kenzo Nishiguchi, Koji Nagata, Masaru Tanokura, Kenji Sonomoto, Jiro Nakayama, Structure-activity relationship of gelatinase biosynthesis-activating pheromone of Enterococcus faecalis., Journal of bacteriology, 10.1128/JB.01029-08, 191, 2, 641-650, 2009.01, [URL], The expression of pathogenicity-related extracellular proteases, namely, gelatinase and serine protease, in Enterococcus faecalis is positively regulated by a quorum-sensing system mediated by an autoinducing peptide called gelatinase biosynthesis-activating pheromone (GBAP). GBAP is an 11-amino-acid-residue cyclic peptide containing a lactone linkage. To study the structure-activity relationship of GBAP, we synthesized a series of GBAP analogues and evaluated their activities by a gelatinase-inducing assay and newly developed receptor-binding assays in which fluorescence-labeled peptides bound onto the FsrC-overexpressing Lactococcus lactis cell surface were observed by fluorescent microscopy and quantified by using a fluorophotometer. Alanine-scanning analysis of GBAP showed that the entire ring region was involved in the GBAP agonist activity, while side chains of the tail region were not strictly recognized. The alanine substitution of Phe(7) or Trp(10) almost abolished their receptor-binding abilities and GBAP agonist activities, suggesting that these two aromatic side chains are strongly involved in receptor interaction and activation. Furthermore, the Trp(10) substitution with natural and unnatural aromatic amino acids, except pentafluorophenylalanine, caused no loss of agonist activity. This suggested the importance of a negative electrostatic potential created by an pi-electron cloud on the aromatic ring surface. Structural analysis of GBAP with nuclear magnetic resonance spectroscopy revealed that the ring region adopted a hairpin-like fold and was tightly packed into a compact form. The side chain of Trp(10) was partially buried in the core structure, contributing to the stabilization of the compact form, while that of Phe(7) was extended from the core structure into the solvent and was probably directly involved in receptor binding.. |
| 27. | Toshio Fujii, Colin Ingham, Jiro Nakayama, Marke Beerthuyzen, Ryoko Kunuki, Douwe Molenaar, Mark Sturme, Elaine Vaughan, Michiel Kleerebezem, Willem De Vos, Two homologous agr-like quorum-sensing systems cooperatively control adherence, cell morphology, and cell viability properties in Lactobacillus plantarum WCFS1, Journal of Bacteriology, 10.1128/JB.01489-07, 190, 23, 7655-7665, 2008.12, [URL], A two-component regulatory system of Lactobacillus plantarum, encoded by genes designated lamK and lamR (hpk10 and rrp10), was studied. The lamK and lamR genes encode proteins which are highly homologous to the quorum-sensing histidine kinase LamC and the response regulator LamA, respectively. Transcription analysis of the lamKR operon and the lamBDCA operon and liquid chromatography-mass spectrometry analysis of production of the LamD558 autoinducing peptide were performed for ΔlamA, ΔlamR, ΔlamA ΔlamR deletion mutants and a wild-type strain. The results suggested that lamA and lamR are cooperating genes. In addition, typical phenotypes of the ΔlamA mutant, such as reduced adherence to glass surfaces and filamentous cell morphology, were enhanced in the ΔlamA ΔlamR mutant. Microarray analysis suggested that the same cell wall polysaccharide synthesis genes, stress response-related genes, and cell wall protein-encoding genes were affected in the ΔlamA and ΔlamA ΔlamR mutants. However, the regulation ratio was more significant for the ΔlamA ΔlamR mutant, indicating the cooperative effect of LamA and LamR.. |
| 28. | Jiro Nakayama, Hiroyuki Hoshiko, Mizuki Fukuda, Hidetoshi Tanaka, Naoshige Sakamoto, Shigemitsu Tanaka, Kazutoshi Ohue, Kenji Sakai, Kenji Sonomoto, Molecular monitoring of bacterial community structure in long-aged nukadoko: pickling bed of fermented rice bran dominated by slow-growing lactobacilli., Journal of bioscience and bioengineering, 10.1263/jbb.104.481, 104, 6, 481-489, 2007.12, [URL], Nukadoko is the fermented rice bran bed traditionally used for pickling vegetables in Japan. Here, we investigate the bacterial community structure of nukadoko using several culture-independent methods. Denaturing gradient gel electrophoresis (DGGE) and sequence analysis of V2-V3 16S rRNA gene (16S rDNA) fragments amplified from a long-aged nukadoko bacterial community indicated seven predominant operational taxonomic units (OTUs) closely related to known Lactobacillus species. Phylogenetic analysis of these OTUs indicated a major cluster consisting of six OTUs including a dominant OTU closely related to Lactobacillus acidifarinae and one distinct OTU corresponding to Lactobacillus acetotolerans. L. acetotolerans was commonly detected as a dominant species in samples from different seasons. The succession of microbial community structure in the fermentation and ripening processes was investigated using a laboratory model nukadoko. The L. acidifarinae-like bacteria grew rapidly with a pH decrease in the first few days after inoculation, whereas L. acetotolerans grew slowly and became dominant after one week. Real-time quantitative polymerase chain reaction (Q-PCR) showed that the doubling time of L. acetotolerans was 12 h, while that of total bacteria was 4 h. Real-time quantitative reverse transcription polymerase chain reaction (Q-RT-PCR) targeting 16S rRNA showed a low metabolic activity of L. acetotolerans throughout the fermentation and ripening processes. Fluorescence in situ hybridization (FISH) showed that L. acetotolerans was a dominant bacterium in the ripening period and had a low metabolic activity. These results indicate that the slow-growing L. acetotolerans stably dominated nukadoko microbiota after the L. acidifarinae-like bacteria mainly contributed to the lactic acid fermentation of the rice bran.. |
