Estrogen is a key regulator of the intestinal microbiota• Estrogen promotes the growth of bacteria that produce SCFAs.• Estrogen upregulates the antimicrobial peptide IAP to reduce  Proteobacteria abundance and lipopolysaccharide biosynthesis.• The gradual loss of ERβ during CRC development exacerbates the  decrease in gut microbiota diversity and pathogens enrichment. The gene discussed is ESR2; the disease is colorectal carcinoma.