2023-03-13 ノースカロライナ州立大学(NCState)
研究者らは、どの菌種のBSHを選択するかが重要であると述べている。人体内の菌叢には、BSH酵素を持つ細菌があり、それらが胆汁酸を化学的に変化させることで、胆汁酸プールを変更することができる。プロバイオティクスに加え、別の治療法を併用することで、C.diff感染などの腸内細菌感染症を治療する新しいアプローチが可能になるかもしれない。
<関連情報>
- https://news.ncsu.edu/2023/03/the-right-cocktail-of-gut-enzymes-can-stop-c-diff-in-its-tracks/
- https://www.nature.com/articles/s41564-023-01337-7
胆汁酸ハイドロラーゼが胆汁酸の景観を形成し、ネズミの腸内でClostridioides difficileの成長を制限する Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut
Matthew H. Foley,Morgan E. Walker,Allison K. Stewart,Sarah O’Flaherty,Emily C. Gentry,Shakshi Patel,Violet V. Beaty,Garrison Allen,Meichen Pan,Joshua B. Simpson,Caroline Perkins,Molly E. Vanhoy,Michael K. Dougherty,Sarah K. McGill,Ajay S. Gulati,Pieter C. Dorrestein,Erin S. Baker,Matthew R. Redinbo,Rodolphe Barrangou & Casey M. Theriot
Nature Microbiology Published:13 March 2023
DOI:https://doi.org/10.1038/s41564-023-01337-7
Abstract
Bile acids (BAs) mediate the crosstalk between human and microbial cells and influence diseases including Clostridioides difficile infection (CDI). While bile salt hydrolases (BSHs) shape the BA pool by deconjugating conjugated BAs, the basis for their substrate selectivity and impact on C. difficile remain elusive. Here we survey the diversity of BSHs in the gut commensals Lactobacillaceae, which are commonly used as probiotics, and other members of the human gut microbiome. We structurally pinpoint a loop that predicts BSH preferences for either glycine or taurine substrates. BSHs with varying specificities were shown to restrict C. difficile spore germination and growth in vitro and colonization in pre-clinical in vivo models of CDI. Furthermore, BSHs reshape the pool of microbial conjugated bile acids (MCBAs) in the murine gut, and these MCBAs can further restrict C. difficile virulence in vitro. The recognition of conjugated BAs by BSHs defines the resulting BA pool, including the expansive MCBAs. This work provides insights into the structural basis of BSH mechanisms that shape the BA landscape and promote colonization resistance against C. difficile.
