Abstract
Down syndrome, or trisomy 21 (T21), is a genetic neurodevelopmental disorder (NDD) often associated with various health challenges. In this population, physiological alterations remain poorly recognized, including dysregulated interactions among systems that play important roles in maintaining homeostasis. Common challenges include nutritional deficiencies, impaired metabolic detoxification, a hypoxia-like state, and gut dysbiosis. This study investigates the impact of dietary interventions and nutrient supplementation on the physiological profiles of individuals with T21. Using a database from the “Integración Down” Institute in Mexico City, we analyzed a panel of 121 biochemical markers before and after a 10-month intervention period. The interventions comprised dietary restriction alone (D) and dietary restriction with nutrient supplementation (D + S), aimed at modifying the participants’ physiological profiles. Our findings demonstrate changes in several physiological markers following the interventions, mainly in response to D + S. In particular, we observed changes in dysbiosis markers related to bacterial and fungal overgrowth; the D + S protocol reduced biomarkers associated with fungal overgrowth. Biomarkers related to nutritional deficiency and a hypoxia-like state (described for T21) showed changes, especially in the D + S group. Increases in red‑blood‑cell indices and decreases in markers of metabolic pathway disruption suggest improved energy metabolism. This research highlights the potential of dietary interventions to ameliorate T21-associated comorbidities and improve overall health outcomes in this population. Further research is needed to explore the long-term effects and optimal strategies for personalized nutritional management in individuals with T21. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-32212-6.