Unravelling the potential of synbiotics in ameliorating COVID-19 complications: A concise review

Abstract

The ongoing COVID-19 pandemic has highlighted the need for innovative strategies to mitigate the severe complications associated with infection caused by SARS-CoV-2. Developing empirical studies posited that the gut microbiota play a key role in modulating the immune response and overall health. This review explores the potential of synbiotics, a combination of probiotics and prebiotics, as a promising therapeutic approach to ameliorate COVID-19 complications. We conducted a comprehensive review of the literature to assess the impact of synbiotics on key aspects of the pathogenesis of this disease. Several studies indicate that synbiotics can bolster the gut microbiome, enhance mucosal barrier function, and regulate the immune system. These effects may be particularly beneficial in COVID-19, where immune dysregulation and cytokine storm are implicated in severe disease. We discuss the mechanisms through which synbiotics influence the gut axis, modulating the immune response and potentially reducing the risk of acute respiratory distress syndrome and other complications. Furthermore, synbiotics may help manage gastrointestinal symptoms often associated with COVID-19 and support the recovery of patients. While current research is promising, further clinical trials are needed to validate the safety and efficacy of synbiotics in the context of COVID-19. This review underscores the potential of synbiotics as an adjunctive therapy to conventional treatments for COVID-19, offering a novel and integrated approach to improve patient outcomes and reduce the burden of this health challenge worldwide.

Keywords

SARS-CoV-2 / COVID-19 / Synbiotics / Prebiotics / Probiotics

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Funding

This study receives no extramural funding.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

Oti VB designed the study, performed literature search, and wrote the first draft. Oti VB, Adah OF, Dzator J, Omoloye NAY and Kandagor B read the manuscript, made corrections to the manuscript, reviewed, and edited the content of the entire manuscript. All authors approved the final copy of the manuscript before submission.

References

[1] Lamers MM, Haagmans BL. SARS-CoV-2 pathogenesis. Nat Rev Microbiol 2022; 20(5): 270-284.

[2] Friedel DM, Cappell MS. Diarrhea and coronavirus disease 2019 infection. Gastroenterol Clin 2023; 52(1): 59-75.

[3] Baj J, Karakuła-Juchnowicz H, Teresiński G, Buszewicz G, Ciesielka M, Sitarz R, et al. COVID-19: Specific and non-specific clinical manifestations and symptoms: The current state of knowledge. J Clin Med 2020; 9(6): 1753.

[4] Hirani H. Technological innovations for effective pandemic response. Florida: CRC Press; 2022.

[5] Reuben RC, Danladi MMA, Saleh DA, Ejembi PE. Knowledge, attitudes and practices towards COVID-19: An epidemiological survey in North-Central Nigeria. J Community Health 2021; 46: 457-470.

[6] Dhakal S, Charoen P, Pan-Ngum W, Luvira V, Sivakorn C, Hanboonkunupakarn B, et al. Severity of COVID-19 in patients with diarrhoea: A systematic review and meta-analysis. Trop Med Infect 2023; 8(2): 84.

[7] Xavier-Santos D, Padilha M, Fabiano GA, Vinderola G, Cruz AG, Sivieri K, et al. Evidences and perspectives of the use of probiotics, prebiotics, synbiotics, and postbiotics as adjuvants for prevention and treatment of COVID-19: A bibliometric analysis and systematic review. Trends Food Sci 2022; 120: 174-192.

[8] Litten-Brown JC, Corson AM, Clarke L. Porcine models for the metabolic syndrome, digestive and bone disorders: A general overview. Animal 2010; 4(6): 899-920.

[9] Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, et al. Prebiotics: Definition, types, sources, mechanisms, and clinical applications. Foods 2019; 8(3): 92.

[10] Tzounis X, Rodriguez-Mateos A, Vulevic J, Gibson GR, Kwik-Uribe C, Spencer JPE. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. Am J Clin Nutr 2011; 93(1): 62-72.

[11] Loomis AK, Kabadi S, Preiss D, Hyde C, Bonato V, St. Louis M, et al. Body mass index and risk of nonalcoholic fatty liver disease: Two electronic health record prospective studies. J Clin Endocrinol Metab 2016; 101(3): 945-952.

