The potential application of probiotics and prebiotics for the prevention and treatment of COVID-19

Amin N Olaimat, Iman Aolymat, Murad Al-Holy, Mutamed Ayyash, Mahmoud Abu Ghoush, Anas A Al-Nabulsi, Tareq Osaili, Vasso Apostolopoulos, Shao-Quan Liu, Nagendra P Shah, Amin N Olaimat, Iman Aolymat, Murad Al-Holy, Mutamed Ayyash, Mahmoud Abu Ghoush, Anas A Al-Nabulsi, Tareq Osaili, Vasso Apostolopoulos, Shao-Quan Liu, Nagendra P Shah

Abstract

COVID-19 is a pandemic disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This new viral infection was first identified in China in December 2019, and it has subsequently spread globally. The lack of a vaccine or curative treatment for COVID-19 necessitates a focus on other strategies to prevent and treat the infection. Probiotics consist of single or mixed cultures of live microorganisms that can beneficially affect the host by maintaining the intestinal or lung microbiota that play a major role in human health. At present, good scientific evidence exists to support the ability of probiotics to boost human immunity, thereby preventing colonization by pathogens and reducing the incidence and severity of infections. Herein, we present clinical studies of the use of probiotic supplementation to prevent or treat respiratory tract infections. These data lead to promising benefits of probiotics in reducing the risk of COVID-19. Further studies should be conducted to assess the ability of probiotics to combat COVID-19.

Keywords: Applied microbiology; SARS-CoV-2.

Conflict of interest statement

Competing interestsThe authors declare no competing interests.

© The Author(s) 2020.

