Anti-obesity Effect Of GOS In Regulating Bile Acids Homeostasis Via Enterohepatic Circulation Based On FMT

In recent years,the incidence of obesity has gradually increased,and the risk of cardiovascular and cerebrovascular diseases,type 2 diabetes,coronary heart disease and other diseases has also increased.How to control the occurrence and development of obesity has become a public health problem that needs to be solved urgently in the world.Numerous reports have demonstrated a close link between the gut microbiota and obesity,and the gut microbiome has emerged as a key factor in the pathophysiology of obesity.Therefore,the gut microbiota opens up new ideas for the prevention and treatment of obesity.Faecal microbiota transplantation(FMT),which is known for transferring host phenotypes to reshape the gut microbiota,has become a new therapy for obesity and has begun to be trialled in the clinic.Galacto-oligosaccharide(GOS),as a prebiotic,can selectively promote the growth of intestinal beneficial bacteria,inhibit the reproduction of harmful bacteria,and regulate the balance of intestinal flora after entering the intestine.Therefore,in this study,by constructing a pseudo-sterile model,we explored the anti-obesity mechanism of transplanted GOS interfering with the fecal flora of obese mice.In this study,a pseudo-sterile mouse model was established by administering mixed antibiotics to deplete the intestinal flora.The activity results showed that transplantation of fecal bacteria from GOS intervening obese mice could significantly reduce body weight and fat body ratio in obese mice;significantly decreased WAT fat index and increased BAT fat index,improve adipocyte hypertrophy and hepatocyte lipid accumulation;significantly down-regulate serum and liver TG,TC,LDL-C levels,increased serum HDL-C levels,and significantly decreased serum and liver TBA levels.Therefore,transplantation of fecal bacteria from GOS-interventional obese mice can exert a good lipid-lowering effect.The results of gut microbiota and bile acid profiles showed that the fecal microbiota of obese mice transplanted with GOS intervention could increase the diversity and richness of intestinal microflora,reduce the content of BAs in the body and increase the excretion of BAs in vitro,thereby improving the homeostasis of BAs.The Spearman correlation analysis of four items of blood lipids,intestinal flora and BAs showed that transplantation of GOS to interfere with the fecal flora of obese mice could increase the abundance of Bifidobacterium,reduce the concentrations of T-α-MCA and T-β-MCA in serum,and decrease the fecal flora of obese mice.TG,TC,LDL-C levels;increase the abundance of Bacteroides,promote fecal CA excretion,reduce TG,TC,LDL-C levels,thereby exerting anti-obesity effects.Mechanistic studies showed that transplantation of GOS to interfere with the fecal flora of obese mice could inhibit the expression of mouse BAs synthase CYP7A1,CYP8B1,and CYP27A1;activate the FXR-SHP and FXR-FGF15-FGFR4 signaling pathways in the liver and ileum,resulting in the inhibition of CYP7A1,reducing the synthesis of BAs;inhibiting the expression of transporters OSTα,OSTβ,MRP2 and NTCP,reducing the entry of BAs into the liver,increasing the excretion of BAs,and maintaining the homeostasis of BAs.In conclusion,transplantation of GOS to intervene the fecal microbiota of obese mice can reshape the gut microbiota structure.And this can play an anti-obesity effect by regulating the abundance of Bifidobacterium and Bacteroides,inhibiting the synthesis of BAs,reducing the expression of transport-related factors,maintaining the homeostasis of BAs in the body,and reducing the levels of TG,TC,and LDL-C.