Comprehensive Study Of Untargeted Metabolomics And 16S RRNA Reveals The Mechanism Of Fecal Microbiota Transplantation In Improving Type 2 Diabetes

Objective: Type 2 diabetes(T2D)is an extremely complex metabolic disease characterized by impaired metabolism of major energy substances resulting in hyperglycemia,and weight gain,body fat distribution,and body mass index also play important roles in the development of type 2 diabetes.Fecal microbiota transplantation(FMT),It’s a new type of therapy that works by altering the gastrointestinal microbiota,has been applied in the treatment of an increasing number of diseases in recent years.Previous studies have reported using FMT as a potential therapy for T2 D,but the mechanism remains largely unclear.In the present study,we investigated the role of FMT in T2 D and its underlying mechanisms.Methods: After 6 weeks of insulin resistance induced by high fat and high sugar diet,120mg/kg streptozotocin(STZ)was injected intrabitoneally to induce T2 D mouse model.Continuous monitoring of blood glucose for two weeks,blood glucose level >11.1mmol/L twice is considered to be successful modeling.Mice were random Ly divided into normal control group(n = 7),T2 D group(n = 7),metformin(MET)-treated group(n = 7),and FMT group(n = 7).The MET group was orally administered 0.2 g/kg MET,the FMT group was orally administered 0.3 m L of bacterial solution,and The other two groups were given the same amount of normal saline for four weeks.Fasting blood glucose(FBG),body weight and health status of mice were monitored weekly.After the experiment,feces and serum were collected for 16 S r RNA sequencing and non-targeted metabolomics and biochemical indicators detection,respectively.Results: Our results showed that FMT has a curative effect on T2 D by ameliorating hyperlipidemia and hyperglycemia.By 16 S r RNA sequencing and serum untargeted metabolomic analysis,we found that FMT could restore the disorders of gastrointestinal microbiota in T2 D mice,and corticosterone,progesterone,L-urobilin,etc.can be used as biomarkers after FMT treatment.Meanwhile,our bioinformatics analysis suggested that steroid hormone biosynthesis,arginine and proline metabolism,and unsaturated fatty acid biosynthesis could be the potential regulatory mechanisms of FMT.Conclusions: Taken together,our study comprehensively revealed the role of FMT in the treatment of T2 D.The study show that the donor gut microbiota could effectively colonize the host gut and improve the clinical symptoms of T2 D mice after FMT treatment.