Keywords
weaning
microbiota
intercellular junctions
immunomodulation
probiotics
antioxidants
How to Cite
Funding data
-
Ministry of Education and Science of Ukraine
Grant numbers Project No. 0125U001550, 07-03-2025).
Abstract
The modulation of the intestinal barrier integrity in piglets during the early postnatal period is pivotal to the restriction of the propagation of enteric diseases agents, digestive efficiency, and performance. This review focuses on the primary morpho-functional changes occurring in the piglets’ intestine after birth, including the development of the physical, chemical, and immune barriers. Critical stages in the maturation of intercellular adhesion and its role in keeping epithelial integrity are revised in detail. Particular stress is laid on the regulation of local immunity, including macrophage and dendritic cell involvement, secretory IgA production, and antimicrobial peptide synthesis. The mechanisms of interaction between intestinal microbiota and the immune system are discussed in respect of the stability of microbial community and adaptive immunity regulation. The roles of beneficial bacteria, including Lactobacillus, Bifidobacterium, and Clostridia, in infection resistance and intestinal epithelium metabolism are analyzed. Special emphasis is placed on the impact of weaning on intestinal barrier integrity, given that weaning stress is often accompanied by dysbiosis, disturbed microbial composition, and inflammation. Current approaches to keeping intestinal barrier functioning are reviewed, including the use of probiotics, prebiotics, synbiotics, exogenous enzymes, and antioxidant strategies. The efficacy of biologically active compounds, including short-chain and medium-chain fatty acids, polyphenols, and trace elements that strengthen intercellular junctions, modulate immune responses, and control inflammation, is discussed. The role of immunomodulators that activate local immunity, stimulate IgA production, and enhance antimicrobial defense is also considered. This comprehensive literature review highlights the mechanisms of intestinal barrier development in piglets, emphasizing its significance for animal health. The described data can be used to develop new strategies for managing piglet health and optimization of nutrition during weaning.
References
Amatucci, L., Luise, D., Correa, F., Bosi, P., Trevisi, P. 2022. Importance of breed, parity and sow colostrum components on litter performance and health. Animals: an open access journal from MDPI, 12, 10, 1230. https://doi.org/10.3390/ani12101230
Arike, L., Hansson, G.C. 2016. The densely o-glycosylated muc2 mucin protects the intestine and provides food for the commensal bacteria. Journal of molecular biology, 428, 16, 3221–3229. https://doi.org/10.1016/j.jmb.2016.02.010
Azevedo, M.S.P., Zhang, W., Wen, K., Gonzalez, A.M., Saif, L.J., Yousef, A.E., Yuan, L. 2012. Lactobacillus acidophilus and Lactobacillus reuteri modulate cytokine responses in gnotobiotic pigs infected with human rotavirus. Beneficial Microbes, 3, 1, 33–42. https://doi.org/10.3920/BM2011.0041
Ballabh, P., Braun, A., Nedergaard, M. 2004. The blood–brain barrier: an overview: Structure, regulation, and clinical implications. Neurobiology of Disease, 16, 1, 1–13. https://doi.org/10.1016/J.NBD.2003.12.016
Bao, X. and Wu, J. 2021. Impact of food-derived bioactive peptides on gut function and health. Food research international, 147, 110485. https://doi.org/10.1016/j.foodres.2021.110485
Barea, R., Nieto, R., Vitari, F., Domeneghini, C., Aguilera, J.F. 2011. Effects of pig genotype (Iberian v. Landrace × Large White) on nutrient digestibility, relative organ weight and small intestine structure at two stages of growth. Animal: an international journal of animal bioscience, 5, 4, 547–557. https://doi.org/10.1017/S1751731110002181
Bemark, M., Pitcher, M.J., Dionisi, C., Spencer, J. 2024. Gut-associated lymphoid tissue: a microbiota-driven hub of B cell immunity. Trends in Immunology, 45, 3, 211. https://doi.org/10.1016/J.IT.2024.01.006
Blavi, L., Solà-Oriol, D., Llonch, P., López-Vergé, S., Martín-Orúe, S.M., Pérez, J.F. 2021. Management and feeding strategies in early life to increase piglet performance and welfare around weaning: a review. Animals: an open access journal from MDPI, 11, 2, 302. https://doi.org/10.3390/ani11020302
Bontempo, C., Gallo, L.P., Mattiacci, M., Valente, S., Astolfi, A., Conte, M., La Manna, G., Pasquinell, G., Gargiulo, M., Olivieri, F., Capri, M. 2026. Barrier breakdown in ageing and age-related diseases: The potential role of hierarchical epigenetic control of microRNAs on surfactant collectins, S100 alarmins and fibronectin. Ageing research reviews, 114, 103003. https://doi.org/10.1016/j.arr.2025.103003
Brandtzaeg, P., Kiyono, H., Pabst, R., Russell, M.W. 2008. Terminology: nomenclature of mucosa-associated lymphoid tissue. Mucosal immunology, 1, 1, 31–37. https://doi.org/10.1038/mi.2007.9
Brown, M.F., Leibowitz, B.J., Chen, D., He, K., Zou, F., Sobol, R.W., Beer-Stolz, D., Zhang, L., Yu, J. 2015. Loss of caspase-3 sensitizes colon cancer cells to genotoxic stress via RIP1-dependent necrosis. Cell death & disease, 6, 4, e1729. https://doi.org/10.1038/cddis.2015.104