References

    1. Lehtoranta L, Pitkäranta A, Korpela R. Probiotics in respiratory virus infections. Eur. J. Clin. Microbiol. Infect. Dis. 2014;33:1289–1302. doi: 10.1007/s10096-014-2086-y.
    1. Zolnikova O, Komkova I, Potskherashvili N, Trukhmanov A, Ivashkin V. Application of probiotics for acute respiratory tract infections. Ital. J. Med. 2018;12:32–38. doi: 10.4081/itjm.2018.931.
    1. European Respiratory Society. The Global Impact of Respiratory Disease. 2nd edn. (Forum of International Respiratory Societies, 2017).
    1. Rodriguez-Morales AJ, et al. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med. Infect. Dis. 2020;34:101623. doi: 10.1016/j.tmaid.2020.101623.
    1. Xie M, Chen Q. Insight into 2019 novel coronavirus—an updated intrim review and lessons from SARS-CoV and MERS-CoV. Int. J. Infect. Dis. 2020;94:119–124. doi: 10.1016/j.ijid.2020.03.071.
    1. Zhu N, et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020;382:727–733. doi: 10.1056/NEJMoa2001017.
    1. Zu ZY, et al. Coronavirus disease 2019 (COVID-19): a perspective from China. Radiology. 2020;296:E15–E25. doi: 10.1148/radiol.2020200490.
    1. Jiang F, et al. Review of the clinical characteristics of Coronavirus Disease 2019 (COVID-19) J. Gen. Intern. Med. 2020;35:1545–1549. doi: 10.1007/s11606-020-05762-w.
    1. Lu C-W, Liu X-F, Jia Z-F. 2019-nCoV transmission through the ocular surface must not be ignored. Lancet. 2020;395:e39. doi: 10.1016/S0140-6736(20)30313-5.
    1. World Health Organization (WHO). Coronavirus disease (COVID-19) Pandemic. (2020).
    1. Lee PI, Hu YL, Chen PY, Huang YC, Hsueh PR. Are children less susceptible to COVID-19? J. Microbiol. Immunol. Infect. 2020;53:371–372. doi: 10.1016/j.jmii.2020.02.011.
    1. Zimmerman P, Curtis N. Coronavirus infections in children including COVID-19: an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children. Pediatr. Infect. Dis. J. 2020;39:355–368. doi: 10.1097/INF.0000000000002660.
    1. Guan W, et al. Clinical characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020;382:1708–1720. doi: 10.1056/NEJMoa2002032.
    1. Holshue ML, et al. First case of 2019 novel coronavirus in the United States. N. Engl. J. Med. 2020;382:929–936. doi: 10.1056/NEJMoa2001191.
    1. Wu Y, et al. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol. Hepatol. 2020;5:434–435. doi: 10.1016/S2468-1253(20)30083-2.
    1. Xiao F, et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterol. 2020;158:1831–1833. doi: 10.1053/j.gastro.2020.02.055.
    1. Kopel J, Perisetti A, Gajendran M, Boregowda U, Goyal H. Clinical insights into the gastrointestinal manifestations of COVID-19. Dig. Dis. Sci. 2020;65:1932–1939. doi: 10.1007/s10620-020-06362-8.
    1. Zuo, T. et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterol. 10.1053/j.gastro.2020.05.048 (2020).
    1. Tang, L. et al. Clinical significance of the correlation between changes in the major intestinal bacteria species and COVID-19 severity. Engineering.10.1016/j.eng.2020.05.013 (2020).
    1. Barcik W, Boutin RCT, Sokolowska M, Finlay BB. The role of lung and gut microbiota in the pathology of asthma. Immunity. 2020;52:241–255. doi: 10.1016/j.immuni.2020.01.007.
    1. Chehrazi N, Cipriano LE, Enns EA. Dynamics of drug resistance: optimal control of an infectious disease. Oper. Res. 2019;67:619–650. doi: 10.1287/opre.2018.1817.
    1. Bustamante M, et al. Probiotics and prebiotics potential for the care of skin, female urogenital tract, and respiratory tract. Folia Microbiol. (Praha). 2020;65:245–264. doi: 10.1007/s12223-019-00759-3.
    1. Hauptmann M, Schaible UE. Linking microbiota and respiratory disease. FEBS Lett. 2016;590:3721–3738. doi: 10.1002/1873-3468.12421.
    1. Sender, R., Fuchs, S. & Milo, R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 10.1371/journal.pbio.1002533 (2016).
    1. Rajilić-Stojanović M, de Vos WM. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol. Rev. 2014;38:996–1047. doi: 10.1111/1574-6976.12075.
    1. Zhang YJ, et al. Impacts of gut bacteria on human health and diseases. Int. J. Mol. Sci. 2015;16:7493–7519. doi: 10.3390/ijms16047493.
    1. Davison G, Kehaya C, Wyn Jones A. Nutritional and physical activity interventions to improve immunity. Am. J. Lifestyle Med. 2014;10:152–169. doi: 10.1177/1559827614557773.
    1. Bassis, C. M. et al. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. MBio.10.1128/mBio.00037-15 (2015).
    1. Dickson, R. P. et al. Bacterial topography of the healthy human lower respiratory tract. MBio. 10.1128/mBio.02287-16 (2017).