| 29. | Prapa Songjinda, Jiro Nakayama, Atsushi Tateyama, Shigemitsu Tanaka, Mina Tsubouchi, Chikako Kiyohara, Taro Shirakawa, Kenji Sonomoto, Differences in developing intestinal microbiota between allergic and non-allergic infants A pilot study in Japan, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb.70154, 71, 9, 2338-2342, 2007.11, [URL], The bacterial compositions of feces were monitored in the first 2 months for 15 infants born in Japan, including eight subjects who developed allergy by the age of 2 years. Primer sets targeting six predominant bacterial groups in the infant intestine, Bacteroidaceae, Enterobacteriaceae, bifidobacteria, enterococci, lactobacilli, and the Clostridium perfringens group, were used for real-time PCR to quantitate each population in the feces. The population of Bacteroidaceae was significantly higher in the allergic group at the ages of 1 month (P = 0.03) and 2 months (P = 0.05) than in the non-allergic group, while no statistically significant difference was observed for the other bacterial populations.. |
| 30. | Jiro Nakayama, Emi Tanaka, Reiko Kariyama, Koji Nagata, Kenzo Nishiguchi, Ritsuko Mitsuhata, Yumi Uemura, Masaru Tanokura, Hiromi Kumon, Kenji Sonomoto, Siamycin attenuates fsr quorum sensing mediated by a gelatinase biosynthesis-activating pheromone in Enterococcus faecalis., Journal of bacteriology, 10.1128/JB.00969-06, 189, 4, 1358-1365, 2007.02, [URL], The expression of two Enterococcus faecalis virulence-related proteases, gelatinase (GelE) and serine protease (SprE), is positively regulated by a quorum-sensing system encoded by the fsr gene cluster. In this system, E. faecalis secretes an autoinducing peptide, gelatinase biosynthesis-activating pheromone (GBAP), which triggers the FsrC-FsrA two-component regulatory system controlling the expression of two transcripts, fsrBDC and gelE-sprE. In the present study, we screened actinomycete metabolites for inhibitors of fsr quorum sensing. E. faecalis was cultured with each actinomycete culture supernatant tested, and the production of gelatinase and the production of GBAP were examined using the first screening and the second screening, respectively. Culture supernatant of Streptomyces sp. strain Y33-1 had the most potent inhibitory effect on both gelatinase production and GBAP production without inhibiting E. faecalis cell growth. The inhibitor in the culture supernatant was identified as a known peptide antibiotic, siamycin I. Siamycin I inhibited both gelatinase production and GBAP production at submicromolar concentrations, and it inhibited E. faecalis cell growth at concentrations above micromolar concentrations. Quantitative analysis of fsrBDC and gelE-sprE transcripts revealed that siamycin I suppressed the expression of both transcripts at a sublethal concentration. Siamycin I attenuated gelatinase production even when an overdose of GBAP was exogenously added to the culture. These results suggested that siamycin I inhibited the GBAP signaling via the FsrC-FsrA two-component regulatory system in a noncompetitive manner. The sublethal concentrations of siamycin I also attenuated biofilm formation. Treatment with siamycin could be a novel means of treating enterococcal infections.. |
| 31. | Jiro Nakayama, Shengmin Chen, Nozomi Oyama, Kenzo Nishiguchi, Essam A Azab, Emi Tanaka, Reiko Kariyama, Kenji Sonomoto, Revised model for Enterococcus faecalis fsr quorum-sensing system: the small open reading frame fsrD encodes the gelatinase biosynthesis-activating pheromone propeptide corresponding to staphylococcal agrd., Journal of bacteriology, 10.1128/JB.00865-06, 188, 23, 8321-8326, 2006.12, [URL], Gelatinase biosynthesis-activating pheromone (GBAP) is an autoinducing peptide involved in Enterococcus faecalis fsr quorum sensing, and its 11-amino-acid sequence has been identified in the C-terminal region of the 242-residue deduced fsrB product (J. Nakayama et al., Mol. Microbiol. 41:145-154, 2001). In this study, however, we demonstrated the existence of fsrD, encoding the GBAP propeptide, which is in frame with fsrB but is translated independently of fsrB. It was also demonstrated that FsrB', an FsrD segment-truncated FsrB, functions as a cysteine protease-like processing enzyme to generate GBAP from FsrD. This revised model is consistent with the staphylococcal agr system.. |
| 32. | Mark H J Sturme, Jiro Nakayama, Douwe Molenaar, Yoshiko Murakami, Ryoko Kunugi, Toshio Fujii, Elaine E Vaughan, Michiel Kleerebezem, Willem M 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, 187, 15, 5224-5235, 2005.08, [URL], 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 LamD-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.. |
| 33. | Prapa Songjinda, Jiro Nakayama, Yumiko Kuroki, Shigemitsu Tanaka, Sanae Fukuda, Chikako Kiyohara, Tetsuro Yamamoto, Kunio Izuchi, Taro Shirakawa, Kenji Sonomoto, Molecular monitoring of the developmental bacterial community in the gastrointestinal tract of Japanese infants, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb.69.638, 69, 3, 638-641, 2005.03, [URL], The dynamics of the developmental bacterial community in the Japanese neonatal gastrointestinal tract were examined by monitoring 16S ribosomal RNA gene (rDNA) diversity in fecal samples by PCR and denaturing gradient gel electrophoresis (DGGE). The results showed a certain pattern common in infants without antibiotic treatment, in which aerobes, e.g., Pseudomonas, appeared first and were then immediately replaced by facultative anaerobe, Enterococcus, Streptococcus, and Enterobacteriaceae through the first month, and finally strictly anaerobic Bifidobactrerium appeared.. |
| 34. | Jiro Nakayama, Antoon D L Akkermans, Willem M De Vos, High-throughput PCR screening of genes for three-component regulatory system putatively involved in quorum sensing from low-G + C gram-positive bacteria., Bioscience, biotechnology, and biochemistry, 10.1271/bbb.67.480, 67, 3, 480-489, 2003.03, [URL], Quorum sensing of gram-positive bacteria is often regulated by three-component regulatory system composed of autoinducing peptide, sensor kinase and response regulator. We used PCR to study a gene cassette encoding this three-component regulatory system. Degenerate primers were designed from consensus amino acid sequences in the HPK10 subfamily, mostly involved in quorum sensing. Products amplified from genomic DNA of Lactobacillus, Enterococcus, and Clostridium species were cloned and sequenced; their deduced amino acid sequences were similar to those of members of the HPK10 subfamily. Complete genes for the putative gene cassette were cloned by inverse PCR from L. paracasei E93490 and L. plantarum WCFS6. Phylogenetic analysis grouped the cloned putative HPKs into the HPK10 subfamily. These results indicated the usefulness of this high-throughput gene screening and suggested that the three-component regulatory gene cassette are widely present.. |
