益生菌具有调节机体免疫以缓解呼吸道病毒感染、维持呼吸道健康的作用,然而其作用效果和机制存在菌株特异性。利用不同种和同种不同株的益生菌对H3N2流感病毒感染的动物模型进行实验,以探究不同益生菌对H3N2流感病毒感染的缓解作用,以及对免疫应答和肠道菌群调节作用的差异。结果显示,益生菌缓解了H3N2感染造成的体质量减轻以及肺部血管周和支气管周炎症细胞浸润的症状。此外,益生菌降低小鼠肺部炎症因子的表达,特别是IL-1β和TNF-α;而益生菌对血液中细胞因子的调节作用则存在明显的菌株差异, Bifidobacterium bifidum 2对先天免疫反应细胞因子TNF-α和IL-1β表达的激活作用优于同种不同株的Bifidobacterium bifidum 1,L.acidophilus 1和B.breve 2对IL-6的抑制作用优于同种不同株的益生菌。B.bifidum 2缓解H3N2感染引起的体质量减轻和肺部损伤的效果优于其他菌株,可能与其激活机体先天性免疫应答相关。B.bifidum 2特异性增加肠道菌群中Alloprevotella的丰度可能是激活先天免疫响应的关键。研究结果显示,不同益生菌对肠道菌群组成的调节作用存在菌株特异性,因此,这可能是益生菌缓解H3N2病毒感染存在差异的原因。
Influenza virus infections continue to threaten global health. According to 'lung-gut axis' theory, probiotics can prevent host from respiratory virus infection and maintain respiratory health by regulating the host’s immune response. However, the effect and mechanism of probiotics are strain-specific and unclear. This study explored the prophylactic effects of different probiotics on H3N2 infection, as well as the differences of regulation of immune response and intestinal flora composition. Female ICR mice (3-4 weeks old) were randomly divided into control, model, positive control and probiotics treatment groups. Mice were orally administered bacterial suspension (109 CFU/d) for two weeks before infection. Then, all mice were infected intranasally with a dose of 5-times the 50% lethal dose (5 LD50) of the influenza A virus (H3N2) strain, except control group. Results showed that probiotics relieved symptoms, such as weight loss, pulmonary perivascular and parabronchial inflammatory cell infiltration. Besides, probiotics reduced the levels of inflammatory factors in the lungs, especially IL-1β and TNF-α. Nevertheless, the effects of probiotics on cytokines in the blood were significantly different. Bifidobacterium bifidum 2 activated higher expression of innate immune response cytokines, IL-1β and TNF-α, compared with B. bifidum 1 form the same species. Lactobacillus acidophilus 1 and Bifidobacterium breve 2 led to lower level of IL-6, compared with the other strain form the same species. Probiotics regulated the relative abundance of Tyzzerella,Candidatus, Saccharimona and Odoribacter, which be associated with host immune regulation. B. bifidum reduced the levels of Eubacterium coprostanoligenes group and UBA 1819, while L. acidophilus downregulated the level of Akkermansia. The relative abundance of Ruminococcaceae NK4A214 group and Dubosiella was decreased in B. breve groups. B. bifidum 2 was the most effective strain in relieving weight loss and lung damage after H3N2 infections, which may be associated with the upregulation of innate immune response. Moreover, the mechanism of B. bifidum 2 might related to the increase of Aloprevotella in the gut. In conclusion, different probiotics have different effects on the gut composition, which result in the different regulation of H3N2 virus infection.
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