    1. Fanos V, Pintus MC, Pintus R, Marcialis MA. Lung microbiota in the acute respiratory disease: from coronavirus to metabolomics. J. Pediatr. Neonat. Individ. Med. 2020;9:e090139. doi: 10.7363/090139.
    1. Dang AT, Marsland BJ. Microbes, metabolites, and the gut–lung axis. Mucos. Immunol. 2019;12:843–850. doi: 10.1038/s41385-019-0160-6.
    1. Hufnagl K, Pali-Schöll I, Roth-Walter F, Jensen-Jarolim E. Dysbiosis of the gut and lung microbiome has a role in asthma. Semin. Immunopathol. 2020;42:75–93. doi: 10.1007/s00281-019-00775-y.
    1. Wang H, et al. Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases. World J. Gastroenterol. 2013;19:6794–6804. doi: 10.3748/wjg.v19.i40.6794.
    1. Mukherjee S, Hanidziar D. More of the gut in the lung: how two microbiomes meet in ARDS. Yale J. Biol. Med. 2018;91:143–149.
    1. Otani, S. & Coopersmith, C. M. Gut integrity in critical illness. J. Intens. Care7, 17. 10.1186/s40560-019-0372-6 (2019).
    1. Smyk W, et al. COVID-19: focus on the lungs but do not forget the gastrointestinal tract. Eur. J. Clin. Invest. 2020;50:e13276. doi: 10.1111/eci.13276.
    1. Wan Y, et al. Enteric involvement in hospitalised patients with COVID-19 outside Wuhan. Lancet Gastroenterol. Hepatol. 2020;5:534–535. doi: 10.1016/S2468-1253(20)30118-7.
    1. Sze MA, et al. Changes in the bacterial microbiota in gut, blood, and lungs following acute LPS instillation into mice lungs. PLoS ONE. 2014;9:e111228. doi: 10.1371/journal.pone.0111228.
    1. He Y, et al. Gut–lung axis: the microbial contributions and clinical implications. Crit. Rev. Microbiol. 2017;43:81–95. doi: 10.1080/1040841X.2016.1176988.
    1. Vital M, Harkema JR, Rizzo M, Tiedje J, Brandenberger C. Alterations of the murine gut microbiome with age and allergic airway disease. J. Immunol. Res. 2015;2015:892568. doi: 10.1155/2015/892568.
    1. Tian Y, Rong L, Nian W, He Y. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment. Pharmacol. Ther. 2020;51:843–851. doi: 10.1111/apt.15731.
    1. Suresh Kumar VC, et al. Novelty in the gut: a systematic review and meta-analysis of the gastrointestinal manifestations of COVID-19. BMJ Open Gastroenterol. 2020;7:e000417. doi: 10.1136/bmjgast-2020-000417.
    1. Ciaglia E, Vecchione C, Puca AA. COVID-19 infection and circulating ace2 levels: protective role in women and children. Front. Pediatr. 2020;8:206. doi: 10.3389/fped.2020.00206.
    1. Te Riet L, Van Esch JHM, Roks AJM, Van Den Meiracker AH, Danser AHJ. Hypertension: renin-angiotensin-aldosterone system alterations. Circ. Res. 2015;116:960–975. doi: 10.1161/CIRCRESAHA.116.303587.
    1. Perrone EE, et al. Mechanisms of methicillin-resistant Staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis. Shock. 2012;38:68–75. doi: 10.1097/SHK.0b013e318259abdb.
    1. Budden KF, et al. Emerging pathogenic links between microbiota and the gut-lung axis. Nat. Rev. Microbiol. 2017;15:55–63. doi: 10.1038/nrmicro.2016.142.
    1. FAO/WHO. Guidelines for the Evaluation of Probiotics in Food. (2002).
    1. Bron PA, Van Baarlen P, Kleerebezem M. Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat. Rev. Microbiol. 2012;10:66–78. doi: 10.1038/nrmicro2690.
    1. Saad N, Delattre C, Urdaci M, Schmitter JM, Bressollier P. An overview of the last advances in probiotic and prebiotic field. LWT Food Sci. Technol. 2013;50:1–16. doi: 10.1016/j.lwt.2012.05.014.
    1. Santosa S, Farnworth E, Jones PJH. Probiotics and their potential health claims. Nutr. Rev. 2006;64:265–274. doi: 10.1111/j.1753-4887.2006.tb00209.x.
    1. Al Kassaa, I. New Insights on Antiviral Probiotics: From Research to Applications (Springer, 2016).
    1. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J. Nutr. 1995;125:1401–1412. doi: 10.1093/jn/125.6.1401.
    1. Gibson GR, et al. The international scientific association and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 2017;14:491–502. doi: 10.1038/nrgastro.2017.75.
    1. Guarino MPL, et al. Mechanisms of action of prebiotics and their effects on gastro-intestinal disorders in adults. Nutrients. 2020;12:1037. doi: 10.3390/nu12041037.
    1. Davani-Davari D, et al. Prebiotics: definition, types, sources, mechanisms, and clinical applications. Foods. 2019;8:92. doi: 10.3390/foods8030092.
    1. 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. 2019;119:25–38. doi: 10.1016/j.maturitas.2018.11.002.
    1. Foligne B, et al. A key role of dendritic cells in probiotic functionality. PLoS ONE. 2007;2:e313. doi: 10.1371/journal.pone.0000313.
    1. De Roock S, et al. Gut derived lactic acid bacteria induce strain specific CD4 + T cell responses in human PBMC. Clin. Nutr. 2011;30:845–851. doi: 10.1016/j.clnu.2011.05.005.
