Coronavirus 2019 (COVID-19) 

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus disease (COVID-19) in humans. Common symptoms of COVID-19 include fever, dry cough, shortness of breath, myalgia, and fatigue1. Other uncommon manifestations of the disease include gastrointestinal symptoms such as diarrhoea, nausea, vomiting, and abdominal pain1,2.  

Gut microbiome 

Vaccines have been a promising treatment for preventing viral infectious diseases however, due to mutations in RNA viruses their efficacy can be limited. This can result in recurrent widespread outbreaks. 

Our body is home to microbial communities (bacteria, fungi, archaea, viruses and protozoa) in our gastrointestinal tract (GI), lungs, skin and mouth. These communities exist in a commensal relationship with humans and therefore play a major role in health.  

The bacteria in our GI has the ability to interact with human cells, including our immune cells. These interactions can result in several benefits including GI motility; activating and destroying toxins, genotoxins, and mutagens; transforming bile acid and steroids; producing vitamins; absorbing minerals; metabolizing xenobiotic substances; influencing intestinal permeability and barrier functions; and modulating mucosal and systemic immunity; as well as beneficial effects on the skin and upper respiratory tract. 

If these communities become unbalanced (otherwise known as dysbiosis), whereby there is a decrease in beneficial microorganisms and an increase in harmful microorganisms, it can allow pathogens to cause disease. Dysbiosis can be caused by a number of reasons including long-term antibiotic use, stress, disease, insufficient diet and age3.  

Gut-lung axis and Covid-19 

Recent evidence has shown the existence of beneficial microbes on the lungs. However, the lung has a small number of microbes compared to the gut. These microbes are able to interact with the microbes present in the gut, known as the gut-lung axis. This communication is vital in supporting immune homeostasis4. To learn more about the gut-lung axis, click here.  

One suggested mechanism between the lung and gut microbiota is that increased permeability of the GI tract allows the leakage and migration of the gut microbiota to the lung, modulating its microbiota and immune response5. Secondly, the gut microbial compounds (lipopolysaccharides {LPS}) and metabolites (short chain fatty acids {SCFA}), are involved in the communication between the gut and lung microbial communities. Finally, blood- or lymphatic-mediated circulation of immune cells or inflammatory mediators from the GI tract to the lung can influence lung inflammatory responses5,6.  

Covid-19 infection can result in both respiratory, fever, cough and severe respiratory syndrome symptoms and gastrointestinal symptoms including diarrhoea, vomiting, nausea, loss of appetite, GI bleeding and abdominal pain7. Research shows that COVID-19 patients with GI symptoms such as diarrhoea experienced more severe respiratory disorders than those without GI symptoms8. It has been suggested that COVID-19 may induce lung microbiota disruptions that modulate the GI tract microbiota, resulting in GI tract symptoms. To learn more about COVID-19 and the gut microbiome, read our article here.

Probiotics and their use in respiratory tract infections 

Probiotics are live microorganisms that confer a beneficial effect to human health when administered in adequate amounts whereas prebiotics are substrates that are selectively utilised by host microorganisms conferring a health benefit9. 

Probiotics have been shown to have a number of beneficial immune and health effects including enhancing the bioavailability of nutrients, moderate health, regulate the bacterial ecosystem and interact directly and indirectly with immune cells10.  

Bacterial and viral infections can be treated with vaccines, antibodies and anti-viral mechanisms. However, the control of most infections has not yet been fully achieved. Additionally, antibiotics are not recommended for treating vital infections because of their inactivity against viruses and the disruption of the normal microbiota. Therefore, we look to other approaches and treatments for helping to treat and prevent bacterial and viral respiratory infections. This includes the use of probiotics.  

Probiotics exhibit antimicrobial activity against several pathogens and have been used as antimicrobial agents against viruses that cause respiratory tract infections11. Previous studies have shown the use of probiotic strains in treating and preventing infections caused by influenza A, influenza H1N1, and respiratory syncytial viruses by reducing the infectious symptoms, shortening the duration of infection, reducing the virus levels in the lungs or nasal washings, producing anti-viral components, promoting immune activity, and enhancing health by reducing body weight loss during infections12,13,14,15. 

Additionally, probiotic supplements containing L. paracasei, L. casei, and L. fermentum significantly reduced the incidence of influenza-like symptoms and upper respiratory infection in adults, who commonly experience colds ≥4 times per year16. 

Probiotics and COVID-19 (results recently published in a peer review journal, Gut Microbes. See the full article here)  

As probiotics have been shown to be effective in the past for respiratory infections it has been postulated that probiotics could be used in the treatment and prevention in COVID-19. 

