腸内代謝における細菌酵素の新たな役割が明らかに(New role for bacterial enzyme in gut metabolism revealed)

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2024-02-28 ペンシルベニア州立大学(PennState)

胆汁酸は、消化に関与する重要な役割を果たしており、腸内細菌によって変更されることが知られています。最近の研究では、新しい胆汁酸種がヒトの生後直後に生成され、腸内細菌叢の形成と関連していることが明らかになりました。これらの胆汁酸は、宿主と腸内細菌との間での信号伝達に関与し、健康と疾患の理解に貢献する可能性があります。

<関連情報>

胆汁酸塩加水分解酵素がアミン共役胆汁酸の生成を触媒することが判明 Bile salt hydrolase catalyses formation of amine-conjugated bile acids

Bipin Rimal,Stephanie L. Collins,Ceylan E. Tanes,Edson R. Rocha,Megan A. Granda,Sumeet Solanki,Nushrat J. Hoque,Emily C. Gentry,Imhoi Koo,Erin R. Reilly,Fuhua Hao,Devendra Paudel,Vishal Singh,Tingting Yan,Min Soo Kim,Kyle Bittinger,Joseph P. Zackular,Kristopher W. Krausz,Dhimant Desai,Shantu Amin,James P. Coleman,Yatrik M. Shah,Jordan E. Bisanz,Frank J. Gonzalez,… Andrew D. Patterson
Nature  Published:07 February 2024
DOI:https://doi.org/10.1038/s41586-023-06990-w

腸内代謝における細菌酵素の新たな役割が明らかに(New role for bacterial enzyme in gut metabolism revealed)

Abstract

Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1,2,3,4,5,6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.

医療・健康
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