    1. Fu L, Song J, Wang C, Fu S, Wang Y. Bifidobacterium infantis potentially alleviates shrimp tropomyosin-induced allergy by tolerogenic dendritic cell-dependent induction of regulatory T cells and alterations in gut microbiota. Front. Immunol. 2017;8:1536. doi: 10.3389/fimmu.2017.01536.
    1. Kitazawa H, et al. Expression of mRNA encoding IFNα in macrophages stimulated with Lactobacillus gasseri. FEMS Microbiol. Lett. 1994;120:315–321.
    1. Balzaretti S, et al. A novel rhamnose-rich hetero-exopolysaccharide isolated from Lactobacillus paracasei DG activates THP-1 human monocytic cells. Appl. Environ. Microbiol. 2017;83:e02702–e02716. doi: 10.1128/AEM.02702-16.
    1. Dargahi N, Johnson J, Apostolopoulos V. Streptococcus thermophilus alters the expression of genes associated with innate and adaptive immunity in human peripheral blood mononuclear cells. PLoS ONE. 2020;15:e0228531. doi: 10.1371/journal.pone.0228531.
    1. Dargahi N, Johnson J, Donkor O, Vasiljevic T, Apostolopoulos V. Immunomodulatory effects of Streptococcus thermophilus on U937 monocyte cell cultures. J. Funct. Foods. 2018;49:241–249. doi: 10.1016/j.jff.2018.08.038.
    1. Dargahi N, Matsoukas J, Apostolopoulos V. Streptococcus thermophilus ST285 alters pro-inflammatory to anti-inflammatory cytokine secretion against multiple sclerosis peptide in mice. Brain Sci. 2020;10:126. doi: 10.3390/brainsci10020126.
    1. Kudva A, et al. Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice. J. Immunol. 2011;186:1666–1674. doi: 10.4049/jimmunol.1002194.
    1. Chung YW, Choi JH, Oh TY, Eun CS, Han DS. Lactobacillus casei prevents the development of dextran sulphate sodium-induced colitis in Toll-like receptor 4 mutant mice. Clin. Exp. Immunol. 2008;151:182–189. doi: 10.1111/j.1365-2249.2007.03549.x.
    1. Zendeboodi F, Khorshidian N, Mortazavian AM, da Cruz AG. Probiotic: conceptualization from a new approach. Cur. Opin. Food Sci. 2020;32:103–123. doi: 10.1016/j.cofs.2020.03.009.
    1. Olaimat AN, et al. Emergence of antibiotic resistance in Listeria monocytogenes isolated from food products: a comprehensive review. Compr. Rev. Food Sci. Food Saf. 2018;17:1277–1292. doi: 10.1111/1541-4337.12387.
    1. Khan R, Petersen FC, Shekhar S. Commensal bacteria: an emerging player in defense against respiratory pathogens. Front. Immunol. 2019;10:1–9. doi: 10.3389/fimmu.2019.00001.
    1. Chiba E, et al. Immunobiotic Lactobacillus rhamnosus improves resistance of infant mice against respiratory syncytial virus infection. Int. Immunopharmacol. 2013;17:373–382. doi: 10.1016/j.intimp.2013.06.024.
    1. Eguchi K, Fujitani N, Nakagawa H, Miyazaki T. Prevention of respiratory syncytial virus infection with probiotic lactic acid bacterium Lactobacillus gasseri SBT2055. Sci. Rep. 2019;9:1–2. doi: 10.1038/s41598-019-39602-7.
    1. 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. 2013;110:1810–1818. doi: 10.1017/S0007114513001104.
    1. 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. 2010;51:6–10.
    1. Zhang H, et al. Prospective study of probiotic supplementation results in immune stimulation and improvement of upper respiratory infection rate. Synth. Syst. Biotechnol. 2018;3:113–120. doi: 10.1016/j.synbio.2018.03.001.
    1. Jung YJ, et al. Heat-killed Lactobacillus casei confers broad protection against influenza A virus primary infection and develops heterosubtypic immunity against future secondary infection. Sci. Rep. 2017;7:1–12. doi: 10.1038/s41598-016-0028-x.
    1. Hori T, Kiyoshima J, Shida K, Yasui H. Effect of Intranasal Administration of Lactobacillus casei Shirota on influenza virus infection of upper respiratory tract in mice. Clin. Diagn. Lab. Immunol. 2001;8:593–597. doi: 10.1128/CDLI.8.3.593-597.2001.
    1. Le Noci V, et al. Modulation of pulmonary microbiota by antibiotic or probiotic aerosol therapy: a strategy to promote immunosurveillance against lung metastases. Cell Rep. 2018;24:3528–3538. doi: 10.1016/j.celrep.2018.08.090.
    1. Park MK, et al. Lactobacillus plantarum DK119 as a probiotic confers protection against influenza virus by modulating innate immunity. PLoS ONE. 2013;8:26–29.
    1. Harata G, et al. Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses. Lett. Appl. Microbiol. 2010;50:597–602. doi: 10.1111/j.1472-765X.2010.02844.x.
    1. Marchisio P, et al. Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children. Eur. J. Clin. Microbiol. Infect. Dis. 2015;34:2377–2383. doi: 10.1007/s10096-015-2491-x.
    1. Tomosada Y, et al. Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection. BMC Immunol. 2013;14:40. doi: 10.1186/1471-2172-14-40.
