In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides

IF 12.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology 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

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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.

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非生物寡糖对人体肠道乳酸杆菌适应性的体内操纵

合成聚糖（SGs）含有在自然界中未发现的糖苷键和结构，为有意改变微生物群落特性提供了一种方法。本研究通过单糖聚合生成 SG 低聚糖池，并对其在人体粪便样本体外培养物中增加糖酵解乳杆菌的能力进行了筛选。将 SG 的主要制剂口服给含有 56 种经培养、系统发育多样的人类肠道细菌并以西式饮食喂养的非生物小鼠。在 15 个乳杆菌菌株中，有 3 个菌株的丰度有所增加，其中最显著的是肠乳杆菌。通过分析体内碳水化合物利用机制的表达、使用结合了 SG 寡糖的可回收微观顺磁颗粒以及检测肠杆菌苷水解酶对 SG 的降解情况，对其基本机制进行了表征。研究结果表明，在不同的人类肠道细菌中，SGs 可选择性地共同利用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的方法，可对细菌进行有针对性的操纵。

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来源期刊

Nature chemical biology 生物-生化与分子生物学

CiteScore

23.90

自引率

1.40%

发文量

238

审稿时长

12 months

期刊介绍： Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision. The journal embraces contributions from the growing community of chemical biologists, encompassing insights from chemists applying principles and tools to biological inquiries and biologists striving to comprehend and control molecular-level biological processes. We prioritize studies unveiling significant conceptual or practical advancements in areas where chemistry and biology intersect, emphasizing basic research, especially those reporting novel chemical or biological tools and offering profound molecular-level insights into underlying biological mechanisms. Nature Chemical Biology also welcomes manuscripts describing applied molecular studies at the chemistry-biology interface due to the broad utility of chemical biology approaches in manipulating or engineering biological systems. Irrespective of scientific focus, we actively seek submissions that creatively blend chemistry and biology, particularly those providing substantial conceptual or methodological breakthroughs with the potential to open innovative research avenues. The journal maintains a robust and impartial review process, emphasizing thorough chemical and biological characterization.