微生物学报

Species	Methods	Mechanisms	Phenotypes	References
Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1	Oral gavage (viable bacteria)	Stimulates the induction of acquired humoral immunity of anti-PR8-specific IgG and IgA in serum	Enhance serum titers of influenza virus-neutralizing antibodies and mitigate the adverse reactions of oseltamivir	[7]
Flavonifractor plautii	DAT drinking water	Flavonifractor plautii, produced DAT protected the host by priming the amplification loop of type I IFN signaling and rescued antibiotic-treated influenza-infected mice	1. Delay the rate of body weight loss in mice following influenza virus challenge 2. Attenuate lung pathological injury and cellular apoptosis	[10]
Lactobacillus MI29	Oral gavage (viable bacteria)	Activation of host defense via the gut-lung axis against influenza virus infection	1. Improved survival and delayed body weight loss in influenza-infected mice 2. Decrease viral loads and mitigate histopathological changes in the lungs of influenza-infected mice	[11]
Segmented filamentous bacteria	Oral gavage (viable bacteria)	Induce the appearance of CD4⁺ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria and enhance mucosal immunity	Enhanced resistance to the intestinal pathogen	[39]
Lactiplantibacillus plantarum Lp J1-8, 330, CK10, 920Leuconostoc mesenteroides Lm DRC1506, 218	Oral gavage (viable bacteria)	The detailed mechanism responsible for suppressing viral replication remains to be fully elucidated	1. Increased survival in influenza-infected mice 2. Decrease viral loads in the lungs of influenza-infected mice	[46]
Lactiplantibacillus plantarum nF1	Oral gavage (heat-inactivated bacteria)	Bacterial components may contribute to the anti-influenza virus effect, but the underlying mechanism remains to be clarified	1. Improved survival and delayed body weight loss in influenza-infected mice 2. Decrease viral loads in the lungs of influenza-infected mice	[47]
Limosilactobacillus fermentum PV22	Oral gavage (viable bacteria)	Inhibit norovirus infection by the γ-aminobutyric acid (GABA) produced by PV22	Reduce the titers of norovirus in RAW264.7 cells	[49]
Bifidobacterium pseudolongum NjM1	Oral gavage (viable bacteria)	Acetic acid produced by NjM1 activates the GPR43-NLRP3-MAVS-IFN-I pathway to elicit antiviral responses	1. Promote body weight recovery and prolong survival in influenza-infected mice 2. Alleviate lung pathological injury and reduce viral titers	[51]
Prevotella copri DSM 18205	Oral gavage (viable bacteria)	Reshape gut microbiota and enhance the production of isovaleric acid and isobutyric acid to mediate antiviral activity	1. Improved survival and delayed body weight loss in influenza-infected mice 2. Alleviate lung pathological injury and maintain the integrity of epithelial cells	[52]

Species	Methods	Mechanisms	Phenotypes	References
Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1	Oral gavage (viable bacteria)	Stimulates the induction of acquired humoral immunity of anti-PR8-specific IgG and IgA in serum	Enhance serum titers of influenza virus-neutralizing antibodies and mitigate the adverse reactions of oseltamivir	[7]
Flavonifractor plautii	DAT drinking water	Flavonifractor plautii, produced DAT protected the host by priming the amplification loop of type I IFN signaling and rescued antibiotic-treated influenza-infected mice	1. Delay the rate of body weight loss in mice following influenza virus challenge 2. Attenuate lung pathological injury and cellular apoptosis	[10]
Lactobacillus MI29	Oral gavage (viable bacteria)	Activation of host defense via the gut-lung axis against influenza virus infection	1. Improved survival and delayed body weight loss in influenza-infected mice 2. Decrease viral loads and mitigate histopathological changes in the lungs of influenza-infected mice	[11]
Segmented filamentous bacteria	Oral gavage (viable bacteria)	Induce the appearance of CD4⁺ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria and enhance mucosal immunity	Enhanced resistance to the intestinal pathogen	[39]
Lactiplantibacillus plantarum Lp J1-8, 330, CK10, 920Leuconostoc mesenteroides Lm DRC1506, 218	Oral gavage (viable bacteria)	The detailed mechanism responsible for suppressing viral replication remains to be fully elucidated	1. Increased survival in influenza-infected mice 2. Decrease viral loads in the lungs of influenza-infected mice	[46]
Lactiplantibacillus plantarum nF1	Oral gavage (heat-inactivated bacteria)	Bacterial components may contribute to the anti-influenza virus effect, but the underlying mechanism remains to be clarified	1. Improved survival and delayed body weight loss in influenza-infected mice 2. Decrease viral loads in the lungs of influenza-infected mice	[47]
Limosilactobacillus fermentum PV22	Oral gavage (viable bacteria)	Inhibit norovirus infection by the γ-aminobutyric acid (GABA) produced by PV22	Reduce the titers of norovirus in RAW264.7 cells	[49]
Bifidobacterium pseudolongum NjM1	Oral gavage (viable bacteria)	Acetic acid produced by NjM1 activates the GPR43-NLRP3-MAVS-IFN-I pathway to elicit antiviral responses	1. Promote body weight recovery and prolong survival in influenza-infected mice 2. Alleviate lung pathological injury and reduce viral titers	[51]
Prevotella copri DSM 18205	Oral gavage (viable bacteria)	Reshape gut microbiota and enhance the production of isovaleric acid and isobutyric acid to mediate antiviral activity	1. Improved survival and delayed body weight loss in influenza-infected mice 2. Alleviate lung pathological injury and maintain the integrity of epithelial cells	[52]

