Effects Of Lactobacillus On Intestinal Microecology And Oral Immunity

Probiotics are beneficial to the host,such as improving the host gut microflora,controlling intestinal infections and enhancing immunity.Oral vaccine can induce an effective mucosal immune response in intestine.However,both probiotics and vaccines have the problem of inactivation due to acid and enzyme environment of the gastrointestinal tract when they are orally administered.Although antigenic proteins can be effectively delivered to the intestine,antigenic proteins,as hydrophilic macromolecules,are difficult to pass through the tight junctions of the intestinal epithelium,which greatly limiting the immunization effects of oral vaccines.When the antigens are carried on the nanoparticles,they can be easily uptaken by antigen presenting cells and further transported to lymphoid organs,which is favorable for enhancing immunity.Microencapsulation technology can effectively overcome the inactivation of probiotics and antigen proteins in the gastrointestinal tract.Alginate microcapsules are suitable for oral delivery carriers because sodium alginate microcapsules not only have good biocompatibility and biodegradability,but also show excellent pH-sensitive release properties.In this paper,probiotics and antigen are embedded in alginate microcapsules,which play a good role in isolation and protection,to achieve better efficacy when reaching the intestine.Firstly,the preparation parameters of calcium alginate microcapsules were optimized by orthogonal design.The microcapsules containing Lactobacillus acidophilus and OVA-loaded nanospheres(OVA-NPs)were fabricated under the optimal conditions.The effects of different content of Lactobacillus acidophilus of microcapsules were investigated.The microcapsules were characterized,their release profiles in simulated gastrointestinal environment and their distributions in vivo were studied.Nanoparticles were prepared by nano-precipitation method,and OVA were loaded on the surface of nanospheres,which were furtuer encapsulated into the alginate microcapsules.The results showed that the microcapsules with dianeters of about 30 μm spherical shape and better dispersibility,which is suitable for oral delivery.Next,we studied the immunomodulatory effects of probiotics on the intestinal microenvironment before and after encapsulating into microcapsules.The results showed that Lactobacillus acidophilus-loaded microcapsules not only increased the food intake of mice,but also greatly promoted the proliferation of mice,intestinal epithelial cells and the transformation of splenic lymphocytes,enhanced phagocytic capacity of spleen macrophages,humoral immunity and lymphocyte differentiation in peripheral blood T lymphocyte subsets.Finally,the immune effect of oral administration of OVA-NPs-loaded microcapsules before and after the regulation of gut microenvironment was studied.The results suggested that the regulation of intestinal microenvironment is helpful for improving oral immunity.Compared with the control group,Lactobacillus with microcapsules containing OVA-NPs significantly promoted mucosal IgA antibody production and intestinal epithelial cells proliferation,enhanced the expression of chemokine CCL2 and intestinal tissue surface molecules CD11c as well as co-stimulatory molecules CD86.In summary,Lactobacillus can effectively improve intestinal micro-ecological environment and have a positive effect on oral immunity.