Effects Of Short-term Very Low-calorie Restriction On Gut Microbiota And Small Molecular Metabolites In Plasma And Feces Of Type 2 Diabetes Patients

Objectives:The purpose of our study was to evaluate the effect of short-term very low-calorie restriction(VLCR)on glycemic control in patients with type 2 diabetes.We also wanted to explore mechanisms by identifying markers of gut microbiota and metabolites in feces and plasma.Methods:This trial was conducted in14 adult patients with type 2 diabetes.They were received VLCR for 9 days in the hospital(calorie intake 300-600 kcal/d).Before and after VLCR,body weight(BW),waist circumference(WC),blood pressure(BP),heart rate(HR)were measured,and body mass index(BMI)was calculated according to their height and weight.Professional instrument detected fasting blood glucose(FBG),2 hours postprandial blood glucose(2hPBG),fasting insulin(FINS),triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C).According to the formula to calculate the homeostasis model assessment-insulin resistance(HOMA-IR).We also detected indicators such as liver and kidney function and electrolytes.The estimated glomerular filtration rate(eGFR)was calculated to evaluate renal function.All data were analyzed using the SPSS Sample Power software.Plasma and feces samples were collected before and after VLCR.Fecal samples were tested for microbial diversity using 16S rDNA technology,and metabolites in plasma and fecal samples were detected by untargeted metabolomics technology.Professional software was used to analyze the differences of gut microbiota and metabolites in plasma and feces before and after VLCR.Results:After 9 days of VLCR,BW,BMI,WC,BP,HR,FBG,2hPBG,FINS,HOMA-IR,TG,alkaline phosphatase and blood urea nitrogen of 14 T2DM patients were significantly reduced(P<0.05).No effect were seen on TC,HDL-C,LDL-C,eGFR,alanine aminotransferase,aspartate amino transferase,gamma glutamyl transferase,creatinine,uric acid,albumin,calcium and phosphorus(P>0.05).The gut microbiota a diversity did not differ before and after treatment.The abundance ofBacteroidetes increased significantly,and the Firmicutes/Bacteroidetes ratio decreased from 11.79 to 4.20.According to the analysis of the differences between groups,the Parabacteroides distasonis was the key differential species,and its abundance increased significantly after VLCR.L-arginine,an amino acid metabolite in plasma,was increased after VLCR.Plasma levels of three lipid metabolites,PC(14:0/20:4(8Z,11Z,14Z,17Z),LysoPC(16:1(9Z)),and LysoPC(18:1(11Z))decreased after VLCR.The lipid metabolites LysoPC(18:1(11Z))and bile acid metabolites glycincholic acid in feces were reduced after VLCR.Conclusions:VLCR can improve the body weight and glucose and lipid metabolism of T2DM patients,with good clinical efficacy and no serious adverse events.Parabacteroides distasonis and LysoPC(18:1(11Z))may be markers of VLCR.After VLCR,increased abundance of Parabacteroides distasonis may improve insulin resistance in T2DM patients by reducing LysoPC(18:1)and reducing inflammation in the body.