日本庆应义塾大学医学院Kenya Honda和美国麻省理工学院和哈佛大学布罗德研究所Ramnik J. Xavier共同合作，近期取得重要工作进展。他们研究提出，共生菌群可以通过生态控制抑制肠杆菌科细菌在肠道中的定植。相关研究成果2024年9月18日在线发表于《自然》杂志上。

据介绍，长期使用抗生素或炎症状况可能导致肠道中潜在致病微生物的持续定植和生长，并可能使免疫失调和组织损伤永久化。革兰氏阴性肠杆菌科肠道病原菌对传统抗生素治疗特别顽固，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。

研究人员从健康人的粪便样本中分离并筛选出能够强烈和特异性抑制肠道肠杆菌科的共生细菌群。其中一个精心设计的系统由18种共生菌株组成，通过调节葡萄糖酸盐的可用性有效地控制了生态位，从而重新建立了定植抗性，缓解了小鼠由克雷伯氏菌和埃希氏菌引起的肠道炎症。

总之，这一研究表明，以活细菌疗法的形式利用这些活动可能是对抗促炎、抗微生物肠杆菌科感染日益增长威胁的一种有前景的解决方案。

附：英文原文

Title: Commensal consortia decolonize Enterobacteriaceae via ecological control

Author: 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, Straar, 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

Issue&Volume: 2024-09-18

Abstract: 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.

DOI: 10.1038/s41586-024-07960-6

Source: https://www.nature.com/articles/s41586-024-07960-6