Excessive fat deposition can trigger metabolic diseases, and it is crucial to identify factors that can break the link between fat deposition and metabolic diseases. Healthy obeseLaiwu pigs(LW) are high in fat content but resistant to metabolic diseases. In this study, we compared the fecal microbiome, fecal and blood metabolome, and genome of LW andLulai pigs(LU) to identify factors that can block the link between fat deposition and metabolic diseases. Our results show significant differences in Spirochetes andTreponema, which are involved in carbohydrate metabolism, between LW and LU. The fecal and blood metabolome composition was similar, and some anti-metabolic disease components of blood metabolites were different between the two breeds of pigs. The predicted differential RNA is mainly enriched in lipid metabolism and glucose metabolism, which is consistent with the functions of differential microbiota and metabolites. The down-regulated geneRGP1is strongly negatively correlated withTreponema. Our omics data would provide valuable resources for further scientific research on healthy obesity in both human and porcine.