Work

ApoE COG 133 mimetic peptide improves survival, infection burden, and Clostridioides difficile toxin-A-induced intestinal damage in mice

Year: 2025

Type: article

Abstract: Apolipoprotein E (ApoE = protein; APOE = gene), a lipid carrier that modulates inflammatory responses, may influence Clostridioides difficile ( C. difficile ) infection (CDI) outcomes. We explored the role of the APOE gene using apoE-deficient mice challenged by C. difficile toxin A (TcdA)-induced enteritis, and the potential use of the ApoE mimetic peptide in repairing the intestinal damage induced by TcdA. 4-cm ileal loops from C57BL/6 wild-type and APOE knockout (−/−) were ligated and injected with either PBS or TcdA (50 µg). After 4 h of incubation, the intestinal loops were harvested for measurement of length, weight, volume of secretion, and histopathology scores. In mouse ileal loops, TcdA induced a significant increase in weight/ileal loop length in the wild-type mice. When APOE −/− mice were infected with 1 × 10 4 –10 5 CFUs of C. difficile , they had higher deaths and diarrhea scores compared to wild-type. APOE −/− mice under the toxin A (TcdA) had worse inflammatory changes in the ileal loop. APOE −/− mice treated with COG133 (3 mg/kg) showed fewer deaths, and lower diarrhea scores, but no change in C. difficile shedding. This suggests a potential anti-inflammatory role of COG133 in CDI. More studies are neede to these intial findings in depth.

Source: Experimental Biology and Medicine

DOI: 10.3389/ebm.2025.10638