Cold exposure promotes coronavirus infection by altering the gut microbiota and lipid metabolism to reduce host immunity

Objective:Cold exposure has been suggested to be advantageous for the spread and infection of the coronavirus,and the gut microbiota influences the severity of the infection by modulating host inflammatory and immune responses.However,it remains unclear whether the promotion of viral infection through cold exposure is linked to the gut microbiota.Methods:In this study,we performed an unbiased analysis of gut microbiota,serum,and lung tissue metabolome changes in cold-exposed and virus-infected mice,alongside the assessment of immune-inflammatory indicators in serum and lung tissue.Results:The results revealed that both cold exposure and viral infection significantly decreased the percentage of peripheral blood lymphocytes(CD4^(+)T cells,CD8^(+)T cells,and B cell)and increased the expression of inflammatory factors(IL-6,IL-1β,TNF-α,and IFN-γ).Meanwhile,cold exposure disrupted the homeostasis of gut microbiota,elevating the abundance of pathogenic bacteria(Staphylococcus)and diminishing the abundance of beneficial bacteria(Alistipes).Notably,in virus-infected mice exposed to a cold environment,the reduction in the abundance of beneficial bacteria Alistipes was more pronounced than in cases of single virus infection and cold exposure.Analysis of altered serum and lung tissue metabolites highlighted glycerophospholipids,fatty acids,and eicosanoids as the most affected metabolites by cold exposure.These metabolites,closely associated with virus infection,exhibited a significant correlation with immune-inflammatory indicators.Conclusion:These findings establish a mechanistic connection between cold exposure and virus infection,suggesting that cold exposure-induced dysregulation of gut microbiota and lipid metabolism diminishes host immunity,promoting virus infection.