Study On The Mechanism Of Lactobacillus Plantarum Y-1 Improving Permethrin-Induced Obesity In High-Fat Diet Mice

Pesticides are extensively used in agriculture and for pest control.The issue of pesticide residue and its impact on human health has gained significant attention.Studies have found that pesticide exposure may exacerbate the occurrence and development of obesity and metabolic syndrome.Permethrin,a type I synthetic pyrethroid insecticide,mimics natural pyrethrin.Previous research has shown that permethrin may exacerbate fat accumulation,dyslipidemia,and insulin metabolism abnormalities both in vitro and in vivo.Dysbiosis of gut microbiota is considered an essential factor leading to obesity and related metabolic disorders.However,the role of gut microbiota in permethrin-induced obesity is still unclear.Studying changes in serum metabolites caused by external factors is of great significance for understanding the mechanism,prevention,and treatment of obesity and metabolic syndrome.Previous studies have reported that probiotics have the potential to degrade pesticides and improve pesticide-induced metabolic disorders,but their mechanism of action in vivo is unclear.Developing safer and more effective dietary supplements from natural biological sources to prevent or improve permethrin-induced lipid metabolism disorders has broad research prospects.Lactobacillus plantarum Y-1,a potential probiotic,has been found to have activity in d regulating blood sugar,anti-inflammatory,and immune regulation.In this study,we conducted a chronic exposure experiment of permethrin on C57BL/6J mice fed a high-fat diet while intervening with Lactobacillus plantarum Y-1 to evaluate the effect on mouse body weight,fat content,serum lipid levels,and other indicators to explore the alleviating effect of Lactobacillus plantarum Y-1 on permethrin-induced obesity and lipid metabolism disorders.We used metagenomics and non-targeted metabolomics techniques to explore potential mechanisms.The primary results are summarized below:(1)Lactobacillus plantarum Y-1 effectively suppressed the weight gain,epididymal white adipose tissue accumulation,and liver triglyceride accumulation induced by permethrin in high-fat diet-fed mice without affecting their energy intake.It also regulated the abnormal lipid status of total triglycerides,total cholesterol,lowdensity lipoprotein cholesterol,and high-density lipoprotein cholesterol in the serum,improved impaired glucose tolerance and insulin tolerance.Additionally,Y-1 alone increased the body weight of mice but reduced the ratio of epididymal white adipose tissue to body weight,suggesting that Y-1 may promote growth and development without fat accumulation.(2)Lactobacillus plantarum Y-1 demonstrated a regulatory effect on the gut microbiota composition of permethrin-exposed mice.At the phylum level,it downregulated the Firmicutes/Bacteroidetes ratio(F/B).At the genus level,it upregulated the relative abundance of Akkermansia,Lachnoclostridium,and Faecalibacterium,and downregulated the relative abundance of Muribaculum.Despite this,Y-1 did not modify the diversity of the gut microbiota in permethrin-treated mice.Permethrin exposure reduced the abundance of beneficial bacteria in the intestinal flora of high-fat diet mice,such as the relative abundance of B.animalis and E.callanderi was significantly lower than that of C group.The intervention of Lactobacillus plantarum Y-1 promoted the positive enrichment of beneficial bacteria and the reduction of harmful bacteria in the gut microbiota of permethrin exposed mice,such as significantly up-regulated the relative abundance of L.plantarum and B.thetaiotaomicron,but down regulated the relative abundance of C.perfringens.Furthermore,the intervention with Lactobacillus plantarum Y-1 significantly upregulated multiple metabolic pathways associated with short-chain fatty acid production in the intestinal microbiota of permethrin-exposed mice.These metabolic pathways included “Clostridium acetobutylicum acidogenic fermentation”,“pyruvate fermentation to acetate and lactate” “acetyl-Co A fermentation to butanoate II” and“pyruvate fermentation to butanoate”.(3)Lactobacillus plantarum Y-1 had a significant impact on the serum metabolite profile of mice exposed to permethrin.A total of 122 differential metabolites were identified between the permethrin(P)and control(C)groups,while 241 differential metabolites were observed between the Y-1 intervention(Y1-P)and permethrin(P)groups.Permethrin exposure increased the level of the secondary metabolite(1s,3r)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid in serum,which was not eliminated by Y-1 intervention.Conversely,Y-1 intervention increased the levels of arachidonic acid metabolites in permethrin exposure mice serum,including prostaglandin h2,15-deoxy-δ12,14-prostaglandin j2,and 11-dehydro thromboxane b2.Meanwhile,the level of testosterone glucuronide was increased and the level of 2-arachidonoyl glycerol was decreased.Additionally,Y-1 intervention significantly impacted metabolic pathways such as "steroid hormone biosynthesis" and "arachidonic acid metabolism" in permethrin-exposed mice.The study also found that the changes in serum metabolites induced by permethrin exposure and Lactobacillus plantarum Y-1 intervention were closely related to gut microbiota composition and host serum lipid levels.