Insulin-like growth factor I (IGF-I) is one important family of growth factors, which plays key role in intestinal growth, regeneration, and damage repair. However, the low natural abundance of IGF-I limits its research opportunities and practical application in the fields of medicine and animal husbandry. In this study, a tandem repeat strategy was used to express three copies of the same pIGF-I3 protein in L. lactis. The activity of recombinant pIGF-I3 (rpIGF-I3) was further examined by a mouse model of dextran sulfate sodium (DSS)–induced colitis. In addition, the potential of recombinant L. lactis expressing pIGF-I3 to reduce inflammatory disease was evaluated. pIGF-I3 could be expressed in L. lactis by the detection of SDS–PAGE and Western blot. Experimental colitis was induced in BALB/c mice by administration of 5 % DSS in drinking water, and the clinical symptoms were observed in DSS-treated mice. Oral administration of recombinant L. lactis expressing pIGF-I3 improved the colonic architecture, and significantly reduced the increase of colonic damage score (P < 0.05). Furthermore, recombinant L. lactis expressing pIGF-I3 treatment significantly reduced serum DAO activity and colonic MPO level, and elevated colonic occludin level compared to the DSS group (P < 0.05). The pIGF-I3 expressed in L. lactis has good biological activity, and oral administration of recombinant L. lactis expressing pIGF-I3 attenuated the symptoms and development of DSS-induced colitis in mice. These suggested that L. lactis could be a potential host bacterium for production and delivery of IGF-I against intestinal diseases.

Long noncoding RNAs (lncRNAs) play crucial roles in various biological processes, and they are considered to be closely associated with the pathogenesis of intestinal diseases. However, the role and expression of lncRNAs in intestinal damage during weaning stress remain unknown. Herein, we investigated the expression profiles of jejunal tissue from weaning piglets at 4 and 7 d after weaning (groups W4 and W7, respectively) and from suckling piglets on the same days (groups S4 and S7, respectively). Genome-wide analysis of lncRNAs was also performed using RNA sequencing technology. A total of 1809 annotated lncRNAs and 1612 novel lncRNAs were obtained from the jejunum of piglets. In W4 vs. S4, a total of 331 lncRNAs showed significant differential expression, and a total of 163 significantly differentially expressed lncRNAs (DElncRNAs) was identified in W7 vs. S7. Biological analysis indicated that DElncRNAs were involved in intestinal diseases, inflammation, and immune functions, and were mainly enriched in the Jak-STAT signaling pathway, inflammatory bowel disease, T cell receptor signaling pathway, B cell receptor signaling pathway and intestinal immune network for IgA production. Moreover, we found that lnc_000884 and target gene KLF5 were significantly upregulated in the intestine of weaning piglets. The overexpression of lnc_000884 also significantly promoted the proliferation and depressed apoptosis of IPEC-J2 cells. This result suggested that lnc_000884 may contribute to repairing intestinal damage. Our study identified the characterization and expression profile of lncRNAs in the small intestine of weaning piglets and provided new insights into the molecular regulation of intestinal damage during weaning stress.

Zinc-L-selenomethionine (Zn-L-SeMet), a novel organic selenium (Se) source, shows great potential in alleviating oxidative stress. This study first evaluated the potential of Zn-L-SeMet to improve the health of weaned piglets and investigated underlying molecular mechanisms. In vivo, 240 weaned piglets were assigned to five dietary groups, namely, a control group (basal diet without Se) and four groups supplemented with Zn-L-SeMet (0.1, 0.2, 0.3, or 0.4 mg Se/kg in basal diet) for 42 days. In vitro, an oxidative stress model was established using hydrogen peroxide (H₂O₂) in porcine intestinal epithelial cells (IPEC-J2) to investigate the mechanisms of Zn-L-SeMet against oxidative damage. The results showed that Zn-L-SeMet improved growth performance, enhanced antioxidant and immune function, stimulated thyroid hormone secretion, and upregulated expression of selenoprotein genes. In vitro, Zn-L-SeMet reduced H₂O₂-induced apoptosis, promoted IPEC-J2 viability, and enhanced activities of antioxidant enzymes, while reducing lactate dehydrogenase release, malondialdehyde and reactive oxygen species levels. Furthermore, Zn-L-SeMet significantly increased the expression levels of Keap1, NQO1, HO-1, ARE, p-Nrf2, p-PI3K, and p-AKT, and protein ratio of p-Nrf2/Nrf2, PI3K/PI3K, and p-AKT/AKT compared to the H₂O₂ group (p < 0.05). In conclusion, Zn-L-SeMet improves health status with antioxidant potential in weaned piglets, and the mechanism is associated with activation of PI3K/AKT and Nrf2/Keap1 pathways.

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.