腸内酵母研究が新規治療薬開発につながる可能性(How Studying Yeast in the Gut Could Lead to New, Better Drugs)

ad

2026-02-24 ノースカロライナ州立大学(NC State)

ノースカロライナ州立大学(NC State University)の研究チームは、腸内で機能する新たな薬剤送達法として、酵母を活用する技術を開発した。遺伝子改変した酵母を経口投与することで、腸内で治療用分子を産生・放出させる仕組みを構築。酵母は胃酸や消化酵素に耐えやすく、安全性も高いことから、腸内炎症や感染症などへの応用が期待される。動物モデル実験では、標的部位での安定した薬剤発現と治療効果が確認された。本研究は、従来の薬剤投与に代わる持続的かつ局所的な治療戦略として、マイクロバイオームを活用した創薬の可能性を示す成果となった。

<関連情報>

無菌マウス腸管に対するサッカロミセス・ボウラディのトランスクリプトーム応答 Transcriptomic responses of Saccharomyces boulardii to the germ-free mouse gut

Genan Wang,Deniz Durmusoglu & Nathan Crook
BMC Genomics  Published:18 February 2026
DOI:https://doi.org/10.1186/s12864-026-12661-7 An unedited version of this manuscript

Abstract

Live biotherapeutic products (LBPs) are a promising therapeutic class due to their ability to perform metabolic functions in close proximity to their animal host. Of these, Saccharomyces boulardii (Sb) stands out due to its ability to secrete high titers of proteins, long shelf life when freeze-dried, resistance to both phage and antibiotics, and palatability. Despite growing evidence of Sb’s suitability as an LBP, knowledge regarding its physiological responses to the gut environment remains very limited. Here, we colonize germ-free mice with Sb and measure Sb’s transcriptome in the cecum and colon. We find that in the germ-free gut, Sb’s transcriptome is distinct from its transcriptome during axenic culture and is characterized by upregulation of genes involved in fatty acid oxidation, such as POX1, FOX2, SPS19, PXA1, and PXA2, and amino acid intake, including SNO1 and SNZ1, and GDH3. Moreover, the result indicated that Sb utilizes a multi-faceted adaptation strategy, characterized by SNF1/AMPK-driven metabolic flexibility, TOR suppression for stress adaptation, and MSN2/MSN4 activation for resistance to oxidative and osmotic stress. We further compare estimates of promoter activity between this work and prior studies of promoter activity in Sb. Taken together, this work sheds light on the physiology of Sb during passage through the gut and suggests routes to improve its therapeutic properties.

有機化学・薬学
ad
ad
Follow
ad
タイトルとURLをコピーしました