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In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2024-10-23 , DOI: 10.1038/s41589-024-01763-6
Darryl A. Wesener, Zachary W. Beller, Megan F. Hill, Han Yuan, David B. Belanger, Cheryl Frankfater, Nicolas Terrapon, Bernard Henrissat, Dmitry A. Rodionov, Semen A. Leyn, Andrei Osterman, Johan E. T. van Hylckama Vlieg, Jeffrey I. Gordon

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.



中文翻译:


非生物低聚糖对人体肠道拟杆菌适应性的体内操作



含有自然界中未鉴定的糖苷键和结构的合成聚糖 (SG) 提供了一种故意改变微生物群落特性的方法。在这里,通过单糖聚合产生 SG 寡糖库,并筛选它们在人粪便样品的离体培养物中增加溶糖拟杆菌的能力。将先导 SG 制剂口服给携带 56 种培养的、系统发育多样化的人类肠道细菌联盟的 gnotobiotic 小鼠,并喂食西方饮食。15 种拟杆菌菌株中有 3 种的丰度增加,最突出的是肠芽孢杆菌。通过分析碳水化合物利用机制的体内表达,使用具有结合 SG 寡糖的可检索微观顺磁性颗粒并通过单个纯化的 B. ininalis 糖苷水解酶测定 SG 降解来表征潜在机制。结果表明,SGs 可以选择性地在不同的人类肠道拟杆菌中吸收碳水化合物利用机制,并展示了一种识别人工碳水化合物结构以进行靶向细菌操作的方法。

更新日期:2024-10-23
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