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抗生素和抗体治疗艰难梭菌后肠道微生物组的演替。

Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile.

机构信息

Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America.

出版信息

PLoS One. 2012;7(10):e46966. doi: 10.1371/journal.pone.0046966. Epub 2012 Oct 10.

Abstract

Antibiotic disruption of the intestinal microbiota may cause susceptibility to pathogens that is resolved by progressive bacterial outgrowth and colonization. Succession is central to ecological theory but not widely documented in studies of the vertebrate microbiome. Here, we study succession in the hamster gut after treatment with antibiotics and exposure to Clostridium difficile. C. difficile infection is typically lethal in hamsters, but protection can be conferred with neutralizing antibodies against the A and B toxins. We compare treatment with neutralizing monoclonal antibodies (mAb) to treatment with vancomycin, which prolongs the lives of animals but ultimately fails to protect them from death. We carried out longitudinal deep sequencing analysis and found distinctive waves of succession associated with each form of treatment. Clindamycin sensitization prior to infection was associated with the temporary suppression of the previously dominant Bacteroidales and the fungus Saccinobaculus in favor of Proteobacteria. In mAb-treated animals, C. difficile proliferated before joining Proteobacteria in giving way to re-expanding Bacteroidales and the fungus Wickerhamomyces. However, the Bacteroidales lineages returning by day 7 were different from those that were present initially, and they persisted for the duration of the experiment. Animals treated with vancomycin showed a different set of late-stage lineages that were dominated by Proteobacteria as well as increased disparity between the tissue-associated and luminal cecal communities. The control animals showed no change in their gut microbiota. These data thus suggest different patterns of ecological succession following antibiotic treatment and C. difficile infection.

摘要

抗生素破坏肠道微生物群可能导致对病原体的易感性,而这种易感性可以通过细菌逐渐生长和定植来解决。演替是生态理论的核心,但在脊椎动物微生物组的研究中并没有广泛记录。在这里,我们研究了抗生素治疗和暴露于艰难梭菌后仓鼠肠道中的演替。艰难梭菌感染在仓鼠中通常是致命的,但可以通过中和 A 和 B 毒素的中和单克隆抗体 (mAb) 来保护。我们将治疗与中和单克隆抗体 (mAb) 进行了比较,发现与万古霉素治疗相比,mAb 治疗的效果更为显著。我们进行了纵向深度测序分析,发现与每种治疗形式相关的独特演替波。感染前使用克林霉素敏化与先前占主导地位的拟杆菌门和真菌 Saccinobaculus 的暂时抑制有关,有利于变形菌门。在 mAb 治疗的动物中,艰难梭菌在与变形菌门一起让位于重新扩张的拟杆菌门和真菌 Wickerhamomyces 之前大量繁殖。然而,第 7 天返回的拟杆菌门谱系与最初存在的不同,并且在实验过程中持续存在。万古霉素治疗的动物表现出不同的晚期谱系,这些谱系以变形菌门为主,同时组织相关和腔肠粪便群落之间的差异也增加了。对照动物的肠道微生物群没有变化。这些数据表明,抗生素治疗和艰难梭菌感染后,生态演替的模式不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40a3/3468616/fd65024448e6/pone.0046966.g001.jpg

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