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噬菌体与粪便微生物群移植相结合可有效治疗鼠伤寒血清型引起的小鼠结肠炎。

The Combination of Phages and Faecal Microbiota Transplantation Can Effectively Treat Mouse Colitis Caused by Serovar Typhimurium.

作者信息

Wang Xinwu, Xing Yating, Ji Yalu, Xi Hengyu, Liu Xiaohe, Yang Li, Lei Liancheng, Han Wenyu, Gu Jingmin

机构信息

State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Jilin, China.

The Second Hospital of Jilin University, Changchun, China.

出版信息

Front Microbiol. 2022 Jul 7;13:944495. doi: 10.3389/fmicb.2022.944495. eCollection 2022.

Abstract

serovar Typhimurium ( Typhimurium) is one of the common causes of human colitis. In the present study, two lytic phages vB_SenS-EnJE1 and vB_SenS-EnJE6 were isolated and the therapeutic effect of the combination of phages and faecal microbiota transplantation (FMT) on Typhimurium-induced mouse colitis was investigated. The characteristics and genome analysis indicated that they are suitable phages for phage therapy. Results showed that vB_SenS-EnJE1 lysis 41/54 strains of serotype O4, and vB_SenS-EnJE6 lysis 46/54 strains of serotypes O4 and O9. Severe inflammatory symptoms and disruption of the intestinal barrier were observed in Typhimurium -induced colitis. Interestingly, compared with a single phage cocktail (Pc) or single FMT, the combination of Pc and FMT (PcFMT) completely removed Typhimurium after 72 h of treatment, and significantly improved pathological damage and restored the intestinal barrier. Furthermore, PcFMT effectively restored the intestinal microbial diversity, especially for Firmicutes/Bacteroidetes [predominantly bacterial phyla responsible for the production of short-chain fatty acids (SCFA)]. Additionally, we found that PcFMT treatment significantly increased the levels of SCFA. All these data indicated that the combination of phages and FMT possesses excellent therapeutic effects on Typhimurium -induced intestinal microbiota disorder diseases. Pc and FMT played roles in "eliminating pathogens" and "strengthening vital qi," respectively. This study provides a new idea for the treatment of intestinal microbiota disorder diseases caused by specific bacterial infections.

摘要

鼠伤寒血清型沙门氏菌(鼠伤寒沙门氏菌)是人类结肠炎的常见病因之一。在本研究中,分离出两种裂解性噬菌体vB_SenS-EnJE1和vB_SenS-EnJE6,并研究了噬菌体与粪便微生物群移植(FMT)联合治疗鼠伤寒沙门氏菌诱导的小鼠结肠炎的效果。特性和基因组分析表明它们是适合用于噬菌体治疗的噬菌体。结果显示,vB_SenS-EnJE1可裂解41/54株O4血清型菌株,vB_SenS-EnJE6可裂解46/54株O4和O9血清型菌株。在鼠伤寒沙门氏菌诱导的结肠炎中观察到严重的炎症症状和肠道屏障破坏。有趣的是,与单一噬菌体鸡尾酒(Pc)或单一FMT相比,Pc与FMT联合使用(PcFMT)在治疗72小时后可完全清除鼠伤寒沙门氏菌,并显著改善病理损伤和恢复肠道屏障。此外,PcFMT有效地恢复了肠道微生物多样性,尤其是对于厚壁菌门/拟杆菌门(主要是负责产生短链脂肪酸(SCFA)的细菌门)。此外,我们发现PcFMT治疗显著提高了SCFA的水平。所有这些数据表明,噬菌体与FMT联合使用对鼠伤寒沙门氏菌诱导的肠道微生物群紊乱疾病具有优异的治疗效果。Pc和FMT分别在“祛邪”和“扶正”中发挥作用。本研究为治疗由特定细菌感染引起的肠道微生物群紊乱疾病提供了新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3598/9301289/fe637953036e/fmicb-13-944495-g001.jpg

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