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Early-Life Prevention of Cardiovascular-Kidney-Metabolic Syndrome: The DOHaD Perspective on Resveratrol and
Chien-Ning Hsu1,2,3, Ying-Jui Lin4,5,6,7, Chih-Yao Hou8
1Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Abstract:
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.
Insights
Early life interventions targeting oxidative stress and gut dysbiosis show promise for preventing cardiovascular-kidney-metabolic (CKM) syndrome. Preclinical studies highlight antioxidants like resveratrol and short-chain fatty acids (SCFAs) for CKM conditions.
Area of Science:
- Integrative biology
- Developmental origins of health and disease (DOHaD)
- Nutritional science
Background:
- Cardiovascular-kidney-metabolic (CKM) syndrome links cardiovascular, kidney, and metabolic diseases.
- Emerging evidence suggests CKM syndrome may originate in early life, aligning with DOHaD principles.
- Perinatal oxidative stress and gut dysbiosis are implicated in CKM development.
Purpose of the Study:
- To review preclinical findings on early-life factors influencing CKM syndrome.
- To examine the role of antioxidants (resveratrol) and gut microbiota modulators (SCFAs) in animal models.
- To identify the translational gap for early-life interventions in CKM syndrome.
Main Methods:
- Literature review of preclinical studies.
- Analysis of animal models investigating perinatal oxidative stress and gut dysbiosis.
- Evaluation of resveratrol, SCFAs, and their derivatives in mitigating CKM conditions.
Main Results:
- Animal studies demonstrate that resveratrol and SCFAs can modulate gut microbiota and oxidative stress.
- Resveratrol derivatives show improved bioavailability in preclinical models.
- Early-life interventions targeting these pathways show potential in mitigating CKM development.
Conclusions:
- Preclinical evidence supports early-life interventions for CKM syndrome prevention.
- Resveratrol and SCFAs show promise in modulating key risk factors.
- Human studies are crucial to validate these findings and bridge the translational gap.
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