Immune regulation of intestinal probiotics

The gastrointestinal microbial ecosystem is the most complex and largest micro-ecological system in humans and animals. It is estimated that there are more than 400 bacterial species in the adult intestine [1]. Animals start from birth, these bacteria enter the gastrointestinal tract, and in different parts, the number and types of bacteria are different. With age, nutritional changes and other factors, the gastrointestinal flora occurs differently. Because of this change, the gastrointestinal flora itself and the body are always in a dynamic equilibrium. The balance and stability of the intestinal microflora have an important effect on the physiological functions of the body, and have a profound impact on the health of its host. . In general, these bacterial flora can be roughly divided into beneficial bacteria, harmful bacteria, and beneficial bacteria. The number of beneficial bacteria and harmful bacteria within the normal ratio range and existing in the normal ecological site will not cause disease. Belongs to the normal flora. Intestinal probiotics mainly include Bifidobacterium, Lactobacillus, Bacillus, and Clostridium butyricum [2]. Intestinal probiotics can stabilize the microenvironment through non-immunological regulation, that is, through the in vivo colonization, adhesion, and competition occupying position to improve the endogenous host defense mechanism; in addition to this, the probiotics can improve the body's humoral immunity And cellular immune levels to improve the body's immune defense function.

1. Colonization, adhesion, and competition in place

Probiotics adhere to the surface of intestinal epithelial cells and then settle in the human gastrointestinal tract, which is considered as a necessary condition for probiotics to exert their physiological functions. When the animal is born, the intestinal tract is sterile, but shortly after birth, bacteria are gradually colonized by the newborn from the outside environment in a certain time sequence, becoming a permanent flora, with specific bacteria in specific parts of the intestinal mucosa. Adhesion. Adhesion is the first step in colonization, which enables probiotics to expand the flora. The adhesion of probiotics reduced the invasion of pathogenic microorganisms. Bernet et al. [3] reported that L. acidophilus can inhibit the adhesion of the pathogenic bacteria Escherichia coli and Salmonella typhimurium to the Caco-2 cell line, and this inhibitory effect is dose-dependent. The acidophilus can inhibit the entry of E. coli, S. typhimurium and Yersinia pseudotuberculosis into Caco-2 cells. Other reports indicate that similar results were obtained with two different Bifidobacterium strains (B. breve and B. infantis) [4]. It has been experimentally observed that E. bifidum can secrete a protein that prevents E. coli from binding to receptors on the intestinal mucosa and inhibits the adhesion of E. coli [5]. Some people also speculate that the competition between lactic acid bacteria and pathogenic bacteria adhesion to the intestinal mucosa is due to the effects of extracellular fluids. Studies have shown that extracellular polyunsaturated fatty acids have an important influence on the adhesion of lactic acid bacteria to intestinal epithelial cells [6][7]. In short, probiotics and the intestinal mucosa together constitute a protective barrier that prevents the invasion of bacteria, viruses, and food antigens. It also stimulates the immune organs of the intestines and exerts stronger immune functions. By colonizing mucosal surfaces, including protons adsorbed on surface and membrane receptors, probiotics degrade viscous proteins and use this endogenous nutrients to maintain a stable quantity, which allows for better metabolic and immunomodulatory effects. Adhesion of probiotics interacts with the mucosal surface, which can effectively stimulate the immune response and repel pathogenic bacteria from the intestinal epithelium through competitive repulsion.

2, humoral immunity

The basic feature of humoral immunity is the stimulation of the production of different types of antibodies through the interaction of antigens with mature B cells expressing specific antibodies. Secretory IgA (sIgA) is formed after IgA binds to secretory bodies synthesized by intestinal epithelial glandular cells. The secretory slice is a glycoprotein with a molecular weight of 83KD. It acts as a specific receptor of IgA in the synthesis, secretion and transport of sIgA. It has an important role in protecting sIgA from the degradation of proteolytic enzymes in the intestinal lumen and does not activate complement. sIgA is released into the lumen of the intestine through intestinal mucosal epithelial cells and mixed with the normal flora on the surface of the intestinal mucosa, which can inhibit the colonization of pathogenic microorganisms and penetration of harmful intestinal antigens and maintain the balance of normal flora in the intestinal tract [8]. Experiments have shown that mice inoculated with Lactobacillus thermophilus and Lactobacillus casei, both caused an increase in the production of sIgA and the production of sIgA cells in the small intestine of the mice in a dose-dependent manner [9]. Another study showed that the number of IgM+B cells in the intestinal lamina propria increased after instillation of lactic acid bacteria, and the number of cells secreting IgA and CD4+ T cells also increased in a dose-dependent manner. CD4+ T cells play a very important role in inducing specific immune responses and they are involved in the conversion of IgM to IgA. It is generally believed that the increase in the amount of secretory IgA during the induction of intestinal mucosal immune responses by probiotics is due to the fact that antigenic substances such as probiotic metabolites or whole cells can enter the collecting lymph node through M cells and activate Th2 cells in CD4+ Th2 cells. Under the action of released cytokines (IL-5), the IgM+B cells on the Pyle's junction are converted to IgA+B cells, and antigen presenting cells of the Ile's knot in the small intestine privilegy layer can induce T Antigen-specific proliferative responses of cells [10]. In addition, Bifidobacterium in the intestinal tract through the induction of immunogenic reactions to enhance the body's immune function, the mechanism is that Bifidobacterium stimulates the immune cells of the intestine, through the increase of intestinal IgA plasma cell production ability to play a role in disease prevention. When mice were fed with B. longum cytoplasm and Lactobacillus acidophilus, the specific IgG and IgA produced by the body was significantly higher than that of the control group [11]. Lactobacillus rhamnosus GG was administered to infants infected with rotavirus, and the humoral immunity was elevated compared to the control, accompanied by an increase in specific antibody secreting cells [12]. Studies on infants have shown that milk allergies are generally associated with local IgA deficiency and IgE-mediated hypersensitivity reactions. Studies on children with dermatitis caused by cow's milk allergy have shown that the clinical symptoms of the infant have been further aggravated by the withdrawal of the probiotics. [13].