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

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贾艳娥 , 邹扬 , 蒲丽霞 , 王帅

微生物学报 | 综述 2026,66(5): 2061-2071

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微生物学报 | 综述 2026, 66(5): 2061-2071

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

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贾艳娥, 邹扬, 蒲丽霞, 王帅

作者信息

中国农业科学院兰州兽医研究所，甘肃兰州

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

Yan’e JIA, Yang ZOU, Lixia PU, Shuai WANG

Affiliations

Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China

出版时间: 2026-05-04 doi: 10.13343/j.cnki.wsxb.20250920

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摘要

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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。

关键词

呼吸道病毒 / 免疫系统 / 微生物群 / 作用机制

Abstract

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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.

Key words

respiratory viruses / immunity system / microbiota / mechanism

引用本文

贾艳娥, 邹扬, 蒲丽霞, 王帅. 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. 微生物学报, 2026 , 66 (5) : 2061 -2071 . DOI: 10.13343/j.cnki.wsxb.20250920

Yan’e JIA, Yang ZOU, Lixia PU, Shuai WANG. Research advances in the interactions among respiratory viruses, the immune system, and gut microbiota[J]. Acta Microbiologica Sinica, 2026 , 66 (5) : 2061 -2071 . DOI: 10.13343/j.cnki.wsxb.20250920

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呼吸道病毒感染是全球范围内威胁人类健康的重要公共卫生问题，其感染机体后所导致的高发病率和高死亡率凸显了探索有效预防策略的迫切需求^[1-4]。作为宿主免疫系统的重要调节因子，肠道微生物在抗病毒防御中的作用备受关注。大量研究表明，肠道微生物不仅可通过分泌抗菌肽(antimicrobial peptides, AMPs)、代谢营养物质以及维持黏膜屏障完整性参与构建宿主免疫防御体系，还能通过调控Ⅰ型干扰素应答、免疫细胞分化等途径影响抗病毒免疫应答的平衡^[5-8]。相反，肠道微生物失调可导致天然免疫缺陷和适应性免疫异常，进而增加机体对呼吸道病毒的易感性^[9]。此外，益生菌干预可通过菌体组分、诱导干扰素应答以及重塑“肠道-呼吸道轴”免疫稳态等机制发挥抗病毒效应^[10-13]。

呼吸道病毒、免疫系统与肠道微生物群三者之间存在复杂的双向互作关系。总体而言，肠道微生物群通过塑造宿主免疫系统功能，影响呼吸道病毒的感染进程与结局；而呼吸道病毒感染也可通过免疫介导的炎症反应，反向重塑肠道微生物群的组成与功能。宿主的肠道微生物及其代谢物可通过影响免疫抑制性细胞和炎症细胞的代谢与功能状态，例如髓源性抑制细胞(myeloid-derived suppressor cells, MDSCs)、调节性T细胞(tegulatory T cells, Tregs)、CD4⁺辅助T细胞(CD4⁺ T helper cells, Th)以及自然杀伤性细胞(natural killer cells, NK)等的分化与功能，维持宿主免疫稳态，进而影响免疫应答^[14]。然而，微生物群-免疫系统-病毒感染这三者互作的分子机制尚未被完全阐明，尤其是菌群代谢产物与宿主表观遗传调控之间的相互作用机制，以及微生物群诱导的免疫稳态长效保护机制等关键科学问题，仍需深入探索。因此，系统理解肠道微生物群在抗病毒免疫中的调控作用，对开发新型、靶向病毒感染的预防策略具有重要的理论意义和潜在应用价值。

