Objective To investigate the effect of 2,3 sialic acid residues on the adhesion and invasion of Escherichia coli to intestinal epithelial cells. Methods The differentiated colon epithelial cell line (HT-29-Gal) was selected as the object of study, ST3Gal overexpression cell line (ST3Gal/HT-29-Gal), interference cell line (ST3Gal-sh/HT-29-Gal) and control cell line (Ctr/HT-29-Gal) were obtained by adenovirus transfection. These cell lines were co-cultured with Escherichia coli (EPEC or EHEC O157∶H7). Bacterial staining and bacterial gradient dilution clonal counting were used to count the number of bacteria adherent to colon epithelial cell lines. These cell lines were co-cultured with invasive Escherichia coli (EIEC), and the bacteria attached to the surface of colon epithelial cells were killed by gentamicin. Then the number of bacteria invaded into colon epithelial cells was counted by bacterial gradient dilution cloning counting assays. Finally, the effect of ST3Gal on the barrier function of intestinal epithelial cells by the permeability (FD4) and transmembrane resistance (TEER) experiments.Results Bacterial staining and bacterial gradient dilution clonal count assays showed that the number of bacteria (EPEC or EHEC O157∶H7) adherent to the surface of ST3Gal/HT-29-Gal cells was lower than Ctr/HT-29-Gal cells (P＜0.05 or P＜0.01). The number of bacteria (EIEC) invaded into ST3Gal/HT-29-Gal cells was higher than Ctr/HT-29-Gal cells (P＜0.01). The TEER values of ST3Gal/HT-29-Gal cells was lower than Ctr/HT-29-Gal cells (P＜0.01). The permeability of ST3Gal/HT-29-Gal cells was higher than Ctr/HT-29-Gal cells (P＜0.01). The expression of MUC2 mRNA and protein in ST3Gal/HT-29-Gal cells was lower than Ctr/HT-29-Gal cells (P＜0.01), while the opposite results were confirmed in ST3Gal-sh/HT-29-Gal cells. Conclusion α2,3 sialic acid residues inhibites bacterial(EPEC and EHEC O157∶H7) adhesion to the surface of colon epithelial cells, promoting bacterial(EIEC) invaded into colon epithelial cells