Probiotics as Promising Immunomodulatory Agents to Prevent COVID-19 Infection: A Narrative Review
After the outbreak in December 2019, Coronavirus Disease (COVID-19) has become a global health problem because of its rapid spread throughout the world. To date, there are no effective therapies to treat or prevent COVID-19 infection. Probiotic bacteria are widely used to prevent gastrointestinal infections by modulating intestinal microbiota. Therefore, this literature review focuses on the potential possessed by probiotic bacteria for the prevention of future COVID-19 infections. Information was extracted from PubMed and Google Scholar using the keywords: "COVID-19", "immunomodulator", "inflammation", and "probiotic" and synthesized into this narrative review. The results showed that probiotic bacteria have immunomodulatory activity that can increase immunity against pathogens by regulating the immune system through modulation of intestinal microbiota and interactions with the lymphatic system in the digestive tract. The ability of the immune system regulation by probiotic bacteria has the effect of increasing the body's defense mechanisms against pathogens that infect the respiratory tract. However, further evidence is still needed regarding the effect of probiotic immunomodulators in combating future COVID-19 infections.
Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents. 2020 Mar;55(3):105924.
Guo Y-R, Cao Q-D, Hong Z-S, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Mil Med Res. 2020 Mar;7(1):1-10.
Sun P, Lu X, Xu C, Sun W, Pan B. Understanding of COVID-19 based on current evidence. J Med Virol. 2020 Feb:0-1.
Malemud CJ. Immunomodulators in Autoimmunity and Viral Infections. J Clin Cell Immunol. 2018 Jan;09(01).
Kanauchi O, Andoh A, AbuBakar S, Yamamoto N. Probiotics and Paraprobiotics in Viral Infection: Clinical Application and Effects on the Innate and Acquired Immune Systems. Curr Pharm Des. 2018;24:710-717.
Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pacific J allergy Immunol. 2020 Mar;38(1):1-9.
Jin X, Lian JS, Hu JH, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020:1-8.
Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020 Mar.
Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM, Suliman BA. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine. 2018 Jan;104:8-13.
Raoult D, Zumla A, Locatelli F, Ippolito G, Kroemer G. Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses. Cell Stress. 2020 Mar;4(4):66-75.
Lehtoranta L, Pitkäranta A, Korpela R. Probiotics in respiratory virus infections. Eur J Clin Microbiol Infect Dis. 2014 Aug;33(8):1289-1302.
Mohanty D, Ray P. Evaluation of probiotic and antimicrobial properties of lactobacillus strains isolated from dairy products. Int J Pharm Sci. 2016 Oct;8(11):230-234.
Monteagudo-Mera A, Rastall RA, Gibson GR, Charalampopoulos D, Chatzifragkou A. Adhesion mechanisms mediated by probiotics and prebiotics and their potential impact on human health. Appl Microbiol Biotechnol. 2019 Aug;103(16):6463-6472.
Garcia-Gonzalez N, Prete R, Battista N, Corsetti A. Adhesion properties of food-associated lactobacillus plantarum strains on human intestinal. Front Microbiol. 2018 Oct;9:1-11.
Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: Mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 2013 Jan;6(1):39-51.
Zhang C xing, Wang H yu, Chen T xin. Interactions between Intestinal Microflora/Probiotics and the Immune System. Biomed Res Int. 2019 Nov;2019.
McFarland L V. Systematic review and meta-analysis of saccharomyces boulardii in adult patients. World J Gastroenterol. 2010 May;16(18):2202-2222.
Arora T, Singh S, Sharma RK. Probiotics: Interaction with gut microbiome and antiobesity potential. Nutrition. 2013 Apr;29(4):591-596.
Bellikci-Koyu E, Sarer-Yurekli BP, Akyon Y, et al. Effects of regular kefir consumption on gut microbiota in patients with metabolic syndrome: A parallel-group, randomized, controlled study. Nutrients. 2019 Sep;11(9):1-23.
Lazarenko LM, Babenko LP, Bubnov R V, Demchenko OM, Zotsenko VM, Boyko N V. Imunobiotics are the novel biotech drugs with antibacterial and immunomodulatory properties. Mikrobiol Zh. 2017;7(1):66-75.
