The Intervention Study Of Lactobacillus Reuteri On Metabolic Syndrome In Mice Induced By High-fat Diet

Long-term high-fat diet can lead to excessive energy intake and cause metabolic syndrome,including a series of metabolic disorders such as hyperglycemia,hyperlipidemia,insulin resistance and obesity,which has become a major public health problem and clinical challenge worldwide.Metabolic syndrome can not only directly affect body weight and insulin resistance,but also influence gut microbiota.Changing lifestyle and medication are the main treatment methods of metabolic syndrome at present.But the two treatments are not ideal,and are accompanied by side effects and adverse reactions such as gastrointestinal discomfort.Probiotics have received a lot of attention in recent years for their potential benefits against a variety of diseases,including metabolic syndrome.In this study,we first compared the whole genomes and selected strains of Lactobacillus reuteri with relatively distant genetic relationships.Then a mouse model of metabolic syndrome induced by high-fat diet was established.In addition,different strains were given respectively to compare the intervention effects and improvement pathways on metabolic syndrome.Finally,the reasons for the difference in the intervention effects of different strains were analyzed by genome comparison.The main results are as follows:Firstly,the whole genomes of 74 strains of L.reuteri were compared and analyzed.Based on cluster analysis and phylogenetic tree,12 strains of L.reuteri with different genetic relationships were selected for 12 weeks of the animal experiment.The intervention effects of the strains on metabolic syndrome were evaluated by weight,blood glucose,blood lipids,liver tissue sections and other related indexes.The results showed that different genotypes of L.reuteri had different effects on metabolic syndrome.Among them,L.reuteri FGSZY33L6 could reduce weight gain and alleviate the disorders of glucose and lipid metabolism,and had the best effect on metabolic syndrome.However,L.reuteri FHNXY12L1 had no effect on all indexes.Secondly,appetite,energy conversion efficiency,cytokines,short chain fatty acids and changes in gut microbiota were taken as entry points to explore the alleviating ways of effective L.reuteri.The results showed that L.reuteri FGSYC2L3,L.reuteri FSCDJY33-3,L.reuteri AA3-8,L.reuteri FGSZY33L6 and L.reuteri FYNLJ109L1 might slow weight gain,epididymis fat ratio and insulin resistance index by reducing dietary intake and energy conversion efficiency.L.reuteri FGSZY33L6 and L.reuteri FYNLJ109L1 could improve metabolic syndrome by decreasing the liver IL-6 and TNF-?,pro-inflammatory cytokines related to insulin resistance,and increasing the anti-inflammatory cytokine IL-10.Only L.reuteri FGSZY33L6 intervention increased butyric acid level,which may alleviate obesity and insulin sensitivity induced by high-fat diet.In addition,L.reuteri FGSZY33L6 and L.reuteri FYNLJ109L1 could improve the dysregulated gut microbiota and regulate the imbalance damaged by high-fat diet.Finally,based on specific genomic analysis,homology analysis and gene functional annotation were carried out between the best remission L.reuteri FGSZY33L6 and the ineffective L.reuteri FHNXY12L1.And the specific genes of L.reuteri FGSZY33L6 were analyzed.Some are genes of unknown function,others include replication,recombination and repair,transcription,cell cycle control,cell division,chromosome segmentation,cell wall/membrane/membrane biogenesis,inorganic ion transport and metabolism,carbohydrate transport and metabolism,amino acid transport and metabolism and so on.Through KEGG annotation,the number of genes in glycine,serine and threonine metabolism,starch and sucrose metabolism and galactose metabolism were different between the two strains of L.reuteri,which might be the reason for the difference in the remission effect.