1 呼吸道病毒感染与肠道微生物概述

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1.1 呼吸病毒感染及危害

呼吸道病毒可通过空气传播途径感染宿主，其感染可引发呼吸道黏膜及上皮组织的病理性损伤，严重时会致使呼吸系统功能衰竭，甚至危及生命。据统计，全球每年约有400万人死于呼吸道感染^[15]。在美国，因急性呼吸道感染和“流感样疾病”就诊人群的发病率为9.5%^[1]。常见的呼吸道病毒包括鼻病毒(Rhinovirus, RhV)、严重急性呼吸系统综合征冠状病毒(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)和A型流感病毒(influenza A virus, IAV)等。这些病毒感染后会对宿主呼吸道和肺脏造成严重损伤，诱发多种呼吸道疾病，如哮喘、支气管炎和肺炎等，严重情况下可导致死亡^[16]。据世界卫生组织(World Health Organization, WHO)统计数据显示，全球每年约有十亿人感染H1N1和H3N2亚型流感病毒，相关死亡的人数约为29万-65万^[4]。自SARS-CoV-2流行以来，全球累计已有超过7亿人感染，死亡人数超过700万^[2]。上述数据表明，呼吸道病毒感染已成为严重威胁人类生命健康和公共卫生安全的全球性挑战。

呼吸道病毒感染可引起宿主免疫系统功能异常并诱导过度炎症反应。研究发现，SARS-CoV-2感染的患者常伴有强烈的免疫应答反应，其CD4⁺、CD8⁺ T细胞水平显著低于健康人群^[17]；IAV的病毒蛋白可通过不同机制靶向天然免疫关键分子，调控干扰素的产生与信号转导，以促进病毒自身复制^[18-19]。上述研究表明，呼吸道病毒感染会影响宿主的免疫应答，从而削弱其抗病毒功能。此外，呼吸道病毒感染还可引起肠道微生物组成和结构的改变，导致肠道微生物紊乱，进而引发继发性感染^[20-21]。变化的肠道微生物及其代谢物可通过增强黏膜屏障功能、分泌抗病毒肽以及调节天然免疫和适应性免疫应答等多种途径，参与宿主对呼吸病毒感染的防御^[5-6,8]。随着抗病毒药物的广泛应用及多种外界因素的持续干预，呼吸道病毒不断发生进化。因此，深入研究呼吸道病毒与宿主之间的相互作用机制，系统解析宿主抗病毒免疫调控网络，并挖掘宿主新的作用靶点，对于抗病毒药物或免疫微生态制剂的研发具有重要意义，也将为保障公共卫生健康提供理论依据。

1.2 肠道微生物及功能

宿主是由多种组织、器官及其共生微生物构成的复杂系统。肠道微生物是指定殖于宿主胃肠道黏膜表面及肠腔微环境中的微生物集合体，主要由细菌、古菌、真菌和病毒等组成。这些微生物通过黏附于宿主黏膜表面，与宿主形成紧密的共生关系，在维持机体的能量代谢、上皮细胞完整性、免疫功能调控及神经系统发育等方面发挥关键作用^[22-24]。肠道微生物具有多种重要的生理功能，包括参与营养物质代谢、抵御外来病原体入侵以及维持宿主内环境稳态等，对宿主健康至关重要^[25]。

1.2.1 代谢营养物质

肠道微生物在宿主的营养物质代谢及内环境稳态维持中发挥着不可替代的作用，其核心功能主要体现在两大关键代谢过程中。首先，肠道微生物可对摄入的膳食纤维进行发酵分解，将这些膳食纤维转化为可被宿主利用的代谢物，同时产生多种活性代谢物，包括甲烷、氢气和二氧化碳等气体，甲酸盐、乙酸盐、丙酸盐等一系列短链脂肪酸，乳酸盐、琥珀酸盐等小分子有机酸，以及甲醇、乙醇等醇类物质。这些产物共同构成了宿主能量代谢和物质合成的重要底物库^[22]。其次，对于宿主体内未被消化系统完全分解的蛋白质，肠道微生物可通过分泌胞外蛋白酶将其进一步降解为多肽、氨基酸及其他代谢物^[22,26]，从而实现营养物质的再次利用，并有效维持机体代谢稳态。这两类代谢过程相互协同，不仅为宿主提供必需的代谢原料，弥补宿主自身消化酶体系的功能局限，还促进了对膳食纤维和未完全消化蛋白质的充分利用，从而建立并维持了肠道微生物与宿主之间互利共生的稳固关系。