[12] Davani-Davari D, Karimzadeh I, Khalili H. The potential effects of anabolic-androgenic steroids and growth hormone as commonly used sport supplements on the kidney: A systematic review. BMC Nephrol 2019; 20: 1-12.

[13] Desai AG, Qazi GN, Ganju RK, El-Tamer M, Singh J, Saxena AK, et al. Medicinal plants and cancer chemoprevention. Curr Drug Metab 2008; 9(7): 581-91.

[14] Gogineni VK, Morrow LE, Malesker MA. Probiotics: Mechanisms of action and clinical applications. J Prob Health 2013; 1(1): 1-11.

[15] Mackowiak PA. Recycling Metchnikoff: Probiotics, the intestinal microbiome and the quest for long life. Front Public Health 2013; 1: 52.

[16] Schroeder B, Duncker S, Barth S, Bauerfeind R, Gruber AD, Deppenmeier S, et al. Preventive effects of the probiotic Escherichia coli strain Nissle 1917 on acute secretory diarrhea in a pig model of intestinal infection. Dig Dis Sci 2006; 51: 724-731.

[17] Parvez S, Malik KA, Ah Kang S, Kim HY. Probiotics and their fermented food products are beneficial for health. J Appl Microbiol 2006; 100(6): 1171-1185.

[18] Masood MI, Qadir MI, Shirazi JH, Khan IU. Beneficial effects of lactic acid bacteria on human beings. Crit Rev Microbiol 2011; 37(1): 91-98.

[19] Yadav MK, Kumari I, Singh B, Sharma KK, Tiwari SK. Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics. Appl Microbiol Biotechnol 2022; 106(2): 505-521.

[20] Garg M, Kaur S, Sharma A, Kumari A, Tiwari V, Sharma S, et al. Rising demand for healthy foods-anthocyanin biofortified colored wheat is a new research trend. Front Nutr 2022; 9: 878221.

[21] Shim WJ, Song YK, Hong SH, Jang M. Identification and quantification of microplastics using Nile Red staining. Mar Pollut Bull 2016; 113(1-2): 469-476.

[22] Markowiak P, Śliżewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients 2017; 9(9): 1021.

[23] Sharma M, Shukla G. Metabiotics: One step ahead of probiotics: An insight into mechanisms involved in anticancerous effect in colorectal cancer. Front Microbiol 2016; 7: 1940.

[24] Swanson KS, Gibson GR, Hutkins R, Reimer RA, Reid G, Verbeke K, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat Rev Gastroenterol Hepatol 2020; 17(11): 687-701.

[25] Yang ZR, Thomson R, McNeil P, Esnouf RM. RONN: the bio-basis function neural network technique applied to the detection of natively disordered regions in proteins. Bioinform 2005; 21(16): 3369-3376.

[26] Cicero AFG, Fogacci F, Bove M, Giovannini M, Borghi C. Impact of a short-term synbiotic supplementation on metabolic syndrome and systemic inflammation in elderly patients: A randomized placebo-controlled clinical trial. Europ J Nutr 2021; 60: 655-663.

[27] Roy D. Media for the isolation and enumeration of bifidobacteria in dairy products. Int J Food Microbiol 2001; 69(3): 167-182.

[28] Al-Sheraji SH, Ismail A, Manap MY, Mustafa S, Yusof RM, Hassan FA . Prebiotics as functional foods: A review. J Functional Foods 2013; 5(4): 1542-1553.

[29] Shinde T, Perera AP, Vemuri R, Gondalia SV, Karpe AV, Beale DJ, et al. Synbiotic supplementation containing whole plant sugar cane fibre and probiotic spores potentiates protective synergistic effects in mouse models of IBD. Nutrients 2019; 11(4): 818.

[30] Lau RI, Su Q, Lau ISF, Ching JYL, Wong MCS, Lau LHS, et al. A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): A randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 2024; 24(3): 256-265.

[31] Vaezi M, Ravanshad S, Akbari Rad M, Zarrinfar H, Kabiri M. The effect of synbiotic adjunct therapy on clinical and paraclinical outcomes in hospitalized COVID-19 patients: A randomized placebo-controlled trial. J Med Virol 2023; 95(2): e28463.

[32] Wischmeyer PE, Tang H, Ren Y, Bohannon L, Jiang D, Bergens M, et al. Efficacy of probiotic treatment as post-exposure prophylaxis for COVID-19: A double-blind, Placebo-Controlled Randomized trial. Clin Nutr 2024; 43(1): 259-267.

