Congenital foot deformities are complex diseases influenced by genetic, environ mental, and nutritional factors. In recent years, research has increasingly focused on the effects of trace elements during pregnancy (such as zinc, selenium, copper, iron, and phosphate) on fetal development. Although observational studies sug gest that these trace elements may be associated with congenital deformities, their causal relationship remains unclear. This study employs the Mendelian Random ization method, using genetic variants as instrumental variables for analysis.The results show that although the OR for Zinc is 92.21 (95% CI: 0.0008–10098024, p = 0.445), for Selenium the OR is 6.21×10-6 (95% CI: 2.71×10-15–14233.68, p = 0.276), for Copper the OR is 0.96 (95% CI: 0.823–1.128, p = 0.646), for Iron the OR is 0.023 (95% CI: 2.10×10-8–24289.32, p = 0.593), and for Phosphate the ORis 0.96 (95% CI: 0.667–1.374, p = 0.812). These data did not reach statistical significance, suggesting that the causal relationship between the levels of these trace elements and congenital foot deformities is unclear. However, further anal ysis revealed that selenium may reduce the risk of congenital foot deformities by regulating the gut microbiota class.Bacilli, with a significant interaction observed between selenium and this microbiota. Although sensitivity analyses (IVW and MREgger methods) were unable to confirm the direct effect of selenium on con genital foot deformities, considering the role of class.Bacilli.id.1673 strengthened selenium’s indirect effect. Despite the overall results not reaching statistical sig nificance, this study provides new clues for further exploration of the complex relationships between trace elements, gut microbiota, and congenital deformities, particularly the potential role of gut microbiota in modulating the relationship between nutritional elements and developmental abnormalities.

The authors have declared that no competing interests exist.

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The data used in this study were obtained from publicly available Genome-Wide Association Studies (GWAS) datasets, which have been ethically approved by the relevant institutions, and informed consent was obtained from the participants. Therefore, no additional ethical approval is required for this study.

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