People often say "I" when referring to themselves, but they should say "we" to be precise. "I" is, of course, the body given to me by my parents, and this "I" is the parasitic and symbiotic life form in us.
1. Everyone has tiny "partners" who live and die
Like all animals, the inner and outer surfaces of the human body are also inhabited by a large number of microorganisms, which have formed a close relationship with humans in the process of hundreds of thousands of years of evolution, and play important roles in the human digestive, immune, endocrine and nervous systems.
During the normal delivery of the baby, a large number of microorganisms in the mother's birth canal are vaccinated, which is equivalent to the most important large-scale compound immunization injection in a lifetime; After leaving the birth canal, a loud cry, the lungs instantly expanded, and began to breathe air for the first time, accompanied by countless mixed microbial air into the respiratory tract, which is equivalent to the second immunity; Immediately after the first sip of milk, more than 700 microorganisms in breast milk begin to pave the way for the child's healthy development and microbial colonization of the digestive tract, and it is no exaggeration to say that this is the third immunity in life.
After that, the ever-changing air, breast milk at different stages, mother's skin, family and friends, and various microorganisms in the living environment continue to accumulate.
For these attached microorganisms, the human body is undoubtedly a paradise rich in nutrients, suitable temperature and stable environment. In the continuous battle of wits and mutual selection and exclusion with human immunity, most of the microorganisms are blocked outside the mucosa, harmful are expelled, and harmless can coexist with the human body under certain restrictions (such as antimicrobial peptides and pH value). So scientists vividly concluded: the intestine is the most biodiverse place in the world!
By the age of 3, with the improvement of the development stage, the microorganisms on the surface of the mucosa of the human body are basically determined, and most of the intestinal microorganisms will accompany us for life and play an important role in lifelong health and disease.
No wonder life scientists have joked in recent years: symbiotic microbes are your real companions.
In fact, the skin is the outer surface of the human body, the digestive tract, respiratory tract and genitourinary tract of the human body are the inner surface of the human body, and the inner surface of the human body with various mucosal types is the real main interface of the contact between the human body and microorganisms, also known as the "zoo of the human body".
Affected by ambient temperature, humidity, nutrition, ultraviolet rays and other factors, the density of skin microorganisms on the outer surface of the human body is naturally much lower than that of mucosal surfaces, especially the mucosa of the digestive tract and the mucosa of the respiratory tract. The constant temperature and humidity and nutrient-rich mucosal interface is a paradise that nourishes most microorganisms.
After living in peace for a long time, these microorganisms do not like the invasion and occupation of their homes by newly arrived organisms. Therefore, they react differently when it comes to bacterial or viral infections.
Speaking of infections, we are still most concerned about respiratory infectious viruses such as influenza A virus and new coronavirus, and the human symbiotic microorganisms that bear the brunt of the infection of these viruses and actively participate in the battle mainly include two categories: respiratory microorganisms (also known as airway flora) and digestive microorganisms (also known as intestinal flora).
Both the airway flora and the intestinal flora are tiny but complex ecosystems containing hundreds or thousands of completely different microbial communities (flora), rather than individual bacteria.
2. Friends and enemies among friends
Among them, the microorganisms that are beneficial to the human body, we call them beneficial bacteria / good bacteria, the number of such bacteria does not account for the majority, but it is essential for human health, equivalent to the friends of the human body and the enemies of the virus. Among them, live supplementation can produce beneficial effects on the human body, so it is also called probiotics.
For those pathogenic and possibly pathogenic microorganisms, respectively called harmful bacteria / bad bacteria, mainly pathogenic bacteria and conditional pathogenic bacteria opportunistic pathogens), although the number of these microorganisms is also small, but may become an accomplice of the virus when infected, may be fatal to the human body.
Most microorganisms are "neutral" and neutral bacteria that see the wind and rudder. When beneficial bacteria are in a dominant position and the human body is healthy, these microorganisms can also play beneficial effects on the human body, such as the synthesis of vitamins; But when the human body is fragile or pathogenic bacteria and conditioned pathogenic bacteria are in a dominant position, these microorganisms will also "add fuel to the fire" and "help the abuse" to protect themselves.
