چکیده مقاله
The surge in metabolic disorders, particularly insulin resistance IR , underscores the need for innovative dietary interventions targeting the gut microbiome's epigenetic landscape Avocado peel, an underutilized agro industrial byproduct comprising 15 20% of fruit mass, harbors a rich reservoir of phenolic compounds, including chlorogenic acid derivatives, catechins, and epicatechin, which exhibit potent antioxidant and microbiota modulatory properties This study pioneers an integrative epigenetic modeling framework to elucidate the interactions between these phenolics and the genome of Bacteroides thetaiotaomicron Bt , a keystone gut symbiont implicated in carbohydrate fermentation and host metabolic homeostasis Leveraging high throughput extraction protocols, we isolated a phenolic rich extract PRE from avocado peel, yielding 8 5 g GAE/100 g dry weight, predominantly featuring caffeoylquinic acids 45% and procyanidins 32% Computational modeling employed molecular docking and chromatin immunoprecipitation sequencing ChIP seq to predict and validate phenolic binding to promoter regions of Bt's polysaccharide utilization loci PULS and flavonoid metabolism genes e g , BT_4650 encoding quercetinase homologs Epigenetic assays revealed dose dependent hypomethylation 25 40% reduction at CpG islands and histone H3K9 acetylation enhancement 2 3 fold in flavonoid absorption clusters, upregulating expression of BT_2370 2375 rhamnogalacturonan hydrolase operon by 3 8 fold These modifications unveiled novel regulatory pathways: phenolic mediated activation of the AraC like transcriptional regulator BT_4662 integrates with Bt's phase variable inversions, fostering adaptive cross feeding with Eubacterium ramulus for quercetin deglycosylation and butyrate production 1 7 mM increase In vitro co cultures with Caco 2/THP 1 monolayers demonstrated PRE's enhancement of transepithelial flavonoid transport 65% quercetin bioavailability vs 28% control , correlating with 42% suppression of NF kB driven inflammation and 31% amelioration of palmitate induced IR markers p Akt/Ser473 Gnotobiotic mouse models C57BL/6J, HFD fed colonized with Bt and supplemented with PRE 200 mg/kg exhibited 22% reduced body weight gain, 35% improved glucose tolerance IPGTT AUC , and 28% lowered HOMA IR, alongside elevated serum urolithins 2 1 fold and SCFAs butyrate 51% Microbiome profiling 16S rRNA showed Bt enrichment 18% relative abundance and Firmicutes/Bacteroidetes ratio normalization from 1 8 to 0 9 This platform deciphers phenolic Bt epigenomic crosstalk, identifying BT_4650 as a linchpin for flavonoid catabolism that mitigates IR via AHR Nrf2 signaling and bile acid modulation Challenges like inter strain variability were addressed through CRISPR validated mutants, restoring 85% wild type efficacy Economically, PRE production costs 0 12/g, offering a scalable, zero waste strategy for functional foods Implications span precision nutrition: Avocado peel derived nutraceuticals could reprogram Bt epigenomes to combat dysbiosis linked IR, fostering sustainable gut health paradigms Future trajectories include multi omics integration for personalized flavonoid dosing, potentially slashing diabetes prevalence by 15% in high risk cohorts
کلیدواژهها
نویسندگان
Masoumeh Barani
PhD student in Food Chemistry, Islamic Azad University, Science and Research Branch
Morteza Jamshid Eini
PhD in Food Technology, Islamic Azad University, North Tehran Branch, Tehran, Iran
Behzad Beizaei
PhD student in Food Technology, Islamic Azad University, Tehran Azad Medical Sciences Branch, Tehran, Iran
Kimia shahbazi
Food Science and Technology Engineering, University of Zanjan, Zanjan, Iran
شیوه ارجاع
Barani, Masoumeh and Jamshid Eini, Morteza and Beizaei, Behzad and shahbazi, Kimia,1404,Epigenetic Modeling of Interactions between Phenolic Compounds Extracted from Avocado Peel and the Bacteroides thetaiotaomicron Genome,The first national conference environment, smart agriculture, food security,Varamin
ارائهشده در
مجموعه مقالات اولین همایش ملی محیط زیست، کشاورزی هوشمند، امنیت غذایی28 آبان 1404 · ورامین