Animal Neurobiology Laboratory, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, PR China; MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety & Jiangsu Engineering Laboratory of Animal Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, PR China.
Animal Neurobiology Laboratory, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, PR China.
Comp Immunol Microbiol Infect Dis. 2021 Apr;75:101611. doi: 10.1016/j.cimid.2021.101611. Epub 2021 Jan 20.
Gut-lung axis injury is a common finding in patients with respiratory diseases as well as in animal model of influenza virus infection. Influenza virus damages the intestinal microecology while affecting the lungs. Rifaximin, a non-absorbable derivative of rifamycin, is an effective antibiotic that acts by inhibiting bacterial RNA synthesis. This study aimed to determine whether rifaximin-perturbation of the intestinal microbiome leads to protective effects against influenza infection, via the gut-lung axis. Our results showed that influenza virus infection caused inflammation of and damage to the lungs. The expression of tight junction proteins in the lung and colon of H1N1 infected mice decreased significantly, attesting that the barrier structure of the lung and colon was damaged. Due to this perturbation in the gut-lung axis, the intestinal microbiota became imbalanced as Escherichia coli bacteria replicated opportunistically, causing intestinal injury. When influenza infection was treated with rifamixin, qPCR results from the gut showed significant increases in Lactobacillus and Bifidobacterium populations, while Escherichia coli populations markedly decreased. Furthermore, pathology sections and western blotting results illustrated that rifaximin treatment strengthened the physical barriers of the lung-gut axis through increased expression of tight junction protein in the colon and lungs. These results indicated that rifaximin ameliorated lung and intestine injury induced by influenza virus infection. The mechanisms identified were the regulation of gut flora balance and intestinal and lung permeability, which might be related to the regulation of the gut-lung axis. Rifaximin might be useful as a co-treatment drug for the prevention of influenza virus infection.
肠-肺轴损伤是呼吸系统疾病患者以及流感病毒感染动物模型中的常见现象。流感病毒损害肠道微生态，同时影响肺部。利福昔明是利福霉素的一种不可吸收衍生物，是一种有效的抗生素，通过抑制细菌 RNA 合成发挥作用。本研究旨在确定利福昔明是否通过肠-肺轴扰乱肠道微生物组，从而对流感感染产生保护作用。我们的结果表明，流感病毒感染导致肺部炎症和损伤。感染 H1N1 的小鼠肺部和结肠中紧密连接蛋白的表达显著降低，证明肺和结肠的屏障结构受损。由于这种肠-肺轴的紊乱，肠道微生物群变得失衡，大肠杆菌趁机复制，导致肠道损伤。当流感感染用利福昔明治疗时，来自肠道的 qPCR 结果显示乳酸杆菌和双歧杆菌的数量显著增加，而大肠杆菌的数量明显减少。此外，病理学切片和 Western blot 结果表明，利福昔明治疗通过增加结肠和肺部中紧密连接蛋白的表达，增强了肺-肠轴的物理屏障。这些结果表明，利福昔明改善了流感病毒感染引起的肺和肠损伤。确定的机制是肠道菌群平衡和肠肺通透性的调节，这可能与肠-肺轴的调节有关。利福昔明可能是预防流感病毒感染的一种有用的联合治疗药物。