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Picture and text to understand the human body's war with influenza A and the new coronavirus 1: Type I interferon reaction is the key
, Food and Heart introduced the role of innate immunity and specific immunity in fighting against influenza A virus and new coronavirus infection, but did not mention the earliest and most enduring link of this encounter - mucosal immunity.
3. Love and kill with the "little friends" in the respiratory tract
The human respiratory tract is equivalent to an open bottle with a small mouth and a large belly, but the lower the branch, the finer the aperture.
Human lungs are exposed to 5,000-20,000 liters of air every day filled with microorganisms and particles, which are dealt with by the respiratory epithelial barrier, also known as the airway barrier.
Similar to the intestinal epithelial barrier (intestinal barrier), the airway barrier is also made up of four barriers. The surface of the respiratory tract belongs to the inner surface of the human body, and the respiratory tract belongs to the outside of the human body to the outside, from the outside to the inside (from the lumen of the respiratory tract to the inside) in order:
Microbial barrier. It consists mainly of microorganisms that inhabit the surface of respiratory epithelial cells. Airway microbes are the gatekeeper of human respiratory health, and microbes vary greatly from part of the airway to airway.
Common nasal colonizing bacteria include Staphylococcus, Streptococcus, Moraxella, Propionibacterium and Corynebacterium; The microbial diversity of the nasopharynx is higher, in addition to Moraxella, Streptococcus species, Neisseria, Haemophilus and Posenix; It is also natural that the microbial diversity of the oropharyngeal areas where food circulates continuously on a daily basis is higher, including Przetella, Streptococcus, Weroncius, Neisseria, Bacteroides, Fusobacter, Rochezia and Ciliated.
In addition to bacteria, a variety of viruses (such as rhinovirus, adenovirus, and human coronavirus) and fungi (such as Candida, Aspergillus, and Penicillium) can be detected in the upper respiratory tract of healthy people.
Healthy airway flora is self-interested, not only can they play the role of "colonization resistance" (that is, forming a stable symbiotic relationship with the host during evolution, determining their own "territory" and preventing new microorganisms from "staying"), but also promote airway mucosal immunity, innate immunity, and specific immunity.
Chemical barriers. It is mainly composed of mucus secreted by respiratory epithelial cells, which can be divided into inner mucus layer and outer mucus layer, including various mucins, antimicrobial peptides and immunoglobulins. Mucus does more than just lubricate, it also "catches" tiny pollen dust particles and microorganisms.
Unlike intestinal epithelial mucus, the mucus at the bottom of the respiratory tract is thin and the surface mucus is thick, equivalent to a thick and heavy accumulation with lubricating oil or small wheels underneath, which helps the body to expel sticky nasal discharge and sputum.
The physical properties of normal mucus lie between a viscous liquid and a soft and elastic solid, similar to an intermediate state such as honey and jelly. Its unique properties and its "tube brush" protein make mucus a perfect trap for foreign bodies such as particles and bacteria.
What is particularly interesting is that the direction of movement of the airway and intestinal contents (containing a large amount of mucus) is fixed, the airway is up and the intestine is down, such as inhaling air with dust and bacteria will rush back through the nose, and finally flow out in the form of nasal discharge or swallow into the digestive tract in the form of saliva; Food must be digested along a one-way street and excreted through the exit. Once the retrograde grade or movement stops, there will be problems.
Physical barriers. Respiratory epithelial cells are mainly composed of cilia cells, goblet cells, basal cells and club cells, etc., these cells vary in size, seem to be multi-layered, but are actually fixed on the basement membrane, just like a flat layer of millet rice and mung beans and soybeans.
Of the tracheal epithelial cells, about 60% are ciliated cells and 20% are goblet cells. As the airway deepens and branches, the percentage of ciliated cells and goblet cells decreases, and the number of club cells and other types of cells increases
Goblet cells are the main secretory cells, responsible for secreting mucus, ciliated cells secrete antimicrobial peptides, various epithelial cells can secrete mucin, plus immunoglobulin secreted by intradermal plasma cells, etc., to constitute respiratory mucus.
Ciliated cells have a large number of cilia (about 6.5-7 microns long) at the tip, because the digestive tract can drive the unidirectional movement of objects through intestinal autonomic peristalsis, while the respiratory tract is completely different, with an ingenious magical design, which allows mucus to flow to the throat through the swing of its own cilia, either swallowing or coughing up.