Capurso, L. 2016. I probiotici [Probiotics]. Recenti progressi in medicina, 107, 6, 267–277. https://doi.org/10.1701/2296.24682
Casazza, R.L. and Lazear, H.M. 2019. Why Is IFN-λ Less Inflammatory? One IRF Decides. Immunity, 51, 3, 415–417. https://doi.org/10.1016/j.immuni.2019.08.019
Castillo Zuniga, J., Fresno Rueda, A.M., Samuel, R.S., St-Pierre, B., Levesque, C.L. 2024. Impact of Lactobacillus- and Bifidobacterium-based direct-fed microbials on the performance, intestinal morphology, and fecal bacterial populations of nursery pigs. Microorganisms, 12, 9, 1786. https://doi.org/10.3390/microorganisms12091786
Chang, S.Y., Lee, J.H., Oh, H.J., An, J.W., Song, D.C., Cho, H.A., Park, S.H., Jeon, K.H., Cho, S.Y., Kim, D.J., Kim, M.S., Cho, J.H. 2023. Effect of different ratios of phytogenic feed additives on growth performance, nutrient digestibility, intestinal barrier integrity, and immune response in weaned pigs challenged with a pathogenic Escherichia coli. Journal of animal science, 101, skad148. https://doi.org/10.1093/jas/skad148
Chen, H., Hu, H., Chen, D., Tang, J., Yu, B., Luo, J., He, J., Luo, Y., Yu, J., Mao, X. 2017. Dietary pectic oligosaccharide administration improves growth performance and immunity in weaned pigs infected by rotavirus. Journal of agricultural and food chemistry, 65, 14, 2923–2929. https://doi.org/10.1021/acs.jafc.7b00039
Chen, J., Xu, Y.-R., Kang, J.-X., Zhao, B.-C., Dai, X.-Y., Qiu, B.-H., Li, J.-L. 2022. Effects of alkaline mineral complex water supplementation on growth performance, inflammatory response, and intestinal barrier function in weaned piglets. Journal of Animal Science, 100, 10, skac251. https://doi.org/10.1093/jas/skac251
Chen, X., Chen, L., Jia, G., Zhao, H., Liu, G., Huang, Z. 2023. L-theanine improves intestinal barrier functions by increasing tight junction protein expression and attenuating inflammatory reaction in weaned piglets. Journal of Functional Foods, 100, 105400. https://doi.org/10.1016/j.jff.2022.105400
Chethan, G.E., Garkhal, J., Sircar, S., Malik, Y.P.S., Mukherjee, R., Sahoo, N.R., Agarwal, R.K., De, U.K. 2017. Immunomodulatory potential of β-glucan as supportive treatment in porcine rotavirus enteritis. Veterinary immunology and immunopathology, 191, 36–43. https://doi.org/10.1016/j.vetimm.2017.07.012
Chin, A.M., Hill, D.R., Aurora, M., Spence, J.R. 2017. Morphogenesis and maturation of the embryonic and postnatal intestine. Seminars in cell & developmental biology, 66, 81–93. https://doi.org/10.1016/j.semcdb.2017.01.011
Cui, Z., Wang, X., Hou, Z., Liao, S., Qi, M., Zha, A., Yang, Z., Zuo, G., Liao, P., Chen, Y., Tan, B. 2020. Low-protein diet supplemented with medium-chain fatty acid glycerides improves the growth performance and intestinal function in post-weaning piglets. Animals: an open access journal from MDPI, 10, 10, 1852. https://doi.org/10.3390/ani10101852
Cui, Z., Wang, X., Liao, S., Qi, M., Zha, A., Zuo, G., Liao, P., Chen, Y., Guo, C., Tan, B. 2022. Effects of medium-chain fatty acid glycerides on nutrient metabolism and energy utilization in weaned piglets. Frontiers in veterinary science, 9, 938888. https://doi.org/10.3389/fvets.2022.938888
Dahmer, P.L., Leubcke, G.E., Lerner ,A.B., Jones, C.K. 2020. Effects of medium-chain fatty acids as alternatives to ZnO or antibiotics in nursery pig diets. Translational Animal Science, 4, 3, 1–8. https://doi.org/10.1093/TAS/TXAA151
Dong, L., Li, H.M., Wang, S.N., Wan, T.L., Yu, L.H., Wang, H.R. 2021. Meishan neonatal piglets tend to have higher intestinal barrier function than crossbred neonatal piglets. Animal: an international journal of animal bioscience, 15, 1, 100037. https://doi.org/10.1016/j.animal.2020.100037
Du, Y., Li, H., Xu, W., Hu, X., Wu, T., Chen, J. 2023. Cell surface-associated protein elongation factor Tu interacts with fibronectin mediating the adhesion of Lactobacillus plantarum HC-2 to Penaeus vannamei intestinal epithelium and inhibiting the apoptosis induced by LPS and pathogen in Caco-2 cells. International journal of biological macromolecules, 224, 32–47. https://doi.org/10.1016/j.ijbiomac.2022.11.252
Dubreuil, J.D. 2017. Enterotoxigenic Escherichia coli targeting intestinal epithelial tight junctions: An effective way to alter the barrier integrity. Microbial Pathogenesis, 113, 129–134. https://doi.org/https://doi.org/10.1016/j.micpath.2017.10.037
Dzierva, L., dos Santos, M.C., de Almeida, L.M., da Rocha, C., Bassi, L.S., Muramatsu, K., Maiorka, A. 2023. Feed particle size and amylase supplementation in diets for nursery piglets: Digestibility and growth performance. Livestock Science, 271, 105211. https://doi.org/10.1016/j.livsci.2023.105211
Edison, L.K., Ragitha, V.M., Pradeep, N.S. 2022. Beta-glucanases in animal nutrition. In Microbial beta glucanases: molecular structure, functions and applications. 73–83. https://doi.org/10.1007/978-981-19-6466-4_5
Elefson, S.K., Lu, N., Chevalier, T., Dierking, S., Wang, D., Monegue, H.J., Matthews, J.C., Jang, Y.D., Chen, J., Rentfrow, G.K., Adedokun, S.A., Lindemann, M. D. 2021. Assessment of visceral organ growth in pigs from birth through 150 kg. Journal of animal science, 99, 9, skab249. https://doi.org/10.1093/jas/skab249