| 35. | Jiro Nakayama, Reiko Kariyama, Hiromi Kumon, Description of a 23.9-kilobase chromosomal deletion containing a region encoding fsr genes which mainly determines the gelatinase-negative phenotype of clinical isolates of Enterococcus faecalis in urine., Applied and environmental microbiology, 10.1128/AEM.68.6.3152-3155.2002, 68, 6, 3152-3155, 2002.06, [URL], Expression of virulence-related extracellular proteases, gelatinase, and serine protease of Enterococcus faecalis is regulated by a quorum-sensing system encoded by the fsr gene cluster. In this study, a 23.9-kb chromosomal deletion containing the fsr gene cluster region was found to be present in the majority (79%) of gelatinase-negative clinical isolates of E. faecalis from urine.. |
| 36. | Takaaki Horii, Hiromichi Nagasawa, Jiro Nakayama, Functional analysis of TraA, the sex pheromone receptor encoded by pPD1, in a promoter region essential for the mating response in Enterococcus faecalis, Journal of Bacteriology, 10.1128/JB.184.22.6343-6350.2002, 184, 22, 6343-6350, 2002.01, [URL], Conjugative transfer of a bacteriocin plasmid, pPD1, of Enterococcus faecalis is induced in response to a peptide sex pheromone, cPD1, secreted from plasmid-free recipient cells. cPD1 is taken up by a pPD1 donor cell and binds to an intracellular receptor, TraA. Once a recipient cell acquires pPD1, it starts to produce an inhibitor of cPD1, termed iPD1, which functions as a TraA antagonist and blocks self-induction in donor cells. In this study, we discuss how TraA transduces the signal of cPD1 to the mating response. Gel mobility shift assays indicated that TraA is bound to a traA-ipd intergenic region, which is essential for cPD1 response. DNase I footprinting analysis suggested the presence of one strong (tab1) and two weak (tab2 and tab3) TraA-binding sites in the intergenic region. Primer extension analysis implied that the transcriptional initiation sites of traA and ipd were located in the intergenic region. Northern analysis showed that cPD1 upregulated and downregulated transcription of ipd and traA, respectively. The circular permutation assay showed that TraA bent a DNA fragment corresponding to the tab1 region, and its angle was changed in the presence of cPD1 or iPD1. From these data, we propose a model that TraA changes the conformation of the tab1 region in response to cPD1 and upregulates the transcription of ipd, which may lead to expression of genes required for the mating response.. |
| 37. | Jiro Nakayama, Yong Cao, Takaaki Horii, Shohei Sakuda, Hiromichi Nagasawa, Chemical synthesis and biological activity of the gelatinase biosynthesis-activating pheromone of enterococcus faecalis and its analogs, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb.65.2322, 65, 10, 2322-2325, 2001.10, [URL], An 11-residue peptide lactone, termed the gelatinase biosynthesis-activating pheromone (GBAP), triggers the production of the pathogenicit)-related extracellular proteases, gelatinase and serine protease, in Enterococcus faecalis. In this study, we synthesized GBAP and its analogs and examined their gelatinase biosynthesis-inducing activity. This study on the structure-activity relationship shows that a lactone ring was indispensable for the activity.. |
| 38. | Jiro Nakayama, Yong Cao, Takaaki Horii, Shohei Sakuda, Antoon D L Akkermans, Willem M. De Vos, Hiromichi Nagasawa, Gelatinase biosynthesis-activating pheromone: a peptide lactone that mediates a quorum sensing in Enterococcus faecalis, Molecular Microbiology, 10.1046/j.1365-2958.2001.02486.x, 41, 1, 145-154, 2001.01, [URL], Biosynthesis of gelatinase, a virulence factor of Enterococcus faecalis, was found to be regulated in a cell density-dependent fashion in which its production is active in late log to early stationary phase. Addition of early stationary phase culture filtrate to medium shifted the onset of gelatinase production to that of mid-log phase, suggesting that E. faecalis secretes a gelatinase biosynthesis-activating pheromone (GBAP). GBAP was isolated from culture supernatant of E. faecalis OG1S-P. Structural analysis suggested GBAP to be an 11-residue cyclic peptide containing a lactone structure, in which the α-carboxyl group of the C-terminal amino acid is linked to a hydroxyl group of the serine of the third residue. A synthetic peptide possessing the deduced structure showed GBAP activity at nanomolar concentrations as did natural GBAP. Database searches revealed that GBAP corresponds to a C-terminal part of a 242-residue FsrB protein. Northern analysis showed that GBAP slowly induces the transcription of two operons, fsrB-fsrC encoding FsrB and a putative histidine kinase FsrC and gelE-sprE encoding gelatinase GelE and serine protease SprE. Strains with an insertion mutation in either fsrC or a putative response regulator gene fsrA failed to respond to GBAP, suggesting that the GBAP signal is transduced by a two-component regulatory system.. |
| 39. | Jiro Nakayama, Yuuichiro Takanami, Akinori Suzuki, Analysis of pheromone binding and pheromone reception by Enterococcus faecalis, Advances in Experimental Medicine and Biology, 418, 1033-1035, 1997.10. |