There can be more than 100 cilia on the surface of a fully differentiated cilia cell, and each cilia can be shaken more than 1000 times per minute, moving the mucus in the trachea up by about 0.5-1 cm/min.
Club cells can differentiate into ciliated cells and goblet cells, while basal cells are pluripotent stem cells that can differentiate various types of epithelial cells to renew and repair the epithelium.
There are tight junctions (free side, close to cilia) and adhesion proteins (basal side, close to the basement membrane) between different epithelial cells, which ensure that foreign bodies cannot invade through the cell-to-cell space.
Immune barrier. Within the airway epithelium, large numbers of immune cells (such as macrophages, plasma cells, dendritic cells, and T cells) reside long-term, and more immune cells are recruited in the event of infection. Among them, macrophages are the most abundant immune cells in the airway lumen.
Normally, subepithelial plasma cells synthesize secretory immunoglobulin A (SIgA), which are then transported to the surface of epithelial cells and, together with antimicrobial peptides, act as "immune rejection" and stop microbial adhesion.
Because the airways are often exposed to factors such as contaminants, pathogens, and allergens, airway epithelial cells are often in the process of continuous damage to apoptosis and repair. Intermediates and basal cells continuously differentiate to replenish ciliated cells and goblet cells, while macrophages are responsible for removing apoptotic cell debris. This process is particularly like those roads that are constantly being tinkered with, crushed and repaired in a dynamic equilibrium that is repeated over and over again.
Under mucus capture, cilia clearance, immunoglobulin and antimicrobial peptide isolation, and screening of mucosal immune cells, microorganisms that cannot be symbiotic will be eliminated, and the number of microorganisms that can be symbiotic is maintained in a relatively stable number, and microorganisms and hosts coexist symbiotically.
The type of intestinal barrier is similar to the airway barrier, and it is also composed of four parts: microbial barrier, mucus barrier, physical barrier, and immune barrier. However, intestinal epithelial cell types differ from airways, and the intestinal lumen is more nutritious, pH changes more drastically, oxygen partial pressure is also significantly different, and the microbial community in the intestinal lumen is larger.
The intestine is the largest immune organ in the human body, 70-80% of the body's immune cells are located in the intestine, most of the immune cells will go to other organs to work (such as other internal organs, mammary glands, airways and genital tract mucosa, etc.) after the intestine "study", affecting the immune status of the whole body. The recognition of pathogenic signals and normal signals learned in the intestine, and the recognition of its own components and foreign components, will determine whether these cells can make a rapid, effective, and moderate immune response in the future.
4. Are there "little friends" in the lungs?
Organs such as the nose, pharynx, larynx and trachea, bronchi belong to the conduction airway, as the name suggests, mainly responsible for transmitting oxygen and carbon dioxide, and the epithelium here belongs to the pseudo-multilayer ciliated columnar epithelium mentioned above.
The terminal bronchi and alveoli belong to the respiratory airways and are responsible for gas exchange. The composition of the alveolar epithelium is relatively simple, mainly composed of 2 types of alveolar epithelial cells, type 1 alveolar epithelial cells are responsible for the exchange of oxygen and carbon dioxide, and type 2 alveolar epithelial cells are responsible for secreting surfactants, maintaining alveolar surface tension and maintaining a high elastic state of alveoli.
Therefore, there are relatively few cilia in the lungs (bronchi + alveoli), but the total number of active cilia in healthy adults can reach about 300 billion.
There are no cilia in the alveoli, no thick mucus, and only a thin layer of surfactant outside the epithelial cells. There are alveolar macrophages inside and outside the alveoli, which are responsible for cleaning up microorganisms entering the alveoli, keeping the bacterial load in the alveoli low to ensure gas exchange function.
Microorganisms in the lungs come mainly through the nose and mouth, especially the oropharynx. The low bacterial load of the alveoli relies heavily on mechanisms that remove microorganisms reaching the lower respiratory tract, such as mucociliary clearance and coughing machinery, as well as innate and specific immune responses. These mechanisms keep the alveoli in a "near-sterile" state.
