Encapsulated tannic acid protects against ETEC-induced intestinal damage via modulating gut microbiota and barrier...

Enterotoxigenic Escherichia coli (ETEC) can cause diarrheal disease in both humans and young livestock, posing substantial challenges to intestinal health. This study investigated the protective effects and mechanisms of encapsulated tannic acid (ETA) against ETEC-induced intestinal injury. ETA was successfully prepared, and in vitro digestion experiments showed that the release rate of tannic acid was 10.27% in simulated gastric fluid, with a cumulative release rate of 78.97% in simulated intestinal fluid after 360 min, indicating its excellent controlled-release property. In vivo, 500 mg/kg ETA was selected as the optimal dose and alleviated ETEC-induced growth inhibition, reduced the spleen weight ratio, and mitigated intestinal inflammation. Histologically, ETA improved intestinal morphology by increasing villus height and decreasing crypt depth, and its efficacy was better than that of TA. ETA also attenuated inflammation by downregulating TNF-α, IL-1β, IL-8 and the TLR4/MYD88/TAK1 pathway, relieved oxidative stress by increasing SOD activity and decreasing MDA content, and restored intestinal barrier function. Additionally, In vitro, 0.6% ETA digestion supernatant alleviated ETEC-induced damage in IPEC-J2 cells. ETA also reshaped ETEC-induced cecal microbiota dysbiosis by reducing α-diversity, increasing the abundance of beneficial bacteria and decreasing pathogenic bacteria, and restored short-chain fatty acid levels. Mechanistically, antibiotic-induced gut microbiota depletion abolished the protective effects of ETA, while fecal microbiota transplantation from ETA-treated donors replicated these protective effects. These findings demonstrate that ETA attenuates ETEC-induced intestinal injury through gut microbiota modulation, providing a promising strategy for the prevention and treatment of bacterial enteritis.