COVID-19Medical Evidence of Probiotics Against COVID-19

Medical Evidence of Probiotics Against COVID-19

Medical interventions for COVID-19, including vaccination, are underway, but there is no definitive answer as to when they will be widely available. Coupled with the outbreak of mutated viruses, the effectiveness of vaccination remains highly variable. Therefore, more preventive measures are necessary.

Fortunately, The body has its own defense system: The immune system, and Probiotics can strengthen this complex network against infections such as coronaviruses.

Probiotics As A New Direction In The Fight Against COVID-19

Probiotics are a new direction in the fight against COVID-19, as they can balance the intestinal micro-ecology and are expected to strengthen the immune system against viruses and bacteria. Probiotic supplementation is the fastest and safest way to increase the number of beneficial bacteria in the body, as the intestinal microbiota contains many different types of microorganisms, each group is responsible for a different job.

Recently, international medical experts have identified probiotic species that are resistant to COVID-19, and many new studies and clinical reports have been published. A variety of symptoms caused by COVID-19, including pneumonia, severe respiratory infections and organ failure, have been identified.

Therefore, air droplets are the main source of transmission of SARS-CoV-2, and the gastrointestinal tract may also be involved in the etiology of coronavirus. RNA of SARS-CoV-2 has also been found in intestinal and stool samples of patients and in sewage pipes.

SARS-CoV-2 can infect intestinal absorptive cells and thus act as a carrier for COVID-19. A large body of clinical data has shown that intestinal infections are common in coronaviruses and aggravate the severity of the disease.

Probiotics are critical microorganisms that can have beneficial effects on the host when consumed in adequate doses. Medical data suggest that specific strains of probiotics can help prevent viral and bacterial infections such as sepsis, gastroenteritis and respiratory syndromes.

Mechanisms of Probiotic Effects on Viral Respiratory Infections

Probiotics can control drug-related diarrhea and gastrointestinal infections, as well as other sites of infection such as respiratory tract infections and sepsis. Viruses are a major cause of upper respiratory tract infections and the beneficial effects of probiotics in the prevention of upper respiratory tract infections have been confirmed in a number of studies of 13 randomized controlled trials including 4,230 young people and children treated with probiotics, in which the risk of upper and lower respiratory tract infections was reduced by a factor of 2 and, notably, the severity of the infection was significantly reduced.

In addition, there was a randomized, double-blind, placebo-controlled study of 523 young people who received Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, and Bifidobacterium bifidum MF 20/3. Bifidobacterium bifidum) MF 20/5, and added some minerals and vitamins, the results showed that the duration of influenza attack was shorter and the number of fever days was also reduced.

Lactobacillus brevis also showed encouraging results in a study of 1,692 school children and greatly reduced the incidence of respiratory infections from influenza.

Therefore, it can be concluded that probiotics have an effective contribution to the mitigation of coronavirus outbreak events.

In general, the following mechanisms have been proposed for the effect of probiotics on viral respiratory infections (Figure 1).

  1. Direct effect of trapping strategies
  2. activation of the immune response by interleukins, NK cells, Th1 and IgA (immunoglobulin A)
  3. Induction of mucosal protection (possible attachment of enteric mucin to the virus and inhibition of viral replication)
  4. Production of antiviral components, such as bacteriocins and hydrogen peroxide (H2O2)
  5. Induction of low levels of nitric oxide (NO) production and dehydrogenase formation in host cells
  6. Immunomodulation of immune cells (e.g. macrophages and dendritic cells [DCs])
  7. Induced differentiation of CD8+ T cells into CTLs, which kill infected cells
  8. Differentiation of CD4+ T cells into Th1 and Th2 cells (and induction of B cells by Th2 cells)
Antiviral effect of probiotics during respiratory viral infections
Antiviral effect of probiotics during respiratory viral infections

Probiotics Help Reduce Bacterial Infections

In addition to viral infections, probiotics can help reduce bacterial infections such as lower respiratory tract infections in adults, and much of the experimental data was obtained from a randomized controlled trial of 2,000 patients with pneumonia infections.

In this study, results from more than 1,800 adults showed a reduction in the incidence of events. As shown in the study from China, COVID-19 may be accompanied by an imbalance in the intestinal flora, which can cause serious infections, and a probiotic strain can help to restore the stability of the intestine.

The intestinal flora has a systemic effect on the host’s immune response and has important effects on the immune response in nearby mucosal sites, such as the lungs.

The consumption of specific strains of Bifidobacteria and Lactobacilli can have a positive effect on the clearance of influenza virus from the respiratory tract.

Some probiotic strains have enhanced levels of type I interferon, which increases the number and function of antigen-presenting cells, natural killer cells and T cells, and increases the levels of specific antibodies in the body and mucosal areas.

There is evidence that probiotic strains can improve the stability between pro-inflammatory and immunomodulatory cytokines that allow clearance of viruses, and that they are best suited to avoid acute respiratory distress syndrome, the main symptom of COVID-19. A randomized control design containing adolescents used Lactobacillus DR7 to inhibit plasma pro-inflammatory cytokines (e.g., IFN-γ and TNF-α); another trial in young adults showed improvements in anti-inflammatory cytokines (e.g., IL-4 and IL-10) and reduced levels of plasma cell peroxidation and oxidative stress.

Patients with COVID-19 may experience certain cytokine storms and this regulatory function is very important. Oral consumption of probiotic strains would facilitate the emergence of an intestinal immune response, which is key to host defense: probiotic strains are known to improve the firmness of tight junctions.

