Propamocarb Exposure Induce Gut Microbiota Dysbiosis And Relevant Effect In Mice

A great number of microbes harbor in our gut,they are named gut microbiota.Recently,we recognized their important roles in human health,the gut microbiota could regulate energy metaboilism and storage,immune,growth and development,nervous system and heaviors.Previous studies found environmental pollutes including antibiotics,heavy metal,POPs,agrochemicals and food additive could induce gut microbial dysbiosis,which will further aggrevate or even induce some diseases.Propamocarb(PM)is a widly used fungicide,which has the property of broad spectrum and within absorption.PM is used to treat fungal diseases in vegetables,fruits,follows and lawn.When PM enter the intestine,it may influence the gut microbiota and metabolism.This study aim to investigate the effect of PM exposure on mice gut microbiota and change in physiology.Firstly,we exposed ICR male mice to 3,30,300 mg/L PM through drinking water for 4 weeks.We found heapatic TG significantly increased,pyruvate slightly increased;hepatic genes,which regulate energy metabolism,including Cherbp,Fatp2,Acox,Screbp1 c,Scd1 and Dgat1 were significantly down-regulated at transcriptional levels;using RT-PCR and high-throughput sequencing for 16 S r RNA gene,we found mice gut microbial composition was altered at phylum and genus levels;colonic LPL levels significantly increased both at transcriptional and protein levels,SCFA receptor GPR41 significantly decreased at transcriptional levels;energy metabolism-related fecal metabolites including succinate,lactate,glycerol,nicotinate,trehalose,galactose,bile acids and SCFA were significantly altered;otherwise,trimethylamine(TMA)was also significantly increased,this compound could aggregate atherosclerosis by transferming to trimethylamine oxide(TMAO).These results indicated short-term PM exposure at high dosages could induce gut microbial dysbiosis,influence microbial metabolic profiles and host energy metabolism.Then we investigated the influence of chronic PM exposure at low dosage on mice,C57BL/6J male mice were treated with 1,3,10 mg/L PM for 10 weeks.Althrough body weight,hepatic TG and hepatic cholesterol didn't changed significantly,genes which regulated glycolysis,FA transportation,?-oxidation,TG transportation,FA synthesis,FA release and TG synthesis were significantly suppressed in the liver;gene regulate bile acids enterohepatic circulation were dramatically reduced at transcriptional levels,meanwhile,BA receptor FXR significantly increase d;hepatic total BA levels significantly increased,serous BA profiles detected by UPLCMS/MS were altered by PM,among them,TCA,UDCA,?MCA,?MCA,T?MCA and T?MCA remarkably increased;high-throughput sequencing for 16 S RNA gene found gut microbial composition in fecal and cecal content were significantly altered,dominant species were changed after PM exposure;the concentration fecal metabolites measured by NMR like creatine,fumarate,lactate,Trehalose and galactose were significantly changed,as well as TMA;hepaitc FMO3,which could oxide TMA to TMAO,significantly increased at protein levels;cardiac NO levels significantly increased,whereas the transcription and activity NO synthase significantly decreased,inflammatory factor NF-?B also significantly increased at transcriptional levels.These results indicated chronic low dosage PM exposure could significantly influenced mice energy metaboilism and BA metabolism at transcriptional levels,althrough no change in physical indexes,metabolic changes were also associated with gut microbiota and their metabolism,increased fecal TMA further induced dysfounction in the heart,these results meant PM exposure may induce CVD.Above study explores the effect of PM on mice gut microbiota and metabolism,and the results help to evaluate toxicology effects of PM.