Bioaccessibility and synthesis of chronobiotics during in vitro gastrointestinal digestion of pistachio (PistaciaveraL.) to mitigate diseases linked to chronodisruption

Abstract

This research aimed to evaluate the in vitro chronobiotic potential of Phyto-melatonin(PTM) during gastrointestinal digestion, its fermentative behavior (phenolic acids and other compounds), and potential production of chronobiotics (short-chain fatty acids or SCFAs production). The chemical and nutraceutical composition of dry roasted and salted pistachios with seedcoat (SC)(PN + SC) and without(PN) was evaluated. Both samples were digested under static in vitro simulated physiological conditions comprising oral, gastric, intestinal, and colonic stages.ThePTMbioaccessibilityduring in vitro gastrointestinal digestion and colonic fermentation simulation was quantified.TheidentificationandquantificationofSCFAsandother colonic metabolites were conducted using SPME-GC-MS, followed by an untargeted metabolomical analysis. Results: PN + SC hadsignificantly(p < 0.05) lowerlipids(−7.9) andprotein(−1.1), buthighercarbohydrate(+8.4) andtotaldietary fiber(+4.8) content(g/100g)thanPN.PN + SC hadhighestcontent oftotalphenols(+42%), totalflavonoids(+54%), andPMT(+21%) (p < 0.05) comparedtoPN.Thebioaccessibilitywaslowforboth pistachiosamples[Oral:1.92and3.41%,PN + SC andPN;gastric: 0.83 and1.63%;intestinal[60min]:1.79and2.55;colonic[6h]: 0.32 and0.36%).Chemo-informaticsandan in silico analysisof PTM suggestthatitwasabsorbedwhenchewedbytheparticipants. The highestSCFAswereproducedat12hduring in vitro colonic fermentationforbothpistachiosamples,wherePN + SC displayedthe highest(p < 0.05) value(51mmol/L),followedbyPN(25.9mmol/L). SCFAs,derivedfrombacterialfermentationofdietaryfibers,can actaschronobioticsinperipheralclocks.TheSCFAsmolarratio remainedalmostconstantforbothpistachiosamples:butyric > pro- pionic > acetic.Somemetaboliteswithchronobioticpotential(e.g., indole,benzaldehyde,phenolicacids,andaliphatic/aromatichydro- carbons)weredetected,sample-dependent,throughtheuntargeted metabolomics. Conclusions: Pistachio’sdigestionincreasesthebioaccessibilityof PTMandthebiosynthesisofcolonicmetabolites(SCFAs,among others),allwithchronobioticpotentialtomitigatediseaseslinkedto chronodisruption. FundingSources: The fundingreceivedbyCONACyT/FOPESis appreciated.