Nature ( IF 50.5 ) Pub Date : 2024-09-18 , DOI: 10.1038/s41586-024-07960-6 Munehiro Furuichi 1, 2 , Takaaki Kawaguchi 1, 2 , Marie-Madlen Pust 3, 4 , Keiko Yasuma-Mitobe 1 , Damian R Plichta 3 , Naomi Hasegawa 1 , Takashi Ohya 1, 2 , Shakti K Bhattarai 5 , Satoshi Sasajima 1 , Yoshimasa Aoto 6 , Timur Tuganbaev 1, 7 , Mizuki Yaginuma 1 , Masahiro Ueda 2, 6 , Nobuyuki Okahashi 2, 8, 9 , Kimiko Amafuji 6 , Yuko Kiridoshi 6 , Kayoko Sugita 1 , Martin Stražar 3 , Julian Avila-Pacheco 3 , Kerry Pierce 3 , Clary B Clish 3 , Ashwin N Skelly 1 , Masahira Hattori 2, 10 , Nobuhiro Nakamoto 11 , Silvia Caballero 12 , Jason M Norman 12 , Bernat Olle 12 , Takeshi Tanoue 1, 2 , Wataru Suda 2, 10 , Makoto Arita 2, 7, 9 , Vanni Bucci 5 , Koji Atarashi 1, 2, 7 , Ramnik J Xavier 3, 4, 13 , Kenya Honda 1, 2, 7
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 damage1,2. Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment3,4, although an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy5,6,7. 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.
中文翻译:
共生联盟通过生态控制对肠杆菌科细菌进行去定植
潜在病原微生物在肠道中的持续定植和生长可能是由于长期使用抗生素或炎症状况造成的,并可能使免疫失调和组织损伤长期存在1,2。革兰氏阴性肠杆菌科肠道病原体对常规抗生素治疗特别顽固3,4,尽管新出现的证据表明,操纵共生微生物群可能是一种实用的替代治疗策略5,6,7。在这里,我们从健康人的粪便样本中分离并下选了可以强烈和特异性地抑制肠道肠杆菌科的共生细菌联盟。其中一个精心设计的联盟由 18 种共生菌株组成,通过调节葡萄糖酸盐的可用性有效控制生态位,从而重新建立定植抗性并减轻小鼠克雷伯氏菌和埃希氏菌驱动的肠道炎症。以活细菌疗法的形式利用这些活动可能代表着一种很有前途的解决方案,以对抗促炎、耐微生物药物的肠杆菌科感染日益增长的威胁。