Efficacy And Safety Of Low Carbohydrate And Calorie Restriction Diet Combined With Probiotics For Weight Loss In Male Obese Patients

ObjectiveThe potential of probiotics for weight loss and lipid regulation was revealed,but it was difficult to achieve great weight loss with only probiotics supplementation.Therefore,this study was conducted aiming to evaluate the efficacy and safety of probiotics combined with low carbohydrate and calorie restriction diet for 12 weeks in male obese patients,and the 16S rDNA sequencing data of the subjects’ feces were analyzed retrospectively to explore the intestinal flora factors affecting their weight loss efficacy.MethodsThis study is a single-center,randomized,double-blind,placebo,controlled clinical trial for 12 weeks.44 male obese patients were recruited and randomly assigned to group taking a low carbohydrate and calorie restriction diet combined with probiotic compound(LCD-P)or low carbohydrate and calorie restriction diet combined with placebo(LCD-C).Indicators of anthropometric measurements(Weight,BMI,Waist circumference,Waist to hip ratio),body composition(Body fat rate,Body fat mass,Muscle mass,Subcutaneous fat volume,Visceral fat volume,Belly fat volume)and glucose and lipid metabolism(Fasting plasma glucose,Fasting serum insulin,HOMAIR,TG,TC,LDL,HDL,sd-LDL)were measured to evaluate effectiveness,while adverse events were recorded to assess safety.According to the clustering of weightloss efficacy indexes,the patients were divided into two groups:significant weight-loss efficacy group(SG)and general weight-loss efficacy group(GG),for analysis to clarify intestinal microbiota factors affecting individual differences in LCD-P weight loss efficacy.Results1.After 12 weeks of intervention,anthropometric indicators,body composition indicators and glucose and lipid metabolism of LCD-P were improved compared with baseline,but there was no significant difference compared with LCD-C(P>0.05)Sensitivity analysis showed that subcutaneous fat volume(difference between groups was-218.65±62.76 cm3)and muscle mass(difference between groups was-0.48±0.22 kg)decreased significantly in LCD-P(p<0.05).The incidence of adverse events was similar between the two groups(P>0.05).2.There was no significant difference in the overall composition and diversity of gut microbiota between the weight loss efficacy subgroups in LCD-P at baseline.3.The relative abundance of Ruminococcaceae at baseline was negatively correlated with △Wt%,△SFV%,△VFV%,△BFV%,while the relative abundance of Alcaligenaceae Sutterella was also negatively correlated with △ WHR%,△ VFV%,△BFV%(P<0.05).The ROC model suggested that only the relative abundance threshold of Ruminococcaceae at baseline was predictive of weight loss after LCD-P intervention(AUC=0.845,p=0.007).4.In LCD-P-SG,Ruminococcaceae was symbiotic with Ruminococcaceae Ruminococcus at baseline and with o_Streptophyta、o_Clostridiales、Veillonellaceae Phascolarctobacterium、Lachnospiraceae Dorea、Clostridiaceae Clostridium after intervention.No symbiotic relationship was seen with Ruminococcaceae at baseline and the Ruminococcaceae co-excluded with Actinomycetaceae Actinomyces after the intervention in LCD-P-GG.5.After the intervention,the relative abundance of Odoribacteraceae Odoribacter was positively correlated with the weight loss efficacy(r=0.481,P=0.027),and the ROC model constructed with the weight loss efficacy showed that when the threshold was 0.003,the AUC reached 0.773(P=0.035).Conclusion1.LCD-P was effective and safe for weight loss.Compared with the low-carbon and energy-limited diet intervention,combining with probiotics compound intervention did not obviously enhance the efficacy of weight loss,but significantly reduced the subcutaneous fat volume.2.The overall composition and diversity of intestinal flora had little influence on the weight loss efficacy of LCD-P.3.The relative abundance of Ruminococcaceae at baseline correlated with the weight loss efficacy of LCD-P and had good predictive power,which could be used as a reference for clinical practice of LCD-P in individualized precision therapy of obesity.The higher relative abundance of Ruminococcaceae at baseline could was beneficial to strengthen the symbiotic relationship between Ruminococcaceae and the beneficial bacteria after the intervention of LCD-P,thus enhancing the weight loss efficacy of LCD-P.4.The effective response of Odoribacteraceae Odoribacter affects the weight loss efficacy of LCD-P.Targeted improvement of the relative abundance of Odoribacteraceae Odoribacter after intervention may be the key to enhance the weight loss efficacy of LCD-P.