Erbs, G., Jakobsen, J.T., Schmidt, S.T., Christensen, D., Bailey, M., Jungersen, G. 2025. Retinoic acid-adjuvanted vaccine induces antigen-specific secretory IgA in the gut of newborn piglets. Vaccine, 46, 126672. https://doi.org/10.1016/j.vaccine.2024.126672
Ferret-Bernard, S. and Le Huërou-Luron, I. 2020. Development of the intestinal immune system in young pigs – role of the microbial environment. In The suckling and weaned piglet. Eds. S. Ferret-Bernard, I. Le Huërou-Luron, Wageningen Academic Publishers. 159–177. https://doi.org/10.3920/978-90-8686-894-0_6
Flannigan, K.L. and Denning, T.L. 2018. Segmented filamentous bacteria-induced immune responses: a balancing act between host protection and autoimmunity. Immunology, 154, 4, 537–546. https://doi.org/10.1111/IMM.12950
Fujita, H., Chiba, H., Yokozaki, H., Sakai, N., Sugimoto, K., Wada, T., Kojima, T., Yamashita, T., Sawada, N. 2006. Differential expression and subcellular localization of claudin-7, -8, -12, -13, and -15 along the mouse intestine. The journal of histochemistry and cytochemistry: official journal of the Histochemistry Society, 54, 8, 933–944. https://doi.org/10.1369/jhc.6A6944.2006
Ghazavi, F., Huysentruyt, J., De Coninck, J., Kourula, S., Martens, S., Hassanni, B., Wartewig, T., Divert, T., Roelandt, R., Popper, B., Hiergeist, A., Tougaard, P., Vanden Berghe, T., Joossens, M., Berx, G., Takahashi, N., Wahida, A., Vandenabeele, P. 2022. Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state. Proceedings of the National Academy of Sciences of the United States of America, 119, 6, e2024508119. https://doi.org/10.1073/pnas.2024508119
Greenwood-Van Meerveld, B., Johnson, A.C., Grundy, D. 2017. Gastrointestinal Physiology and Function. In Gastrointestinal Pharmacology. Eds. B. Greenwood-Van Meerveld, Handbook of Experimental Pharmacology, vol 239. Springer, Cham. https://doi.org/10.1007/164_2016_118
Grela, E.R., Świątkiewicz, M., Florek, M., Bąkowski, M., Skiba, G. 2021. Effect of inulin source and a probiotic supplement in pig diets on carcass traits, meat quality and fatty acid composition in finishing pigs. Animals: an open access journal from MDPI, 11, 8, 2438. https://doi.org/10.3390/ani11082438
Guidoni, P.B., Pasternak, J.A., Hamonic, G., MacPhee, D.J., Harding, J.C.S. 2021. Decreased tight junction protein intensity in the placenta of porcine reproductive and respiratory syndrome virus-2 infected fetuses. Placenta, 112, 153–161. https://doi.org/10.1016/j.placenta.2021.07.300
Gurunathan, S., Thangaraj, P., Kim, J.H. 2023. Postbiotics: functional food materials and therapeutic agents for cancer, diabetes, and inflammatory diseases. Foods, 13, 1, 89. https://doi.org/10.3390/foods13010089
Han, X., Hu, X., Jin, W., Liu, G. 2024. Dietary nutrition, intestinal microbiota dysbiosis and post-weaning diarrhea in piglets. Animal Nutrition, 17, 188–207. https://doi.org/10.1016/j.aninu.2023.12.010
Hanczakowska, E., Świątkiewicz, M., Natonek-Wiśniewska, M., Okoń, K. 2016. Medium chain fatty acids (MCFA) and/or probiotic Enterococcus faecium as a feed supplement for piglets. Livestock Science, 192, 1–7. https://doi.org/10.1016/J.LIVSCI.2016.08.002
Hartsock, A. and Nelson, W.J. 2008. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1778, 3, 660–669. https://doi.org/10.1016/j.bbamem.2007.07.012
He, Y., Liang, J., Liu, Y., Zhou, X., Peng, C., Long, C., Huang, P., Feng, J., Zhang, Z. 2023. Combined supplementation with Lactobacillus sp. and Bifidobacterium thermacidophilum isolated from Tibetan pigs improves growth performance, immunity, and microbiota composition in weaned piglets. Journal of animal science, 101, skad220. https://doi.org/10.1093/jas/skad220
Hedemann, M.S. and Knudsen, K.E.B. 2007. Resistant starch for weaning pigs – effect on concentration of short chain fatty acids in digesta and intestinal morphology. Livestock Science, 108, 1–3, 175–177. https://doi.org/10.1016/j.livsci.2007.01.045
Huang, S., Yu, Q., Xie, L., Ran, L., Wang, K., Yang, Y., Gan, L., Song, Z. 2021. Inhibitory effects of Lactobacillus plantarum metabolites on porcine epidemic diarrhea virus replication. Research in veterinary science, 139, 32–42. https://doi.org/10.1016/j.rvsc.2021.07.002
Hung, P.H.S., Thi Dung, H., Thao, L.D., Van Chao, N., Thi Hoa, N., Thi Hien, B., Mondal, A., Nsereko, V., Phung, L.D. 2025. Effects of Saccharomyces cerevisiae fermentation-derived postbiotics supplementation in sows and piglets' diet on intestinal morphology, and intestinal barrier function in weaned pigs in an intensive pig production system. Veterinary immunology and immunopathology, 283, 110934. https://doi.org/10.1016/j.vetimm.2025.110934
Inoue, R. and Tsukahara, T. 2021. Composition and physiological functions of the porcine colostrum. Animal science journal = Nihon chikusan Gakkaiho, 92, 1, e13618. https://doi.org/10.1111/asj.13618
Jackman, J.A., Boyd, R.D., Elrod, C.C. 2020. Medium-chain fatty acids and monoglycerides as feed additives for pig production: towards gut health improvement and feed pathogen mitigation. Journal of animal science and biotechnology, 11, 44. https://doi.org/10.1186/s40104-020-00446-1
