The influence of "good" bacteria in the digestive system on immunity - interview with prof. dr hab. n. med. Wojciech Cichy from the Medical University in Poznań.
It is true that our immune system comes from the gut. A request for an explanation of this why, it is the intestine that plays such a key role in building immunity?
As much as 60-70% of the immune system is located in the intestines. Yes, the immune system is distributed to many organs throughout the human body. These are: bone marrow, spleen, thymus, digestive system, lymph nodes, tonsils. However, most of the immune cells are located within the immune tissue of the gastrointestinal tract and are known as: GALT. The relations between GALT and the bacteria that inhabit the intestines are bilateral: on the one hand, GALT controls the bacteria and monitors whether there is an overgrowth of pathogenic microorganisms, on the other hand - without commensal bacteria it is not able to properly assess the scale of the demand for antibodies produced (the "cross-reaction"). talk ").
As we know, our immunity is formed in utero. What are the main factors influencing the colonization of "good" bacteria in the digestive system?
Indeed, in the light of the latest data, it is believed that colonization begins in utero, although until recently it was considered sterile in the womb (the "sterile womb" paradigm). Amniotic fluid is probably involved in the transport of bacteria (or actually the bacterial metabolome) from the mother to the uterine cavity. Moreover, the microbiota (metabolome) has an influence on the emerging and developing immune system already during pregnancy. This is confirmed by research on rodents: in mice that were exposed to antibiotics in the prenatal period, lower numbers of neutrophils (leukocytes that capture and destroy foreign antigens) in the blood and their precursors in the bone marrow were noticed.
The colonization of the intestines by bacteria in the postpartum period is influenced by:
- gestational age,
- exposure to antibiotics and other medications,
- type of delivery (natural vs. caesarean section),
- way of feeding (breastfeeding vs. modified milk),
- genetics (to a lesser extent than the other factors).
Immediately after birth, these external factors - through the gastrointestinal tract - shape the innate immunity of the baby and thus the ability to maintain and maintain he alth. So - to some extent - the development of resistance depends on the bacteria ingastrointestinal tract: the more favorable (eubiotic) their quantitative and qualitative composition, the better it is for the immune response. It is assumed that unfavorable circumstances in this regard at an early stage of a child's development may contribute to the occurrence of allergies and asthma.
Why are short-chain fatty acids so important and contribute to the development of innate immunity?
Short-chain fatty acids (SCFA) are metabolites of bacteria (one of the components of the metabolome) that not only affect the process of cell production in the bone marrow (myelopoiesis), but also induce the secretion of antibacterial proteins, mucus synthesis and the formation of the intestinal barrier . They are a source of energy for colonocytes, i.e. cells of the colon epithelium. They stimulate the hematopoiesis (hematopoiesis) of dendritic cells (DCs) specialized in the fight against infection and cancer, as well as macrophage precursors. They also fulfill many other functions. Butyric acid has special properties, as it increases the functional capacity of regulatory T cells (Treg). These are lymphocytes that suppress an overly increased response from the immune system, and therefore play an essential role in the remission of autoimmune and allergic diseases.
What role does retinoic acid play in building acquired immunity?
Acquired immunity is the type of immunity that meets antigens throughout life to then develop the appropriate antibodies. In this way, the next time we come into contact with these microbes, our body will quickly recognize them and fight them. This system supports in many ways, incl. retinoic acid (RA), the production of which is partially dependent on the microbiota. It is helpful in maintaining the balance in the immune system: between pro-inflammatory and anti-inflammatory responses. It has been proven that in mice deficient in retinoic acid, for example, the group of SFB bacteria (segmented filamentous bacteria) is reduced. These are microorganisms that occur mainly in the ileum and cecum. They are responsible for the formation of Th17 pro-inflammatory lymphocytes, which are essential in the fight against pathogenic bacteria and fungi. Retinoic acid is also indirectly involved in the expansion of Treg cells and defense immunoglobin type A (IgA).
What is the function of the intestinal barrier and how can we seal it?
The intestinal barrier is a structure made up of only one layer of intestinal epithelial cells, covered with a protective layer of mucus with the microbiota that resides in it, as well as the cells of the blood, lymphatic, immune and nervous systems under the epithelium. Essenti altight connections are an element of the intestinal barrier, thanks to which epithelial cells adhere tightly to each other. They determine the selectivity of transport of substances reaching the bloodstream from the gastrointestinal tract, and thanks to them, larger antigens and bacterial metabolites do not cross the intestinal barrier. To maintain the proper function of the intestinal barrier, microorganisms are particularly important, because they largely determine the condition of the mucus or epithelium. The intestinal bacteria also affect the proper functioning of the lymphatic system of the digestive tract, i.e. GALT.
What is intestinal dysbiosis? What are its causes and does dysbiosis affect the immune system?
