Transcriptomic, metabolomic and metagenomic approaches were performed to investigate the multifaceted health effects of municipal effluents (ME) on mice. After chronic exposure for 90 days, alterations in liver gene expression, serum and urine metabolic profiles. A total of 4446 differentially expressed genes (DEGs) were identified, which related to 107 KEGG pathways. Metabolomics identified 8 and 10 differential altered metabolites (DAMs) in serum and urine, respectively. Moreover, the ME exposure also induced some perturbations of the gut microbiota, which related to co-metabolism and immune responses. Nine mice in each group were selected and the livers of every three mice were homogenized together to obtain a total RNA sample. Three RNA samples in the treated or control group were hybridized separately onto three arrays to compare the genomic expression between the two groups.