1.2.2 保护宿主免受病原侵害

肠道上皮细胞会持续分泌由黏液糖蛋白组成的黏稠凝胶状黏液层，该结构是宿主肠道黏膜屏障的重要组成部分。在生理稳态条件下，黏液层通过其物理屏障作用，有效阻止病原体与肠上皮细胞直接接触，从而阻挡病原微生物的入侵，保护宿主免受感染^[27]。然而，部分致病性微生物在进化过程中获得了突破黏液屏障的特殊机制，能够成功穿越黏液层并引发感染。幽门螺杆菌(Helicobacter pylori)能通过自身分泌的尿素酶分解环境中的尿素，以此提高细胞周围的pH值，从而降低黏液层的黏稠度和屏障功能，有利于病原突破黏液层侵袭上皮细胞，最终感染宿主^[28]。因此，肠道黏液层作为宿主抵御病原的第一道物理防线，在正常生理状态下能够维持稳定而有效的防御屏障，但在面对具有特殊侵袭策略的致病菌时其完整性可能被破坏，从而增加致病病原感染机体的风险。

1.2.3 维持宿主稳态

宿主内环境稳态的维持依赖于多种微生物及其代谢产物的协同参与。其中，肠道微生物及其代谢物可通过调控免疫抑制性细胞与炎症细胞的代谢过程，对宿主的免疫稳态产生影响^[14]。研究表明，小鼠肠道中的罗伊氏乳杆菌(Lactobacillus reuteri)能够诱导结肠FOXP3⁺调节性T细胞(Tregs)的扩增，从而有效缓解肠道炎症^[29]。此外，梭状芽胞杆菌(Clostridium)和次级胆汁酸的增加对于犬慢性炎症性肠病也具有缓解作用^[30]。在多种共生菌及其代谢物的协同调控下，宿主能够维持相对稳定的内环境，抵抗病原体的侵袭。然而，当特定微生物组成或功能发生改变，即出现菌群失调时可能增加宿主对某些病原体的易感性，从而促进疾病的发生与发展。目前尚不明确肠道微生物失调是否是某些疾病产生的诱因，或是疾病进程本身导致肠道微生物失调，其潜在分子机制仍待进一步研究和深入阐明^[31]。

2 肠道微生物的抗病毒机制

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2.1 肠道微生物在机体免疫防御中的作用

当病毒入侵黏膜表面时需要突破机体的3道免疫防线：黏膜免疫防线、天然免疫防线和适应性免疫防线^[16,32]。多种共生菌和益生菌在这3道免疫防御体系中发挥重要的调控作用，通过参与维持黏膜屏障功能、调节免疫应答等过程，增强宿主抵抗病毒感染能力。

2.1.1 促进黏膜屏障的功能

肠道上皮细胞表面覆盖一层凝胶状的黏液层，该黏液层可阻止病原微生物直接接触和侵入肠道上皮细胞，并限制病原微生物穿过上皮细胞进入皮下组织。肠道黏液是由杯状细胞产生的高效网状糖蛋白，包括高度糖基化的黏蛋白、由各种氨基糖组成的寡糖、乙酰半乳糖胺和半乳糖等组成的单糖^[32]。这些黏蛋白不仅在营养物质向上皮细胞转运过程中起到润滑作用，还具有选择性渗透功能。因此，黏液层是宿主第一道防御体系中的重要组成物质。作为分隔宿主肠道上皮与肠腔微生物群的关键物理与功能屏障，肠道黏液层的完整性和功能可受特定肠道细菌的定殖及代谢活动影响，如调控黏液合成、分泌及结构重塑，增强黏液层的屏障防御功能^[33]。例如，肠道中的嗜黏蛋白阿克曼氏菌(Akkermansia muciniphila)可将黏蛋白转化成对宿主有益的副产物，有助于维持宿主肠道稳态和黏膜屏障完整性。此外，该菌还可竞争性结合某些降解黏蛋白的细菌，抑制其降解黏蛋白，从而提高宿主的代谢功能和免疫应答^[5]。因此，肠道黏液层不仅承担润滑和选择性渗透等生理功能，也是宿主第一道防御体系的重要组成部分，其屏障防御功能受特定肠道细菌(如嗜黏蛋白阿克曼氏菌)定殖及代谢活动的动态调控，在肠道稳态维持、黏膜屏障完整性保护及宿主代谢与免疫调节中发挥关键作用。

