Department of Plant & Wildlife Sciences, Brigham Young University, Provo, Utah, USA.
Department of Biology, Brigham Young University, Provo, Utah, USA.
Appl Environ Microbiol. 2018 Aug 17;84(17). doi: 10.1128/AEM.00662-18. Print 2018 Sep 1.
Animal-associated microorganisms (microbiota) dramatically influence the nutritional and physiological traits of their hosts. To expand our understanding of such influences, we predicted bacterial genes that influence a quantitative animal trait by a comparative genomic approach, and we extended these predictions via mutant analysis. We focused on starvation resistance (SR). We first confirmed that SR responds to the microbiota by demonstrating that bacterium-free flies have greater SR than flies bearing a standard 5-species microbial community, and we extended this analysis by revealing the species-specific influences of 38 genome-sequenced bacterial species on SR. A subsequent metagenome-wide association analysis predicted bacterial genes with potential influence on SR, among which were significant enrichments in bacterial genes for the metabolism of sulfur-containing amino acids and B vitamins. Dietary supplementation experiments established that the addition of methionine, but not B vitamins, to the diets significantly lowered SR in a way that was additive, but not interactive, with the microbiota. A direct role for bacterial methionine metabolism genes in SR was subsequently confirmed by analysis of flies that were reared individually with distinct methionine cycle mutants. The correlated responses of SR to bacterial methionine metabolism mutants and dietary modification are consistent with the established finding that bacteria can influence fly phenotypes through dietary modification, although we do not provide explicit evidence of this conclusion. Taken together, this work reveals that SR is a microbiota-responsive trait, and specific bacterial genes underlie these influences. Extending descriptive studies of animal-associated microorganisms (microbiota) to define causal mechanistic bases for their influence on animal traits is an emerging imperative. In this study, we reveal that starvation resistance (SR), a model quantitative trait in animal genetics, responds to the presence and identity of the microbiota. Using a predictive analysis, we reveal that the amino acid methionine has a key influence on SR and show that bacterial methionine metabolism mutants alter normal patterns of SR in flies bearing the bacteria. Our data further suggest that these effects are additive, and we propose the untested hypothesis that, similar to bacterial effects on fruit fly triacylglyceride deposition, the bacterial influence may be through dietary modification. Together, these findings expand our understanding of the bacterial genetic basis for influence on a nutritionally relevant trait of a model animal host.
动物相关微生物（微生物组）极大地影响宿主的营养和生理特征。为了扩大我们对这种影响的理解，我们通过比较基因组方法预测了影响动物数量性状的细菌基因，并通过突变分析对这些预测进行了扩展。我们专注于饥饿抗性（SR）。我们首先通过证明无菌蝇比携带标准 5 种微生物群落的蝇具有更高的 SR 来证实 SR 对微生物组有反应，并且我们通过揭示 38 个基因组测序细菌物种对 SR 的种特异性影响扩展了这一分析。随后的宏基因组关联分析预测了对 SR 有潜在影响的细菌基因，其中细菌基因对含硫氨基酸和 B 族维生素代谢的富集显著。膳食补充实验表明，向饮食中添加蛋氨酸而不是 B 族维生素，以与微生物组相加但不相互作用的方式显著降低了 SR。随后通过分析单独饲养在不同蛋氨酸循环突变体中的蝇，证实了细菌蛋氨酸代谢基因在 SR 中的直接作用。SR 对细菌蛋氨酸代谢突变体和饮食修饰的相关反应与已建立的发现一致，即细菌可以通过饮食修饰来影响蝇表型，尽管我们没有提供这一结论的明确证据。总之，这项工作表明 SR 是一种对微生物组有反应的特征，并且特定的细菌基因是这些影响的基础。将对动物相关微生物（微生物组）的描述性研究扩展到定义其对动物性状影响的因果机制基础是当务之急。在这项研究中，我们揭示了饥饿抗性（SR），动物遗传学中的一个模型数量性状，对微生物组的存在和身份有反应。使用预测分析，我们揭示了氨基酸蛋氨酸对 SR 有关键影响，并表明细菌蛋氨酸代谢突变体改变了携带细菌的蝇的正常 SR 模式。我们的数据进一步表明，这些影响是相加的，我们提出了一个未经测试的假设，即类似于细菌对果蝇三酰甘油沉积的影响，细菌的影响可能是通过饮食修饰。总的来说，这些发现扩展了我们对影响模型动物宿主营养相关特征的细菌遗传基础的理解。
