Stochastic changes over time and not founder effects drive cage effects in microbial community assembly in a mouse model
Stochastic changes over time and not founder effects drive cage effects in microbial community assembly in a mouse model
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DOI：
10.1038/ismej.2013.106
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发表时间：
2013-11-01
期刊：
影响因子：
11
通讯作者：
Fodor, Anthony A.
中科院分区：
文献类型：
--
作者：
McCafferty, Jonathan;Muehlbauer, Marcus;Fodor, Anthony A.
母体传播和笼子效应是微生物组研究中强有力的混淆因素。为了评估笼微环境对小鼠肠道微生物组的影响，研究人员使用Illumina 16S rRNA测序技术对两组无菌（GF）野生型（WT）小鼠进行了为期8周的监测，其中一组小鼠用成年WT小鼠的微生物群灌胃，另一组小鼠则从笼微环境中获取微生物组。我们的研究结果表明，WT小鼠从GF转移到特定无病原体（SPF）条件下的笼效应需要数周的时间才能发展，并且不会通过初始灌胃治疗消除。最初的灌胃影响了，但并没有消除变形菌群随着时间的推移而减少的连续模式。一项将16S rRNA序列映射到最近测序的全基因组的分析表明，随着时间的推移，微生物基因组的功能潜力发生了显著变化，从强调群落组装早期的发病机制和运动性转向后来的代谢过程。功能上，从笼子中自然获得微生物群落的小鼠，而不是用普通生物群落灌胃的小鼠，在葡聚糖硫酸钠诱导的炎症中表现出笼子效应。我们的研究结果表明，虽然创始群落存在长期影响，但随着时间的推移，这些影响会被笼微环境和连续的群落聚集所缓解，这两者必须在微生物组小鼠实验的解释中明确考虑。
Maternal transmission and cage effects are powerful confounding factors in microbiome studies. To assess the consequences of cage microenvironment on the mouse gut microbiome, two groups of germ-free (GF) wild-type (WT) mice, one gavaged with a microbiota harvested from adult WT mice and another allowed to acquire the microbiome from the cage microenvironment, were monitored using Illumina 16S rRNA sequencing over a period of 8 weeks. Our results revealed that cage effects in WT mice moved from GF to specific pathogen free (SPF) conditions take several weeks to develop and are not eliminated by the initial gavage treatment. Initial gavage influenced, but did not eliminate a successional pattern in which Proteobacteria became less abundant over time. An analysis in which 16S rRNA sequences are mapped to the closest sequenced whole genome suggests that the functional potential of microbial genomes changes significantly over time shifting from an emphasis on pathogenesis and motility early in community assembly to metabolic processes at later time points. Functionally, mice allowed to naturally acquire a microbial community from their cage, but not mice gavaged with a common biome, exhibit a cage effect in Dextran Sulfate Sodium-induced inflammation. Our results argue that while there are long-term effects of the founding community, these effects are mitigated by cage microenvironment and successional community assembly over time, which must both be explicitly considered in the interpretation of microbiome mouse experiments.