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

Apolipoprotein E (ApoE = protein; APOE = gene), a lipid carrier that modulates inflammatory responses, may influence <i>Clostridioides difficile</i> (<i>C. difficile</i>) infection (CDI) outcomes. We explored the role of the APOE gene using apoE-deficient mice challenged by <i>C. difficile</i> 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 × 10⁴-10⁵ CFUs of <i>C. difficile</i>, 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 <i>C. difficile</i> shedding. This suggests a potential anti-inflammatory role of COG133 in CDI. More studies are neede to these intial findings in depth.