Jørgensen, P.B., Eriksen, L.L., Fenton, T.M., Bailey, M., Agace, W.W., Mörbe, U.M. 2022. The porcine large intestine contains developmentally distinct submucosal lymphoid clusters and mucosal isolated lymphoid follicles. Developmental & Comparative Immunology, 131, 104375. https://doi.org/10.1016/j.dci.2022.104375
Kavanova, K., Kostovova, I., Moravkova, M., Kubasova, T., Crhanova, M. 2025. In vitro characterization of lactic acid bacteria and bifidobacteria from wild and domestic pigs: probiotic potential for post-weaning piglets. BMC microbiology, 25, 1, 8. https://doi.org/10.1186/s12866-024-03711-9
Kim, J.H., Ko, G.P., Son, K.H., Ku, B.H., Bang, M.A., Kang, M.J., Park, H.Y. 2022. Arazyme in combination with dietary carbohydrolases influences odor emission and gut microbiome in growing-finishing pigs. Science of The Total Environment, 848, 157735. https://doi.org/10.1016/j.scitotenv.2022.157735
Kolachala, V.L., Bajaj, R., Wang, L., Yan, Y., Ritzenthaler, J.D., Gewirtz, A.T., Roman, J., Merlin, D., Sitaraman, S.V. 2007. Epithelial-derived fibronectin expression, signaling, and function in intestinal inflammation. The Journal of biological chemistry, 282, 45, 32965–32973. https://doi.org/10.1074/jbc.m704388200
Konieczka, P., Ferenc, K., Jørgensen, J.N., Hansen, L.H.B., Zabielski, R., Olszewski, J., Gajewski, Z., Mazur-Kuśnirek, M., Szkopek, D., Szyryńska, N., Lipiński, K. 2023. Feeding Bacillus-based probiotics to gestating and lactating sows is an efficient method for improving immunity, gut functional status and biofilm formation by probiotic bacteria in piglets at weaning. Animal nutrition (Zhongguo xu mu shou yi xue hui), 13, 361–372. https://doi.org/10.1016/j.aninu.2023.03.003
Kovanda, L., Park, J., Park, S., Kim, K., Li, X., Liu, Y. 2023. Dietary butyrate and valerate glycerides impact diarrhea severity and immune response of weaned piglets under ETEC F4-ETEC F18 coinfection conditions. Journal of Animal Science, 101, skad401. https://doi.org/10.1093/jas/skad401
Kumar, D., Shepherd, F.K., Springer, N.L., Mwangi, W., Marthaler, D.G. 2022. Rotavirus infection in swine: genotypic diversity, immune responses, and role of gut microbiome in rotavirus immunity. Pathogens (Basel, Switzerland), 11, 10, 1078. https://doi.org/10.3390/pathogens11101078
Kurz, A. and Seifert, J. 2021. Factors influencing proteolysis and protein utilization in the intestine of pigs: a review. Animals: an open access journal from MDPI, 11, 12, 3551. https://doi.org/10.3390/ani11123551
Kuthyar, S., Diaz, J., Avalos-Villatoro, F., Maltecca, C., Tiezzi, F., Dunn, R.R., Reese, A.T. 2023. Domestication shapes the pig gut microbiome and immune traits from the scale of lineage to population. Journal of Evolutionary Biology, 36, 12, 1695–1711. https://doi.org/10.1111/jeb.14227
Lallès J.P., Boudry G., Favier C., Le Floc’h N., Luron I., Montagne L., Oswaldb I.P., Piéb S., Piela C., Sève B. 2004. Gut function and dysfunction in young pigs: physiology. Animal Research, 53, 4, 301–316. https://doi.org/10.1051/animres:2004018
Lee, J.J., Choi, S.H., Cho, J.H., Choe, J., Kang, J., Kim, S., Park, S., Kyoung, H., Seo, D., Cho, J.Y., Park, I.H., Oh, S., Kim, H.B., Song, M. 2019. Effects of dietary carbohydrases on productive performance and immune responses of lactating sows and their piglets. Journal of animal science and technology, 61, 6, 359–365. https://doi.org/10.5187/jast.2019.61.6.359
Leong, Y.Y. and Tong, L. 2015. Barrier Function in the Ocular Surface: From Conventional Paradigms to New Opportunities. The Ocular Surface, 13, 2, 103–109. https://doi.org/10.1016/j.jtos.2014.10.003
Lewis A.J. and Southern L.L. 2000. Anatomy of the digestive system and nutritional physiology. In Swine nutrition. Eds. A.J. Lewis, 2nd edition, CRC Press. 51–84.
Li, H., Zhang, Y., Xi, J., Wang, C., Yi, D., Wu, T., Wang, L., Zhao, D., Hou, Y. 2023a. Dietary supplementation with mono-lactate glyceride enhances intestinal function of weaned piglets. Animals: an open access journal from MDPI, 13, 8, 1303. https://doi.org/10.3390/ani13081303
Li, J., Feng, S., Wang, Z., He, J., Zhang, Z., Zou, H., Wu, Z., Liu, X., Wei, H., Tao, S. 2023b. Limosilactobacillus mucosae-derived extracellular vesicles modulates macrophage phenotype and orchestrates gut homeostasis in a diarrheal piglet model. NPJ biofilms and microbiomes, 9, 1, 33. https://doi.org/10.1038/s41522-023-00403-6
Li, L., Wang, H., Dong, S., Ma, Y. 2023c. Supplementation with alpha-glycerol monolaurate during late gestation and lactation enhances sow performance, ameliorates milk composition, and improves growth of suckling piglets. Journal of Animal Science and Biotechnology, 14, 1, 47. https://doi.org/10.1186/S40104-023-00848-X
Li, L., Wang, H., Zhang, N., Zhang, T., Ma, Y. 2022. Effects of α-glycerol monolaurate on intestinal morphology, nutrient digestibility, serum profiles, and gut microbiota in weaned piglets. Journal of Animal Science, 100, 3, skac046. https://doi.org/10.1093/jas/skac046
