Resveratrol as a Multi‐Domain Modulator of Oxidative Stress, Gut Dysbiosis, and Epigenetic Remodeling in Obesity: A Systems Biology Interpretation

Obesity is increasingly recognized as a chronic inflammatory redox disorder sustained by gut dysbiosis and maladaptive epigenetic programming. A "lock-in" model describes how gut dysbiosis induced reactive oxygen species (ROS) stabilize inflammatory signaling and establish epigenetic metabolic scars in adipose tissue, thereby perpetuating obesity even after the initial triggers subside. Resveratrol, a dietary stilbenoid, acts as a tri-axis therapeutic candidate by: (1) Restoring redox balance via Nrf2 activation and SIRT1 signaling, (2) Reshaping the gut microbiota to enhance SCFA production and barrier integrity, and (3) Reprogramming obesity-associated epigenetic alterations, including DNA methylation and miRNA dysregulation. By targeting oxidative, microbial, and epigenetic dimensions simultaneously, resveratrol offers a novel strategy to erase metabolic memory and disrupt obesity chronicity.