| 40. | Jiro Nakayama, Don B. Clewell, Akinori Suzuki, Targeted disruption of the PD78 gene (traF) reduces pheromone-inducible conjugal transfer of the bacteriocin plasmid pPD1 in Enterococcus faecalis, FEMS Microbiology Letters, 10.1016/0378-1097(95)00118-O, 128, 3, 283-288, 1995.05, [URL], Bacterial sex pheromone, cPD1, induces sexual aggregation of Enterococcus faecalis harboring the bacteriocin plasmid, pPD1, and enables pPD1 to transfer at high frequency in a liquid culture. PD78 is a cPD1-inducible cell surface protein encoded by pPD1. The PD78 gene, traF, was disrupted by homologous recombination between pPD1 and an artificial vector having a deletion in the middle portion of traF. The disruption of traF did not affect the cPD1-inducible aggregation but reduced the transfer frequency of pPD1 to 2% of the wild-type level.. |
| 41. | Jiro Nakayama, Yukitsugu Ono, Akinori Suzuki, Isolation and Structure of the Sex Pheromone Inhibitor, iAM373, of Enterococcus faecalis, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb.59.1358, 59, 7, 1358-1359, 1995.01, [URL], An Enterococcus faecalis plasmid, pAM373, has a high frequency of transfer in a liquid medium when induced by a recipient-produced sex pheromone, cAM373. The sex pheromone inhibitor against cAM373, termed iAM373, was isolated from a culture supernatant of E. faecalis harboring pAM377 (=pAM373::Tn917), and its structure was identified as a heptapeptide, H-Ser-Ile-Phe-Thr-Leu-Val-Ala-OH.. |
| 42. | Jiro Nakayama, Yuki Abe, Yukitsugu Ono, Akira Isogai, Akinori Suzuki, Isolation and Structure of the Enterococcus faecalis Sex Pheromone, cOB1, that Induces Conjugal Transfer of the Hemolysin/Bacteriocin Plasmids, pOB1 and pYI1, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb.59.703, 59, 4, 703-705, 1995.01, [URL], A bacterial sex pheromone, cOB1, which induces conjugal transfer of the Enterococcus faecalis hemolysin-bacteriocin (Hly/Bac) plasmid, pOB1, was isolated from the culture broth of pOB1-free E. faecalis. Its structure was found to be a hydrophobic octapeptide, H-Val-Ala-Val-Leu-Val-Leu-Gly-Ala-OH. The cOB1 peptide induced the mating response of not only pOB1 but also another incompatibility group Hly/Bac plasmid, pYI1.. |
| 43. | Jiro Nakayama, K. Yoshida, H. Kobayashi, A. Isogai, D. B. Clewell, A. Suzuki, Cloning and characterization of a region of Enterococcus faecalis plasmid pPD1 encoding pheromone inhibitor (ipd), pheromone sensitivity (traC), and pheromone shutdown (traB) genes, Journal of Bacteriology, 10.1128/jb.177.19.5567-5573.1995, 177, 19, 5567-5573, 1995.01, [URL], Bacteriocin plasmid pPD1 in Enterococcus faecalis encodes a mating response to recipient-produced sex pheromone cPD1. Once a recipient acquires pPD1, transconjugants apparently shut off cPD1 activity in broth culture and no longer behave as recipients for pPD1. This event is performed by synthesis of the pheromone inhibitor iPD1 and also by repression of cPD1 production, the so-called 'pheromone shutdown.' A 5.4-kb EcoRV-HincII segment of pPD1, which expressed iPD1 in Escherichia coli, was sequenced and found to be organized as traC-traB-traA-ipd; each open reading frame is analogous to that found in other pheromone plasmids, pAD1 and pCF10, and thus is designated in accordance with the nomenclature in pAD1. The ipd gene encodes a peptide consisting of 21 amino acids, in which the C-terminal eight residues correspond to iPD1. The putative TraC product has a strong similarity to oligopeptide-binding proteins found in other bacterial species, as do pheromone-binding proteins of pCF10 and pPD1. A strain carrying traC- disrupted pPD1 required a concentration of cPD1 fourfold higher than that needed by the wild-type strain for induction of sexual aggregation. These results suggest that the TraC product contributes to pheromone sensitivity as o pheromone-binding protein. A strain transformed with traB-disrupted pPD1 produced a high level of cPD1 similar to that produced by plasmid-free recipients and underwent self-induction. Thus, the TraB product contributes to cPD1 shutdown.. |
| 44. | Jiro Nakayama, R. E. Ruhfel, G. M. Dunny, A. Isogai, A. Suzuki, The prgQ gene of the Enterococcus faecalis tetracycline resistance plasmid pCF10 encodes a peptide inhibitor, iCF10, Journal of Bacteriology, 10.1128/jb.176.23.7405-7408.1994, 176, 23, 7405-7408, 1994.01, [URL], Conjugative transfer of the Enterococcus faecalis tetracycline resistance plasmid pCF10 is stimulated by a peptide pheromone, cCF10. Once a recipient strain acquires pCF10 and thus becomes a pheromone-responsive donor, cCF10 activity is no longer detected in culture filtrates. Here we show that pCF10 encodes a peptide inhibitor, iCF10, secreted by donor cells; this inhibitor antagonizes the cCF10 activity in culture filtrates. In order to detect and quantitate iCF10, we developed a reverse-phase high-performance liquid chromatography assay in which the inhibitor peptide elutes separately from the pheromone; this type of assay enabled us to determine that lack of pheromone activity in donor culture filtrates was due to secretion of a mixture of iCF10 and cCF10, rather than abolition of cCF10 secretion. The gene encoding iCF10, prgQ, is located on the EcoRI-C fragment of pCF10. The open reading frame comprising the prgQ gene encodes a 23-amino-acid precursor that resembles a signal peptide. This precursor is cleaved to the mature heptapeptide iCF10 during the secretion process.. |
| 45. | Jiro Nakayama, Hiroshi Watarai, Akira Isogai, Akinori Suzuki, Immunological Characterization of Pheromone-induced Proteins Associated with Sexual Aggregation in Enterococcus faecalis, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb.56.264, 56, 2, 264-269, 1992.01, [URL], Sexual aggregation involved in conjugative transfer of the Enterococcus faecalis plasmids pPDl and pADl is enhanced by sex pheromones cPDl and cADl, respectively, which are excreted from recipient cells. PD78 (78kDa) and AD74 (74kDa) were detectable on the surface of donors harboring pPDl and pAD1, respectively, at the time of cell aggregation. The proteins PD78 and AD74 were purified and used to raise anti-PD78 and anti-AD74 antibodies. The antibodies blocked the sexual aggregation and the plasmid transfer. Anti-AD74 antibody reacted to both 153 kDa proteins extracted from cPDl and cADl-induced donor cells after lysozyme digestion of cell wall. Pheromone-induced synthesis of PD78 and AD74, when both plasmids were present in the same cell, was independent.. |
