Experimental evaluation of the importance of colonization history in early-life gut microbiota assembly.
Experimental evaluation of the importance of colonization history in early-life gut microbiota assembly.
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DOI：
10.7554/elife.36521
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发表时间：
2018-09-18
期刊：
影响因子：
7.7
通讯作者：
Walter J
中科院分区：
文献类型：
--
作者：
Martínez I;Maldonado-Gomez MX;Gomes-Neto JC;Kittana H;Ding H;Schmaltz R;Joglekar P;Cardona RJ;Marsteller NL;Kembel SW;Benson AK;Peterson DA;Ramer-Tait AE;Walter J
控制肠道微生物群聚集的因素尚不清楚。在这里，我们验证了这样一个假设，即个体间微生物群的变化可能仅仅是由肠道在生命早期定植的顺序和时间的差异引起的。在实验中，小鼠按顺序接种两个复杂的种子群落或四种菌株和一个种子群落的混合物，结果表明，定殖顺序既影响群落组装的结果，也影响个体殖民者的生态成功。在Rag1-/-小鼠中也发生了历史偶然性和优先效应，这表明适应性免疫系统不是这些过程的主要贡献者。总之，本研究在一个严格控制宿主和环境因素的模型中建立了可测量的定殖历史对肠道微生物群组装的影响，阐明了宿主相关微生物群落中高度无法解释的个体性的潜在原因。生活在人类胃肠道中的微生物群落，也被称为肠道微生物群，对健康至关重要。这个群落的紊乱会导致慢性疾病。每个人都有一个独特而稳定的肠道微生物群落，就像个人的“指纹”一样。研究表明，个体的遗传、饮食、环境、生活方式和生理状态都对个体肠道微生物组的变化有很小的影响。然而，只有不到30%的差异可以解释，即使是拥有相同基因、饮食和生活方式的同卵双胞胎，也有不同的肠道微生物群。这表明其他未知因素也可能影响这些微生物群落。微生物群落和肠道构成了一个生态系统，这个生态系统可能受到许多与管理热带雨林或珊瑚礁等生态系统相同的生态规则的约束。然而，许多研究忽视了生态学在塑造肠道微生物群中的作用。例如，众所周知，生物到达群落的顺序可能会影响它们相互作用和聚集成群落的方式。有可能在婴儿早期被引入胃肠道的细菌也会改变他们肠道微生物群的组成，从而引入目前尚未解释的变异。现在，Martínez等人表明，第一批在小鼠肠道中定植的细菌对它们的微生物群有持久的影响。在实验中，基因相同的老鼠被安置在完全相同的条件下，密闭的塑料气泡中。这使得科学家们能够控制年轻老鼠第一次遇到特定微生物和微生物群落的时间。从不同的成年小鼠中收集不同的微生物群落，按顺序引入幼鼠胃肠道。Martínez等人发现，他们首先引入幼鼠的微生物在实验结束时对其肠道微生物组的影响最大。当用四种不同细菌的混合物重复实验时，结果是相似的——早期到达的细菌显示出更多的定植，对微生物群落的影响最大。这表明细菌到达肠道的时间对塑造肠道微生物群非常重要。由于它在现实生活中是高度随机和不可预测的，甚至双胞胎之间也可能不同，这可以解释为什么肠道微生物组如此独特。需要更多的研究来了解抗生素、配方喂养或剖宫产如何影响生命早期的肠道微生物群，从而影响健康。这可能有助于科学家开发更好的方法来影响微生物群以改善健康，例如，通过在生命早期引入有益微生物。
The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence either with two complex seed communities or a cocktail of four bacterial strains and a seed community revealed that colonization order influenced both the outcome of community assembly and the ecological success of individual colonizers. Historical contingency and priority effects also occurred in Rag1-/- mice, suggesting that the adaptive immune system is not a major contributor to these processes. In conclusion, this study established a measurable effect of colonization history on gut microbiota assembly in a model in which host and environmental factors were strictly controlled, illuminating a potential cause for the high levels of unexplained individuality in host-associated microbial communities. The microbial community living in the gastrointestinal tract of humans, also known as the gut microbiome, is essential for health. Disturbances of this community can lead to chronic diseases. Each person has a unique and stable community of gut microbes that is as personal as a ‘fingerprint’. Studies have shown that an individual’s genetics, diet, environment, lifestyle, and physiological state all make small contributions to the variation of the gut microbiome among individuals. However, less than 30% of this variation can be explained, and even identical twins, who share the same genetics and often diets and lifestyle, have distinct gut microbiomes. This suggests that other unknown factors likely shape these microbial communities too. The microbial communities and the gut make up an ecosystem that is likely subject to many of the same ecological rules that govern ecosystems like rainforests or coral reefs. Yet many studies have overlooked the role of ecology in shaping the gut microbiota. For example, it is well known that the order in which organisms arrive in a community may influence how they interact and assemble into communities. It is possible that the order bacteria are introduced into the gastrointestinal tract of babies early in life may also change the make up of their gut microbiome, and thus introduce the variation that is currently unaccounted for. Now, Martínez et al. show that the first types of bacteria to colonize the gut of mice have a lasting impact on their microbiome. In the experiments, genetically identical mice were housed under exactly the same conditions in airtight plastic bubbles. This allowed the scientists to control when the young mice first encountered specific microbes and microbe communities. Distinct microbial communities collected from different adult mice were introduced into the gastrointestinal tract of the young mice in sequence. Martínez et al. found that the microbes they introduced into the young mice first had the strongest influence on their gut microbiome at the end of the experiments. When the experiments were repeated with a cocktail of four different bacteria the results were similar – the earlier arrivals showed enhanced colonization and had the biggest influence on the microbe community. This suggests that the timing of bacterial arrival in the gut is very important to shape the gut microbiome. Since it is highly random and unpredictable in real-life, and likely to differ even among twins, it could explain why the gut microbiome can be so unique. More studies are needed to understand how antibiotics, formula feeding, or cesarean sections affect gut microbiota early in life, and consequently health. This may help scientists develop better ways to influence the microbiota to improve health, for example, by introducing beneficial microbes early in life.