The use of probiotics as current adjuvant therapy for SARS-CoV-2 infection in gastrointestinal disease

Cover Page

Cite item

Full Text

Abstract

Introduction. SARS-CoV-2 is a virus that causes COVID-19 which is currently a pandemic situation. The symptoms of COVID-19 can vary from asymptomatic to acute respiratory distress syndrome. Some patients may also have gastrointestinal manifestations such as diarrhea, vomiting, and abdominal pain. Recently, it is known that some COVID-19 patients also showed microbial dysbiosis with decreased Lactobacillus and Bifidobacterium. With the increasing number of reported cases and gastrointestinal symptoms in COVID-19 patients, we are trying to summarize the possibility of using probiotics as the current adjuvant therapy for gastrointestinal disease due to SARS-CoV-2 infection. Materials and methods. We did a comprehensive literature search on PubMed, Science Direct, Google Scholar and screened bibliographies of other articles. The search yielded 2836 articles and 55 of them met eligibility criteria for this systematic review. Results and discussion. Probiotics can affect the gastrointestinal tract through some mechanism including: 1) competitive exclusion of pathogens and production of antimicrobial substances, 2) enzymatic activities and production of volatile fatty acid, 3) cell adhesion and mucin production, 4) enhancement of epithelial barrier, 5) modulation of the immune system. In recent data, probiotics are used in some COVID-19 patients with gastrointestinal disease. It is also considered to help overcome cytokine storms by suppressing proinflammatory cytokines and enhance the patient’s immunity by modulating the immune system. Conclusion. Probiotics can be used as the current adjuvant therapy to eliminate gastrointestinal disease in SARS-CoV-2 infection and prevent further complications of COVID-19. However, further clinical research still needed to determine the effectiveness of probiotics in COVID-19 patients.

