Commensal consortia decolonize Enterobacteriaceae via ecological control

• 成果类型: Article
• 署名作者: Furuichi, Munehiro; Kawaguchi, Takaaki; Pust, Marie-Madlen; Yasuma-Mitobe, Keiko; Plichta, Damian R.; Hasegawa, Naomi; Ohya, Takashi; Bhattarai, Shakti K.; Sasajima, Satoshi; Aoto, Yoshimasa; Tuganbaev, Timur; Yaginuma, Mizuki; Ueda, Masahiro; Okahashi, Nobuyuki; Amafuji, Kimiko; Kiridoshi, Yuko; Sugita, Kayoko; Strazar, Martin; Avila-Pacheco, Julian; Pierce, Kerry; Clish, Clary B.; Skelly, Ashwin N.; Hattori, Masahira; Nakamoto, Nobuhiro; Caballero, Silvia; Norman, Jason M.; Olle, Bernat; Tanoue, Takeshi; Suda, Wataru; Arita, Makoto; Bucci, Vanni; Atarashi, Koji; Xavier, Ramnik J.; Honda, Kenya
• 署名单位: Keio University; RIKEN; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Massachusetts System; UMass Chan Medical School; University of Massachusetts Worcester; Keio University; Keio University; University of Osaka; Keio University; Waseda University; Keio University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4915
• DOI: 10.1038/s41586-024-07960-6
• 发表日期: 2024-09-26
• 页码: 878-+
• 关键词: escherichia-coli; mediated inflammation; gut microbiota; metabolism; oxidation; alignment; promotes; bacteria; drives; genes

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.