使用协作交叉来确定宿主基因在定义小鼠肠道微生物群中的作用
Aravindh Nagarajan1,2, Kristin Scoggin1,2,3, Jyotsana Gupta2
1Interdisciplinary Program in Genetics, Texas A&M University, College Station, TX, USA.
Microbiome
|July 7, 2023
概括
主体遗传学显著影响肠道微生物组成. 特定的肠道细菌,如Lachnospiraceae和Parasutterella,在小鼠感染沙门氏菌Typhimurium后影响健康结果.
科学领域:
- 微生物组研究的研究.
- 遗传学 遗传学 是一个
- 免疫学 免疫学 免疫学
背景情况:
- 人的肠道微生物群,一个复杂的细菌群体,对于营养加工至关重要,并影响疾病的发展.
- 众所周知,宿主基因会影响肠道微生物的组成,但具体的遗传影响需要更深入的研究.
- 协作交叉 (CC) 鼠提供了一个基因多样性,但可复制的模型,用于研究宿主基因与肠道微生物群的相互作用.
研究的目的:
- 为了研究宿主基因对肠道微生物组成的影响,使用基因多样化的协作交叉 (CC) 小鼠.
- 识别与特定肠道细菌种类相关的宿主遗传位点 (定量特征位点 - QTL).
- 探索肠道微生物组成和沙门氏菌Typhimurium感染后的健康结果之间的关系.
主要方法:
- 来自167只小鼠的便样本的16S rRNA基因测序. 在28个CC菌株中.
- 使用Qiime2管道进行生物信息分析以确定细菌组成.
- 定量特征位置 (QTL) 地图绘制,以将遗传区域与细菌品种丰富度联系起来.
- Enrichr和Genecards的分析将已识别的基因与人类疾病途径和GWAS数据联系起来.
- 沙门氏菌 Typhimurium 感染模型,以评估微生物组成对感染结果的影响.
- 基于感染前微生物群的机器学习分类来预测宿主遗传和感染结果.
主要成果:
- 在不同的CC小鼠菌株中观察到肠道细菌组成的显著变化,在类层面上.
- 确定了17个显著的QTL,将14个细菌属与9个小鼠染色体上的特定位置联系起来.
- 这些QTL区域内的宿主基因与肥胖,葡萄糖平衡,免疫力和神经疾病有关,这表明它们在塑造肠道微生物群中的作用.
- 拉克诺斯皮拉属的丰度增加和帕拉苏特雷拉菌的丰度减少与S. Typhimurium感染后更好的健康结果相关.
- 机器学习模型使用感染前便微生物数据准确预测了CC菌株和感染结果.
结论:
- 宿主基因在塑造肠道微生物组的组成和维持其平衡中发挥着重要作用.
- 特定的肠道细菌种群,如Lachnospiraceae和Parasutterella,可能会影响宿主健康和抗病能力,特别是在肠道病原体感染后.
- 该研究强调了使用基因多样化的小鼠模型和机器学习来解开复杂的主机微生物群相互作用及其健康影响的潜力.
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