Alleviating effect of intestinal alkaline phosphatase on Enterotoxigenic Escherichia coli K99-induced diarrhea

Antibiotics are commonly used to treat Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea, but bacterial resistance is worsening and efficacy is unsatisfactory. Based on the functions of intestinal alkaline phosphatase (IAP) such as degrading lipopolysaccharide (LPS), anti-inflammation, and enhancing intestinal barrier function, this study evaluated its therapeutic effect in mice. Thirty SPF BALB/c mice were randomly divided into five groups: the control group, the ETEC model group, and three IAP intervention groups (200, 300, and 400 U/mL). All groups received daily gavage for 3 consecutive days: the Control and ETEC groups were given phosphate-buffered saline (PBS), while the three IAP groups received IAP at their respective doses. On day 4, the model and intervention groups were pretreated with cimetidine followed by ETEC challenge. On day 7, intestinal permeability, inflammatory factors, barrier function, morphological structure, and intestinal LPS level were detected. Results showed IAP alleviated weight loss and reduced disease activity index (DAI), with 400 U/mL restoring DAI to baseline within 96 h. The 300 and 400 U/mL groups degraded LPS content in colonic contents, reduced bacterial load in the liver, improved jejunal morphology, upregulated Occludin, ZO-1, MUC2 expressions, enhanced antioxidant capacity, and downregulated inflammatory factors and TLR4/MyD88/NF-κB pathway genes (all P < 0.05). The 400 U/mL group further reduced diamine oxidase and D-lactate (P < 0.05). In conclusion, IAP effectively alleviated ETEC-induced diarrhea in mice, providing a theoretical basis for the development of novel therapeutic agents against diarrhea.