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Clinical and Scientific Rationale for Use of Probiotics as Adjuvant in COVID-19

Written By :  Hina Zahid
Medically Reviewed By :  Dr. Kamal Kant Kohli
Published On 2020-11-25 07:15 GMT   |   Update On 2021-02-04 08:27 GMT
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SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2) - responsible for COVID- 19 (coronavirus disease 2019) infections, has clinically affected more than 12.3 million people across 215 countries. (1) There has been continuously emerging evidence bringing out the association of gut dysbiosis and the possible need for interventions to correct the same for the management of COVID-19 infections.

COVID-19 & Gut Dysbiosis

While the clinical features of COVID-19 are associated with acute respiratory restrictions, cough, sore throat, and fever, followed by multi-organ failure and often secondary infections. (2) , it has been reported that there is a strong correlation between the progression of the disease and the composition of gut microbiota. Some patients with COVID-19 have manifested intestinal microbial dysbiosis, with a decrease in cell numbers of Lactobacillus and Bifidobacterium (3)
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Hence it has been suggested that the use of probiotics might help normalize the stability of the intestinal microbiota and lower the risk of secondary infections.
Animals remain one of the most important "constituents" with the human ecosystem, with human microbiota often cited as an 'organ system' in itself, and as such, they must be considered as a primary source, or incubator, of novel viral diseases and outbreaks in humans. A particularly pertinent example of this is the COVID-19 pandemic.(4) It may be interesting to review and consider the potential of probiotics as a valuable integrative approach for treating COVID-19 infections
Probiotic Synthesized Bacteriocins and its role in Microbial Infections
There have been reports indicating the successful clinical use of probiotics in the treatment of various intestinal, respiratory, and urogenital diseases caused by viruses.
The potential suggested primary mechanisms of probiotic action against viruses include direct probiotic cell interaction with the target viruses, production of antiviral metabolites and modulation of the host's immune system (5). Other possible mechanisms of actions include modulation of the host microbiota, interaction with eukaryotic epithelial cells and effects on the electrolyte potential (6).Virtually all bacteria, including Lactic Acid Bacillus (LAB) probiotics, are known to produce ribosomally synthesized substances which are protein in nature and exhibit bactericidal activity. These substances are collectively termed as bacteriocins (7). Several other bacteriocins have also been demonstrated to be active against viruses.
Bacteriocins and Modulation of Gut Microbiota and Correcting Gut Dysbiosis
The potential of bacteriocins to alter the gut microbiota by targeting detrimental components without having a negative influence on beneficial microorganisms is an idealistic concept. The host is colonized by trillions of microbes in a symbiotic association, and some of these microbes could turn pathogenic during dysbiosis (8)
Probiotic strains like Lactic Acid Bacillus (LAB) produce a wide variety of antimicrobial compounds consisting of metabolites like hydrogen peroxide, short-chain fatty acids, and lactic acid to bacteriocin-like inhibitory substances (BLIS) and bacteriocins. (9). LAB also has a significant role in keeping the human and animal gut microbiome in a balanced state (10) and in maintaining the integrity of the gut wall. (11) apart from favourably modulating the immune responses.
Bacteriocins and Immune Modulation Against Viral Infections
Modulation of the immune system seems to be a valid and clinically relevant approach for the prophylaxis of viral infections, including COVID-19 (12) . The immunomodulatory properties of LAB are well documented. Intestinal strains of probiotics can alter the roles of dendritic cells (DC), monocytes/macrophages, T and B lymphocytes, thereby enhancing the phagocytosis of pathogenic bacteria (13). In vitro, studies have indicated that LAB induce the release of proinflammatory cytokines TNF-a and IL-6, thus stimulating nonspecific immunity (14)
Antiviral Properties of Probiotic Bacteriocins
The earliest reports of LAB inactivating viruses were published about 30 years ago. At that time, antiviral activity was mostly ascribed to protein denaturing reactions of hydrogen peroxide and lactic acid produced by Lactobacillus spp., leading to the inactivation of the human immunodeficiency virus type 1 (HIV-1) and human simplex virus type 2 (HSV-2) (15). It is known that probiotic LAB could trigger anti-inflammatory responses in the innate immune system by signalling dendritic cells (DCs) to secrete anti-inflammatory cytokines such as interleukin 10 (IL-10) (16). Probiotics can also down-regulate pro-inflammatory cytokines by interfering with inflammatory signalling pathways such as nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) pathways.
Practical Perspective for Consideration of Probiotics in COVID-19