In the case of influenza A virus or new coronavirus infection, the virus generally gradually penetrates from the mouth and nose along the respiratory tract, and if the immune response is not in the upper respiratory tract to block the virus in time, the virus will penetrate deep into the lower respiratory tract, causing serious infection. At this time, the microbial load and inflammation level of the lungs will increase sharply, the surfactant of the alveoli may be reduced, the immune cells and inflammatory factors will increase significantly, a large amount of protein and fluid will accumulate in the alveoli, and the respiratory function will be significantly disturbed, at this time, people will feel asthma, chest tightness and even respiratory distress due to insufficient oxygen.
If you think of the alveoli as a balloon, a healthy alveoli is an intact balloon that can quickly inflate and expand and quickly deflate and shrink; Lung infection is equivalent to filling a part of the balloon with water, at which time the expansion and retraction will be limited; The situation is even worse if there is water and small holes, which is what happens when the lungs are infected.
As the body's oxygen-producing tissue, the alveoli are surrounded by a large number of capillaries. The carbon dioxide metabolized by each cell in the human body is transported by red blood cells to the alveoli through the blood circulation, and then transported back by oxygen. Access to capillaries from the alveolar cavity requires crossing the qi-blood barrier, which is mainly composed of alveolar epithelial cells and vascular endothelial cells.
Of course, viruses and bacteria that invade the lungs do not stop there, and entering the bloodstream may quickly infect other organs (the infection rate increases dozens or even hundreds of times, the difference in speed is like walking and flying).
After the virus infects the blood, it may not only cause microthrombi, but also cause complications such as the heart and kidneys, causing severe disease and even death, which is more common in the new coronavirus infection.
5. Viruses and bacteria collude
Why is the flu worse than the cold? Why is the new coronavirus so scary?
The scary thing about influenza A and new coronavirus infection is not only the pathogenicity of the virus itself, but also the fact that the virus can join forces with other germs to cause disease.
Deaths from influenza are usually associated with secondary bacterial infections. During the 2009 global outbreak of the H1N1 swine influenza virus, 34% of deaths were caused by secondary pneumonia (bi)coccal infections.
Under normal circumstances, under the colonization resistance of the symbiotic flora of the airway, screening and clearance of the airway mucosa, and surveillance of innate and specific immunity, pathogenic and conditionally pathogenic bacteria are cleared from the respiratory tract or maintained at very low levels and cannot cause disease.
However, in the case of influenza virus infection, viral infection will cause airway epithelial cell damage, reduced antimicrobial peptide secretion, impaired cilia wiggling ability, airway microorganisms can not be cleared in time, and some conditional pathogenic bacteria and pathogenic bacteria such as pneumococcus may proliferate, accumulate and expand.
Viral infection also leads to exposure of sites in epithelial cells, making it easier for conditioned pathogens and pathogenic bacteria to adhere to.
In addition, antiviral immunity stimulated by viral infection can reduce antibacterial immunity, such as reducing the ability of alveolar macrophages and neutrophils to phagocytose bacteria, and reducing the ability of T cells to destroy bacteria.
In addition, respiratory viral infections can cause increased alveolar capillary permeability, and changes in alveolar microenvironment nutritional conditions that are conducive to the growth of pathogenic bacteria.
Taking influenza A virus as an example, when influenza A virus is infected, the sialic acid released after the virus binds to sialic acid receptors is the dream meal of pneumococci. At the same time, pulmonary infection can cause excessive inflammation, increased capillary permeability, and allow nutrients such as glucose and vitamin C in the blood to enter the alveoli, which are the favorite delicacy of pneumococcus.
In short, influenza A virus infection can create a nutritious and relatively safe living environment for pneumococci, allowing pneumococci to proliferate and work together to aggravate the host's disease.
When the virus is infected, some pathogenic bacteria will take advantage of the void, and different pathogenic bacteria will also "pull gangs", than the rosary can promote the proliferation of Pseudomonas aeruginosa, and Pseudomonas aeruginosa can promote the growth of Aspergillus fumigatus; Even some otherwise harmless neutral bacteria (such as enterococci, enterobacteriaceae, actinomycetes) may take the opportunity to fan the flames, such as increasing the expression of virulence factor genes, which will aggravate the host's immune burden, which in turn causes cytokine storms and even immune depletion.