Li, M., Monaco, M.H., Wang, M., Comstock, S.S., Kuhlenschmidt, T.B., Fahey, G.C., Jr Miller, M.J., Kuhlenschmidt, M.S., Donovan, S.M. 2014. Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota. The ISME journal, 8, 8, 1609–1620. https://doi.org/10.1038/ismej.2014.10
Liang, B. and Xing, D. 2023. The Current and Future Perspectives of Postbiotics. Probiotics and antimicrobial proteins, 15, 6, 1626–1643. https://doi.org/10.1007/s12602-023-10045-x
Lim, J.A., Cha, J., Choi, S., Kim, J.H., Kim, D. 2023. Early Colonization of the Intestinal Microbiome of Neonatal Piglets Is Influenced by the Maternal Microbiome. Animals: an open access journal from MDPI, 13, 21, 3378. https://doi.org/10.3390/ani13213378/s1
Liu, F., Li, G., Wen, K., Wu, S., Zhang, Y., Bui, T., Yang, X., Kocher, J., Sun, J., Jortner, B., Yuan, L. 2013. Lactobacillus rhamnosus GG on rotavirus-induced injury of ileal epithelium in gnotobiotic pigs. Journal of pediatric gastroenterology and nutrition, 57, 6, 750–758. https://doi.org/10.1097/MPG.0b013e3182a356e1
Liu, F., Li, J., Ni, H., Azad, M.A.K., Mo, K., Yin, Y. 2023. The effects of phytase and non-starch polysaccharide-hydrolyzing enzymes on trace element deposition, intestinal morphology, and cecal microbiota of growing-finishing pigs. Animals: an open access journal from MDPI, 13, 4, 549. https://doi.org/10.3390/ani13040549
Liu, W., La, A.T.Z., Evans, A., Gao, S., Yu, Z., Bu, D., Ma, L. 2021. Supplementation with sodium butyrate improves growth and antioxidant function in dairy calves before weaning. Journal of animal science and biotechnology, 12, 1, 2. https://doi.org/10.1186/s40104-020-00521-7
Long, S., Hu, J., Mahfuz, S., Ma, H., Piao, X. 2021. Effects of dietary supplementation of compound enzymes on performance, nutrient digestibility, serum antioxidant status, immunoglobulins, intestinal morphology and microbiota community in weaned pigs. Archives of Animal Nutrition, 75, 1, 31–47. https://doi.org/10.1080/1745039X.2020.1852008
Maciag, S.S., Bellaver, F.V., Bombassaro, G., Haach, V., Morés, M.A.Z., Baron, L.F., Coldebella, A., Bastos, A.P. 2022. On the influence of the source of porcine colostrum in the development of early immune ontogeny in piglets. Scientific reports, 12, 1, 15630. https://doi.org/10.1038/s41598-022-20082-1
Mao, X., Gu, C., Hu, H., Tang, J., Chen, D., Yu, B., He, J., Yu, J., Luo, J., Tian, G. 2016. Dietary lactobacillus rhamnosus gg supplementation improves the mucosal barrier function in the intestine of weaned piglets challenged by porcine rotavirus. PloS one, 11, 1, e0146312. https://doi.org/10.1371/journal.pone.0146312
Mao, X., Xiao, X., Chen, D., Yu, B., He, J., Chen, H., Xiao, X., Luo, J., Luo, Y., Tian, G., Wang, J. 2017. Dietary apple pectic oligosaccharide improves gut barrier function of rotavirus-challenged weaned pigs by increasing antioxidant capacity of enterocytes. Oncotarget, 8, 54, 92420–92430. https://doi.org/10.18632/oncotarget.21367
Mao, Y., Yang, Q., Liu, J., Fu, Y., Zhou, S., Liu, J., Ying, L., Li, Y. 2024. Quercetin increases growth performance and decreases incidence of diarrhea and mechanism of action in weaned piglets. Oxidative medicine and cellular longevity, 2024, 5632260. https://doi.org/10.1155/2024/5632260
Marion J., Biernat M., Thomas F., Savary G., Le Breton Y., Zabielski R., Le Huërou-Luron I., Le Dividich J. 2002. Small intestine growth and morphometry in piglets weaned at 7 days of age. effects of level of energy intake. Reproduction, nutrition, development, 42, 4, 339–354. https://doi.org/10.1051/rnd:2002030
Masiuk, D.M. and Nedzvetsky, V.S. 2024a. Muramyl peptide blend ameliorates intestinal inflammation and barrier integrity in cell culture model. Gastroenterologìa, 58, 3, 179–185. https://doi.org/10.22141/2308-2097.58.3.2024.621
Masiuk, D.M., Kokariev, A.V., Buzoianu, S.G., Firth, A.M., Nedzvetsky, V.S. 2024b. An isotonic protein solution favorably modulated the porcine intestinal immune response and cellular adhesion markers and reduced PEDV shedding in vivo. Veterinary Immunology and Immunopathology, 271, 110753. https://doi.org/10.1016/j.vetimm.2024.110753
Masiuk, D.M., Nedzvetsky, V.S., Baydas, G. 2025. Muramyl peptide blend ameliorates intestinal inflammation and barrier integrity in Caco-2 cells. Karbala International Journal of Modern Science, 11, 1, Article 7. https://doi.org/10.33640/2405-609X.3389
Masiuk, D.M., Nedzvetsky, V.S., Kokariev, A.V. 2023a. Features of the functioning of the natural defense mechanisms of piglets under the influence of immunotropic substances. Scientific Messenger of Lviv National University of Veterinary Medicine and Biotechnologies. Series: Veterinary sciences, 25, 112, 181–192. https://doi.org/10.32718/nvlvet11229
Masiuk, D.M., Romanenko, E.R., Herrman, B., Nedzvetsky, V.S. 2023b. Fibronectin measurement as a potential molecular marker for barrier function assessment of piglet intestine. Theoretical and Applied Veterinary Medicine, 11, 2, 3–8. https://doi.org/10.32819/2023.11006
Mesev, E.V., LeDesma, R.A., Ploss, A. 2019. Decoding type I and III interferon signalling during viral infection. Nature Microbiology, 4, 6, 914–924. https://doi.org/10.1038/s41564-019-0421-x
