Commensal consortia decolonize Enterobacteriaceae via ecological control

被引:16
作者
Furuichi, Munehiro [1 ,2 ]
Kawaguchi, Takaaki [1 ,2 ]
Pust, Marie-Madlen [3 ,4 ,5 ]
Yasuma-Mitobe, Keiko
Plichta, Damian R. [3 ]
Hasegawa, Naomi [1 ]
Ohya, Takashi [1 ,2 ]
Bhattarai, Shakti K. [6 ]
Sasajima, Satoshi [1 ]
Aoto, Yoshimasa [7 ]
Tuganbaev, Timur [1 ,8 ]
Yaginuma, Mizuki [1 ]
Ueda, Masahiro [2 ,7 ]
Okahashi, Nobuyuki [2 ,9 ,10 ]
Amafuji, Kimiko [7 ]
Kiridoshi, Yuko [7 ]
Sugita, Kayoko [1 ]
Strazar, Martin [3 ]
Avila-Pacheco, Julian [3 ]
Pierce, Kerry [3 ]
Clish, Clary B. [3 ]
Skelly, Ashwin N. [1 ]
Hattori, Masahira [2 ,11 ]
Nakamoto, Nobuhiro [12 ]
Caballero, Silvia [13 ]
Norman, Jason M. [13 ]
Olle, Bernat [13 ]
Tanoue, Takeshi [1 ,2 ,13 ]
Suda, Wataru [2 ,11 ]
Arita, Makoto [2 ,8 ,10 ]
Bucci, Vanni [6 ]
Atarashi, Koji [1 ,2 ,8 ]
Xavier, Ramnik J. [3 ,4 ,5 ,14 ]
Honda, Kenya [1 ,2 ,8 ]
机构
[1] Keio Univ, Dept Microbiol & Immunol, Sch Med, Tokyo, Japan
[2] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan
[3] Broad Inst MIT & Harvard, Infect Dis & Microbiome Program, Cambridge, MA 02142 USA
[4] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA
[5] Harvard Med Sch, Boston, MA 02115 USA
[6] UMass Chan Med Sch, Dept Microbiol & Physiol Syst, Program Microbiome Dynam, Worcester, MA USA
[7] Keio Univ, Sch Med, JSR, Med & Chem Innovat Ctr, Tokyo, Japan
[8] Keio Univ, Human Biol Microbiome Quantum Res Ctr Bio2Q, Tokyo, Japan
[9] Osaka Univ, Grad Sch Informat Sci & Technol, Dept Bioinformat Engn, Osaka, Japan
[10] Keio Univ, Grad Sch Pharmaceut Sci, Div Physiol Chem & Metab, Tokyo, Japan
[11] Waseda Univ, Grad Sch Adv Sci & Engn, Cooperat Major Adv Hlth Sci, Tokyo, Japan
[12] Keio Univ, Dept Internal Med, Sch Med, Div Gastroenterol & Hepatol, Tokyo, Japan
[13] Vedanta Biosci, Cambridge, MA USA
[14] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
关键词
ESCHERICHIA-COLI; MEDIATED INFLAMMATION; GUT MICROBIOTA; METABOLISM; OXIDATION; ALIGNMENT; DYNAMICS; PROMOTES; BACTERIA; DRIVES;
D O I
10.1038/s41586-024-07960-6
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
Persistent colonization and outgrowth of potentially pathogenic organisms in the intestine can result from long-term antibiotic use or inflammatory conditions, and may perpetuate dysregulated immunity and tissue damage(1,2). Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment(3,4), although an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy(5-7). Here we isolated and down-selected commensal bacterial consortia from stool samples from healthy humans that could strongly and specifically suppress intestinal Enterobacteriaceae. One of the elaborated consortia, comprising 18 commensal strains, effectively controlled ecological niches by regulating gluconate availability, thereby re-establishing colonization resistance and alleviating Klebsiella- and Escherichia-driven intestinal inflammation in mice. Harnessing these activities in the form of live bacterial therapies may represent a promising solution to combat the growing threat of proinflammatory, antimicrobial-resistant Enterobacteriaceae infection.
引用
收藏
页码:878 / +
页数:27
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