Antioxidants, Gut Microbiota, and Cardiovascular Programming: Unraveling a Triad of Early-Life Interactions

Cardiovascular disease (CVD) remains the leading cause of global mortality, despite advances in adult-focused prevention and therapy. Mounting evidence supports the Developmental Origins of Health and Disease (DOHaD) paradigm, which identifies early-life exposures as critical determinants of long-term cardiovascular health. Among the key mechanistic pathways, oxidative stress and gut microbiota dysbiosis have emerged as central, interrelated contributors to cardiovascular programming. Prenatal and postnatal insults can induce sustained redox imbalance and disrupt microbial homeostasis. This disruption creates a feed-forward loop that predisposes offspring to CVD later in life. Antioxidants offer a promising reprogramming strategy by targeting both oxidative stress and gut microbiota composition. Preclinical studies demonstrate that maternal antioxidant interventions-such as vitamins, amino acids, melatonin, polyphenols, N-acetylcysteine, and synthetic agents-can restore redox homeostasis, modulate gut microbial communities, and attenuate cardiovascular risk in offspring. This review synthesizes current evidence on how oxidative stress and gut microbiota act together to shape cardiovascular trajectories. It also examines how antioxidant-based therapies may disrupt this pathological axis during critical developmental windows. Although human data remain limited due to ethical and practical constraints, advancing microbiota-targeted antioxidant interventions may offer a transformative approach to prevent CVD at its origins.