Formononetin Mediated Gut Microbiota And Metabolic Biomarkers Modulation In Dosage Dependent Manner

Formononetin(FMNT)is an Isoflavone that has been studied for its anti-hyperglycemic and anti-diabetic effects.However,the effect of FMNT on gut dysbiosis and metabolic complications associated with western-style diet consumption has not been reported yet.Moreover,the association between gut microbiota,obesity is not understood completely.The aim of current study is to evaluate the gut modulating effect of FMNT and improvements of metabolic disorders in male and female DIO mice models.In current research the mice models of dietary induced obesity established.All mice were divided into five groups: primary Normal control groups NC(NC-Male and NC-Female)fed with regular chow diet and the distilled water and Western style diet were administered to mice in second group the WSD group(WSD-male,WSD-female).Third group of mice were administered 20mg/kg bodyweight and WSD diet was named as LDT(Low dose treatment group;LDT-Male,LDT-Female).Fourth group turned into MDT(Medium dose treatment group MDT;MDT-Male,MDT-female).Furthermore,three different dosages(LDT,MDT,and HDT)of FMNT were administered group wise for 28 days.Afterwards,metabolic parameters tests(such as serum glucose,insulin,leptin,LDL and HDL,OGTT),tissue histology and 16 S r RNA gene sequencing for gut microbiota and q PCR for the expression of certain mi RNAs and m RNAs were also performed.This aim of study was to investigate effect of FMNT on gut microbiota and amelioration of metabolic disorders in both genders in dosage dependent manner.Results indicate that FMNT at60mg/kg dosage can effectively regulate the certain gut microbiota groups,body weight,and hyperglycemia,and insulin resistance,leptin levels and improve HDL to LDL ratio in both genders.High dose of FMNT create toxicity due to increase in Bacteriodates may lead to metabolic endotoxemia in males,but it is beneficial to female which due to its phytoestrogenic properties.FMNT treatment suppressed Porphyromonadaceae(uncultured Alistipes)while augmented maximum Genera from family Lachnospiracy and clostradiacea but at specie level FMNT increased Clostridium aldenense,Clostridiaceae unclassified,Eubacterium plexicaum;acetate and butyrate producing bacteria.Moreover,FMNT regulated the expression of specific liver mi RNA involved in pathogenesis of obesity and down regulated m RNA expression levels of pro-inflammatory cytokines IL-6,IL-22 and TNF-α.Additionally,FMNT maintained intestinal membrane integrity by regulating expression of Muc-2and occluding.Thus,findings indicates that FMNT can be a potential prebiotic which can effectively reshape gut microbiota;improve host metabolism and systemic inflammation preventing deleterious effects of western style diet by elevating acetate,lactate and butyrate producers.