Expression of Growth Hormone in Lactococcus lactis and Its Effect on Intestinal Barrier Damage in Mice with DSS-Induced Colitis

Growth hormone has the potential to modulate inflammatory responses, alleviate intestinal injury, and preserve intestinal health. However, its limited availability from natural sources restricts further research and practical applications. Therefore, we optimized the coding sequence for porcine growth hormone (pGH) and constructed recombinant Lactococcus lactis (L. lactis) expressing pGH. The effect of L. lactis (pNZ8148-pGH) against intestinal damage was evaluated in mice with DSS-induced colitis. Orally administered L. lactis (pNZ8148-pGH) attenuated the symptoms of DSS-induced colitis, including weight loss, colon shortening, and elevated colonic damage scores (CDS), and improved colonic tissue morphology. Compared with the DSS group, L. lactis (pNZ8148-pGH) significantly reduced serum diamine oxidase (DAO) activity, colonic myeloperoxidase activity, and serum D-lactate and endotoxin levels while increasing colonic occludin and claudin-1 levels. Colonic tumor necrosis factor-α, interleukin-2 (IL-2), and interleukin-6 levels decreased significantly, whereas the interleukin-10 (IL-10) level increased after L. lactis (pNZ8148-pGH) administration. Furthermore, L. lactis (pNZ8148-pGH) significantly increased the numbers of colonic Ki67- and PCNA-positive cells and their positive indices. In addition, compared with the DSS group, L. lactis (pNZ8148) significantly decreased CDS, serum DAO activity, and colonic IL-2 level while increasing colonic occludin and IL-10 levels. In conclusion, oral administration of L. lactis (pNZ8148-pGH) maintained intestinal barrier integrity, suppressed inflammation, promoted mucosal repair, and alleviated DSS-induced colitis.