About the authors

Denny Budiyono

Sebelas Maret University

Author for correspondence.
Email: denny.budiyono@yahoo.co.id

General Practitioner, Faculty of Medicine

Indonesia, Surakarta

A. M. Intan

Sebelas Maret University

Email: intanardyla1608@gmail.com

Sp.PD., M. Kes, Dr. Moewardi Hospital, Faculty of Medicine

Indonesia, Surakarta

P. A. Nurhasan

Sebelas Maret University

Email: dr.nurhasan21@staff.uns.ac.id

Sp.PD., M. Kes, Dr. Moewardi Hospital, Faculty of Medicine

Indonesia, Surakarta

References

  1. Bahreini-Esfahani N., Moravejolahkami A.R. Can Synbiotic Dietary Pattern Predict Lactobacillales Strains in Breast Milk? Breastfeed. Med., 2020, vol. 15, no. 6, pp. 387–393. doi: 10.1089/bfm.2019.0301
  2. Baud D., Dimopoulou Agri V., Gibson G.R., Reid G., Giannoni E. Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic. Front. Public Health, 2020, vol. 8: 186. doi: 10.3389/fpubh.2020.00186
  3. Bermudez-Brito M., Plaza-Díaz J., Muñoz-Quezada S., Gómez-Llorente C., Gil A. Probiotic mechanisms of action. Ann. Nutr. Metab., 2012, vol. 61, no. 2, pp. 160–174. doi: 10.1159/000342079
  4. Bradley C.P., Teng F., Felix K.M., Sano T., Naskar D., Block K.E., Huang H., Knox K.S., Littman D.R., Wu H.J. Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut–lung Axis Th17 Cells Expressing Dual TCRs. Cell Host Microbe, 2017, vol. 22, no. 5, pp. 697–704.e4: doi: 10.1016/j.chom.2017.10.007
  5. Budden K.F., Gellatly S.L., Wood D.L.A., Cooper M.A., Morrison M., Hugenholtz P., Hansbro P.M. Emerging pathogenic links between microbiota and the gut–lung axis. Nat. Rev. Microbiol., 2017, vol. 15, no. 1, pp. 55–63. doi: 10.1038/nrmicro.2016.142
  6. Canfora E.E., Jocken J.W.E., Blaak E.E. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat. Rev. Endocrinol., 2015, vol. 11, no. 10, pp. 577–591. doi: 10.1038/nrendo.2015.128
  7. Chan J.F.W., Yuan S., Kok K.H., To K.K.W., Chu H., Yang J., Xing F., Liu J., Yip C.C.Y., Poon R.W.S., Tsoi H.W., Lo S.K.F., Chan K.H., Poon V.K.M., Chan W.M., Ip J.D., Cai J.P., Cheng V.C.C., Chen H., Hui C.K.M., Yuen K.Y. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet, 2020, vol. 395, no. 10223, pp. 514–523. doi: 10.1016/S0140-6736(20)30154-9
  8. Channappanavar R., Fehr A.R., Vijay R., Mack M., Zhao J., Meyerholz D.K., Perlman S. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe, 2016, vol. 19, no. 2, pp. 181–193. doi: 10.1016/j.chom.2016.01.007
  9. Channappanavar R., Zhao J., Perlman S. T cell-mediated immune response to respiratory coronaviruses. Immunol. Res., 2014, vol. 59, no. 1–3, pp. 118–128. doi: 10.1007/s12026-014-8534-z
  10. Chousterman B.G., Swirski F.K., Weber G.F. Cytokine storm and sepsis disease pathogenesis. Semin. Immunopathol., 2017, vol. 39, no. 5, pp. 517–528. doi: 10.1007/s00281-017-0639-8
  11. Dang A.T., Marsland B.J. Microbes, metabolites, and the gut–lung axis. Mucosal Immunol., 2019, vol. 12, no. 4, pp. 843–850. doi: 10.1038/s41385-019-0160-6
  12. Dhar D., Mohanty A. Gut microbiota and Covid-19 — possible link and implications. Virus Res., 2020, vol. 285: 198018. doi: 10.1016/j.virusres.2020.198018
  13. Enaud R., Prevel R., Ciarlo E., Beaufils F., Wieërs G., Guery B., Delhaes L. The Gut–lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks. Front. Cell Infect. Microbiol., 2020, vol. 10: 9. doi: 10.3389/fcimb.2020.00009
  14. Giorgetti G., Brandimarte G., Fabiocchi F., Ricci S., Flamini P., Sandri G., Trotta M.C., Elisei W., Penna A., Lecca P.G., Picchio M., Tursi A. Interactions between Innate Immunity, Microbiota, and Probiotics. J. Immunol. Res., 2015, 2015: 501361. doi: 10.1155/2015/501361
  15. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X., Liu L., Shan H., Lei C.L., Hui D.S.C., Du B., Li L.J., Zeng G., Yuen K.Y., Chen R.C., Tang C.L., Wang T., Chen P.Y., Xiang J., Li S.Y., Wang J.L., Liang Z.J., Peng Y.X., Wei L., Liu Y., Hu Y.H., Peng P., Wang J.M., Liu J.Y., Chen Z., Li G., Zheng Z.J., Qiu S.Q., Luo J., Ye C.J., Zhu S.Y., Zhong N.S.; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med., 2020, vol. 382, no. 18, pp. 1708–1720. doi: 10.1056/NEJMoa2002032
  16. Hasannejad-Bibalan M., Hekmatnezhad H. A light shining through darkness: probiotic against COVID-19. J Curr Biomed Rep, 2020, vol. 1, no. 1, pp. 1–2. doi: 10.52547/jcbior.1.1.1
  17. Hasan N., Yang H. Factors affecting the composition of the gut microbiota, and its modulation. Peer J., 2019, vol. 7: e7502. doi: 10.7717/peerj.7502