2.1.2 分泌抗病毒的抗菌肽

抗菌肽是宿主固有免疫体系分泌的一类具有高度异质性的生物活性分子，其在分子质量、空间构象、抗微生物作用机制及与细胞受体结合模式方面均存在显著差异。由细菌分泌的抗菌肽又被称为细菌素。尽管目前尚缺乏充分证据证明细菌素的产生能提高该菌株在胃肠道内的竞争力或直接对宿主健康有益，但能否产生细菌素仍是筛选和评价益生菌菌株的一个重要标准^[34]。值得注意的是，部分细菌素具有明确的抗病毒功能。现有研究表明，细菌素主要通过2种模式发挥抗病毒作用。第1种是阻断病毒进入细胞，如纳米比亚马杜拉放线菌(Actinomadura namibiensis)产生的羊毛硫抗生素通过直接结合呼吸道合胞病毒囊膜表面的磷脂酰乙醇，破坏病毒囊膜结构，阻止病毒进入细胞并有效抑制病毒感染^[6]；第2种是抑制病毒在细胞内的复制，研究发现奥司他韦可显著抑制血液和支气管肺泡灌洗液中流感病毒特异性的免疫球蛋白A (immunoglobulin A, IgA)和免疫球蛋白G (immunoglobulin G, IgG)产生，从而削弱宿主的抗病毒体液免疫应答，增加再次感染的风险。然而，德氏乳杆菌保加利亚亚种(Lactobacillus delbrueckii subsp. bulgaricus) OLL1073R-1能够特异性诱导IgA和IgG的产生，发挥免疫调节作用，从而减轻奥司他韦的不良反应，进一步抑制流感病毒复制，延缓病毒粒子的释放^[7]。

2.1.3 调节抗病毒天然免疫和适应性免疫功能

天然免疫系统是机体抵御外源病原体的第一道非特异性防御屏障，具有反应迅速的特点，主要由物理性屏障、细胞内模式识别受体以及免疫细胞(如NK、巨噬细胞等)共同组成^[35]。当外源病原体感染机体后，天然免疫防御系统会被激活，刺激免疫细胞产生Ⅰ型干扰素，发挥抗病毒作用。若天然免疫系统未能阻止病原体的入侵，适应性免疫系统将被激活^[36]。尽管适应性免疫反应较为延迟，但其针对特定病原体具有高度特异性，主要由抗体介导的B细胞反应、Th、细胞毒性T细胞共同参与。此外，适应性免疫系统可形成免疫记忆，当相同病原再次入侵时记忆性T细胞能迅速应答并发挥抗病毒功能^[37]。综上所述，肠道微生物通过多层次调控宿主免疫反应，抵抗病毒入侵。其整体作用机制如图1所示。

2.2 肠道微生物失调与流感病毒感染的关系

与健康个体相比，宿主共生菌群在组成或功能上发生的任何变化都可称为菌群失调^[38]。菌群失调的发生有诸多内在因素和外在影响。研究表明，新型冠状病毒、呼吸道合胞病毒、流感病毒等呼吸道病毒感染会引起肠道微生物失调，并引发宿主新陈代谢紊乱、免疫系统异常等一系列反应^[9,20-21]。宿主在生理稳态下，肠道共生菌可被天然免疫系统中的模式识别受体识别，促进肠道上皮细胞的更新和完整性，维持肠道稳态，抵御外源病原体的入侵^[39]；同时肠道共生菌还可通过调节辅助T细胞成熟和促进Th17细胞分化，维持肠道免疫系统的稳态平衡^[40]。例如，肠道中的共生菌分段丝状菌(segmented filamentous bacteria, SFB)能够诱导血清淀粉样蛋白A (serum amyloid A, SAA)的产生，SAA作用于固有层树突状细胞，促进Th17细胞分化，从而抑制肠道病原菌的生长^[6,39]。由此可见，肠道共生菌与宿主保持紧密的共生关系，在宿主免疫系统的稳态中发挥重要作用。此外，菌群的代谢物如短链脂肪酸、胆汁酸、氨基酸等，同样是维持免疫稳态的重要信号分子^[41-43]。肠道细菌衍生的代谢物及其结构组分可通过肠系膜淋巴系统和体循环从肠道转运到肺部，可能进一步诱导肺部免疫反应^[11]。综上所述，肠道微生物的失调不仅会导致局部免疫功能障碍，还可能引发系统性的免疫反应，诱导肠道乃至全身多种器官的炎症反应，造成组织损伤和疾病进展，增加继发性感染的风险^[20]。