| 46. | Jiro Nakayama, Hiroshi Watarai, Akira Isogai, Akinori Suzuki, C-Terminal Identification of AD74, a Proteolytic Product of Enterococcus faecalis Aggregation Substance Application of Liquid Chromatography/Mass Spectrometry, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb.56.127, 56, 1, 127-131, 1992.01, [URL], Sexual aggregation involved in conjugative transfer of Enterococcus faecalis plasmid pADl is enhanced by the sex pheromone cADl, which is excreted from recipient cells. A membrane-anchored 137 kDa protein is a pADl-encoded aggregation substance designated asal, which is responsible for cell-cell contact and leads to the aggregation of cells. An AD74 protein is a proteolytic product corresponding to the N-terminal half of asal. The C-terminal of AD74 was identified as lysine at position 510 (K-510) by liquid chromatography/mass spectrometry (LC/MS): it indicates that asal is cleaved specifically between K-510 and G-511.. |
| 47. | Don B. Clewell, Linda T. Pontius, Florence Y. An, Yasuyoshi Ike, Akinori Suzuki, Jiro Nakayama, Nucleotide sequence of the sex pheromone inhibitor (iAD1) determinant ofEnterococcus faecalis conjugative plasmid pAD1, Plasmid, 10.1016/0147-619X(90)90019-9, 24, 2, 156-161, 1990.09, The determinant for the peptide sex pheromone inhibitor iAD1 (iad) on the hemolysin/bacteriocin plasmid pAD1 ofEnterococcus faecalis was sequenced. The sequence reveals a 22-amino-acid precursor with the car{ballot box}yl-terminal 8 residues corresponding to iAD1. It appears that iAD1 is a component of its own signal sequence. © 1990 Academic Press, Inc. All rights reserved.. |
| 48. | Seiichi Taguchit, Izumi Kumagai, Jiro Nakayama, Akinori Suzuki, Kin Ichiro Miura, Efficient extracellular expression of a foreign protein in smptomyos using secretory protease inhibitor (SSI) gene fusions, Nature Biotechnology, 10.1038/nbt1089-1063, 7, 10, 1063-1066, 1989.10, [URL], Using the gene for a secreted protease inhibitor, Streptomyces subtilisin inhibitor (SSI), we have established a secretory expression system for the products of foreign genes in Streptomyces. A sex pheromone peptide, cADl, of Enterococcus fae- calis was expressed and secreted as a stable complete fusion protein with SSI in amounts comparable to the native SSI in S. lividans 66. Recombinant cADl, isolated from the fusion protein by chemical digestion with BrCN, has the same amino acid composition and sequence, retention time on reverse phase HPLC, molecular mass, and biological activity as authentic cADl. This system should be useful for the efficient expression of other foreign gene products, and as a model for heterologous gene expression in Streptomyces. © 1989 Nature Publishing Group.. |
| 49. | Akira Isogai, Shouhei Sakuda, Jiro Nakayama, Satoshi Watanabe, Akinori Suzuki, Isolation and Structural Elucidation of a New Cyclitol Derivative, Streptol, as a Plant Growth Regulator, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb1961.51.2277, 51, 8, 2277-2279, 1987.01, [URL], A new cyclitol derivative, streptol (1), was isolated from a culture filtrate of an unidentified Streptomyces sp., and the structure of 1 was determined as 1d-(1,2,4/3)-5- hydroxymethyl-5-cyclohexene-l,2,3,4-tetrol. This structure was elucidated with NMR and MS spectrometry, and the absolute configuration was determined from the CD spectrum of the tetrabenzoate of the hydrogenolized compound of 1. Streptol inhibited the root growth of lettuce seedlings at a concentration above 13 ppm.. |
主要総説, 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. | 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. |
| 4. | 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). |
| 5. | 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. |
| 6. | 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. |
| 7. | 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. |
| 8. | 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. |
| 9. | 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. |
| 10. | 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. |
| 11. | 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. |
| 12. | 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. |
| 13. | 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. |
| 14. | 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. |
| 15. | 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. |
| 16. | 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. |
| 17. | 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. |
| 18. | 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. |
| 19. | 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. |
| 20. | Jiro Nakayama, Pyrosequence-based 16S rRNA profiling of gastro-intestinal microbiota, Bioscience & Microflora, 29(2), 83-96, 2010.04. |
| 21. | 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. |
| 22. | 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. |
| 23. | 中山二郎、園元謙二, 乳酸菌の世界における細胞間コミュニケーション, 日本農芸化学会誌, 76(9): 837-839, 2002.09. |
| 24. | Sturme, M. H. J., M. Kleerebezem, J. Nakayama, A. D. L. Akkermans, E. E. Vaughan and W. M. de Vos, Cell to cell communication by autoinducing peptides in gram-positive bacteria, Antonie van Leeuwenhoek, 10.1023/A:1020522919555, 81, 233-243, 2002.01, [URL]. |
| 25. | 中山二郎, 日和見感染腸球菌におけるクオーラムセンシング, 化学と生物, 40(6), 406-412, 2002.01. |
| 26. | 中山二郎, グラム陽性細菌のクオーラムセンシング−バクテリオシンの生産制御と病原因子の発現調節−, 日本乳酸菌学会誌, 12(1), 2-13, 2001.01. |
| 27. | 中山二郎, ペプチドフェロモンにより制御されるグラム陽性細菌の集団行動, 蛋白質核酸酵素, 46(4), 315-322 (2001)., 2001.01. |
| 28. | 中山 二郎, 細菌の生育を制御する"サイトカイン"様タンパク質, 化学と生物, 10.1271/kagakutoseibutsu1962.38.247, Vol.38, No.4, pp.247-248, 2000.04. |
| 29. | 中山二郎, 腸球菌の性フェロモンシグナリングに関する生物有機化学的・分子生物学的研究, 日本農芸化学会誌, 73(11), 1155-1166, 1999.01. |
| 30. | 中山 二郎, 永田 晋治, 質量分析によるペプチド・タンパク質の構造解析(2), 化学と生物, Vol.34, No.7, pp.481-486, 1996.07. |
| 31. | 中山 二郎, 質量分析によるペプチド・タンパク質の構造解析(1), 化学と生物, Vol.34, No.6, pp.416-420, 1996.06. |
| 32. | 中山 二郎, 鈴木 昭憲, 細菌の性フェロモン (生物の情報伝達物質), 化学と工業, Vol.43, No.10, pp.p1677-1681, 1990.10. |
主要学会発表等
学会活動
学協会役員等への就任
2023.06～2024.06, 日本腸内細菌学会, 評議員.
