Exploring the antioxidant mechanisms of millet polyphenols: regulation of Nrf2 and NF-κB and their impact on gut microbiota

Abstract Dietary polyphenols of Millets have received more attention after the FAO declared 2023 the “International Year of Millets”. The question we addressed is how the human body addresses the xenobiotic nature of millet polyphenols during absorption. Our primary objective was to elucidate the molecular mechanisms underlying the antioxidative effects exhibited by polyphenol-derived metabolites. Furthermore, we underscored the mounting evidence substantiating a bidirectional synergistic relationship between gut microbiota and the bioavailability of dietary phenols. We conducted a literature search using specific databases such as Pubmed and Google Scholar. We used various combinations of keywords such as millets, phenolic compounds, polyphenol metabolism, antioxidant activity, bioavailability, gut microbiota, and gut health environment. Our inclusion criteria were to select articles reporting on phenolic compounds found in millets, their antioxidant properties, and mechanisms of action. We excluded editorial/letters, conference proceedings, or other types of articles to maintain a sharp focus on our objectives. We reviewed the antioxidant potentials of dietary polyphenols identified in several varieties of millet crops for the first time, presented a mechanistic insight into the antioxidative bioactivity, and assessed a strong association between gut microbiota and phenolic bioavailability. Millets are viewed as future crops, and there is an increased interest in using millets as a superfood and antioxidant dietary source. This is the first review to examine the antioxidant capabilities of phenolic compounds produced in different millet varieties. Further, establishing a favorable two-way link between microbiota and polyphenolic bioavailability would be a significant way forward. Graphical Abstract