Because ACE2, the coronavirus's invasion portal, is more widely expressed (including the airways and other systems), ACE2 plays a key role in the angiotensin system. Symptoms caused by coronavirus infection tend to be more severe and may promote bacterial infection through similar mechanisms.
Existing studies have shown that:
Novel coronavirus infection will disturb the intestinal flora and airway flora, causing an increase in the demeanor of conditioned pathogenic bacteria and pathogenic bacteria, and an upregulation of gene expression related to bacterial virulence factors.
and 15-16% of patients with COVID-19 develop secondary bacterial infections, the most common of which is pneumococcus, followed by Klebsiella pneumoniae and Haemophilus influenzae. Of those who die, about half have secondary bacterial infections.
Even after the virus is cleared, the abnormalities of the flora caused by the virus can persist for some time, and some of the sequelae are associated with this.
Pneumonia is one of the leading causes of disease death in modern people. In Japan, doctors recommend that people over 50 years of age and people with chronic respiratory diseases be regularly screened for pathogenic bacteria such as pneumococcus, Klebsiella, Pseudomonas aeruginosa, and Candida, and if positive, intervention must be carried out before there are other diseases. Because these harmful microorganisms are more likely to contribute to respiratory viral infections, it is more difficult to treat, and it also increases the risk of death.
Some people may say: it is not the same to kill viruses after virus infection and directly supplement antibiotics to kill bacteria, which is so troublesome.
It's actually completely different. Antibiotic use, ostensibly aggressive treatment, often does more harm than good to the patient.
In the long run, the use of antibiotics is also forcing more microorganisms to develop resistance, leading to the emergence of superbugs and superfungi, making it likely that the next infection will be incurable. China has become the world's most affected area for multidrug-resistant bacteria.
Even in the short term, drinking may not quench thirst, because antibiotics can destroy the helpers of the body's immune system.
6. The health helper of the human body - good bacteria
When overwhelmed by a large "army" of pathogens such as germs, bacteria and fungi, the immune system is often overwhelmed, but it has its own countermeasures.
In fact, the human immune system is far smarter than we think. When viruses collude with bacteria or fungi, the human body has long found its own helper, which is beneficial bacteria. (Probiotics mainly refer to the live microorganisms that we supplement from the outside world that are beneficial to people, and these foreign probiotics and the original beneficial microorganisms in the human body are beneficial bacteria).
Studies of influenza viruses have shown that oral or nasal administration of certain probiotic strains can
Enhances airway antiviral type I interferon response;
Enhances Th1 cell response of airway mucosa and lymph nodes;
Facilitate rapid and efficient recruitment of immune cells into the airways;
Enhance the number of NK cells and improve the antiviral ability of NK cells;
Promote antibody secretion and inhibit viral replication.
In addition, oral or nasal administration of specific probiotic strains can also help improve the increased permeability of the qi-blood barrier caused by viral infection and inhibit thrombosis, thereby reducing the risk of severe complications.
The formation of microthrombus is one of the important causes of serious complications and even death caused by the new coronavirus, so probiotics may also reduce the severity of new coronavirus infection and the risk of death.
Clinical evidence shows that oral probiotics can reduce the symptoms of new coronavirus infection, reduce the risk of severe disease, and accelerate recovery. (For more information, please refer to .)
A summary of the latest scientific research on the new coronavirus – what daily life factors can help us fight the virus
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It is understandable that probiotics administered through the nose regulate airway flora, improve airway immunity, and enhance the role of respiratory viruses such as influenza virus and new coronavirus. But why does oral probiotics regulate intestinal flora and enhance airway antiviral ability?
Good intestinal flora can not only enhance the intestinal mucosal immunity, but also promote the production of "trained" immune cells in the intestine, promote the secretion of appropriate and appropriate amounts of cytokines by immune cells, release some active substances that regulate immunity (such as short-chain fatty acids), and some of the bacteria's own components can also be used as antigen signals to regulate immunity.
A May 2022 study in Immunity showed that some gut bacteria can also wrap their own DNA fragments and send them to the host, thereby enhancing the host's systemic type I interferon response and helping the host resist viral infections in various parts of the body.