[33] Khanna D, Lin CJF, Furst DE, Goldin J, Kim G, Kuwana M, et al. Tocilizumab in systemic sclerosis: A randomised, double-blind, placebo-controlled, Phase 3 trial. The Lancet Res Med 2020; 8(10): 963-974.

[34] Singh K, Rao A. Probiotics: A potential immunomodulator in COVID-19 infection management. Nutr Res 2021; 87: 1-12.

[35] Ahlawat A, Wiedensohler A, Mishra SK. An overview on the role of relative humidity in airborne transmission of SARS-CoV-2 in indoor environments. Aerosol Air Qual Res 2020; 20(9): 1856-1861.

[36] Meng L, Hua F, Bian Z. Coronavirus disease 2019 (COVID-19): emerging and future challenges for dental and oral medicine. J Dental Res 2020; 99(5): 481-487.

[37] Ahanchian H, Ranjbar A, Reihani H, Yazdi AP, Jafari SA, Kiani MA, et al. Synbiotic for prevention of SARS-CoV2 infection in high-risk hospital staffs: A randomized controlled trial. Open J Nurs 2021; 11(5): 281-290.

[38] Antunes KH, Fachi JL, de Paula R, da Silva EF, Pral LP, Dos Santos AÁ, et al. Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response. Nat Comm 2019; 10(1): 3273.

[39] Smith TJ, Rigassio-Radler D, Denmark R, Haley T, Touger-Decker R. Effect of Lactobacillus rhamnosus LGG® and Bifidobacterium animalis ssp. lactis BB-12® on health-related quality of life in college students affected by upper respiratory infections. Br J Nutr 2013; 109(11): 1999-2007.

[40] Sly PD, Galbraith S, Islam Z, Holt B, Troy N, Holt PG. Primary prevention of severe lower respiratory illnesses in at-risk infants using the immunomodulator OM-85. J Allergy Clin Immunol 2019; 144(3): 870-872.

[41] Baud D, Dimopoulou Agri V, Gibson GR, Reid G, Giannoni E . Using probiotics to flatten the curve of coronavirus disease COVID-2019 pandemic. Front Public Health 2020; 8: 186.

[42] Villena J, Chiba E, Tomosada Y, Salva S, Marranzino G, Kitazawa H, et al. Orally administered Lactobacillus rhamnosus modulates the respiratory immune response triggered by the viral pathogen-associated molecular pattern poly (I: C). BMC Immunol 2012; 13(1): 1-15.

[43] Belkina TV, Averina OV, Savenkova EV, Danilenko VN. Human intestinal microbiome and the immune system: The role of probiotics in shaping an immune system unsusceptible to COVID-19 infection. Biol Bull Rev 2021; 11: 329-343.

[44] Maldonado Galdeano C, Cazorla SI, Lemme Dumit JM, Vélez E, Perdigón G . Beneficial effects of probiotic consumption on the immune system. Ann Nutr Metab 2019; 74(2): 115-124.

[45] Chan CKY, Tao J, Chan OS, Li HB, Pang H. Preventing respiratory tract infections by synbiotic interventions: A systematic review and meta-analysis of randomized controlled trials. Adv Nutr 2020; 11(4): 979-88.

[46] Ahanchian H, Jafari SA, Ansari E, Ganji T, Kiani MA, Khalesi M, et al. A multi-strain synbiotic may reduce viral respiratory infections in asthmatic children: A randomized controlled trial. Electr Physician 2016; 8(9): 2833.

[47] Ringel-Kulka T, Kotch JB, Jensen ET, Savage E, Weber DJ. Randomized, double-blind, placebo-controlled study of synbiotic yogurt effect on the health of children. J Pediatr 2015; 166(6): 1475-1481.

[48] Mak JWY, Chan FKL, Ng SC. Probiotics and COVID-19: One size does not fit all. Lancet Gastroenterol Hepatol 2020; 5(7): 644-645.

[49] Kurian SJ, Unnikrishnan MK, Miraj SS, Bagchi D, Banerjee M, Reddy BS, et al. Probiotics in prevention and treatment of COVID-19: Current perspective and future prospects. Arch Med Res 2021; 52(6): 582-594.