2021.05～2023.05, 日本農芸化学会西日本支部, 会長.
2021.05～2023.05, 日本農芸化学会, 理事.
2018.04～2021.03, 日本農芸化学会, 学術活動強化委員.
2012.04～2021.03, 日本農芸化学会 , 参与.
2019.04～2021.03, 日本農芸化学会, 産学官学術交流委員.
2015.04～2017.03, 日本農芸化学会西日本支部, 幹事.
2009.04～2010.03, 日本生物工学会九州支部, 理事.
2007.04～2011.03, 日本乳酸菌学会, 理事.
2003.11～2007.05, 日本乳酸菌学会, 評議員.
学会大会・会議・シンポジウム等における役割
2022.11.14～2022.11.16, 9th TNO Beneficial Microbes Conference, 座長（Chairmanship）.
2023.03.14～2021.03.17, 日本農芸化学会2022年度広島大会, 座長（Chairmanship）.
2021.09.18～2021.09.18, Visionary100農芸化学シンポジウム：健康長寿社会に向けての腸内細菌科学の新展開, 世話人代表.
2021.03.18～2021.03.21, 日本農芸化学会2021年度仙台大会, 座長（Chairmanship）.
2021.05.22～2021.05.24, 8th TNO Beneficial Microbes Conference, 座長（Chairmanship）.
2020.03.26～2020.03.29, 日本農芸化学会2020年度福岡大会, 大会実行委員.
2018.11.26～2018.11.28, 7th TNO Beneficial Microbes Conference, 座長（Chairmanship）.
2017.07.10～2017.07.11, 日本乳酸菌学会年大会, 実行委員.
2017.10.09～2017.10.11, 6th TNO Beneficial Microbes Conference, 座長（Chairmanship）.
2018.03.15～2016.03.18, 日本農芸化学会2017年度大会, 座長（Chairmanship）.
2016.10.02～2016.10.02, Visonary農芸化学100シンポジウム, 座長（Chairmanship）.
2016.03.17～2016.03.20, 日本農芸化学会2016年度大会, 座長（Chairmanship）.
2016.10.10～2016.10.12, 5th TNO Beneficial Microbes Conference, 座長（Chairmanship）.
2016.09.28～2016.09.30, 第68回日本生物工学会, 座長（Chairmanship）.
2015.10.26～2015.10.28, 第67回日本生物工学会, 座長（Chairmanship）.
2015.03.16～2015.03.18, 4th TNO Beneficial Microbes Conference, 座長（Chairmanship）.
2015.03.26～2015.03.29, 日本農芸化学会2015年度大会, 座長（Chairmanship）.
2014.03.27～2014.03.30, 日本農芸化学会2014年度大会, 座長（Chairmanship）.
2010.06～2010.06.01, 第16回腸内細菌学会, 座長（Chairmanship）.
2012.03.26～2012.03.28, 3rd TNO Beneficial Microbes Conference, 座長（Chairmanship）.
2011.09.06～2011.09.10, International Union of Microbiological Societies 2011 Congress, 座長（Chairmanship）.
2011.11.06～2011.11.09, 4th ASM Conference on Cell-cell Communication in Bacteria , 座長（Chairmanship）.
2010.08～2010.08.01, 3rd ASM Conference on Enterococci, 座長（Chairmanship）.
2010.03～2010.03.01, 日本農芸化学会, 座長（Chairmanship）.
2009.03～2009.03.01, 日本農芸化学会, 座長（Chairmanship）.
2007.03～2007.03.01, 日本農芸化学会, 座長（Chairmanship）.
2008.03～2008.03.01, 日本農芸化学会, 座長（Chairmanship）.
2006.03～2006.03.01, 日本農芸化学会, 座長（Chairmanship）.
2005.03～2005.03.01, 日本農芸化学会, 座長（Chairmanship）.
2004.03～2004.03.01, 日本農芸化学会, 座長（Chairmanship）.
2004.07～2004.07.01, 日本乳酸菌学会, 座長（Chairmanship）.
2004.12～2004.12.01, 乳酸菌と健康, 司会（Moderator）.
2016.10.02～2016.10.02, 日本農芸化学会創立100周年に向けたシンポジウム, オーガナイザー.
2016.10.10～2016.10.12, 5th TNO Beneficial Microbes Conference, アドバイザリー.
2016.09.28～2016.09.30, 第68回日本生物工学会, オーガナイザー.
2015.10.28～2015.10.28, 第67回日本生物工学会, オーガナイザー.
2015.03.26～2015.03.28, 第88回日本細菌学会シンポジウム, オーガナイザー.
2015.03.16～2015.03.18, 4th TNO Beneficial Microbes Conference, アドバイザリー.
2012.03.26～2012.03.28, 3rd TNO Beneficial Microbes Conference, アドバイザリー.
2004.12～2004.12.01, 日本学術会議・日本乳酸菌学会合同セミナー, 実行委員長.
2003.11～2003.11.01, 日本乳酸菌学会秋季セミナー, オーガナイザー.
2008.08～2008.08.01, 日本生物工学会九州支部市民フォーラム, 実行委員.
2010.10～2010.10.01, 日本生物工学会第62回大会, 大会総務.
2010.08.01～2010.08.04, 3rd ASM conference on Enterococci, アドバイザリー.
学会誌・雑誌・著書の編集への参加状況
2022.09, Microbiome Science, 国内, 編集委員.
2022.09, Frontiers in Microbiology, 国際, 編集委員.
2015.04～2019.03, 日本農芸化学会誌（化学と生物）, 国内, 編集委員.
2014.09, Advances in Microbiology, Infectious Diseases and Public Health, 国際, 編集委員.
2011.09～2024.03, Bioscience of Microbiota, Food and Health, 国内, 編集委員.
