Liu Mingjiang, Liu Tengwen, Wang Xuerui, Yu Chenglong, Qin Tao, Li Jingui, Zhang Mina, Li Zhenxuan, Cui Xuran, Xu Xiaolong, Liu Qingquan
College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
Front Microbiol. 2022 Aug 8;13:947112. doi: 10.3389/fmicb.2022.947112. eCollection 2022.
Severe influenza A virus infection leads to overwhelming inflammatory responses and cellular apoptosis, which causes lung injury and contributes to high mortality and morbidity. The gut microbiome altered in response to the infection might influence the disease progression and the treatment outcome. Cangma Huadu (CMHD) granules, an in-hospital preparation of traditional Chinese medicine, have been shown to be favorable in the clinical treatment of influenza. However, the effects and mechanisms of CMHD granules on severe influenza pneumonia and its mechanisms are not well-known. In this study, a lethal influenza A (H1N1) A/Puerto Rico/8/34 virus (PR8)-infected mice model was established, and the 16S ribosomal RNA (16S rRNA) V3-V4 region sequencing of the intestinal microbiome was conducted. We revealed that the oral administration of CMHD granules protects mice against higher mortality, enhanced weight loss, overwhelmed interferon-γ concentration, lung viral titers, and severe lung pathological injury in PR8-infected mice. CMHD granules' administration downregulated the levels of interleukin (IL)-1β, tumor necrosis factor-α, and malondialdehyde, while it upregulated the levels of IL-10, superoxide dismutase, and glutathione peroxidase. Subsequently, it decreased the protein ratio of B-cell lymphoma-2/Bcl-2-associated X and the expression of cleaved caspase-3. The diversity and compositions of the gut microbes were altered profoundly after the administration of CMHD granules in PR8-infected mice. A higher abundance of , , , and was observed in the CMHD group, and a higher abundance of and was observed in the positive drug Ribavirin group. The linear discriminant analysis effect size also revealed a higher proportion of and characterized in the CMHD group. These results demonstrated that CMHD granules are a promising strategy for managing severe influenza and attenuating severe lung damage reducing viral titer, inflammatory responses, and oxidative stress. The mechanisms are involved in repressed Bcl-2-regulated apoptosis and altered composition and diversity of the gut microbiome.
甲型流感病毒严重感染会引发强烈的炎症反应和细胞凋亡，导致肺损伤，并致使高死亡率和高发病率。因感染而改变的肠道微生物群可能会影响疾病进展和治疗结果。苍麻化毒（CMHD）颗粒是一种院内制剂中药，已被证明在流感临床治疗中效果良好。然而，CMHD颗粒对重症流感肺炎的作用及其机制尚不清楚。在本研究中，建立了致死性甲型流感病毒A（H1N1）A/波多黎各/8/34病毒（PR8）感染小鼠模型，并对肠道微生物群进行16S核糖体RNA（16S rRNA）V3-V4区域测序。我们发现，口服CMHD颗粒可保护小鼠免受更高死亡率、体重减轻加剧、干扰素-γ浓度过高、肺病毒滴度和PR8感染小鼠严重肺病理损伤的影响。给予CMHD颗粒可下调白细胞介素（IL）-1β、肿瘤坏死因子-α和丙二醛水平，同时上调IL-10、超氧化物歧化酶和谷胱甘肽过氧化物酶水平。随后，它降低了B细胞淋巴瘤-2/Bcl-2相关X蛋白的比例以及裂解的半胱天冬酶-3的表达。在PR8感染小鼠中给予CMHD颗粒后，肠道微生物的多样性和组成发生了深刻变化。在CMHD组中观察到较高丰度的[具体微生物名称1]、[具体微生物名称2]、[具体微生物名称3]和[具体微生物名称4]，在阳性药物利巴韦林组中观察到较高丰度的[具体微生物名称5]和[具体微生物名称6]。线性判别分析效应大小还显示，CMHD组中[具体微生物名称7]和[具体微生物名称8]的比例更高。这些结果表明，CMHD颗粒是治疗重症流感和减轻严重肺损伤、降低病毒滴度、炎症反应和氧化应激的一种有前景的策略。其机制涉及抑制Bcl-2调节的细胞凋亡以及改变肠道微生物群的组成和多样性。