3, cellular immunity

There are a large number of lymphoid tissues in the gastrointestinal tract, including mainly epithelial lymphocytes (IEL) and lamina propria lymphocyte (LPL) plasma cells and Peyer'sian lymphocytes accumulate into aggregative lymphoid tissues with a certain morphological structure. Probiotics have an activating effect on intestinal intraepithelial lymphocytes. Intestinal intraepithelial lymphocytes are located between epithelial cells with absorption functions in the small intestine and colon, mainly T cells and NK cells. γ and δ T cells are the most abundant in T cells, and More than 75% are CD8+ T cells, and studies suggest that the main function of intraepithelial T cells is cell killing [8]. In vitro experiments have demonstrated that Lactobacillus cell wall extracts can significantly enhance the natural killing activity of epithelial lymphocytes [14]. Latent membrane lymphocytes are located in the intrinsic layer of the intestinal mucosa and contain large numbers of T and B lymphocytes, as well as macrophages and mast cells. The ratio of CD4 to CD8 in T lymphocytes is high and has a strong role in killer response. B cells secrete IgA cells. The macrophages in the lamina propria are in an activated state and produce cytokines. The appearance time of latent lymphocytes is approximately coincident with the time of immune response after antigen stimulation. There is no lymphocyte in the intestinal mucosa of newborn animals. Lymphocytes and plasma cells begin to appear in the lamina propria within 10 days after birth. Epithelial lymphocytes and lamina propria lymphocytes play a more powerful role in the prevention of the invasion of intestinal pathogenic microorganisms due to local cytokine production [15]. Macrophages are important immune cells of the body and can phagocytose and kill a variety of pathogenic microorganisms. Their functional status directly reflects the body's non-specific immune status. It can also phagocytose antigenic substances and be combined with intracellular MHC molecules after digestion. It is expressed on the cell surface and initiates different immune responses in the body. Cytokines secreted by macrophages can promote immune cell proliferation, differentiation, or enhance immune responses. Macrophages can also suppress the immune response by themselves or by secretions. It has been reported [16] that the freeze-dried powder of Lactobacillus was injected into the test animals orally or intraperitoneally. The results showed that the phagocytic activity of macrophages was enhanced. It has been reported that Lactobacillus thermophilus can induce the production of IFN-α and IFN-b in rat peripheral macrophage culture [17] Human studies have shown that Lactobacillus bulgaricus can activate macrophage function and stimulate the body to produce an immune response. The mechanism by which probiotics activate macrophage function in the body is unclear. Studies have found that cells and cell wall portions of lactic acid bacteria can activate macrophages in the host [18]. Other studies have shown that Bifidobacterium genomic DNA can also effectively activate macrophages, and it can inhibit the immune system by inhibiting the secretion of cytokines, increasing the level of NO production, and killing activity of tumor cells. The role of tumor growth [19]. The cell disruption of L. acidophilus and Bifidobacterium longum (the intact cells have been removed) also has the effect of activating the activity of macrophages. In addition, the results of Perdigon et al. also showed that both L. casei's viable and heat-killing bacteria are Showed to promote phagocytosis, Lac-tobacillusacidophilus and S. thermophilus have similar results [20].

4 Conclusion

Probiotics are beneficial bacteria in the intestines of healthy livestock and poultry. They can inhibit the growth of pathogenic microorganisms, improve the immune response of the host, increase the level of antibodies, and increase the activity of macrophages. It plays an important role. Probiotics are not limited to the enhancement of mucosal immune activity. The immune function also regulates the immune function of the system. It not only plays a role in humoral immunity, but also has a greater function in cellular immunity. To make probiotics play a better role in improving the number of probiotics in the body, there are generally two ways to directly take live bacterial preparations or take up growth factors such as active peptides, oligosaccharides, etc. Probiotics have been used in place of antibiotics in recent years The treatment of bacterial diseases in animals has also been reported frequently. There are more and more researches on probiotic growth factor. With the deepening of research on probiotics, its application in animal husbandry production, feed industry and veterinary clinic will also be applied. More extensive, it is of great significance to improve the production performance of livestock and poultry, and development has broad prospects.

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