Microcin C7 (McC) as a viable immunomodulator peptide can be a potential solution for pathogenic microbial infection in the post-antibiotic era and has gained substantial attention. This study was designed to evaluate the immunomodulatory activity of Microcin C7 in a cyclophosphamide (CTX)-induced immunodeficient mouse model. We show that Microcin C7 treatment significantly alleviated the CTX-caused body weight loss, improved the feed and water consumption to improve the state of the mice, and elevated the absolute number and proportion of peripheral blood lymphocytes as well as the level of hemoglobulin. We further aim to characterize the phenotypes of the immune function and intestinal health profiles. The results demonstrate that Microcin C7 treatment increased serum levels of immunoglobulin A (IgA), IgG, interleukin 6, and hemolysin, promoted splenic lymphocyte proliferation induced by concanavalin A and LPS, and enhanced the phagocytosis of peritoneal macrophages immunized by sheep red blood cells. Additionally, Microcin C7 treatment decreased levels of diamine oxidase and d-lactate, ameliorated CTX-induced intestinal morphological damage, and increased the levels of zonula occluden 1, occludin, claudin-1, mucin 2, and secretary IgA in the jejunum and colon. Moreover, Microcin C7 administration is sufficient to reverse CTX-induced intestinal microbiota dysbiosis by increasing the number of Lactobacillus and Bifidobacterium, decreasing the number of Escherichia coli in colonic contents. Collectively, our results demonstrate that Microcin C7 may have protective and immunomodulatory functions and could be a potential candidate used in animal feed, functional foods, and immunological regimens..
Keywords: Microcin C7; cyclophosphamide; gut microflora; immunomodulatory; intestinal epithelial barrier; intestinal mucosal immunity.