Villena J, Chiba E, Vizoso-Pinto MG, et al. Immunobiotic Lactobacillus rhamnosus strains differentially modulate antiviral immune response in porcine intestinal epithelial and antigen presenting cells. BMC Microbiol. 2014 May;14(1):1-14.
Tada A, Zelaya H, Clua P, et al. Immunobiotic Lactobacillus strains reduce small intestinal injury induced by intraepithelial lymphocytes after Toll-like receptor 3 activation. Inflamm Res. 2016 Oct;65(10):771-783.
Zhang H, Yeh C, Jin Z, et al. Prospective study of probiotic supplementation results in immune stimulation and improvement of upper respiratory infection rate. Synth Syst Biotechnol. 2018 Jun;3(2):113-120.
Dickson RP, Erb-Downward JR, Huffnagle GB. The role of the bacterial microbiome in lung disease. Expert Rev Respir Med. 2013 Jun;7(3):245-257.
Rosa DD, Dias MMS, Grześkowiak ŁM, Reis SA, Conceição LL, Peluzio MDCG. Milk kefir: Nutritional, microbiological and health benefits. Nutr Res Rev. 2017 Jun;30(1):82-96.
Oeser K, Maxeiner J, Symowski C, Stassen M, Voehringer D. T cells are the critical source of IL-4/IL-13 in a mouse model of allergic asthma. Allergy Eur J Allergy Clin Immunol. 2015 Nov;70(11):1440-1449.
Li B, Zheng J, Zhang X, Hong S. Probiotic Lactobacillus casei Shirota improves efficacy of amoxicillin-sulbactam against childhood fast breathing pneumonia in a randomized placebo-controlled double blind clinical study. J Clin Biochem Nutr. 2018 Nov;63(3):233-237.
Natarajan N, Pluznick JL. From microbe to man: The role of microbial short chain fatty acid metabolites in host cell biology. Am J Physiol - Cell Physiol. 2014 Dec;307(11):C979-C985.
Shukla SD, Budden KF, Neal R, Hansbro PM. Microbiome effects on immunity, health and disease in the lung. Clin Transl Immunol. 2017 Mar;6(3):e133-12.
He Y, Wen Q, Yao F, Xu D, Huang Y, Wang J. Gut–lung axis: The microbial contributions and clinical implications. Crit Rev Microbiol. 2017 Feb;43(1):81-95.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Jan;395(10223):497-506.
Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the Eye of the Cytokine Storm. Microbiol Mol Biol Rev. 2012 Mar;76(1):16-32.
Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015 Jul;74(1):5-17.
Qian LJ, Kang SM, Xie JL, et al. Early-life gut microbial colonization shapes Th1/Th2 balance in asthma model in BALB/c mice. BMC Microbiol. 2017 Jun;17(1):1-8.
Grayson MH, Camarda LE, Hussain SRA, et al. Intestinal microbiota disruption reduces regulatory T cells and increases respiratory viral infection mortality through increased IFNγ production. Front Immunol. 2018 Jul;9(JUL):7-9.
Mortaz E, Adcock IM, Folkerts G, Barnes PJ, Paul Vos A, Garssen J. Probiotics in the management of lung diseases. Mediators Inflamm. 2013 May;2013.
Vareille-Delarbre M, Miquel S, Garcin S, et al. Immunomodulatory effects of lactobacillus plantarum on inflammatory response induced by klebsiella pneumoniae. Infect Immun. 2019 Oct;87(11).
Wu CT, Chen PJ, Lee YT, Ko JL, Lue KH. Effects of immunomodulatory supplementation with Lactobacillus rhamnosus on airway inflammation in a mouse asthma model. J Microbiol Immunol Infect. 2016 Oct;49(5):625-635.
Kuo C, Lim S, King NJC, et al. Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo. Respirology. 2011 Feb;16(2):367-377.
Azad MAK, Sarker M, Wan D. Immunomodulatory Effects of Probiotics on Cytokine Profiles. Biomed Res Int. 2018 Oct;2018.
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