Microbiota-induced changes in drosophila melanogaster host gene expression and gut morphology.
Microbiota-induced changes in drosophila melanogaster host gene expression and gut morphology.
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DOI：
10.1128/mbio.01117-14
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发表时间：
2014-05-27
期刊：
影响因子：
6.4
通讯作者：
Lemaitre B
中科院分区：
文献类型：
--
作者：
Broderick NA;Buchon N;Lemaitre B
为了阐明宿主与其微生物群之间复杂关系的机制，我们使用了遗传上易于处理的模型黑腹果蝇。与以前的研究一致，微生物群的组成和多样性都很简单。然而，单苍蝇的分析显示，高interfly的变异性与喂养的差异。为了了解这种简单而可变的财团的影响，我们比较了传统饲养的苍蝇的肠道转录组，为他们的axenically饲养的同行。我们对两个野生型果蝇品系的分析确定了121个上调和31个下调基因。这些基因中的大多数与免疫反应、组织稳态、肠道生理学和代谢相关。通过比较年轻和年老果蝇的转录组，我们确定了时间响应基因，并表明微生物群的整体影响在年老果蝇中更大。此外，野生型基因表达与免疫缺陷系的比较显示，53%的上调基因通过免疫缺陷（Imd）途径发挥作用。这些基因不仅包括经典的免疫反应基因，还包括参与信号传导、基因表达和代谢的基因，揭示了免疫和其他系统之间新的和意想不到的联系。鉴于这些发现，我们进一步表征了肠道相关微生物对肠道形态和上皮结构的影响。结果表明，微生物群通过影响上皮更新率、细胞间距和上皮中不同细胞类型的组成来影响肠道形态。因此，虽然肠道中的细菌是高度可变的，但微生物群的影响对宿主生理学具有深远的影响。动物的肠道与微生物不断联系，这些相互作用被认为在动物发育和生理学中具有重要作用。然而，我们对这些协会的建立和运作的机制知之甚少。在这里，我们使用果蝇来了解微生物群如何影响宿主功能。重要的是，我们发现微生物群对宿主生理学具有深远的影响，从免疫力到肠道结构。我们的研究结果验证了这一概念，即复杂的宿主-微生物关系的重要见解，可以从使用一个完善的和遗传上易于处理的无脊椎动物模型。
To elucidate mechanisms underlying the complex relationships between a host and its microbiota, we used the genetically tractable model Drosophila melanogaster. Consistent with previous studies, the microbiota was simple in composition and diversity. However, analysis of single flies revealed high interfly variability that correlated with differences in feeding. To understand the effects of this simple and variable consortium, we compared the transcriptome of guts from conventionally reared flies to that for their axenically reared counterparts. Our analysis of two wild-type fly lines identified 121 up- and 31 downregulated genes. The majority of these genes were associated with immune responses, tissue homeostasis, gut physiology, and metabolism. By comparing the transcriptomes of young and old flies, we identified temporally responsive genes and showed that the overall impact of microbiota was greater in older flies. In addition, comparison of wild-type gene expression with that of an immune-deficient line revealed that 53% of upregulated genes exerted their effects through the immune deficiency (Imd) pathway. The genes included not only classic immune response genes but also those involved in signaling, gene expression, and metabolism, unveiling new and unexpected connections between immunity and other systems. Given these findings, we further characterized the effects of gut-associated microbes on gut morphology and epithelial architecture. The results showed that the microbiota affected gut morphology through their impacts on epithelial renewal rate, cellular spacing, and the composition of different cell types in the epithelium. Thus, while bacteria in the gut are highly variable, the influence of the microbiota at large has far-reaching effects on host physiology. The guts of animals are in constant association with microbes, and these interactions are understood to have important roles in animal development and physiology. Yet we know little about the mechanisms underlying the establishment and function of these associations. Here, we used the fruit fly to understand how the microbiota affects host function. Importantly, we found that the microbiota has far-reaching effects on host physiology, ranging from immunity to gut structure. Our results validate the notion that important insights on complex host-microbe relationships can be obtained from the use of a well-established and genetically tractable invertebrate model.