Fecal Microbiota Was Reshaped in UCP1 Knock-In Pigs via the Adipose-Liver-Gut Axis and Contributed to Less Fat Deposition.

The relationship between the host gut microbiota and obesity has been well documented in humans and mice; however, few studies reported the association between the gut microbiota and fat deposition in pigs. In a previous study, we generated uncoupling protein 1 (UCP1) knock-in pigs (UCP1 pigs), which exhibited a lower fat deposition phenotype. Whether the gut microbiota was reshaped in these pigs and whether the reshaped gut microbiota contributes to the lower fat content remain unknown. Here, we revealed that the fecal microbiota composition and metabolites were significantly altered under both chow diet (CD) and high-fat/high-cholesterol (HFHC) diet conditions in UCP1 pigs compared to those in wild-type (WT) pigs. The abundance of and and the level of metabolite hyodeoxycholic acid (HDCA) from feces were observed to be significantly increased in UCP1 pigs. An association analysis revealed that and were significantly negatively related to backfat thickness. In addition, after fecal microbiota transplantation (FMT), the mice that were orally gavaged with feces from UCP1 pigs exhibited less fat deposition under both CD and high-fat diet (HFD) conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Consistently, HDCA-treated mice also exhibited reduced fat content. Mechanistically, we found that UCP1 expression in white adipose tissue alters the gut microbiota via the adipose-liver-gut axis in pigs. Our study provides new data concerning the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolites in the regulation of fat deposition in pigs. This article investigated the effect of the ectopic expression of UCP1 on the regulation of fecal microbiota composition and metabolites and which alters the fat deposition phenotype. Bacteria, including and , and the metabolite HDCA were found to be significantly increased in feces of UCP1 pigs and had a negative relationship with backfat thickness. Mice with fecal microbiota transplantation phenocopied the UCP1 pigs under both CD and HFD conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Our study provides new data regarding the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolic production in the regulation of fat deposition in pigs.