呼吸道病毒、免疫系统与肠道微生物群相互作用的研究进展

Research advances in the interactions among respiratory viruses, the immune system, and gut microbiota

摘要:

呼吸道病毒感染严重威胁全球公共卫生安全，探索有效预防呼吸道病毒感染的策略具有重要的临床意义。肠道微生物群通过重塑免疫微环境形成抗感染免疫的关键调节网络，维持宿主免疫稳态，从而增强宿主的抗病毒防御功能。肠道微生物失调则可能引发宿主免疫稳态紊乱，导致天然免疫应答缺陷以及适应性免疫激活异常，从而增加宿主对呼吸道病毒的易感性。本研究从多维度阐述肠道微生物群在宿主抗病毒免疫反应中的核心作用：(1) 系统阐述肠道微生物通过分泌抗菌肽、代谢营养物质、维持黏膜屏障完整性、调节宿主免疫稳态等生理功能，构建免疫防御屏障的重要性；(2) 分析肠道微生物处于平衡和失调状态时，通过调控Ⅰ型干扰素应答、免疫细胞分化等途径形成的抗病毒免疫调控网络；(3) 探讨益生菌通过抑制病毒增殖、改善宿主免疫功能、减少继发感染以及恢复肠道微生物平衡等机制发挥抗病毒效应。尽管微生物群-免疫系统-病毒感染的三元互作网络已取得突破性进展，但其动态平衡的分子机制及精准调控策略仍亟待深入探索，尤其是菌群代谢产物与宿主表观遗传调控的相互作用机制、微生物群诱导的免疫稳态在抗病毒中的长效保护机制等方面，仍需通过多组学技术进行系统揭示。

Abstract:

Respiratory viral infections pose a severe threat to global public health security, and exploring effective strategies to prevent them is of clinical significance. The gut microbiota plays a crucial role in regulating anti-infective immunity by remodeling the immune microenvironment, maintaining the immune homeostasis and boosting antiviral defenses of the host. Conversely, dysbiosis of the gut microbiota can disrupt immune homeostasis, resulting in impaired innate immune responses and abnormal activation of adaptive immunity, thereby raising the risk of respiratory viral infections in the host. This study elaborates on the essential role of the gut microbiota in the antiviral immune response of the host across multiple aspects. (1) It thoroughly explains how the gut microbiota contributes to forming an immune defense barrier by performing physiological functions such as secreting antimicrobial peptides, metabolizing nutrients, preserving mucosal barrier integrity, and modulating immune homeostasis of the host. (2) It analyzes the antiviral immune regulatory network that involves the regulation of type I interferon responses and immune cell differentiation, all within the context of gut microbiota balance and dysbiosis. (3) It explores how probiotics exert antiviral effects through mechanisms such as inhibiting viral proliferation, improving the host’s immune response, reducing secondary infections, and restoring gut microbiota balance. Although breakthroughs have been made in understanding the ternary interaction network of the microbiota, the immune system, and viral infection, the molecular mechanisms behind its dynamic balance and precise regulation still urgently need detailed investigation. Specifically, the mechanisms of interactions between gut microbiota metabolites and host epigenetic regulation, along with the long-term protective strategies of microbiota-induced immune homeostasis against viral infection, remain to be systematically revealed through multi-omics technologies.