Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
Key Laboratory of Tropical Diseases Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, 510080, China.
Microbiome. 2023 Jul 24;11(1):157. doi: 10.1186/s40168-023-01597-9.
BACKGROUND: Secondary bacterial infections and pneumonia are major mortality causes of respiratory viruses, and the disruption of the upper respiratory tract (URT) microbiota is a crucial component of this process. However, whether this URT dysbiosis associates with the viral species (in other words, is viral type-specific) is unclear. RESULTS: Here, we recruited 735 outpatients with upper respiratory symptoms, identified the infectious virus types in 349 participants using multiplex RT-PCR, and profiled their upper respiratory microbiome using the 16S ribosomal RNA gene and metagenomic gene sequencing. Microbial and viral data were subsequently used as inputs for multivariate analysis aimed at revealing viral type-specific disruption of the upper respiratory microbiota. We found that the oropharyngeal microbiota shaped by influenza A virus (FluA), influenza B virus (FluB), respiratory syncytial virus (RSV), and human rhinovirus (HRV) infections exhibited three distinct patterns of dysbiosis, and Veillonella was identified as a prominent biomarker for any type of respiratory viral infections. Influenza virus infections are significantly correlated with increased oropharynx microbiota diversity and enrichment of functional metabolic pathways such as L-arginine biosynthesis and tetracycline resistance gene tetW. We used the GRiD algorithm and found the predicted growth rate of common respiratory pathogens was increased upon influenza virus infection, while commensal bacteria, such as Streptococcus infantis and Streptococcus mitis, may act as a colonization resistance to the overgrowth of these pathogens. CONCLUSIONS: We found that respiratory viral infections are linked with viral type-specific disruption of the upper respiratory microbiota, particularly, influenza infections uniquely associated with increased microbial diversity and growth rates of specific pathogens in URT. These findings are essential for clarifying the differences and dynamics of respiratory microbiota in healthy participants and acute respiratory viral infections, which contribute to elucidating the pathogenesis of viral-host-bacterial interactions to provide insights into future studies on effective prevention and treatment of respiratory tract infections. Video Abstract.
背景:继发细菌感染和肺炎是呼吸道病毒导致死亡的主要原因,而上呼吸道(URT)微生物组的破坏是这一过程的关键组成部分。然而,这种 URT 微生态失调是否与病毒种类有关(换句话说,是否具有病毒特异性)尚不清楚。
结果:在这里,我们招募了 735 名有上呼吸道症状的门诊患者,通过多重 RT-PCR 鉴定了 349 名参与者中的感染病毒类型,并使用 16S 核糖体 RNA 基因和宏基因组基因测序对其上呼吸道微生物组进行了分析。随后,将微生物和病毒数据作为输入,用于多变量分析,旨在揭示上呼吸道微生物组中病毒特异性的破坏。我们发现,甲型流感病毒(FluA)、乙型流感病毒(FluB)、呼吸道合胞病毒(RSV)和人类鼻病毒(HRV)感染所塑造的口咽微生物群表现出三种不同的失调模式,而韦荣球菌被确定为任何类型呼吸道病毒感染的突出生物标志物。流感病毒感染与口咽微生物群多样性增加和功能代谢途径(如 L-精氨酸生物合成和四环素耐药基因 tetW)的富集显著相关。我们使用 GRiD 算法发现,流感病毒感染后常见呼吸道病原体的预测生长速度增加,而共生细菌,如婴儿链球菌和酿脓链球菌,可能对这些病原体的过度生长起到定植抵抗作用。
结论:我们发现,呼吸道病毒感染与上呼吸道微生物组的病毒特异性破坏有关,特别是流感感染与 URT 中特定病原体的微生物多样性和生长速度的增加独特相关。这些发现对于阐明健康参与者和急性呼吸道病毒感染中呼吸道微生物组的差异和动态至关重要,有助于阐明病毒-宿主-细菌相互作用的发病机制,为呼吸道感染的有效预防和治疗提供新的思路。
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