Data_Sheet_1_Lactobacillus mucosae exerted different antiviral effects on respiratory syncytial virus infection in mice.docx

Respiratory syncytial virus (RSV) infection is a constant threat to the health of young children, and this is mainly attributed to the lack of effective prevention strategies. This study aimed to determine whether Lactobacillus (L.) mucosae, a potential probiotic, could protect against respiratory viral infection in a mouse model. Naive 3–4-week-old BALB/c mice were orally administered with three L. mucosae strains (2.5 × 108 CFU/mouse) 7 days before RSV infection (105 TCID50/mouse). Results showed that all three strains inhibited RSV replication and reduced the proportions of inflammatory cells, including granulocytes and monocytes in the blood. The L. mucosae M104R01L3 treatment maintained stable weight in mice and increased interferon (IFN)-β and tumor necrosis factor (TNF)-α levels. The L. mucosae DCC1HL5 treatment increased interleukin (IL)-1β and IL-10 levels. Moreover, the M104R01L3 and DCC1HL5 strains increased the proportions of Akkermansia, Alistipes, and Anaeroplasma which contributed to the advantageous modulation of the gut microbiota. Besides, L. mucosae affected the gut levels of short-chain fatty acids (SCFAs) that are important for the antiviral response. L. mucosae 1,025 increased acetate, propionate, and butyrate levels, whereas L. mucosae M104R01L3 increased the level of acetate in the gut. L. mucosae M104R01L3 may protect against viral infection by upregulating the IFN-β levels in the lungs and its antiviral effect may be related to the increase of acetate levels in the gut. In conclusion, the three L. mucosae strains exerted antiviral effects against RSV infection by differentially regulating immune responses and intestinal micro-ecological balance. This study can provide a reference for studying the mechanisms underlying the antiviral effects of L. mucosae.

呼吸道合胞病毒（Respiratory syncytial virus, RSV）感染始终威胁幼儿的健康，这主要缘于当前尚无有效的预防策略。本研究旨在探究潜在益生菌黏膜乳杆菌（Lactobacillus mucosae, L. mucosae）是否可在小鼠模型中抵御呼吸道病毒感染。将未感染过病毒的3~4周龄BALB/c小鼠于RSV感染（10^5 50%组织细胞感染量（50% Tissue Culture Infectious Dose, TCID50）/只）前7天，经口灌服3株黏膜乳杆菌（2.5×10^8 菌落形成单位（Colony-Forming Unit, CFU）/只）。结果表明，3株菌株均可抑制RSV复制，并降低血液中粒细胞、单核细胞等炎性细胞的比例。其中黏膜乳杆菌M104R01L3处理组可维持小鼠体重稳定，并上调干扰素（Interferon, IFN）-β与肿瘤坏死因子（Tumor necrosis factor, TNF）-α的表达水平；黏膜乳杆菌DCC1HL5处理组则可上调白细胞介素（Interleukin, IL）-1β与IL-10的表达水平。此外，M104R01L3与DCC1HL5菌株可提高阿克曼菌属（Akkermansia）、理研菌属（Alistipes）及厌氧原体属（Anaeroplasma）的相对丰度，有助于实现肠道菌群的有益调控。同时，黏膜乳杆菌可影响肠道短链脂肪酸（Short-chain fatty acids, SCFAs）的含量，而这类物质对宿主抗病毒应答至关重要：黏膜乳杆菌1025可上调乙酸、丙酸与丁酸的含量，黏膜乳杆菌M104R01L3则可提升肠道内乙酸的含量。黏膜乳杆菌M104R01L3或可通过上调肺部IFN-β的表达水平抵御病毒感染，其抗病毒效应或与肠道乙酸含量升高相关。综上，3株黏膜乳杆菌可通过差异化调控免疫应答与肠道微生态平衡，发挥抗RSV感染的功效。本研究可为探究黏膜乳杆菌抗病毒效应的潜在作用机制提供参考依据。