Michael, H., Paim, F. C., Langel, S.N., Miyazaki, A., Fischer, D.D., Chepngeno, J., Amimo, J., Deblais, L., Rajashekara, G., Saif, L.J., Vlasova, A.N. 2021. Escherichia coli nissle 1917 enhances innate and adaptive immune responses in a ciprofloxacin-treated defined-microbiota piglet model of human rotavirus infection. mSphere, 6, 2, e00074-21. https://doi.org/10.1128/mSphere.00074-21
Moita, V.H.C. and Kim, S.W. 2022. Nutritional and functional roles of phytase and xylanase enhancing the intestinal health and growth of nursery pigs and broiler chickens. Animals: an open access journal from MDPI, 12, 23, 3322. https://doi.org/10.3390/ani12233322
Mörbe, U.M., Jørgensen, P.B., Fenton, T.M., von Burg, N., Riis, L.B., Spencer, J., Agace, W.W. 2021. Human gut-associated lymphoid tissues (GALT); diversity, structure, and function. Mucosal Immunology, 14, 4, 793-802. https://doi.org/10.1038/s41385-021-00389-4
Mowat, A.M. and Agace, W.W. 2014. Regional specialization within the intestinal immune system. Nature reviews, Immunology, 14, 10, 667–685. https://doi.org/10.1038/nri3738
Orengo, J., Hernández, F., Martínez-Miró, S., Sánchez, C.J., Peres Rubio, C., Madrid, J. 2021. Effects of commercial antioxidants in feed on growth performance and oxidative stress status of weaned piglets. Animals: an open access journal from MDPI, 11, 2, 266. https://doi.org/10.3390/ani11020266
Pang, J., Liu, Y., Kang, L., Ye, H., Zang, J., Wang, J., Han, D. 2022. Bifidobacterium animalis promotes the growth of weaning piglets by improving intestinal development, enhancing antioxidant capacity, and modulating gut microbiota. Applied and environmental microbiology, 88, 22, e0129622. https://doi.org/10.1128/aem.01296-22
Pereira, W.A., Franco, S.M., Reis, I.L., Mendonça, C.M.N., Piazentin, A.C.M., Azevedo, P.O.S., Tse, M.L.P., De Martinis, E.C.P., Gierus, M., Oliveira, R.P.S. 2022. Beneficial effects of probiotics on the pig production cycle: An overview of clinical impacts and performance. Veterinary microbiology, 269, 109431. https://doi.org/10.1016/j.vetmic.2022.109431
Pistol, G.C., Pertea, A.M., Taranu, I. 2023. The use of fruit and vegetable by-products as enhancers of health status of piglets after weaning: the role of bioactive compounds from apple and carrot industrial wastes. Veterinary sciences, 11, 1, 15. https://doi.org/10.3390/vetsci11010015
Rao, Z.X., Tokach, M.D., Woodworth, J.C., DeRouchey, J.M., Goodband, R.D., Gebhardt, J.T. 2023. Effects of various feed additives on finishing pig growth performance and carcass characteristics: a review. Animals: an open access journal from MDPI, 13, 2, 200. https://doi.org/10.3390/ani13020200
Raskova Kafkova, L., Brokesova, D., Krupka, M., Stehlikova, Z., Dvorak, J., Coufal, S., Fajstova, A., Srutkova, D., Stepanova, K., Hermanova, P., Stepankova, R., Uberall, I., Skarda, J., Novak, Z., Vannucci, L., Tlaskalova-Hogenova, H., Jiraskova Zakostelska, Z., Sinkora, M., Mestecky, J. Raska, M. 2021. Secretory IgA N-glycans contribute to the protection against E. coli O55 infection of germ-free piglets. Mucosal immunology, 14, 2, 511–522. https://doi.org/10.1038/s41385-020-00345-8
Rick, J.W., Chandra, A., Dalle, Ore, C., Nguyen, A.T., Yagnik, G., Aghi, M.K. 2019. Fibronectin in malignancy: Cancer-specific alterations, protumoral effects, and therapeutic implications. Seminars in oncology, 46, 3, 284–290. https://doi.org/10.1053/j.seminoncol.2019.08.002
Rigo-Adrover, M.D.M., van Limpt, K., Knipping, K., Garssen, J., Knol, J., Costabile, A., Franch, À., Castell, M., Pérez-Cano, F.J. 2018. Preventive effect of a synbiotic combination of galacto- and fructooligosaccharides mixture with bifidobacterium breve m-16v in a model of multiple rotavirus infections. Frontiers in immunology, 9, 1318. https://doi.org/10.3389/fimmu.2018.01318
Ringseis, R. and Eder, K. 2022. Heat stress in pigs and broilers: role of gut dysbiosis in the impairment of the gut-liver axis and restoration of these effects by probiotics, prebiotics and synbiotics. Journal of animal science and biotechnology, 13, 1, 126. https://doi.org/10.1186/s40104-022-00783-3
Saha, S., Namai, F., Nishiyama, K., Villena, J., Kitazawa, H. 2024. Role of immunomodulatory probiotics in alleviating bacterial diarrhea in piglets: a systematic review. Journal of animal science and biotechnology, 15, 1, 112. https://doi.org/10.1186/s40104-024-01070-z
Schäfer, A., Franzoni, G., Netherton, C.L., Hartmann, L., Blome, S., Blohm, U. 2022. Adaptive cellular immunity against African Swine Fever virus Infections. Pathogens (Basel, Switzerland), 11, 2, 274. https://doi.org/10.3390/pathogens11020274
Shatalov, S.A. and Kirici, M. 2024. PCR method application to assess the molecular markers of intestinal barrier integrity in farming broilers. Theoretical and Applied Veterinary Medicine, 12, 4, 31-36. https://doi.org/10.32819/2024.12020
Słupecka-Ziemilska, M., Pierzynowski, S.G., Szczurek, P., Pierzynowska, K., Wychowański, P., Seklecka, B., Koperski, M., Starzyńska, A., Szkopek, D., Donaldson, J., Andrzejewski, K., Woliński, J. 2022. Milk formula enriched with sodium butyrate influences small intestine contractility in neonatal pigs. Nutrients, 14, 20, 4301. https://doi.org/10.3390/nu14204301
