Study On Screening And Mechanism Of Probiotics To Alleviate Respiratory Viral Infection

According to the Global Burden of Disease Report,the main pathogens causing respiratory viral infections are respiratory syncytial virus and influenza virus.The probability of co-infection is higher during the COVID-19 pandemic.Respiratory viruses inhibit antiviral immune responses as a result of immunological escape,resulting in inadequate defense against viral infection.The gut microecology affects respiratory health.It is proved that gut microbiota and its metabolites can improve respiratory viral infection.For example,shortchain fatty acids and deaminotyrosine can protect against respiratory syncytial virus and influenza virus infections respectively.In addition,the probiotics can regulate the immune system to alleviate the pathological damage caused by viral infection.Therefore,we selected experimental strains that produce short-chain fatty or deaminotyrosine,or have immunomodulatory functions,and used these strains to protect against respiratory syncytial virus,H1N1 or wild-type H3N2 infection in animal models.We studied the effects and mechanisms of bacterial strains on viral infection by detection of viral load,lung histopathology,immune responses,and change in intestinal flora and metabolites.The main finding are as follows:(1)After respiratory syncytial virus infection,the viral load and inflammation was significantly reduced in the lungs because of strains treatment.And these bacterial strains can produce short-chain fatty acids.However,different strains had different antiviral mechanisms.Lactobacillus mucosae M104R01L3 activated type I interferon immune response by increasing acetic acid levels in the gut.Bifidobacterium longum CCFM1029 might activate this immune response by increasing the abundance of Turicibacter in the gut.Besides,the the anti-inflammatory effects of Lactobacillus mucosae 1025 and Bifidobacterium longum FGDLZ8M1 were positively correlated with the level of butyrate in the gut.(2)We have found a deaminotyrosine producer,Lactiplantibacillus pentosus CCFM1227 by comparative genomics and fermentation in vitro.And this strain could alleviate symptoms induced by H1N1 infection.The results showed that CCFM1227 increased the content of deaminotyrosine in the gut and the activated the type I interferon immune response.Finally,the viral load and the pathological inflammation were reduced in the lungs.However,according to the results of lung transcriptome analysis,gut-derived desaminotyrosine might indirectly activate the pulmonary type I interferon response by acting on the gut or lymphatic system,rather than directly acting on the lung.In addition,CCFM1227 activated the antigen processing and presentation pathway in the lung,which might be the potential antiviral mechanism.(3)Bacterial strains with immunomodulatory effect were used to interfere with wild-type H3N2 infection.It was found that Bifidobacterium bifidum FSDJN705 could improve body weight loss and pulmonary inflammation,while other strains were useless to protect against wild-type H3N2 infection.The regulatory effect of FSDJN705 on immune system was important to improve the pathological inflammation in the lungs.But,the regulation of other strains on pulmonary inflammatory factors could not improve the viral infection.The FSDJN705 could specifically regulate the composition of gut microbiota and increase the abundance of Bacteroides,which might related to the regulation of immune system.