Dietary Bioactives as Genomic Regulators: A Critical Review of Gene Control, Biomarker Validation, and Translational Barriers in Nutrigenomics

Abstract

Nutrigenomics integrates disciplines such as bioinformatics, molecular biology, and genomics to identify genes and genetic predispositions affecting the risk of diet-related disorders. This review presents a Narrative and Critical Review of the literature, focusing on transparency in combining evidence for complex and rapidly changing fields. The reviewed literature underwent critical analysis to assess the strengths and weaknesses of current evidence and identify research gaps. The methodology ensures that the review not only summarizes key findings but also provides a clear framework for future research directions and discussions on personalized nutrition. The interaction between nutritional and genetic factors is continuous, with nutrients influencing DNA metabolism and gene expression, while genetic variants influence dietary habits. Oxidative stress plays a critical role in the pathogenesis of type 2 diabetes mellitus (T2DM), contributing to insulin resistance and beta-cell dysfunction. Consequently, genes such as NFE2 and NFE2L2, which regulate antioxidant protein expression, are promising targets for mitigation. Precision nutrition is an ambitious endeavor requiring a thorough quantitative understanding of the intricate relationships between an individual's dietary habits, their unique genetic makeup, and their overall health status to deliver precisely tailored and proven beneficial interventions. Nutrigenomics must be considered in conjunction with other critical factors like lifestyle, environment, and cultural influences, as genes are not the sole determinants of an individual’s health. Overcoming these scientific, systemic, and ethical challenges is essential to harness the full potential of nutrigenomics and provide effective, personalized nutrition guidance globally.