Mechanism Of Konjac Glucomannan Treating Obesity By Regulating Gut Microbiota

Obesity is a major chronic disease severely threatening human health,which is highly prevalent in the world currently.Recent research suggests that obesity is closely related to intestinal microflora,the disorder of which may induce systemic chronic inflammation,thus trigger metabolic diseases such as obesity.Oligose is abundant in diet and has diverse and complicated structures.Oligose can not be directly digested and adsorbed by the human body.Instead,it can be decomposed and utilized by intestinal symbiotic bacteria to provide energy.Therefore,oligose is of great significance for maintaining intestinal microfloral homeostasis and protect the intestinal barrier,which is thus frequently referred as prebiotics.Existing research indicates that some specific oligoses can control the pathogenesis and development of obesity through the microflora-related mechanism.The effect of konjac flour(KF)as prebiotics on obesity has been extensively studied,however results from different studies of konjac flour for weight loss control are frequently different.Consequently,the application of konjac flour in weight control is limited to some extent,which can be partly attributed to the lack of understanding of the mechanism of action of konjac flour in weight loss.Currently,the effect of konjac flour on intestinal microflora has not been systemically reported yet.The current study aims to explore the effects of konjac flour on treating obesity,improving inflammation,intestinal barrier function and metabolism,as well as regulating intestinal microflora through clinical trials that strictly control the lifestyle,age and occupation of the subjects of study in combination with animal experiments.All clinical subjects recruited in study were obese patients having similar occupations(civilian post),the body mass index(BMI)?28 kg/m~2,and ages ranging from 25-35years.A total of 69 subjects were enrolled and divided into the placebo group(n=31)and experiment group(n=38),who took 10 g placebo and konjac flour,respectively,everyday(5 g before breakfast and 5 g before dinner)for 5 weeks.On the basis of the clinical trial results,the effects of konjac flour on treating obesity and regulating intestinal microflora are further studied.Additionally,30 mice were randomly divided into control group(n=10),high fat diet(HFD)group(n=10),and konjac flour intervention group(n=10),followed by feeding for 12 weeks.In our clinical trials,konjac flour remarkably reduced the BMI,fat mass,serum triglyceride(TG),glycated haemoglobin A1c(HbA1c),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels in patients(p<0.05 or p<0.01).Meanwhile,high-throughput sequencing and bioinformatics analysis showed that konjac flour treatment notably increased the?-diversity and changed the?-diversity of intestinal microflora in patients(p<0.01).Moreover,konjac flour could also evidently increase the abundances of some of the beneficial microorganisms related to obesity in the intestinal microflora of patients,such as Lachnospiraceae,Roseburia,Solobacterium,R.inulinivorans,Clostridium perfringens and Intestinimonas butyriciproducens.In the meantime,it could reduce the abundances of the harmful microorganisms,such as Lactococcus,Bacteroides fragilis,Lactococcus garvieae,B.coprophilus,B.ovatus and B.thetaiotaomicron(p<0.01).Specifically,C.perfringens was significantly negatively correlated with serum total cholesterol(TC)(p<0.01).In animal experiments,konjac flour could outstandingly reduce the increases in weight,fat mass,and adipocyte size of HFD mice(p<0.05).Besides,enzyme linked immunosorbent assay(ELISA)showed that konjac flour could evidently lower the serum TC,leptin(LEP),thiobarbituric acid-reacting substances(TBARS),IL-6 and lipopolysaccharide(LPS)levels in HFD mice(p<0.05).Fluorescence quantitative PCR also discovered that konjac flour could remarkably up-regulate the expression of intestinal mucosa protein gene Intection and tight junction ZO-1 in HFD mice(p<0.05).Furthermore,konjac flour could markedly up-regulate the expression of energy metabolism genes PPAR?and CPT-1,as well as the fat metabolism gene HLS in HFD mice livers and fat tissues,whereas significantly down-regulate that of fat synthesis gene PPAR?(p<0.05).High-throughput sequencing and bioinformatics analysis suggested that konjac flour could notably increase the?-diversity and change the?-diversity of the intestinal microflora in HFD mice(p<0.01).Moreover,konjac flour could also outstandingly increase the abundances of some obesity-related beneficial microorganisms(such as Megasphaera elsdenii)in the intestinal microflora of HFD mice,while reduce those of harmful microorganisms(such as Alistipes,Alloprevotella,Bacteroides acidifaciens and Parabacteroides goldsteinii)(p<0.01).At the same time,Alistipes was significantly positively correlated with weight,fat mass,serum TC,TG,LEP,IL-6 and LPS contents as well as PPAR?gene expression;whereas significantly negatively correlated with the expression of CPT-1 and HLS genes(p<0.01).In our clinical trials and animal experiments,konjac flour could remarkably increase the abundance of Aerococcaceae,while reduce that of Alistipes finegoldii(p<0.01).Therefore,Aerococcaceae was the potential probiotics,while A.finegoldii was the potential pathogenic bacterium.The clinical and animal experiment resutls from our study suggested that konjac flour can achieve favorable effects on treating obesity,which manifest on reducing weight,fat mass and blood fat,improving inflammatory response,metabolism and intestinal barrier function,as well as regulating intestinal microfloral structure.Therefore,it is speculated that one of the possible mechanisms of action by which konjac flour treats obesity is to improve intestinal microfloral structure,thus regulating metabolism and inflammation.