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通过非生物寡糖对人肠道拟杆菌适应性进行体内操纵。

In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides.

作者信息

Wesener Darryl A, Beller Zachary W, Hill Megan F, Yuan Han, Belanger David B, Frankfater Cheryl, Terrapon Nicolas, Henrissat Bernard, Rodionov Dmitry A, Leyn Semen A, Osterman Andrei, van Hylckama Vlieg Johan E T, Gordon Jeffrey I

机构信息

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.

Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO, USA.

出版信息

Nat Chem Biol. 2025 Apr;21(4):544-554. doi: 10.1038/s41589-024-01763-6. Epub 2024 Oct 23.

DOI:10.1038/s41589-024-01763-6
PMID:39443715
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11949833/
Abstract

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet. The abundances of 3 of 15 Bacteroides strains increased, most prominently B. intestinalis. Underlying mechanisms were characterized by analyzing in vivo expression of the carbohydrate utilization machinery, using retrievable microscopic paramagnetic particles with bound SG oligosaccharides and assaying SG degradation by individual purified B. intestinalis glycoside hydrolases. The results reveal that SGs can selectively co-opt carbohydrate utilization machinery in different human gut Bacteroides and demonstrate a means for identifying artificial carbohydrate structures for targeted bacterial manipulation.

摘要

含有自然界未发现的糖苷键和结构的合成聚糖（SGs）为有意改变微生物群落特性提供了一种手段。在这里，通过单糖聚合生成了SG寡糖库，并筛选了它们在人粪便样本体外培养物中增加解糖拟杆菌的能力。将一种主要的SG制剂口服给予无菌小鼠，这些小鼠携带由56种培养的、系统发育多样的人类肠道细菌组成的群落，并喂食西式饮食。15种拟杆菌菌株中有3种的丰度增加，最显著的是肠拟杆菌。通过分析碳水化合物利用机制的体内表达、使用结合了SG寡糖的可回收微观顺磁颗粒以及测定单个纯化的肠拟杆菌糖苷水解酶对SG的降解来表征潜在机制。结果表明，SGs可以在不同的人类肠道拟杆菌中选择性地共同选择碳水化合物利用机制，并展示了一种识别用于靶向细菌操纵的人工碳水化合物结构的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f0/11949833/3f3825da72bb/41589_2024_1763_Fig13_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f0/11949833/7959dd5ee4e4/41589_2024_1763_Fig8_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f0/11949833/aa853a8a42cf/41589_2024_1763_Fig10_ESM.jpg
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本文引用的文献

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