Swanson, K.S., Gibson, G.R., Hutkins, R., Reimer, R.A., Reid, G., Verbeke, K., Scott, K.P., Holscher, H.D., Azad, M.B., Delzenne, N.M., Sanders, M.E. 2020. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nature reviews. Gastroenterology & hepatology, 17, 11, 687–701. https://doi.org/10.1038/s41575-020-0344-2
Tadesse, S., Corner, G., Dhima, E., Houston, M., Guha, C., Augenlicht, L., Velcich, A. 2017. MUC2 mucin deficiency alters inflammatory and metabolic pathways in the mouse intestinal mucosa. Oncotarget, 8, 42, 71456–71470. https://doi.org/10.18632/oncotarget.16886
Tang, W., Ni, Z., Wei, Y., Hou, K., Valencak, T.G., Wang, H. 2024. Extracellular vesicles of Bacteroides uniformis induce M1 macrophage polarization and aggravate gut inflammation during weaning. Mucosal Immunology, 17, 5, 793–809. https://doi.org/10.1016/J.MUCIMM.2024.05.004
Thomas, L.L., Woodworth, J.C., Tokach, M.D., Dritz, S.S., DeRouchey, J.M., Goodband, R.D., Williams, H.E., Hartman, A.R., Mellick, D.J., McKilligan, D.M., Jones, A.M. 2020. Evaluation of different blends of medium-chain fatty acids, lactic acid, and monolaurin on nursery pig growth performance. Translational animal science, 4, 2, txaa024. https://doi.org/10.1093/tas/txaa024
Tonetti, F.R., Eguileor, A., Llorente, C. 2024. Goblet cells: guardians of gut immunity and their role in gastrointestinal diseases. eGastroenterology, 2, 3, e100098. https://doi.org/10.1136/egastro-2024-100098
Valente Junior, D.T., Genova, J.L., Kim, S.W., Saraiva, A., Rocha, G.C. 2024. Carbohydrases and phytase in poultry and pig nutrition: a review beyond the nutrients and energy matrix. Animals: an open access journal from MDPI, 14, 2, 226. https://doi.org/10.3390/ani14020226
Van der Weken, H., Sanz Garcia, R., Sanders, N.N., Cox, E., Devriendt, B. 2021. Antibody-mediated targeting of antigens to intestinal aminopeptidase n elicits gut iga responses in pigs. Frontiers in Immunology, 12, 753371. https://doi.org/10.3389/fimmu.2021.753371
Van Winkle, J.A., Constant, D.A., Li, L., Nice, T.J. 2020. Selective interferon responses of intestinal epithelial cells minimize tumor necrosis factor alpha cytotoxicity. Journal of virology, 94, 21, e00603-20. https://doi.org/10.1128/JVI.00603-20
Wang, J., Zeng, L., Tan, B., Li, G., Huang, B., Xiong, X., Li, F., Kong, X., Liu, G., Yin, Y. 2016. Developmental changes in intercellular junctions and Kv channels in the intestine of piglets during the suckling and post-weaning periods. Journal of animal science and biotechnology, 7, 4. https://doi.org/10.1186/s40104-016-0063-2
Wang, M., Ren, Y., Guo, X., Ye, Y., Zhu, H., Zhang, J., Huang, Z., Yu, K. 2024. Postbiotics from Lactobacillus delbrueckii alleviate intestinal inflammation by promoting the expansion of intestinal stem cells in s. typhimurium-induced mice. Foods (Basel, Switzerland), 13, 6, 874. https://doi.org/10.3390/foods13060874
Wang, M., Yang, C., Wang, Q.Y., Li, J.Z., Li, Y.L., Ding, X.Q., Yin, J., Yang, H.S., Yin, Y.L. 2020. The growth performance, intestinal digestive and absorptive capabilities in piglets with different lengths of small intestines. Animal: an international journal of animal bioscience, 14, 6, 1196–1203. https://doi.org/10.1017/S175173111900288X
Wei, K., Yang, X., Zhao, H., Chen, H., Bei, W. 2023. Effects of combined application of benzoic acid and 1-monolaurin on growth performance, nutrient digestibility, gut microbiome and inflammatory factor levels in weaned piglets. Porcine health management, 9, 1, 46. https://doi.org/10.1186/s40813-023-00339-5
Wen, C., van Dixhoorn, I., Schokker, D., Woelders, H., Stockhofe-Zurwieden, N., Rebel, J.M.J., Smidt, H. 2021. Environmentally enriched housing conditions affect pig welfare, immune system and gut microbiota in early life. Animal Microbiome, 3, 1, 1–18. https://doi.org/10.1186/S42523-021-00115-2
Wenk, C. 2001. The role of dietary fibre in the digestive physiology of the pig. Animal Feed Science and Technology, 90, 1–2, 21–33. https://doi.org/10.1016/S0377-8401(01)00194-8
Weström, B., Arévalo Sureda, E., Pierzynowska, K., Pierzynowski, S.G., Pérez-Cano, F.J. 2020. The immature gut barrier and its importance in establishing immunity in newborn mammals. Frontiers in immunology, 11, 1153. https://doi.org/10.3389/fimmu.2020.01153
Wiarda, J.E., Loving, C.L. 2022. Intraepithelial lymphocytes in the pig intestine: T cell and innate lymphoid cell contributions to intestinal barrier immunity. Frontiers in immunology, 13, 1048708. https://doi.org/10.3389/fimmu.2022.1048708
Wu, S., Wang, L., Cui, B., Wen, X., Jiang, Z., Hu, S. 2023. Effects of vitamin a on growth performance, antioxidants, gut inflammation, and microbes in weaned piglets. Antioxidants, 12, 12, 2049. https://doi.org/10.3390/antiox12122049
Xia, T., Yang, H., Guo, Y., Guo, T., Xin, L., Jiang, Y., Cui, W., Zhou, H., Qiao, X., Wang, X., Li, J., Shan, Z., Tang, L., Wang, L., Li, Y. 2022. Human dendritic cell targeting peptide can be targeted to porcine dendritic cells to improve antigen capture efficiency to stimulate stronger immune response. Frontiers in immunology, 13, 950597. https://doi.org/10.3389/fimmu.2022.950597
