Data_Sheet_1_Lactiplantibacillus plantarum 0111 Protects Against Influenza Virus by Modulating Intestinal Microbial-Mediated Immune Responses.docx

There are some limitations of traditional influenza vaccines concerning novel mutant strains. Therefore, it is particularly important to develop preventive means for antigen-unrelated types of influenza viruses. Recent studies have shown that probiotics can modulate the immune system and reduce the severity of viral infections. In this study, we investigated the potential of Lactiplantibacillus plantarum 0111 against influenza virus H9N2. Challenge experiments showed that L. plantarum 0111 pretreatments could effectively improve mice’s survival rate and weight loss and reduce the inflammatory cytokines IL-6 and TNF-α in the lungs and bronchoalveolar lavage fluid (BALF) along with the degree of lung and intestinal injury. FMT experiment demonstrates that the protective effect produced by L. plantarum 0111 is associated with gut microorganisms. In addition, 16S high-throughput sequencing of the mouse intestinal microbiota showed that L. plantarum 0111 remodeled the intestinal microbiota after H9N2 infection and maintained the gut microbiota balance. In a mouse model, the oral administration of L. plantarum 0111 increased IFN-β expression in the serum and BALF. At the same time, the transcript levels of IFN-β and related ISGs in the intestine and lungs of mice were also increased. In addition, the activation and polarization of T cells in mesenteric lymph nodes (MLNs) and the spleen were detected by flow cytometry, and the results showed that L. plantarum 0111 modulated cytokines in T cells and increased IgA expression in B cells in the MLNs and spleen. Thus, L. plantarum 0111 may improve gut microbiota-mediated immune responses and thus, resist infection by the influenza virus, and it could be used as an effective preventive measure against the influenza virus.

传统流感疫苗在应对新型突变株方面存在某些局限性。因此，开发针对抗原无关型流感病毒的预防措施尤为重要。近期研究表明，益生菌能够调节免疫系统并减轻病毒感染的严重程度。在本研究中，我们探讨了植物乳杆菌0111对流感病毒H9N2的潜在作用。挑战实验表明，植物乳杆菌0111预处理能够有效提高小鼠的存活率和减轻体重损失，同时降低肺部和支气管肺泡灌洗液（BALF）中的炎症细胞因子IL-6和TNF-α水平，以及肺和肠道损伤的程度。粪便微生物群移植实验显示，植物乳杆菌0111产生的保护作用与肠道微生物有关。此外，对小鼠肠道微生物群的16S高通量测序结果表明，植物乳杆菌0111在H9N2感染后重塑了肠道微生物群，并维持了肠道微生物群的平衡。在动物模型中，口服植物乳杆菌0111增加了血清和BALF中干扰素-β的表达。同时，通过流式细胞术检测到小鼠肠道和肺中的干扰素-β及其相关ISG的转录水平也相应提高。此外，通过流式细胞术检测到回肠淋巴结（MLNs）和脾脏中T细胞的活化和极化，结果显示植物乳杆菌0111调节了T细胞中的细胞因子，并增加了MLNs和脾脏中B细胞的IgA表达。因此，植物乳杆菌0111可能改善肠道微生物群介导的免疫反应，从而抵抗流感病毒的感染，并可作为预防流感病毒的有效措施。