总之，病毒感染、共生菌群与免疫系统之间相互影响。在稳态下，宿主通过共生菌群维持低水平的免疫应答来抵抗病原侵害，共生菌群也是机体完整的免疫应答系统中不可缺少的部分^[44]。然而，当机体受到病毒感染时这种稳态被打破，过度或失衡的免疫应答可诱导炎症反应，进而造成肠道微生物紊乱，主要表现为有益菌减少，有害菌富集，最终造成机体损伤和继发性感染^[9,20-21]。因此，维持机体稳态显得尤为重要，而合理应用益生菌对维持机体的健康具有潜在的益处。

2.3 益生菌在抑制病毒感染中的机制

大量研究表明，益生菌可通过恢复肠道共生菌群与宿主之间的共生关系，增强机体免疫功能、抑制炎症反应，从而维持体内环境稳态^[45]。益生菌作为一种天然产品，能够通过维持肠道屏障的完整性及发挥免疫调节活性，在预防和改善肠道微生物生态失调方面发挥重要作用^[13]。已有多项临床试验和动物研究证实，益生菌在流感病毒感染的防治中有显著效果，其抗流感病毒的机制主要包括抑制病毒增殖、改善宿主免疫功能、减少继发感染以及促进肠道微生物平衡^[46]。例如，人源发酵黏液乳杆菌(Limosilactobacillus fermentum) PV22，植物乳杆菌(Lactiplantibacillus plantarum) nF1、330、CK10，人源肠膜状明串珠菌(Leuconostoc mesenteroides) 218和人源乳杆菌属(Lactobacillus) MI29株，均可减缓小鼠体重下降并降低死亡率，减少小鼠肺脏中的病毒载量^[11,47-49]。在免疫调节方面，益生菌可通过增强外周白细胞的吞噬活性，促进免疫球蛋白(IgA、IgG和IgM)的分泌，以及诱导多种细胞因子，如干扰素-α (interferon-α, IFN-α)、α肿瘤坏死因子(tumor necrosis factor-α, TNF-α)、白细胞介素-1 (interleukin-1, IL-1)等的产生^[50]。此外，部分益生菌的代谢物，如乙酸、异戊酸等，可通过调控天然免疫信号通路或调节 “肺-肠”轴的免疫稳态，提高宿主的抗流感病毒感染的能力^[51-52]；珀氏解黄酮菌(Flavonifractor plautii)的代谢物去胺基酪胺酸(desaminotyrosine, DAT)可放大IFN-I干扰素信号通路，从而抑制流感病毒的感染^[10]。除直接抗病毒作用外，某些益生菌还具有广谱抗菌活性和调节肠道微生物结构的能力，因而可通过抑制继发性细菌感染以及恢复流感病毒感染后期的肠道微生物平衡，进一步缓解疾病症状并促进宿主康复^[53-54]。

综上所述，益生菌可通过其菌体结构组分或代谢产物激活天然免疫信号通路、重塑肠道微生物群结构等机制，协同抑制外源病原感染宿主，具体机制如表1所示。

3 总结与展望

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传染病的诊断、预防和治疗是保障畜禽养殖业高效、稳定发展以及维护人类健康的重要环节。据报道，全球每年有超过1 000万人感染呼吸道病毒，其中约有400万人死于呼吸道病毒引起的疾病^[2,15]。因此，呼吸道病毒感染仍然是威胁公共卫生安全的重要因素，需要持续的流行病学监测、新发传染病的预防，以及探索更加有效的干预措施。研究表明，机体微生物组的状态与病毒的发病机制有关。例如，肠道微生物可通过环境因素、遗传背景及免疫信号等综合因素影响宿主的代谢和免疫应答，在稳态和失调状态下，其介导的抗病毒机制不同^[6,35,39-40]。

