Dobson Adam J, Chaston John M, Newell Peter D, Donahue Leanne, Hermann Sara L, Sannino David R, Westmiller Stephanie, Wong Adam C-N, Clark Andrew G, Lazzaro Brian P, Douglas Angela E
Department of Entomology, Cornell University, Ithaca, New York 14853, USA.
Department of Microbiology, Cornell University, Ithaca, New York 14853, USA.
Nat Commun. 2015 Feb 18;6:6312. doi: 10.1038/ncomms7312.
Animals bear communities of gut microorganisms with substantial effects on animal nutrition, but the host genetic basis of these effects is unknown. Here we use Drosophila to demonstrate substantial among-genotype variation in the effects of eliminating the gut microbiota on five host nutritional indices (weight, protein, lipid, glucose and glycogen contents); this includes variation in both the magnitude and direction of microbiota-dependent effects. Genome-wide association studies to identify the genetic basis of the microbiota-dependent variation reveal polymorphisms in largely non-overlapping sets of genes associated with variation in the nutritional traits, including strong representation of conserved genes functioning in signalling. Key genes identified by the GWA study are validated by loss-of-function mutations that altered microbiota-dependent nutritional effects. We conclude that the microbiota interacts with the animal at multiple points in the signalling and regulatory networks that determine animal nutrition. These interactions with the microbiota are probably conserved across animals, including humans.
动物体内存在肠道微生物群落，对动物营养有重大影响，但这些影响的宿主遗传基础尚不清楚。在这里，我们利用果蝇证明，消除肠道微生物群对五个宿主营养指标（体重、蛋白质、脂质、葡萄糖和糖原含量）的影响在基因型之间存在显著差异；这包括微生物群依赖性影响在幅度和方向上的变化。全基因组关联研究旨在确定微生物群依赖性变异的遗传基础，结果揭示了与营养性状变异相关的基因集中在很大程度上不重叠的多态性，包括在信号传导中起作用的保守基因的强烈代表性。通过功能丧失突变验证了全基因组关联研究确定的关键基因，这些突变改变了微生物群依赖性营养效应。我们得出结论，微生物群在决定动物营养的信号和调节网络中的多个点与动物相互作用。这些与微生物群的相互作用可能在包括人类在内的所有动物中都是保守的。
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