Department of Medical Microbiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Medicine and Allied Health Sciences, University of The Gambia, Banjul, The Gambia.
J Med Virol. 2023 Aug;95(8):e28976. doi: 10.1002/jmv.28976.
The lung-brain axis is an emerging biological pathway that is being investigated in relation to microbiome medicine. Increasing evidence suggests that pulmonary viral infections can lead to distinct pathological imprints in the brain, so there is a need to explore and understand this mechanism and find possible interventions. This study used respiratory syncytial virus (RSV) infection in mice as a model to establish the potential lung-brain axis phenomenon. We hypothesized that RSV infection could disrupt the lung microbiota, compromise immune barriers, and induce a significant shift in microglia phenotype. One week old mice were randomized into the control, Ampicillin, RSV, and RSV+Ampicillin treated groups (n = 6 each). Seven days after the respective treatments, the mice were anaesthetized. Immunofluorescence and real-time qRT-PCR was used to detect virus. Hematoxylin-eosin staining was used to detect histopathology. Malondialdehyde and superoxide dismutase were used to determine oxidative stress and antioxidant capacity. Real-time qRT-PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure Th differentiation in the lung. Real-time qRT-PCR, ELISA, and confocal immunofluorescence were used to determine the microglia phenotype. 16S DNA technology was used to detect lung microflora. RSV infection induces elevated oxidative stress, reduced antioxidant, and significant dysbacteriosis in the lungs of mice. Pulmonary microbes were found to enhance Th1-type immunoreactivity induced by RSV infection and eventually induced M1-type dominant microglia in the brains of mice. This study was able to establish a correlation between the pulmonary microbiome and brain function. Therefore, we recommend a large sample size study with robust data analysis for the long-term effects of antibiotics and RSV infection on brain physiology.
肺脑轴是一个新兴的生物学途径，目前正在微生物组医学领域进行研究。越来越多的证据表明，肺部病毒感染会导致大脑出现明显的病理印记，因此需要探索和理解这种机制，并寻找可能的干预措施。本研究使用呼吸道合胞病毒（RSV）感染小鼠作为模型，来建立潜在的肺脑轴现象。我们假设 RSV 感染可能会破坏肺部微生物群，损害免疫屏障，并导致小胶质细胞表型发生显著变化。1 周龄的小鼠被随机分为对照组、氨苄青霉素组、RSV 组和 RSV+氨苄青霉素组（每组 6 只）。在各自的治疗后 7 天，对小鼠进行麻醉。免疫荧光和实时 qRT-PCR 用于检测病毒。苏木精-伊红染色用于检测组织病理学。丙二醛和超氧化物歧化酶用于测定氧化应激和抗氧化能力。实时 qRT-PCR 和酶联免疫吸附试验（ELISA）用于检测肺中 Th 分化。实时 qRT-PCR、ELISA 和共聚焦免疫荧光用于确定小胶质细胞表型。16S DNA 技术用于检测肺部微生物群。RSV 感染会导致小鼠肺部氧化应激升高、抗氧化能力降低和显著的菌群失调。肺部微生物被发现增强了 RSV 感染诱导的 Th1 型免疫反应，最终导致小鼠大脑中 M1 型主导的小胶质细胞。本研究能够在肺部微生物群和大脑功能之间建立相关性。因此，我们建议进行一项大型样本量研究，并进行稳健的数据分析，以了解抗生素和 RSV 感染对大脑生理学的长期影响。
