Early-Life Prevention of Cardiovascular-Kidney-Metabolic Syndrome: The DOHaD Perspective on Resveratrol and Short-Chain Fatty Acids.

Cardiovascular-kidney-metabolic (CKM) syndrome underscores the interconnected biology of cardiovascular disease, kidney disease, and metabolic disorders such as obesity and type 2 diabetes. Although now recognized as a growing global health burden, accumulating preclinical evidence suggests that CKM syndrome may originate in early life-a concept rooted in the developmental origins of health and disease (DOHaD) framework. Animal studies have greatly enhanced our comprehension of these mechanisms, emphasizing the promise of early interventions that focus on antioxidants and gut microbiota modulation to mitigate the development of CKM conditions. Resveratrol, a natural antioxidant and prebiotic, alongside short-chain fatty acids (SCFAs), a postbiotic, have demonstrated the ability to modulate gut microbiota and oxidative stress in experimental models. Various resveratrol derivatives have also been engineered to improve bioavailability, though their effects remain largely confined to animal studies. This review synthesizes preclinical findings on the impact of perinatal oxidative stress and gut dysbiosis on CKM outcomes, critically examining the roles of resveratrol, SCFAs, and their derivatives in animal models. Finally, we highlight the significant translational gap between experimental research and clinical application, underscoring the need for human studies to validate these early-life intervention strategies.