    1. Zelaya H, et al. Nasal priming with immunobiotic Lactobacillus rhamnosus modulates inflammation–coagulation interactions and reduces influenza virus-associated pulmonary damage. Inflamm. Res. 2015;64:589–602. doi: 10.1007/s00011-015-0837-6.
    1. Kawase M, et al. Heat-killed Lactobacillus gasseri TMC0356 protects mice against influenza virus infection by stimulating gut and respiratory immune responses. FEMS Immunol. Med. Microbiol. 2012;64:280–288. doi: 10.1111/j.1574-695X.2011.00903.x.
    1. Youn HN, et al. Intranasal administration of live Lactobacillus species facilitates protection against influenza virus infection in mice. Antivir. Res. 2012;93:138–43. doi: 10.1016/j.antiviral.2011.11.004.
    1. Robles-Vera I, et al. Antihypertensive effects of probiotics. Curr. Hypertens. Rep. 2017;19:26. doi: 10.1007/s11906-017-0723-4.
    1. Ayyash MM, Sherkat F, Shah NP. The effect of NaCl substitution with KCl on Akawi cheese: Chemical composition, proteolysis, angiotensin-converting enzyme-inhibitory activity, probiotic survival, texture profile, and sensory properties. J. Dairy Sci. 2012;95:4747–4759. doi: 10.3168/jds.2011-4940.
    1. Ayyash M, Olaimat A, Al-Nabulsi A, Liu SQ. Bioactive properties of novel probiotic Lactococcus lactis fermented camel sausages: Cytotoxicity, angiotensin converting enzyme inhibition, antioxidant capacity, and antidiabetic activity. Food Sci. Anim. Resour. 2020;40:155–171. doi: 10.5851/kosfa.2020.e1.
    1. Miremadi F, Ayyash M, Sherkat F, Stojanovska L. Cholesterol reduction mechanisms and fatty acid composition of cellular membranes of probiotic Lactobacilli and Bifidobacteria. J. Funct. Foods. 2014;9:295–305. doi: 10.1016/j.jff.2014.05.002.
    1. Fernández-Fernández FJ. COVID-19, hypertension and angiotensin receptor-blocking drugs. J. Hypertens. 2020;38:1191. doi: 10.1097/HJH.0000000000002468.
    1. Esler M, Esler D. Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? J. Hypertens. 2020;38:781–782. doi: 10.1097/HJH.0000000000002450.
    1. Imai Y, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436:112–116. doi: 10.1038/nature03712.
    1. Yeh TL, et al. The influence of prebiotic or probiotic supplementation on antibody titers after influenza vaccination: A systematic review and meta-analysis of randomized controlled trials. Drug Des. Devel. Ther. 2018;12:217–230. doi: 10.2147/DDDT.S155110.
    1. Infusino F, et al. Diet supplementation, probiotics, and nutraceuticals in SARS-CoV-2 infection: a scoping review. Nutrients. 2020;12:1718. doi: 10.3390/nu12061718.
    1. Xu K, et al. Management of corona virus disease-19 (COVID-19): The Zhejiang experience. Zhejiang Da Xue Xue Bao. Yi Xue Ban. 2020;49:147–157.
    1. Gasmi A, et al. Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic. Clin. Immunol. 2020;215:108409. doi: 10.1016/j.clim.2020.108409.
    1. Makino S, et al. Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1. Br. J. Nutr. 2010;104:998–1006. doi: 10.1017/S000711451000173X.
    1. Merenstein D, et al. Use of a fermented dairy probiotic drink containing Lactobacillus casei (DN-114 001) to decrease the rate of illness in kids: the DRINK study A patient-oriented, double-blind, cluster-randomized, placebo-controlled, clinical trial. Eur. J. Clin. Nutr. 2010;64:669–677. doi: 10.1038/ejcn.2010.65.
    1. Shida K, et al. Daily intake of fermented milk with Lactobacillus casei strain Shirota reduces the incidence and duration of upper respiratory tract infections in healthy middle-aged office workers. Eur. J. Nutr. 2017;56:45–53. doi: 10.1007/s00394-015-1056-1.
    1. Taipale T, et al. Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in infancy. Br. J. Nutr. 2011;105:409–416. doi: 10.1017/S0007114510003685.
    1. Wu D, Lewis ED, Pae M, Meydani SN. Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Front. Immunol. 2019;10:1–19. doi: 10.3389/fimmu.2019.00001.
    1. Landete JM, et al. Probiotic bacteria for healthier aging: immunomodulation and metabolism of phytoestrogens. Biomed. Res. Int. 2017;2017:5939818. doi: 10.1155/2017/5939818.
    1. Liu Y, Tran DQ, Rhoads JM. Probiotics in disease prevention and treatment. J. Clin. Pharmacol. 2018;58(Suppl 10):S164–S179. doi: 10.1002/jcph.1121.
    1. King S, et al. Does probiotic consumption reduce antibiotic utilization for common acute infections? A systematic review and meta-analysis. Eur. J. Public Health. 2019;29:494–499. doi: 10.1093/eurpub/cky185.
    1. Wang Y, et al. Probiotics for prevention and treatment of respiratory tract infections in children: a systematic review and meta-analysis of randomized controlled trials. Med. (Baltim.) 2016;95:e4509. doi: 10.1097/MD.0000000000004509.

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