REVIEW article
Front. Nutr.
Sec. Nutrition and Metabolism
This article is part of the Research TopicClinical Research on Nutrition and Children's Health: Focusing on Genetics, Metabolism, and the Gut MicrobiomeView all 9 articles
Systems Biology Insights into the Molecular Drivers of Childhood Stunting and Implications for Intervention
Provisionally accepted
Genevieve Dable-Tupas1*
Ariane Blanch Amada Maraon1Lorraine Joy Lagdamen Bernolo1Nelly Grace Funa Toñacao1April Dawn Moso Taylaran1Maria Angelica Candelario Plata1
Jason C. Alcano1
Richelle Duque Björvang2
Shamsul Mohd Zain3Vladimir Kobayashi4
Melkamu Arefayine5
Alemayehu Teklu Toni6
Jacus Sabado Nacis7
Gerard Bryan Gonzales8*- 1Davao Medical School Foundation, Davao City, Philippines
- 2Uppsala Universitet, Uppsala, Sweden
- 3Universiti Malaya Faculty of Medicine, Federal Territory of Kuala Lumpur, Malaysia
- 4University of the Philippines Mindanao, Davao City, Philippines
- 5Jimma University, Jimma, Ethiopia
- 6University of Gondar, Gondar, Ethiopia
- 7Wageningen University & Research, Wageningen, Netherlands
- 8Universiteit Gent, Ghent, Belgium
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Childhood stunting is a condition resulting from chronic malnutrition affecting millions globally, with lasting consequences for growth, cognition, and productivity. This review explores the molecular mechanisms underlying stunting, focusing on evidence obtained from systems biology to uncover biochemical pathways and potential biomarkers for early detection and targeted interventions. Key findings highlight the role of disrupted pathways such as the mechanistic target of rapamycin (mTOR) signaling, the tryptophan-kynurenine pathway, one-carbon metabolism, and chronic inflammation associated with environmental enteric dysfunction and dysbiosis of the gut microbiome. These insights emphasize the multifactorial nature of stunting, influenced by nutrition, infections, socioeconomic and maternal factors. Integrating systems biology to support public health strategies may provide avenues for precision nutrition-driven interventions that address specific deficiencies and systemic biochemical disturbances.
Keywords: Metabolomics, microbiome, mTOR, nutrition, stunting, Systems Biology
Received: 05 Dec 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 Dable-Tupas, Maraon, Bernolo, Toñacao, Taylaran, Plata, Alcano, Björvang, Zain, Kobayashi, Arefayine, Toni, Nacis and Gonzales. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Genevieve Dable-Tupas
Gerard Bryan Gonzales
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