| Project/Area Number |
20K15438
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 38020:Applied microbiology-related
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| Research Institution | Keio University |
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Principal Investigator |
Nishiyama Keita 慶應義塾大学, 医学部(信濃町), 講師 (40756029)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 腸内細菌 / ビフィズス菌 / 共生 / 代謝産物 / 定着 / 接着 / 線毛 / 感染予防 |
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| Outline of Research at the Start |
ビフィズス菌はヒト腸内環境の恒常性維持に密接に関わるが，腸内での定着機構は不明な点が多い。申請者は，腸内細菌の相互関係を司る代謝産物に着目し，ヒト便培養液からビフィズス菌の定着因子である線毛の重合反応を誘導する代謝産物AAAを見出した。本研究では，(1)AAA産生菌の分離と同定，(2)AAA産生菌とビフィズス菌のマウス共生モデルを用いた定着試験を実施し，ビフィズス菌の新たな腸内定着機構の証明を目指す。
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| Outline of Final Research Achievements |
The gut microbiome converts aromatic amino acids to several metabolites that potentially regulate biological processes. Here, we show that metabolite 'AAA', produced by intestinal bacteria, upregulates the gene expression of fimbriae of Bifidobacterium, thereby dynamically inducing fimbriae elongation. AAA promoted the intestinal colonization of commensal bacteria, and inhibited the growth of gram-negative pathogenic bacteria through cell membrane disruption. Furthermore, we found that AAA was produced by metabolic exchange between two bacterial species, Bacteroides and Lactobacillus. This study revealed that AAA can act as a signaling molecule that significantly modulates bacterial colonization in the intestine. These findings demonstrate the existence of AAA-mediated trans-species dialogue between microorganisms and provide new insights into understanding the formation and maintenance of human gut microbiota.
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| Academic Significance and Societal Importance of the Research Achievements |
Bifidobacteriumはヒト消化管に生息する共生細菌であり宿主の腸内環境の恒常性維持に密接に関わる。しかし，どのようにしてビフィズス菌はヒト腸内に定着できるのかという疑問に対して不明な点が多い。本研究では，ビフィズス菌の腸管定着因子である線毛発現を誘導する代謝産物AAAを産生する腸内細菌を同定し，ビフィズス菌とこれらの細菌との共生により腸内定着が促進されること，さらにAAAは病原性細菌の生育を抑制する，興味深い共生関係を見出した。これらは，ビフィズス菌の新たな腸内定着機構を明らかにしたと共に，ヒト腸内細菌叢の形成と維持の理解に向けた知見を与えるものと考える。
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