Estrogen or estrogen-like compounds induced elevated IAP levels likely by upregulating the function of the KLF4 transcription factor that targets IAP and subsequent gut microbiome changes lower LPS production and gut permeability, resulting in reduced ME and systemic LGCI with subsequent reduction in the susceptibility to develop WD-induced MS in estrogen-treated males and post-menopausal women. Here, KLF4 is linked to Wilson disease.