Integrated transcriptome-metabolome-microbiome analysis showed that epithelial gene-GSTM3 expression was upregulated in the metabolism of xenobiotics by the cytochrome P450 pathway during the cold season, leading to the downregulation of some harmful metabolites; TLR5 gene expression was upregulated and CD14 gene expression was downregulated in the legionellosis pathway during the cold season. The gene discussed is GSTM3; the disease is legionellosis.