To date (January 2022), there has been one study carried out that has explored the relationship between COVID-19 infection and probiotic use. 300 patients who had tested positive for COVID-19 but were non-hospitalised were recruited. The patients were split into two groups, placebo and probiotic. The probiotic group were given the collection of strains AB21, (2x109 Lactobacillus plantarum KABPTM 033, Lactobacillus plantarum KABPTM 022, Lactobacillus plantarum KABPTM 023, Pediococcus acidilactici KABPTM 021).  

The strains of bacteria were chosen for their unique properties to enhance and support the immune system -  

  1. Immune cell stimulation - AB21™ probiotic strains, specifically L. plantarum KABP™ 033 naturally overexpress a gene (plnG) that activates the immune system 
  2. Enhancement of gut barrier function - AB21™ strengthens the gut barrier and decreases local inflammation due to the production of polyphosphates. 
  3. Anti-inflammatory activity - AB21™ promotes the production of two molecules that balance the inflammatory response. 

The group that took the placebo showed the following results when compared to the placebo -  

  • Increase emission rate, as measured by both the absence of COVID-19 symptoms and a negative RT-PCR test 
  • Reduction in the number of symptomatic patients with COVID-19 
  • Reduction in the duration of specific symptoms 
  • Reduced viral load in nasopharyngeal swabs 
  • Increased specific IgG and IgM levels against SARS-CoV-2 

The study demonstrates the ability of probiotics to support in the recovery of COVID-19 and can be considered amongst other prescribed medication and vaccines.  

It is evident that probiotics can reduce the incidence and severity of diseases, suggesting their promise in the use for COVID-19. Probiotics could be used to help support recovery of COVID-19 by maintaining the human GI or lung microbiota because dysbiosis plays a major role in the susceptibility of people to infectious diseases. 

 

 

References  

  1. Jiang, F. et al. Review of the clinical characteristics of Coronavirus Disease 2019 (COVID-19). J. Gen. Intern. Med. 35, 1545–1549 (2020).
  2. Zu, Z. Y. et al. Coronavirus disease 2019 (COVID-19): a perspective from China. Radiology 296, E15–E25 (2020).
  3. Zhang, Y. J. et al. Impacts of gut bacteria on human health and diseases. Int. J. Mol. Sci. 16, 7493–7519 (2015).
  4. 4. Dang, A. T. & Marsland, B. J. Microbes, metabolites, and the gut–lung axis. Mucos. Immunol. 12, 843–850 (2019)
  5. Fanos, V., Pintus, M. C., Pintus, R. & Marcialis, M. A. Lung microbiota in the acute respiratory disease: from coronavirus to metabolomics. J. Pediatr. Neonat. Individ. Med. 9, e090139, https://doi.org/10.7363/090139 (2020).
  6. Otani, S. & Coopersmith, C. M. Gut integrity in critical illness. J. Intens. Care7, 17. https://doi.org/10.1186/s40560-019-0372-6 (2019)
  7. Smyk, W. et al. COVID-19: focus on the lungs but do not forget the gastrointestinal tract. Eur. J. Clin. Invest. 50, e13276, https://doi.org/10.1111/eci.13276 (2020).
  8. Wan, Y. et al. Enteric involvement in hospitalised patients with COVID-19 outside Wuhan. Lancet Gastroenterol. Hepatol. 5, 534–535 (2020).
  9. FAO/WHO. Guidelines for the Evaluation of Probiotics in Food. https://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf(2002).
  10. Dargahi, N., Johnson, J., Donkor, O., Vasiljevic, T. & Apostolopoulos, V. Immunomodulatory effects of probiotics: can they be used to treat allergies and autoimmune diseases? Maturitas 119, 25–38 (2019).
  11. Al Kassaa, I. New Insights on Antiviral Probiotics: From Research to Applications (Springer, 2016).
  12. Chiba, E. et al. Immunobiotic Lactobacillus rhamnosus improves resistance of infant mice against respiratory syncytial virus infection. Int. Immunopharmacol. 17, 373–382 (2013).
  13. Eguchi, K., Fujitani, N., Nakagawa, H. & Miyazaki, T. Prevention of respiratory syncytial virus infection with probiotic lactic acid bacterium Lactobacillus gasseri SBT2055. Sci. Rep. 9, 1–2 (2019).
  14. Goto, H. et al. Anti-influenza virus effects of both live and non-live Lactobacillus acidophilus L-92 accompanied by the activation of innate immunity. Br. J. Nutr. 110, 1810–1818, https://doi.org/10.1017/S0007114513001104 (2013).
  15. Kawase, M., He, F., Kubota, A., Harata, G. & Hiramatsu, M. Oral administration of Lactobacilli from human intestinal tract protects mice against influenza virus infection. Lett. Appl. Microbiol. 51, 6–10 (2010).
  16. Zhang, H. et al. Prospective study of probiotic supplementation results in immune stimulation and improvement of upper respiratory infection rate. Synth. Syst. Biotechnol. 3, 113–120 (2018).