Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria.
Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria.
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DOI：
10.1371/journal.ppat.1000711
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发表时间：
2010-01
期刊：
影响因子：
6.7
通讯作者：
Hardt WD
中科院分区：
文献类型：
--
作者：
Stecher B;Chaffron S;Käppeli R;Hapfelmeier S;Freedrich S;Weber TC;Kirundi J;Suar M;McCoy KD;von Mering C;Macpherson AJ;Hardt WD
肠道生态系统由一个复杂但极具特色的微生物群落组成。定义这个群落是否允许新细菌物种入侵的参数尚不清楚。特别是，肠道微生物群( = 定植抗性)对肠道病原体感染的抑制作用知之甚少。为了分析肠道沙门氏菌引起的小肠结肠炎的微生物区系介导的保护机制，我们使用了小鼠感染模型和大规模高通量焦磷酸测序。与传统小鼠(CON)相比，具有低复杂性肠道微生物区系(LCM)的小鼠对肠球菌诱导的定植和小肠结肠炎高度敏感。与常规小鼠共居21天后，LCM动物的定植抵抗力部分恢复。16S rRNA序列分析比较了LCM、LCMcon21和Con肠道微生物区系，发现肠道微生物区系的复杂性在常规化后增加，并与对肠球菌感染的抵抗力增加有关。对具有不同程度定植抗性的小鼠进行比较微生物区系分析，使我们能够确定与肠链球菌感染易感性相关的肠道生态系统特征。此外，这个系统使我们能够进一步深入了解非致病共生细菌入侵肠道生态系统的一般原理。拥有高共生大肠杆菌密度的小鼠更容易受到肠球菌引起的肠道炎症的影响。同样，口服接种后，具有高滴度乳杆菌的小鼠被共生的reuri乳杆菌RR菌株更有效地定植。对9只CON小鼠的16S rRNA序列数据进行分析后发现，亲缘关系较近的亲缘关系较近的亲缘关系较远的亲缘关系较近的亲缘关系更为密切。因此，从本质上讲，密切相关物种的存在会增加新进入的物种入侵肠道生态系统的机会。我们提供的证据表明，这一原则可能对预先形成的肠道生态系统中的细菌入侵具有普遍有效性。这可能与人类肠道病原体感染以及益生菌共生细菌的治疗使用有关。肠道中的共生微生物区系数量很高，对人类健康至关重要。它对免疫系统起到有益的作用，并有助于预防胃肠道感染( = 定植抵抗)，其机制尚不清楚。在这里，我们揭示了共生微生物区系的特征，表明了殖民抗性的高或低程度。利用肠道沙门氏菌诱导的小鼠肠道炎症模型和454扩增序列的微生物区系分析，我们发现具有不同类型微生物区系的小鼠对病原体感染表现出不同的敏感性。此外，我们的数据还导致了肠道生态系统生物学中的一个新概念的描述：外部细菌物种对已建立的肠道生态系统的入侵成功与这个肠道生态系统中已经存在的密切相关细菌的丰富有关。我们表明，这一原则不仅适用于肠道病原体感染，也适用于接种有益的肠道细菌。人类对肠道感染的易感程度可能有很大不同。同样，益生菌治疗的效果因人而异。我们的数据可能解释了这些差异，并可用于提高益生菌治疗的有效性，并用于识别有发展为肠道感染风险的患者。
The intestinal ecosystem is formed by a complex, yet highly characteristic microbial community. The parameters defining whether this community permits invasion of a new bacterial species are unclear. In particular, inhibition of enteropathogen infection by the gut microbiota ( = colonization resistance) is poorly understood. To analyze the mechanisms of microbiota-mediated protection from Salmonella enterica induced enterocolitis, we used a mouse infection model and large scale high-throughput pyrosequencing. In contrast to conventional mice (CON), mice with a gut microbiota of low complexity (LCM) were highly susceptible to S. enterica induced colonization and enterocolitis. Colonization resistance was partially restored in LCM-animals by co-housing with conventional mice for 21 days (LCMcon21). 16S rRNA sequence analysis comparing LCM, LCMcon21 and CON gut microbiota revealed that gut microbiota complexity increased upon conventionalization and correlated with increased resistance to S. enterica infection. Comparative microbiota analysis of mice with varying degrees of colonization resistance allowed us to identify intestinal ecosystem characteristics associated with susceptibility to S. enterica infection. Moreover, this system enabled us to gain further insights into the general principles of gut ecosystem invasion by non-pathogenic, commensal bacteria. Mice harboring high commensal E. coli densities were more susceptible to S. enterica induced gut inflammation. Similarly, mice with high titers of Lactobacilli were more efficiently colonized by a commensal Lactobacillus reuteri RR strain after oral inoculation. Upon examination of 16S rRNA sequence data from 9 CON mice we found that closely related phylotypes generally display significantly correlated abundances (co-occurrence), more so than distantly related phylotypes. Thus, in essence, the presence of closely related species can increase the chance of invasion of newly incoming species into the gut ecosystem. We provide evidence that this principle might be of general validity for invasion of bacteria in preformed gut ecosystems. This might be of relevance for human enteropathogen infections as well as therapeutic use of probiotic commensal bacteria. The commensal microbiota, populating the intestinal tract to high levels, is fundamental to human health. It exerts beneficial effects on the immune system and contributes to protection against gastrointestinal infections ( = colonization resistance) by largely unknown mechanisms. Here, we reveal characteristics of the commensal microbiota indicative for a high or low degree of colonization resistance. Using a mouse model for Salmonella enterica induced gut inflammation and microbiota analysis by 454 amplicon sequencing, we show that mice having different types of microbiota exhibit differential susceptibility to pathogen infection. In addition, our data lead to the description of a new concept in gut ecosystem biology: the intrusion-success of an extrinsic bacterial species into an established gut ecosystem is related to the abundance of closely related bacteria, already present in this gut ecosystem. We show that this principle applies not only to enteropathogen infection but also to inoculation with beneficial gut bacteria. Humans can display largely different degrees of susceptibility to enteric infections. Similarly, the effectiveness of probiotic therapy varies greatly from person to person. Our data might explain these differences and could be used for increasing the efficacy of probiotic therapy and for identifying patients at risk of developing enteric infections.
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影响因子：
4.4
作者：
Ashelford, Kevin E.;Chuzhanova, Nadia A.;Weightman, Andrew J.
通讯作者：
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影响因子：
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作者：
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影响因子：
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