Lusk Savannah, Memos Nicoletta K, Rauschmayer Andrea, Ray Russell S
Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States.
Baylor College of Medicine, McNair Medical Institute, Houston, TX, United States.
Front Physiol. 2024 Dec 6;15:1481394. doi: 10.3389/fphys.2024.1481394. eCollection 2024.
Increasing evidence indicates an association between microbiome composition and respiratory homeostasis and disease, particularly disordered breathing, such as obstructive sleep apnea. Previous work showing respiratory disruption is limited by the methodology employed to disrupt, eliminate, or remove the microbiome by antibiotic depletion. Our work utilized germ-free mice born without a microbiome and described respiratory alterations. We used whole-body flow through barometric plethysmography to assay conscious and unrestrained C57BL/6J germ-free (GF, n = 24) and specific-pathogen-free (SPF, n = 28) adult mice (with an intact microbiome) in normoxic (21% O,79% N) conditions and during challenges in hypercapnic (5% CO, 21% O, 74% N) and hypoxic (10% O, 90% N) environments. Following initial plethysmography analysis, we performed fecal transplants to test the ability of gut microbiome establishment to rescue any observed phenotypes. Data were comprehensively analyzed using our newly published respiratory analysis software, , to identify alterations in respiratory parameters, including ventilatory frequency, tidal volume, ventilation, apnea frequency, and sigh frequency. We also considered possible metabolic changes by analyzing oxygen consumption, carbon dioxide production, and ventilatory equivalents of oxygen. We also assayed GF and SPF neonates in an autoresuscitation assay to understand the effects of the microbiome on cardiorespiratory stressors in early development. We found several differences in baseline and recovery cardiorespiratory parameters in the neonates and differences in body weight at both ages studied. However, there was no difference in the overall survival of the neonates, and in contrast to prior studies utilizing gut microbial depletion, we found no consequential respiratory alterations in GF SPF adult mice at baseline or following fecal transplant in any groups. Interestingly, we did see alterations in oxygen consumption in the GF adult mice, which suggests an altered metabolic demand. Results from this study suggest that microbiome alteration in mice may not play as large a role in respiratory outcomes when a less severe methodology to eliminate the microbiome is utilized.
越来越多的证据表明微生物组组成与呼吸稳态及疾病之间存在关联，尤其是与呼吸紊乱有关，如阻塞性睡眠呼吸暂停。以往显示呼吸中断的研究受限于通过抗生素消耗来破坏、消除或去除微生物组所采用的方法。我们的研究利用了出生时没有微生物组的无菌小鼠，并描述了呼吸改变情况。我们使用全身气流通过式气压容积描记法，在常氧（21% O₂，79% N₂）条件下以及在高碳酸血症（5% CO₂，21% O₂，74% N₂）和低氧（10% O₂，90% N₂）环境挑战期间，对清醒且不受束缚的成年C57BL/6J无菌（GF，n = 24）和无特定病原体（SPF，n = 28）小鼠（具有完整微生物组）进行检测。在最初的容积描记法分析之后，我们进行了粪便移植，以测试肠道微生物组建立挽救任何观察到的表型的能力。使用我们新发表的呼吸分析软件对数据进行全面分析，以识别呼吸参数的改变，包括通气频率、潮气量、通气量、呼吸暂停频率和叹息频率。我们还通过分析耗氧量、二氧化碳产生量和氧通气当量来考虑可能的代谢变化。我们还在自动复苏试验中检测了GF和SPF新生小鼠，以了解微生物组对早期发育中心肺应激源的影响。我们发现新生小鼠在基线和恢复时的心肺参数存在一些差异，并且在所研究的两个年龄段的体重也存在差异。然而，新生小鼠的总体存活率没有差异，并且与之前利用肠道微生物消耗的研究相反，我们发现在任何组中，GF和SPF成年小鼠在基线时或粪便移植后均未出现相应的呼吸改变。有趣的是，我们确实观察到GF成年小鼠的耗氧量发生了改变，这表明代谢需求发生了变化。这项研究的结果表明，当采用不太严格的方法来消除微生物组时，小鼠体内微生物组的改变在呼吸结果中可能不会起到很大作用。
