Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides

被引:199
作者
Wu, Meng [1 ,2 ]
McNulty, Nathan P. [1 ]
Rodionov, Dmitry A. [3 ,4 ]
Khoroshkin, Matvei S. [4 ]
Griffin, Nicholas W. [1 ,2 ]
Cheng, Jiye [1 ,2 ]
Latreille, Phil [5 ]
Kerstetter, Randall A. [5 ]
Terrapon, Nicolas [6 ,7 ]
Henrissat, Bernard [6 ,7 ,8 ]
Osterman, Andrei L. [3 ]
Gordon, Jeffrey I. [1 ]
机构
[1] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA
[2] Washington Univ, Sch Med, Ctr Gut Microbiome & Nutr Res, St Louis, MO 63108 USA
[3] Sanford Burnham Prebys Med Discovery Inst, Infect & Inflammatory Dis Ctr, La Jolla, CA 92037 USA
[4] Russian Acad Sci, AA Kharkevich Inst Informat Transmiss Problems, Moscow 127994, Russia
[5] Monsanto Co, St Louis, MO 63167 USA
[6] CNRS, Architecture & Fonct Macromol Biol, F-13288 Marseille 9, France
[7] Aix Marseille Univ, F-13288 Marseille 9, France
[8] King Abdulaziz Univ, Dept Biol Sci, Jeddah 21413, Saudi Arabia
基金
俄罗斯科学基金会; 欧洲研究理事会;
关键词
OUTER-MEMBRANE PROTEINS; COMPARATIVE GENOMICS; BACTERIAL SYMBIONT; THETAIOTAOMICRON; STARCH; INTESTINE; CATALOG;
D O I
10.1126/science.aac5992
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Libraries of tens of thousands of transposon mutants generated from each of four human gut Bacteroides strains, two representing the same species, were introduced simultaneously into gnotobiotic mice together with 11 other wild-type strains to generate a 15-member artificial human gut microbiota. Mice received one of two distinct diets monotonously, or both in different ordered sequences. Quantifying the abundance of mutants in different diet contexts allowed gene-level characterization of fitness determinants, niche, stability, and resilience and yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the community. The approach described is generalizable and should be useful for defining mechanisms critical for sustaining and/or approaches for deliberately reconfiguring the highly adaptive and durable relationship between the human gut microbiota and host in ways that promote wellness.
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页数:8
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