The MR findings were further substantiated through a multimodal validation approach: (1) establishment of a rat goiter model with 16S rRNA sequencing confirmation (α/β-diversity analysis, differential taxa identification by t-test, and PICRUSt2 metabolic prediction); (2) targeted biochemical assays quantifying SCFA concentrations, iodine metabolism parameters, and thyroid hormone profiles; and (3) histopathological and molecular validation (immunohistochemistry and Western blot analysis of NIS expression). Here, SLC5A5 is linked to goiter.