Table_4_Microbiota Modulates Cardiac Transcriptional Responses to Intermittent Hypoxia and Hypercapnia.XLSX

The microbiota plays a critical role in regulating organismal health and response to environmental stresses. Intermittent hypoxia and hypercapnia, a condition that represents the main hallmark of obstructive sleep apnea in humans, is known to induce significant alterations in the gut microbiome and metabolism, and promotes the progression of atherosclerosis in mouse models. To further understand the role of the microbiome in the cardiovascular response to intermittent hypoxia and hypercapnia, we developed a new rodent cage system that allows exposure of mice to controlled levels of O2 and CO2 under gnotobiotic conditions. Using this experimental setup, we determined the impact of the microbiome on the transcriptional response to intermittent hypoxia and hypercapnia in the left ventricle of the mouse heart. We identified significant changes in gene expression in both conventionally reared and germ-free mice. Following intermittent hypoxia and hypercapnia exposure, we detected 192 significant changes in conventionally reared mice (96 upregulated and 96 downregulated) and 161 significant changes (70 upregulated and 91 downregulated) in germ-free mice. Only 19 of these differentially expressed transcripts (∼10%) were common to conventionally reared and germ-free mice. Such distinct transcriptional responses imply that the host microbiota plays an important role in regulating the host transcriptional response to intermittent hypoxia and hypercapnia in the mouse heart.

微生物群（microbiota）在调控机体健康及对环境应激的应答过程中发挥关键作用。间歇性低氧伴高碳酸血症是人类阻塞性睡眠呼吸暂停（obstructive sleep apnea）的核心特征，已有研究表明该病症可引发肠道微生物群与代谢的显著改变，并在小鼠模型中促进动脉粥样硬化（atherosclerosis）进展。为进一步阐明微生物群在机体对间歇性低氧伴高碳酸血症的心血管应答中的作用，本研究开发了一种新型啮齿类动物笼养系统，可在限菌环境（gnotobiotic conditions）下让小鼠暴露于可控浓度的氧气与二氧化碳中。借助该实验装置，本研究解析了微生物群对小鼠心脏左心室在间歇性低氧伴高碳酸血症刺激下的转录应答（transcriptional response）的影响。研究人员在常规饲养与无菌（germ-free）小鼠中均检测到基因表达的显著变化。经间歇性低氧伴高碳酸血症暴露后，常规饲养小鼠中共检测到192个差异表达转录本（differentially expressed transcripts，96个上调、96个下调），无菌小鼠则检测到161个差异表达转录本（70个上调、91个下调）。其中仅19个差异表达转录本（约占10%）在常规饲养与无菌小鼠中共有。这种显著差异的转录应答提示，宿主微生物群在调控小鼠心脏对间歇性低氧伴高碳酸血症的转录应答过程中发挥重要作用。