2006.04～2009.03, 生物工学会誌, 国内, 編集委員.
学術論文等の審査
| 年度 | 外国語雑誌査読論文数 | 日本語雑誌査読論文数 | 国際会議録査読論文数 | 国内会議録査読論文数 | 合計 |
|---|---|---|---|---|---|
| 2022年度 | 16 | 1 | 0 | 0 | 17 |
| 2021年度 | 14 | 0 | 0 | 0 | 14 |
| 2020年度 | 16 | 2 | 0 | 0 | 18 |
| 2019年度 | 16 | 2 | 0 | 0 | 18 |
| 2018年度 | 20 | 6 | 0 | 0 | 26 |
| 2017年度 | 20 | 3 | 0 | 0 | 23 |
| 2016年度 | 20 | 6 | 0 | 0 | 26 |
| 2015年度 | 20 | 0 | 0 | 0 | 20 |
| 2014年度 | 15 | 0 | 0 | 0 | 10 |
| 2013年度 | 10 | 1 | 0 | 0 | 11 |
| 2012年度 | 20 | 1 | 0 | 0 | 20 |
| 2011年度 | 15 | 0 | 0 | 0 | 15 |
| 2010年度 | 6 | 10 | 0 | 0 | 16 |
| 2009年度 | 14 | 0 | 0 | 0 | 14 |
| 2008年度 | 14 | 0 | 0 | 0 | 14 |
| 2007年度 | 12 | 0 | 0 | 0 | 12 |
| 2006年度 | 5 | 0 | 0 | 0 | 5 |
| 2005年度 | 5 | 0 | 0 | 0 | 5 |
| 2004年度 | 1 | 0 | 0 | 0 | 1 |
| 2003年度 | 2 | 0 | 0 | 0 | 2 |
| 2002年度 | 1 | 0 | 0 | 0 | 1 |
その他の研究活動
海外渡航状況, 海外での教育研究歴
ガジャマダ大学, Indonesia, 2023.07～2023.07.
ウダヤナ大学, Indonesia, 2022.11～2022.11.
マヒドン大学, マエファオラーン大学, カセサート大学, Thailand, 2022.07～2022.07.
マヒドン大学, Thailand, 2019.11～2019.11.
マヒドン大学, Thailand, 2019.02～2020.02.
ガジャマダ大学, Indonesia, 2019.10～2019.10.
モンゴル生命科学大学, Mongolia, 2019.07～2019.07.
シンガポール国立大学, Singapore, 2016.08～2016.08.
国立陽明大学, Taiwan, 2013.01～2013.01.
カセサート大学, Thailand, 2012.03～2012.03.
ノッティンガム大学, ワーゲニンゲン大学, UnitedKingdom, Holland, 2011.07～2011.08.
Massachusetts Eye and Ear Infirmary, UnitedStatesofAmerica, 2011.11～2011.11.
ミネソタ大学, UnitedStatesofAmerica, 2011.11～2011.11.
東京大学食の安全センター, Japan, 2011.05～2011.06.
インペリアルカレッジロンドン, ノッテインガム大学, リーズ大学, UnitedKingdom, 2008.01～2008.01.
INRA, France, 2007.01～2007.01.
ワーゲニンゲン大学, Netherlands, 1998.04～1999.09.
外国人研究者等の受入れ状況
2022.11～2022.11, 2週間未満, Universitas Gadja Mada, Indonesia.
2023.01～2023.07, 1ヶ月以上, University of Teheran, Iran.
2022.06～2022.11, 1ヶ月以上, Al-Azhar University, Egypt, .
2020.02～2020.02, 2週間未満, Indonesia.
2019.06～2019.06, Philippines.
2019.06～2019.06, 2週間未満, フィリピン大学マニラ校, Philippines.
2019.05～2019.05, 2週間未満, ガジャマダ大学, Indonesia.
2019.04～2019.05, 1ヶ月以上, Mahidol University, Thailand, .
2018.12～2019.02, 1ヶ月以上, Al-Azhar University, Egypt, .
2018.02～2018.03, 1ヶ月以上, Kasetsart University, Thailand, 外国政府・外国研究機関・国際機関.
2016.02～2016.03, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2015.02～2015.07, 1ヶ月以上, Al-Azhar University, Egypt, 政府関係機関.
2015.02～2015.03, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2011.02～2011.03, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2009.02～2009.03, 1ヶ月以上, King Mongkut Institute Technology Lakkarban, Thailand, 日本学術振興会.
2007.05～2007.06, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2008.03～2008.03, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2008.02～2008.03, 1ヶ月以上, King Mongkut Institute Technology Lakkarban, Thailand, 日本学術振興会.
2007.02～2007.03, 1ヶ月以上, King Mongkut Institute Technology Lakkarban, Thailand, 日本学術振興会.
2006.11～2006.12, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2006.10～2006.11, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2004.10～2004.11, 1ヶ月以上, Mahidol University, Thailand, 日本学術振興会.
2002.02～2002.03, 1ヶ月以上, Mahidol University, Thailand, 日本学術振興会.
2003.11～2003.12, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2004.10～2004.11, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2002.12～2003.01, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2003.11～2003.12, 1ヶ月以上, Kasetsart Univeristy, Thailand, 日本学術振興会.
2001.11～2004.11, 1ヶ月以上, Tanta University, Egypt, .
2004.10～2004.11, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2004.02～2004.04, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2002.11～2003.01, 1ヶ月以上, Kasetsart University, Thailand, 日本学術振興会.
2002.03～2002.03, 2週間以上1ヶ月未満, Kasetsart University, Thailand, 日本学術振興会.
2002.03～2002.03, 2週間以上1ヶ月未満, Ministry of Agriculture and Cooperatives Kaset-klang, Thailand, 日本学術振興会.
受賞
論文賞, 日本生物工学会, 2020.09.
トピックス賞, 日本農芸化学会, 2018.03.
トピックス賞, 日本農芸化学会, 2018.03.
トピックス賞, 日本農芸化学会, 2016.03.
トピックス賞, 日本農芸化学会, 2015.03.
森永賞, 森永奉仕会, 2008.06.