In infection pervasive times of COVID-19, there has been a rampant increase in the use of antibiotics and antimicrobials – as repurposed agents or to prevent the secondary bacterial superinfections like azithromycin, doxycycline etc. In such clinical scenarios, there needs to be a consideration for the management of antibiotic-associated diarrhoea. Antibiotic-Associated Diarrhoea (AAD) can develop from a few hours and may last up to 2 months after antibiotic intake (17). The incidence of AAD reported could be as high as 25% (18). Probiotics like Lactobacillus strains remain one of the preferred probiotics for the management of antibiotic-associated diarrhoeas.(19)
In Summary
Probiotics and their metabolites certainly have considerable potential to affect "germ warfare" against disease-causing viruses and also to be key allies in our efforts to possibly reduce the burden of viral and COVID-19 infections, and more certainly, improve clinical outcomes and recovery in times when every evidential and beneficial intervention matters to the medical fraternity and the society, at large.
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on probiotics, CLICK HERE
References
Adapted from
1 Worldometer, 2020, Coronavirus, https://www.worldometers.info/coronavirus/?utm_campaign=homeADemocracynow(2020)%20dvegas1?
2 Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., et al. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan. China: a descriptive study. Lancet 395, 507–513. doi: 10.1016/S0140-6736(20)30211-7
3 Xu, K., Cai, H., Shen, Y., Ni, Q., Chen, Y., Hu, S., et al. (2020). Management of corona virus disease-19 (COVID-19): the zhejiang experience . Zhejiang Da Xue Xue Bao Yi Xue Ban. 21:49.
4 Tiwari SK, Dicks LMT, Popov IV, Karaseva A, Ermakov AM, Suvorov A, Tagg JR, Weeks R and Chikindas ML (2020) Probiotics at War Against Viruses: What Is Missing from the Picture? Front. Microbiol. 11:1877. doi: 10.3389/fmicb.2020.01877
5 Ichinohe, T., Pang, I., Kumamoto, Y., Peaper, D., Ho, J., Murray, T., et al. (2011). Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. U.S.A. 108, 5354–5359. doi:10.1073/pnas.1019378108
6 Olaya Galán, N., Ulloa Rubiano, J., Velez Reyes, F., Fernandez Duarte, K., Salas Cárdenas, S., et al. (2016). In vitro antiviral activity of Lactobacillus casei and Bifidobacterium adolescentis against rotavirus infection monitored by NSP4 protein production. J. Appl.Microbiol. 120, 1041–1051. doi: 10.1111/jam.13069
7 Alvarez-Sieiro, P., Montalbán-López, M., Mu, D., and Kuipers, O. P. (2016). Bacteriocins of lactic acid bacteria: extending the family. Appl. Microbiol. Biotechnol. 100, 2939–2951. doi: 10.1007/s00253-016-7343-9
8 Turnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., and Gordon, J. I. (2007). The human microbiome project. Nature 449, 804–810. doi: 10.1038/nature06244
9 Dobson, A., Cotter, P. D., Ross, R. P., and Hill, C. (2011a). Bacteriocin production: a probiotic trait? Appl. Environ. Microbiol. 78, 1–6. doi: 10.1128/aem.05576-11
10 Gillor, O., Etzion, A., and Riley, M. A. (2008). The dual role of bacteriocins as anti and probiotics. Appl. Microbiol. Biotechnol. 81, 591–606. doi: 10.1007/s00253-008-1726-5
11 Bajaj, B. K., Claes, I. J. J., and Lebeer, S. (2015). Functional mechanisms of probiotics. J. Microbiol. Biotechnol. Food. Sci. 4, 321–327. doi: 10.15414/jmbfs. 2015.4.4.321-327
12 Jayawardena, R., Sooriyaarachchi, P., Chourdakis, M., Jeewandara, C., and Ranasinghe, P. (2020). Enhancing immunity in viral infections, with special emphasis on COVID-19: a review. Diabetes Metab. Syndr. 14,367–382. doi: 10.1016/j.dsx.2020.04.015
13 Grasemann, H., Stehling, F., Brunar, H.,Widmann, R., Laliberte, T. W., Molina, L., et al. (2007). Inhalation of Moli1901 in patients with cystic fibrosis. Chest 131, 1461–1466. doi: 10.1378/chest.06-2085
14 Isolauri, E., Sutas, Y., Kankaanpaa, P., Arvilommi, H., and Salminen, S. (2001). Probiotics: effects on immunity. Am. J. Clin. Nutr. 73, 444S–450S. doi: 10.1093/ ajcn/73.2.444s
15 Martin, L. S., McDougal, J. S., and Loskoski, S. L. (1985). Disinfection and inactivation of the human lymphotropic virus type III/lymphadenopathy associated virus. J. Infect. Dis. 152, 400–403. doi:10.1093/infdis/152.2.400
16 de LeBlanc, A. M., Del Carmen, S., Zurita-Turk, M., Santos Rocha, C., Van de Guchte, M., Azevedo, V., et al.(2011). Importance of IL-10 modulation by probiotic microorganisms in gastrointestinal inflammatory diseases.ISRN Gastroenterol. 2011:892971. doi: 10.5402/2011/892971
17 Fekety R. Guidelines for the diagnosis and management of Clostridium difficile–associated diarrhea and colitis. Am J Gastroenterol 1997;92: 115:1750–3. 739–50.
18 Bartlett JG. Management of Clostridium difficile infection and other antibi-otic-associated diarrhoeas. Eur J Gastroenterol Hepatol 1996;8:1054–61.
19 Francisco Guarner et al, World Gastroenterology Organisation Global Guidelines Probiotics and prebiotics 2017, 1-35
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Hina Zahid

Hina Zahid Joined Medical Dialogue in 2017 with a passion to work as a Reporter. She coordinates with various national and international journals and association and covers all the stories related to Medical guidelines, Medical Journals, rare medical surgeries as well as all the updates in the medical field. Email: editorial@medicaldialogues.in. Contact no. 011-43720751

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