Bioaccessibility and Synthesis of Chronobiotics During In Vitro Gastrointestinal Digestion of Pistachio (Pistacia vera L.) to Mitigate Diseases Linked to Chronodisruption

Abstract

Abstract Objectives 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). Methods The chemical and nutraceutical composition of dry roasted and salted pistachios with seed coat (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. The PTM bioaccessibility during in vitro gastrointestinal digestion and colonic fermentation simulation was quantified. The identification and quantification of SCFAs and other colonic metabolites were conducted using SPME-GC-MS, followed by an untargeted metabolomic analysis. Results PN + SC had significantly (p < 0.05) lower lipids (−7.9) and protein (−1.1), but higher carbohydrate (+8.4) and total dietary fiber (+4.8) content (g/100g) than PN. PN + SC had highest content of total phenols (+42%), total flavonoids (+54%), and PMT (+21%) (p < 0.05) compared to PN. The bioaccessibility was low for both pistachio samples [Oral: 1.92 and 3.41%, PN + SC and PN; gastric: 0.83 and 1.63%; intestinal [60 min]: 1.79 and 2.55; colonic [6 h]: 0.32 and 0.36%). Chemo-informatics and an in silico analysis of PTM suggest that it was absorbed when chewed by the participants. The highest SCFAs were produced at 12 h during in vitro colonic fermentation for both pistachio samples, where PN + SC displayed the highest (p < 0.05) value (51 mmol/L), followed by PN (25.9 mmol/L). SCFAs, derived from bacterial fermentation of dietary fibers, can act as chronobiotics in peripheral clocks. The SCFAs molar ratio remained almost constant for both pistachio samples: butyric > propionic > acetic. Some metabolites with chronobiotic potential (e.g., indole, benzaldehyde, phenolic acids, and aliphatic/aromatic hydrocarbons) were detected, sample-dependent, through the untargeted metabolomics. Conclusions Pistachio's digestion increases the bioaccessibility of PTM and the biosynthesis of colonic metabolites (SCFAs, among others), all with chronobiotic potential to mitigate diseases linked to chronodisruption. Funding Sources The funding received by CONACyT/FOPES is appreciated.