ポスター賞, アメリカ微生物学会, 2005.08.
論文賞, 日本生物工学会, 2004.10.
農芸化学奨励賞, 日本農芸化学会, 1999.04.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2022年度～2023年度, 挑戦的研究（萌芽）, 代表, エピゲノム修飾をマーカーとした腸内フローラにおける糖尿病合併症制御因子の探索.
2022年度～2024年度, 国際学術研究, 代表, アジア食と健康を繋ぐ腸内フローラの研究拠点の形成.
2020年度～2023年度, 国際共同研究強化(B), 代表, アジア人の食と腸内フローラと生活習慣病に関する国際共同調査.
2019年度～2020年度, 挑戦的研究（萌芽）, 代表, 環状ペプチドクオルモンを用いた腸内細菌の新奇共生戦略.
2017年度～2019年度, 基盤研究(B), 代表, 食と腸内細菌と健康に関するアジア横断研究.
2015年度～2017年度, 基盤研究(B), 代表, 腸内細菌のクオラムセンシングの実態解明と疾病予防および健康増進に向けた制御.
2013年度～2015年度, 基盤研究(B), 代表, アジア人種の食と腸内フローラと健康に関する調査研究.
2012年度～2014年度, 基盤研究(B), 代表, グラム陽性細菌のクオラムセンシングを標的とした抗感染症剤の開発.
2011年度～2013年度, 挑戦的萌芽研究, 代表, ヒト乳幼児における腸内細菌叢形成と宿主免疫系発達の相互作用機序に関する研究.
2009年度～2011年度, 基盤研究(B), 代表, 環状ペプチドクォルモンの生合成酵素および受容体を標的とした抗感染症剤の開発.
2007年度～2008年度, 基盤研究(B), 代表, グラム陽性細菌のクォーラムセンシングを標的とした新規抗菌剤の開発と応用.
2007年度～2008年度, 萌芽研究, 代表, 腸内フローラにおける細菌間相互作用の総合的理解に向けての萌芽的研究.
2007年度～2008年度, 基盤研究(B), 代表, グラム陽性細菌のクォーラムセンシングを標的とした新規抗菌剤の開発と応用.
2005年度～2006年度, 基盤研究(C), 代表, グラム陽性細菌のクォーラムセンシングを標的とした新奇抗菌剤の開発.
2003年度～2004年度, 基盤研究(C), クオーラムセンシングを標的とした抗細菌剤の開発.
科学研究費補助金の採択状況(文部科学省、日本学術振興会以外)
2022年度～2024年度, 研究拠点形成事業, 代表, アジア食と健康を繋ぐ腸内フローラ研究の拠点形成.
2004年度～2006年度, 厚生労働科学研究費補助金 (厚生労働省), 分担, 地域集団でのコホート研究による便中細菌診断妥当性の研究.
2002年度～2003年度, 厚生労働科学研究費補助金 (厚生労働省), 分担, リウマチアレルギー疾患の早期診断に関する研究.
競争的資金(受託研究を含む)の採択状況
2006年度～2007年度, 地域新生コンソーシアム, 分担, 食品機能性対応指標基づく階層的バイオプロセス制御の開発.
2006年度～2008年度, 農林水産省高度化事業, 分担, 乳酸菌バクテリオシンを利用した乳房炎予防・治療抗菌剤の開発 .
共同研究、受託研究(競争的資金を除く)の受入状況
2008.04～2009.03, 代表, 地域イノベーション創出総合支援事業「シーズ発掘試験」／乳幼児期の種々疾病予知・予防のための腸内フローラ解析システムの構築」.
寄附金の受入状況
2021年度, 長瀬科学振興財団, 研究費助成／合成腸内細菌叢を用いたプレ・プロバイオティクスのインビトロ機能解析システムの構築
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2021年度, 公益財団法人発酵研究所, 一般研究助成／各種胆汁酸分子の発芽誘導能を用いた難培養性腸内細菌の分離と日本人腸内細菌叢カクテルの創製.
2020年度, 公益財団法人平和中島財団, 平和中島財団・アジア地域重点学術研究助成/モンゴル国における都市化が腸内細菌叢と健康に与える影響の調査.
2020年度, 株式会社ヴェントゥーノ, 第2回農芸化学中小企業産学・産官連携研究助成/あまおう由来乳酸菌と沖縄もずくフコイダンの腸内フローラ改善効果.
2019年度, 一般財団法人旗影会, 現代食による腸内細菌叢偏倚の実態調査と機構解明.
2018年度, 三島海雲記念財団, アジアにおける食と腸内細菌叢と生活習慣病に関する調査研究 .
2018年度, 一般財団法人旗影会, 現代食による腸内細菌叢偏倚の実態調査と機構解明.
2010年度, ヤクルトﾊﾞｲｵｻｲｴﾝｽ財団, アジア人種の腸内フローラ基盤データベースの構築.
2009年度, ヤクルトﾊﾞｲｵｻｲｴﾝｽ財団, アジア人種の腸内フローラ基盤データベースの構築.
2009年度, （財）食生活研究会, 学術研究助成奨励金／乳幼児期の腸内フローラ形成と食物アレルギー発症の関連性の解析.
2008年度, 三島海雲記念財団, 学術研究助成奨励金／食物アレルギー予知・予防のための乳幼児腸内フローラ解析システムの構築.
2007年度, 日本ワックスマン財団, 学術研究助成奨励金／グラム陽性細菌の環状ペプチドクォルモンの生合成を標的とする抗菌剤の創製.
2006年度, 財団法人加藤記念バイオサイエンス研究振興財団, 加藤記念研究助成／グラム陽性菌のクォーラムセンシングを標的とした新奇抗感染症剤の創製.
2005年度, （株）九電工, 若手学術研究者支援／複合土壌細菌群リサイクルシステムにおける菌叢モニタリング.
2004年度, ダノン健康・栄養普及協会, 学術研究助成金／乳幼児における腸内細菌叢形成とアレルギー罹患についての分子疫学的研究.
2003年度, 財団法人武田科学振興財団, 研究助成金／総合ゲノム分子生物学を基盤としたプロバイオティクス乳酸菌の腸管内環境適応定着機構の解析.
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