宿主体内微生物具有高度多样性，机体的稳态与微生物菌群密切相关。在健康状态下，微生物菌群通过调节机体的代谢和低水平的免疫应答，协同构建有效的防御屏障，确保机体免受外部病原的侵害^[12,44]。微生物菌群在调节机体抵抗外源病原入侵过程中具有不同的机制，如某些肠道微生物的分泌物可以促进黏膜屏障功能；细菌素能抑制病毒进入细胞，或阻断病毒在细胞内的复制及病毒粒子的释放；而益生菌可调节天然免疫和适应性免疫信号分子发挥抗病毒功能等^[7,32,55]。鉴于微生物菌群的多样性和宿主结构的复杂性，微生物菌群及其衍生物在宿主抗病毒中的机制仍有待进一步深入解析。这些机制的发现将有助于开发更多的益生菌用于辅助治疗疾病的策略，减少病毒的感染和传播，降低传染病发病率和死亡率^[13,45]。

菌群失调可能由宿主多种内外部因素共同引起，其中病毒感染是主要原因之一，菌群失调可能会增加机体被病原二次感染的风险^[20]。然而，目前尚不清楚在呼吸道病毒感染患者粪便中检测到的菌群数量和种类的变化，究竟是由抗生素引起还是病毒感染所致^[56]。换言之，菌群失调究竟是由病毒感染直接诱导，还是由抗生素干预所致，抑或二者共同作用，仍缺乏直接证据证明。现有研究更倾向于认为，病毒通过引起宿主病理生理变化间接导致菌群失调^[9,20-21]。相比之下，抗生素被认为是引起菌群失调的直接诱因。在益生菌抑制外源病原感染的机制研究中，首先使用抗生素处理小鼠以显著降低菌群的丰度和多样性，随后再定殖益生菌菌株进行后续研究^{[11,39,47,51]}。此外，流感病毒感染后临床上常使用抗生素治疗，这也是病毒感染导致菌群失调的一个重要原因。在呼吸道病毒感染背景下，除常规的抗生素治疗方法外，益生菌可通过维持肠道屏障的完整性及发挥免疫调节作用，预防或缓解肠道微生态失调，并在呼吸道病毒感染的防治中有显著的效果^[50]。其主要作用机制包括调节宿主天然免疫和适应性免疫信号分子，发挥抗病毒作用。鉴于益生菌在临床使用中具有低成本和安全性的优势，进一步研究和发掘新的益生菌菌株，具有良好的经济价值和临床意义^[45,50]。

基金

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国家自然科学基金(32503068)
兰州市科技计划(2025-3-047)

参考文献

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2026年第66卷第5期

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doi: 10.13343/j.cnki.wsxb.20250920

接收时间：2025-12-10
首发时间：2026-05-09
出版时间：2026-05-04

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收稿日期：2025-12-10
录用日期：2026-01-27

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The National Natural Science Foundation of China(32503068)

国家自然科学基金(32503068)

The Lanzhou Science and Technology Program(2025-3-047)

兰州市科技计划(2025-3-047)