Yang, H.S., Wu, F., Long, L.N., Li, T.J., Xiong, X., Liao, P., Liu, H.N., Yin, Y.L. 2016. Effects of yeast products on the intestinal morphology, barrier function, cytokine expression, and antioxidant system of weaned piglets. Journal of Zhejiang University. Science. B, 17, 10, 752–762. https://doi.org/10.1631/jzus.B1500192
Yang, H., Fan, X., Mao, X., Yu, B., He, J., Yan, H., Wang, J. 2024. The protective role of prebiotics and probiotics on diarrhea and gut damage in the rotavirus-infected piglets. Journal of animal science and biotechnology, 15, 1, 61. https://doi.org/10.1186/s40104-024-01018-3
Yang, S., Liu, G., Savelkoul, H.F.J., Jansen, C.A., Li, B. 2023. Mini-review: microbiota have potential to prevent PEDV infection by improved intestinal barrier. Frontiers in immunology, 14, 1230937. https://doi.org/10.3389/fimmu.2023.1230937
Yang, S., Yang, N., Huang, X., Li, Y., Liu, G., Jansen, C.A., Savelkoul, H.F.J., Liu, G. 2022. Pigs' intestinal barrier function is more refined with aging. Developmental and comparative immunology, 136, 104512. https://doi.org/10.1016/j.dci.2022.104512
Yasui, H., Kiyoshima, J., Ushijima, H. 1995. Passive protection against rotavirus-induced diarrhea of mouse pups born to and nursed by dams fed Bifidobacterium breve YIT4064. The Journal of infectious diseases, 172, 2, 403–409. https://doi.org/10.1093/infdis/172.2.403
Ye, L., Schnepf, D., Staeheli, P. 2019. Interferon-λ orchestrates innate and adaptive mucosal immune responses. Nature reviews. Immunology, 19, 10, 614–625. https://doi.org/10.1038/s41577-019-0182-z
Yin, L., Li, J., Zhang, Y., Yang, Q., Yang, C., Yi, Z., Yin, Y., Wang, Q., Li, J., Ding, N., Zhang, Z., Yang, H., Yin, Y. 2022. Changes in progenitors and differentiated epithelial cells of neonatal piglets. Animal nutrition, 8, 1, 265–276. https://doi.org/10.1016/j.aninu.2021.10.008
You, S., Ma, Y., Yan, B., Pei, W., Wu, Q., Ding, C., Huang, C. 2022. The promotion mechanism of prebiotics for probiotics: A review. Frontiers in nutrition, 9, 1000517. https://doi.org/10.3389/fnut.2022.1000517
Yu, J., Zheng, C., Zheng, J., Duan, G., Guo, Q., Zhang, P., Wan, M., Duan, Y. 2022. Development of intestinal injury and restoration of weaned piglets under chronic immune stress. Antioxidants, 11, 11, 2215. https://doi.org/10.3390/antiox11112215
Yuan, C., Li, Y., Zhang, E., Jin, Y., Yang, Q. 2021. The mechanism of pedv-carrying CD3+ T cells migrate into the intestinal mucosa of neonatal piglets. Viruses, 13, 3, 469. https://doi.org/10.3390/v13030469
Zakariah, M., Molele, R.A., Mahdy, M.A.A., Ibrahim, M.I.A., McGaw, L.J. 2022. Regulation of spermatogenic cell apoptosis by the pro-apoptotic proteins in the testicular tissues of mammalian and avian species. Animal Reproduction Science, 247, 107158. https://doi.org/10.1016/j.anireprosci.2022.107158
Zhang, C., Zhan, K.F., Chen, F.J., Chen, Y.H., Yang, X., Cai, Z.H., Jiang, Y.B., Wang, X.B., Zhang, G.P., Wang, F.Y. 2022. Deoxynivalenol triggers porcine intestinal tight junction disorder: Insights from mitochondrial dynamics and mitophagy. Ecotoxicology and environmental safety, 248, 114291. https://doi.org/10.1016/j.ecoenv.2022.114291
Zhang, H., Li, Y., Wang, T. 2015. Antioxidant capacity and concentration of redox-active trace mineral in fully weaned intra-uterine growth retardation piglets. Journal of animal science and biotechnology, 6, 48. https://doi.org/10.1186/s40104-015-0047-7
Zhang, J., Chen, Y., Guo, X., Li, X., Zhang, R., Wang, M., Zhu, W., Yu, K. 2024. The gut microbial metabolite indole-3-aldehyde alleviates impaired intestinal development by promoting intestinal stem cell expansion in weaned piglets. Journal of animal science and biotechnology, 15, 1, 150. https://doi.org/10.1186/s40104-024-01111-7
Zhao, Z., Xu, S., Zhang, W., Wu, D., Yang, G. 2022. Probiotic Escherichia coli NISSLE 1917 for inflammatory bowel disease applications. Food & Function, 13, 11, 5914–5924. https://doi.org/10.1039/d2fo00226d
Zheng, X., Wang, Y., Zhou, X., Deng, T., Zhao, Y., Fu, Z., Wei, Y., Ma, W., Zhang, S., Guan, W., Chen, F. 2024. Plant essential oils combined with organic acids restored lipopolysaccharide-induced leaky intestine via gut microbial modulation in weaned piglets. Animal nutrition, 18, 419–432. https://doi.org/10.1016/j.aninu.2024.04.020
Zhou, W., Yang, Z., Han, J., Chen, X., Zou, T., You, J., Chen, J. 2024. An updated review of emerging sources of selenium in weaned piglet nutrition. Animals: an open access journal from MDPI, 14, 17, 2599. https://doi.org/10.3390/ani14172599
Zhu, Q., Wang, Y., Liu, Y., Yu, B., He, J., Zheng, P., Mao, X., Huang, Z., Luo, J., Luo, Y., Yan, H., Yu, J. 2022. Effects of a novel protease on growth performance, nutrient digestibility and intestinal health in weaned piglets. Animals: an open access journal from MDPI, 12, 20, 2803. https://doi.org/10.3390/ani12202803
Zollinger, A.J., Smith, M.L. 2017. Fibronectin, the extracellular glue. Matrix biology: journal of the International Society for Matrix Biology, 60-61, 27–37. https://doi.org/10.1016/j.matbio.2016.07.011
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