Dysbiosis is a microbial imbalance in the gut. In this state, there are more pathogenic or metabolic disadvantageous bacteria than beneficial. The following factors contribute to dysbiosis: improper nutrition, stress, chronic medication intake - most often antibiotics, proton pump inhibitors and non-steroidal anti-inflammatory drugs. The composition of the microbiota shapes the type of immune response. In many diseases (including type 2 diabetes, celiac disease, metabolic syndrome, rheumatoid arthritis, AD or psoriasis), dysbiosis is observed. Then, in the diseases mentioned above, the concentration of inflammatory markers increases and the level of anti-inflammatory cytokines decreases.
The intestinal microbiota affects both the cytokine balance (Th1 / Th2 / Th17) and the modulation of non-specific immunity by affecting the synthesis of secreted IgA or defensins (natural antibacterial proteins). Th1 lymphocytes are involved in the cellular immune response (stimulation of these lymphocytes is the onset of inflammatory diseases), Th2 lymphocytes are involved in a humoral response (excessive Th2 response is an increased number of allergic reactions), and Th17 play a role in antimicrobial and antifungal defense and may be important in the pathogenesis of autoimmune diseases.
The role of pro-he alth microbiota - including probiotics - is to act in such a way that the Th1 / Th2 / Th17 cytokine balance, and thus the immune tolerance, is maintained. Gut microbes therefore play the role of the main "trainers" of the immune system.
Can dysbiosis lead to inflammation and what then happens in the body?
As a result of dysbiosis, the structure of the intestinal barrier is disturbed. Antigens enter the bloodstream, including endotoxins (lipopolysaccharide complexes; LPS), mainly from the cell walls of gram-negative bacteria. Endotoxin translocation causes endotoxemia,synthesis of pro-inflammatory cytokines and activation of NF-κB, which enhances the transcription of numerous genes for the production of inflammatory response factors. One of the elements of the innate immune response is the activation of receptors sensitive to various forms of pathogens, including LPS.
Are patients with intestinal dysbiosis more likely to contract the coronavirus?
The first conclusions indicate that it is. In the latest work by Kaijin Xu (2022), it can be read that some COVID-19 patients had dysbiosis, as evidenced by a decline in commensal bacteria of the genusLactobacillusandBifidobacterium. In order to restore eubiosis (microbiological balance), patients were recommended nutritional support and the use of prebiotics or probiotics. This was to reduce the risk of recontamination due to bacterial translocation. However, these are only observations, so far there is no research on this topic.
How do probiotics work on immunity? A request for an explanation of the operating scheme.
Due to the ability of the microbiota to adapt to changing conditions, we have the ability to influence our overall he alth throughout our lives. Probiotics help to rebuild the microbiota and restore microbial homeostasis (this is a rebiotic effect; as a result, dysbiosis is changed to eubiosis).
Probiotics can affect the intestinal barrier through its three components: the intestinal microbiota itself, the intestinal epithelium and GALT, the lymphoid tissue of the digestive system. Within the microbiota, probiotic strains can prevent the adherence of pathogenic bacteria to the intestinal epithelium by competition, as well as - by competing with them for nutrients - inhibit their growth. Besides, they produce antimicrobial proteins that destroy pathogens. Probiotic bacteria also stimulate the growth of comesal bacteria and their metabolic activity. Within the epithelium, thanks to probiotics, the amount of protective mucus is increased, tight junctions between cells are strengthened, which guarantee the integrity of the intestinal barrier. There is also the production of cytoprotective compounds. The probiotic grasping points in GALT concern immunomodulation, stimulation of the anti-inflammatory response and inhibition of the synthesis of inflammatory mediators.
What probiotics can strengthen the intestinal barrier and thus immunity?
Supporting the proper functioning of the immune system can be achieved mainly with the help of appropriately selected, high-quality multi-strain preparations, i.e. polyprobiotics. One of the most recommended is Sanprobi Barrier. It includesa composition of 9 bacterial strains:Bifidobacterium bifidumW23 , Bifidobacterium lactisW51 , Bifidobacterium lactisW52 , Lactobacillus acidophilusW37 , Lactobacillus brevisW63 , Lactobacillus caseiW56 , Lactobacillus salivariusW24 , Lactococcus lactisW19 , Lactococcus lactisW58.
The probiotic bacteria contained in Sanprobi Barrier have a positive effect on immunity by: suppressing the immune response caused by mast cells (mast cells); increasing the secretion of anti-inflammatory interleukin 10 (IL-10), which inhibits pro-inflammatory cytokines, as well as reducing the endotoxin load (LPS), which prevents the appearance of inflammation in the body.
Summarizing, I can say that the modern lifestyle, diet or medications used - do not support the proper functioning of the immune system in humans. Therefore, special care should be taken for the individual "immunity generator", which is the intestinal microbiota in the eubiosis state, with proven action through bacterial metabolomes on both poles, the so-called enterocerebral axis. Some polyprobiotics, especially Sanprobi Barrier, have been shown to play a role in supporting immunity.