Therefore, the use of antibiotics for viral infections has both advantages and disadvantages. Destroying potential pathogens may prevent secondary bacterial infections, but it also eliminates the helper of the immune system; Once the pathogenic bacteria acquire the drug resistance gene, the result will be more harm than good, not only can not eliminate the "accomplice" of the virus, but also equivalent to self-cutting off arms and destroying their teammates in advance.
The probiotics eaten can not only enhance intestinal immunity, but also regulate airway mucosal immunity from a distance, airway innate antiviral immunity and specific antiviral immunity, thereby helping the human body better resist infection and clear the virus faster. (Read on for more.)
Is drinking yogurt to prevent the flu a fantasy?
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In turn, airway viral infections can disrupt airway flora and intestinal flora. Therefore, after the cold is healed/after Yangkang, increase the intake of probiotics and restore normal mucosal immune function, in order to better cope with the next possible viral challenge.
7. Summary
In the war between the virus and the human body, neither side is a "single-handed" deathly fight, and the virus will cause disease together with the harmful bacteria that are already present in the airway. Viral infection can weaken airway mucosal immunity, increase airway barrier permeability, and create favorable conditions for harmful bacteria to invade and multiply.
The combined invasion of a large army of viruses and germs will make the immune system tired and cope, thereby promoting its own proliferation. More than one-third of deaths from influenza and coronaviruses are caused by coinfection with viruses and germs.
Of course, human immunity does not sit still, and it is natural to look for helpers. Beneficial bacteria can not only regulate the intestinal and airway mucosal flora, antagonize harmful bacteria, enhance the "colonization resistance" ability of microorganisms to viral germs, but also enhance mucosal immunity.
For people with a compromised airway barrier (such as smoking, drinking, or chronic airway disease), the virus can invade hundreds or thousands of times faster than people with intact airway barriers, and the difference in speed is as great as trekking through mud and flying.
In the case of smoking, for example, smoking impairs airway cilia clearance. When particles and microorganisms captured by airway mucus cannot be expelled from the airway in time, harmful bacteria gradually accumulate, and the function of immune cells such as macrophages and neutrophils is impaired.
That is to say, for people with normal airway barriers, when the virus is eliminated and the trek reaches the epithelial cells, not only can you not find a helper, but you are still facing the immune cells that are waiting for them, and there is no doubt who wins and who loses at this time. A healthy airway barrier gives the body plenty of time to prepare, and the body may clear the virus with just a few sneezes or coughs.
However, in the case of damaged airway barrier, the virus quickly finds receptors in epithelial cells, and rapid infectious diseases continue to advance to the lungs; At this time, the harmful bacteria that have been lurking and waiting for the opportunity also begin to expand. And the immune cells that were already defending against harmful bacteria were caught off guard, and a new task of anti-virus was added.
Due to the excellent camouflage ability of the virus, the innate immunity can not respond in time, and when the specific immune response comes over, differentiates T cells specifically to deal with the virus, and specifically neutralizes the antibodies of the virus, the number of viruses is already extremely large, and immune cells can only fight in the sea of viruses and germs. At this time, the human body often experiences a lot of discomfort, and with the help of medical treatment and drugs to get out of the danger, but often comes at a huge health cost.
In addition to enhancing mucosal immunity, beneficial bacteria can also enhance antiviral innate immunity and specific immunity, so that the human body can destroy the virus more quickly and effectively with less damage.
Knowing the teammates and helpers in this anti-virus war, you probably no longer are afraid of the new crown virus or influenza virus, and know how to increase your helpers and reduce the teammates of the virus in case the virus strikes. In fact, not only respiratory infection viruses, but also HIV and HPV viruses that threaten human health, are mostly helpless in a huge bacterial environment.
Scientists have long found that people who also carry HIV or HPV, Native Africans and black immigrants to the United States have different chances of getting the disease. Good symbiotic microorganisms are the most reliable protective barrier for human beings, which has been the consensus of life science researchers around the world.
Although we all want our immune system to quickly defeat the virus and recover as soon as possible after infection. However, due to the poor information between micro (immune people) and macro (biological people who can eat and think), people often misread the language of immunity, and many people have been dragging their own immunity.
In the next issue, let's go back to the macro world and see if you've dragged your immunity back.
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