For example, they can serve as fuel for colon cells, temporarily reducing SARS-CoV-2 invasion by increasing butyrate levels. Probiotic strains have also been shown to have antiviral activity, as shown in medical studies.

Vaccines are a promising therapeutic approach to prevent viral infectious diseases. However, as observed for influenza viruses, their efficacy may be limited by mutations in the RNA virus.

This increases the risk of infection due to recurrent widespread outbreaks, making these viruses a serious public health threat.

Microbial communities (bacteria, fungi, archaea, viruses, and protozoa) in the human gastrointestinal tract, lungs, skin, and oral cavity play an important role in human health by forming a commensal relationship with the host cells [1].

The number of commensal bacteria present in the GI tract (1 × 10¹³ CFU) is equal to the number of human cells, and this colonization begins shortly after birth, and their profile and number stabilize at 1 year of age with more than 1000 species of bacteria.

The Gastrointestinal Microbiota Has The Ability To Interact With Human Cells, Including Specific Immune Cells

The Gastrointestinal Microbiota Has The Ability To Interact With Human Cells, Including Specific Immune Cells

These interactions produce a variety of health benefits in the host, including:

  1. regulating gastrointestinal motility
  2. activating and destroying toxins, genotoxins, mutagens
  3. Transformation of bile acids and steroids
  4. production of vitamins
  5. absorption of minerals
  6. metabolizes xenobiotics
  7. affects intestinal permeability and barrier function
  8. regulates mucosal and systemic immunity
  9. beneficial effects on the skin and upper respiratory tract

The microbiota is distributed in the lungs mainly through the upper respiratory tract or along the diffusion of mucosal surfaces. These beneficial microorganisms compete with pathogens that colonize human cells in different organs, thus promoting host health.

This requires a large number of beneficial microorganisms and any imbalance or disruption of this system may lead to an imbalance in the intestinal flora (Dysbiosis), which allows pathogens to cause diseases such as respiratory tract infections.

Prolonged use of antibiotics may also lead to imbalance of the intestinal flora. Therefore, probiotics are also usually recommended for patients who have recently been treated with antibiotics for any disease. Other causes of imbalance of the intestinal flora in the human gastrointestinal tract include exposure to toxins, stress, disease, inadequate diet, and age.

The Gut-Lung Axis & COVID-19

The gastrointestinal tract and lungs are the body compartments that host microbiota, but the lungs contain less microbiota than the intestine [18]. There is growing evidence for a bidirectional communication between the gut and lung, called the gut-lung axis.

This bidirectional crosstalk involves the support of immune homeostasis, and it is believed that inflammation of the gastrointestinal tract leads to inflammation of the lungs through this connection. The exact mechanism of this inflammatory transfer from the gut to the lung has not been fully revealed. However, imbalance of the intestinal and pulmonary microbiota is one of the associated factors.

Imbalance of intestinal flora has been previously shown to be associated with several respiratory diseases, and migration of pulmonary flora to intestinal flora has been observed in several respiratory diseases.

One of the mechanisms behind the bidirectional interaction between the pulmonary and gut flora systems is that increased permeability of the gastrointestinal tract allows leakage and migration of intestinal flora to the lungs, thereby modulating their flora and immune response.

In addition, the two-way gut microbial component includes gut microbial components and metabolic products such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFA).

In addition, blood or lymph mediated circulation of immune cells or inflammatory mediators from the gastrointestinal tract to the lungs can lead to an inflammatory response in the lungs.

In addition to the most common respiratory symptoms (e.g., fever, cough, and severe respiratory syndrome caused by COVID-19 infection), patients have been reported to exhibit gastrointestinal symptoms, including diarrhea, vomiting, nausea, loss of appetite, gastrointestinal bleeding, and abdominal pain.

Patients with COVID-19 found to have gastrointestinal symptoms (e.g., diarrhea) are more likely to develop more severe respiratory disease than those without gastrointestinal symptoms. Although the effect of the gut on lung health is well documented, there is still little available knowledge about the opposite effect of the lung on gut health.

Therefore, why COVID-19 affects the integrity of the gastrointestinal tract is unclear, but imbalance of the intestinal flora may be one of the contributing mechanisms.

Acute lung injury-mediated pulmonary dysfunction is associated with blood-mediated regulation of gut flora, and in the presence of pulmonary allergy, the number of gut flora is also regulated.

As a result, COVID-19 may induce disruption of the pulmonary microbiota, which in turn alters the gastrointestinal microbiota and leads to gastrointestinal symptoms.

Studies suggest that gastrointestinal symptoms in patients infected with COVID-19 may be attributed to tissue and organ damage caused by the immune response.

In addition, angiotensin-converting enzyme 2 (ACE2) is the major host cell receptor for COVID-19. ACE-I and ACE-II are critical enzymes that play an important role in the regulation of blood pressure through the biochemical renin-angiotensin-aldosterone system (RAAS) pathway.

In addition to the lung, ACE2 is expressed via the intestine and direct colonization of intestinal ACE2 receptors via viruses may be responsible for the gastrointestinal symptoms associated with COVID-19.

Instead, dysfunction of the intestinal apoptotic pathway caused by respiratory tract infection is another explanation for COVID-19-associated gastrointestinal symptoms.

Furthermore, since the gastrointestinal tract and the respiratory tract share the same embryonic origin, they may still contribute to COVID-19-related gastrointestinal symptoms, and thus they are structurally similar and interact similarly in physiological and pathological conditions.

All these proposed mechanisms can act individually or together to induce COVID-19-related gastrointestinal disturbances.

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