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中国农业科学院兰州兽医研究所，甘肃兰州

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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Species	Methods	Mechanisms	Phenotypes	References
Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1	Oral gavage (viable bacteria)	Stimulates the induction of acquired humoral immunity of anti-PR8-specific IgG and IgA in serum	Enhance serum titers of influenza virus-neutralizing antibodies and mitigate the adverse reactions of oseltamivir	[7]
Flavonifractor plautii	DAT drinking water	Flavonifractor plautii, produced DAT protected the host by priming the amplification loop of type I IFN signaling and rescued antibiotic-treated influenza-infected mice	1. Delay the rate of body weight loss in mice following influenza virus challenge 2. Attenuate lung pathological injury and cellular apoptosis	[10]
Lactobacillus MI29	Oral gavage (viable bacteria)	Activation of host defense via the gut-lung axis against influenza virus infection	1. Improved survival and delayed body weight loss in influenza-infected mice 2. Decrease viral loads and mitigate histopathological changes in the lungs of influenza-infected mice	[11]
Segmented filamentous bacteria	Oral gavage (viable bacteria)	Induce the appearance of CD4⁺ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria and enhance mucosal immunity	Enhanced resistance to the intestinal pathogen	[39]
Lactiplantibacillus plantarum Lp J1-8, 330, CK10, 920Leuconostoc mesenteroides Lm DRC1506, 218	Oral gavage (viable bacteria)	The detailed mechanism responsible for suppressing viral replication remains to be fully elucidated	1. Increased survival in influenza-infected mice 2. Decrease viral loads in the lungs of influenza-infected mice	[46]
Lactiplantibacillus plantarum nF1	Oral gavage (heat-inactivated bacteria)	Bacterial components may contribute to the anti-influenza virus effect, but the underlying mechanism remains to be clarified	1. Improved survival and delayed body weight loss in influenza-infected mice 2. Decrease viral loads in the lungs of influenza-infected mice	[47]
Limosilactobacillus fermentum PV22	Oral gavage (viable bacteria)	Inhibit norovirus infection by the γ-aminobutyric acid (GABA) produced by PV22	Reduce the titers of norovirus in RAW264.7 cells	[49]
Bifidobacterium pseudolongum NjM1	Oral gavage (viable bacteria)	Acetic acid produced by NjM1 activates the GPR43-NLRP3-MAVS-IFN-I pathway to elicit antiviral responses	1. Promote body weight recovery and prolong survival in influenza-infected mice 2. Alleviate lung pathological injury and reduce viral titers	[51]
Prevotella copri DSM 18205	Oral gavage (viable bacteria)	Reshape gut microbiota and enhance the production of isovaleric acid and isobutyric acid to mediate antiviral activity	1. Improved survival and delayed body weight loss in influenza-infected mice 2. Alleviate lung pathological injury and maintain the integrity of epithelial cells	[52]

Species

Methods

Mechanisms

Phenotypes

References

Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1

Oral gavage (viable bacteria)

Stimulates the induction of acquired humoral immunity of anti-PR8-specific IgG and IgA in serum

Enhance serum titers of influenza virus-neutralizing antibodies and mitigate the adverse reactions of oseltamivir

[7]

Flavonifractor plautii

DAT drinking water

Flavonifractor plautii, produced DAT protected the host by priming the amplification loop of type I IFN signaling and rescued antibiotic-treated influenza-infected mice

1. Delay the rate of body weight loss in mice following influenza virus challenge

2. Attenuate lung pathological injury and cellular apoptosis

[10]

Lactobacillus MI29

Oral gavage (viable bacteria)

Activation of host defense via the gut-lung axis against influenza virus infection

1. Improved survival and delayed body weight loss in influenza-infected mice

2. Decrease viral loads and mitigate histopathological changes in the lungs of influenza-infected mice

[11]

Segmented filamentous bacteria

Oral gavage (viable bacteria)

Induce the appearance of CD4⁺ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria and enhance mucosal immunity

Enhanced resistance to the intestinal pathogen

[39]

Lactiplantibacillus plantarum Lp J1-8, 330, CK10, 920Leuconostoc mesenteroides Lm DRC1506, 218

Oral gavage (viable bacteria)

The detailed mechanism responsible for suppressing viral replication remains to be fully elucidated

1. Increased survival in influenza-infected mice

2. Decrease viral loads in the lungs of influenza-infected mice

[46]

Lactiplantibacillus plantarum nF1

Oral gavage (heat-inactivated bacteria)

Bacterial components may contribute to the anti-influenza virus effect, but the underlying mechanism remains to be clarified

1. Improved survival and delayed body weight loss in influenza-infected mice

2. Decrease viral loads in the lungs of influenza-infected mice

[47]

Limosilactobacillus fermentum PV22

Oral gavage (viable bacteria)

Inhibit norovirus infection by the γ-aminobutyric acid (GABA) produced by PV22

Reduce the titers of norovirus in RAW264.7 cells

[49]

Bifidobacterium pseudolongum NjM1

Oral gavage (viable bacteria)

Acetic acid produced by NjM1 activates the GPR43-NLRP3-MAVS-IFN-I pathway to elicit antiviral responses

1. Promote body weight recovery and prolong survival in influenza-infected mice

2. Alleviate lung pathological injury and reduce viral titers

[51]

Prevotella copri DSM 18205

Oral gavage (viable bacteria)

Reshape gut microbiota and enhance the production of isovaleric acid and isobutyric acid to mediate antiviral activity

1. Improved survival and delayed body weight loss in influenza-infected mice

2. Alleviate lung pathological injury and maintain the integrity of epithelial cells

[52]