  18. Hassan S.A., Sheikh F.N., Jamal S., Ezeh J.K., Akhtar A. Coronavirus (COVID-19): A Review of Clinical Features, Diagnosis, and Treatment. Cureus, 2020, vol. 12, no. 3: e7355. doi: 10.7759/cureus.7355
  19. 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, vol. 43, no. 1, pp. 81–95. doi: 10.1080/1040841X.2016.1176988
  20. Högner K., Wolff T., Pleschka S., Plog S., Gruber A.D., Kalinke U., Walmrath H.D., Bodner J., Gattenlöhner S., Lewe-Schlosser P., Matrosovich M., Seeger W., Lohmeyer J., Herold S. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS Pathog., 2013, vol. 9, no. 2: e1003188. doi: 10.1371/journal.ppat.1003188
  21. Horowitz R.I., Freeman P.R., Bruzzese J. Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases. Respir. Med. Case Rep., 2020, vol. 30: 101063. doi: 10.1016/j.rmcr.2020.101063
  22. Hur K.Y., Lee M.S. Gut Microbiota and Metabolic Disorders. Diabetes Metab. J., 2015, vol. 39, no. 3, pp. 198–203. doi: 10.4093/dmj.2015.39.3.198
  23. Holshue M.L., DeBolt C., Lindquist S., Lofy K.H., Wiesman J., Bruce H., Spitters C., Ericson K., Wilkerson S., Tural A., Diaz G., Cohn A., Fox L., Patel A., Gerber S.I., Kim L., Tong S., Lu X., Lindstrom S., Pallansch M.A., Weldon W.C., Biggs H.M., Uyeki T.M., Pillai S.K.; Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N. Engl. J. Med., 2020, vol. 382, no. 10, pp. 929–936. doi: 10.1056/NEJMoa2001191
  24. Jiang X., Tao J., Wu H., Wang Y., Zhao W., Zhou M., Huang J., You Q., Meng H., Zhu F., Zhang X., Qian M., Qiu Y. Clinical features and management of severe COVID-19: A retrospective study in Wuxi, Jiangsu Province, China. medRxiv, vol. 2020: 2020.04.10.20060335: doi: 10.1101/2020.04.10.20060335
  25. Liang W., Feng Z., Rao S., Xiao C., Xue X., Lin Z., Zhang Q., Qi W. Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus. Gut, 2020, vol. 69, no. 6, pp. 1141–1143. doi: 10.1136/gutjnl-2020-320832
  26. Marsland B.J., Trompette A., Gollwitzer E.S. The Gut–lung Axis in Respiratory Disease. Ann. Am. Thorac. Soc., 2015, vol. 12, Suppl. 2, pp. S150-S156. doi: 10.1513/AnnalsATS.201503-133AW
  27. McAleer J.P., Kolls J.K. Contributions of the intestinal microbiome in lung immunity. Eur. J. Immunol., 2018, vol. 48, no. 1, pp. 39–49. doi: 10.1002/eji.201646721
  28. McAleer J.P., Nguyen N.L., Chen K., Kumar P., Ricks D.M., Binnie M., Armentrout R.A., Pociask D.A., Hein A., Yu A., Vikram A., Bibby K., Umesaki Y., Rivera A., Sheppard D., Ouyang W., Hooper L.V., Kolls J.K. Pulmonary Th17 Antifungal Immunity Is Regulated by the Gut Microbiome. J. Immunol., 2016, vol. 197, no. 1, pp. 97–107. doi: 10.4049/jimmunol.1502566
  29. McFarland L.V. Use of probiotics to correct dysbiosis of normal microbiota following disease or disruptive events: a systematic review. BMJ Open, 2014, vol. 4, no. 8: e005047. doi: 10.1136/bmjopen-2014-005047
  30. Mousa H.A. Prevention and Treatment of Influenza, Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural Therapies. J. Evid. Based Complement. Altern. Med., 2017, vol. 22, no. 1, pp. 166–174. doi: 10.1177/2156587216641831
  31. Musa S. Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now? Arab. J. Gastroenterol., 2020, vol. 21, no. 1, pp. 3–8. doi: 10.1016/j.ajg.2020.03.002
  32. Neurath M.F. COVID-19 and immunomodulation in IBD. Gut, 2020, vol. 69, no. 7, pp. 1335–1342. doi: 10.1136/gutjnl-2020-321269
  33. Pan L., Mu M., Yang P., Sun Y., Wang R., Yan J., Li P., Hu B., Wang J., Hu C., Jin Y., Niu X., Ping R., Du Y., Li T., Xu G., Hu Q., Tu L. Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study. Am. J. Gastroenterol., 2020, vol. 115, no. 5, pp. 766–773. doi: 10.14309/ajg.0000000000000620
  34. Plaza-Díaz J., Ruiz-Ojeda F.J., Gil-Campos M., Gil A. Immune-Mediated Mechanisms of Action of Probiotics and Synbiotics in Treating Pediatric Intestinal Diseases. Nutrients, 2018, vol. 10, no. 1: 42. doi: 10.3390/nu10010042
  35. Plaza-Diaz J., Ruiz-Ojeda F.J., Gil-Campos M., Gil A. Mechanisms of Action of Probiotics. Adv. Nutr., 2019, vol. 10, suppl. 1, pp. S49-S66. doi: 10.1093/advances/nmy063. Erratum in: Adv. Nutr., 2020, vol. 11, no. 4, pp. 1054. doi: 10.1093/advances/nmaa042
  36. Pourhossein M., Moravejolahkami A.R. Probiotics in viral infections, with a focus on COVID-19: A Systematic Review. Authorea, vol. 2020: 158938616.61042433: doi: 10.22541/au.158938616.61042433
  37. Qamar M.A. COVID-19: a look into the modern age pandemic. Z. Gesundh. Wiss., 2022, vol. 30, no. 1, pp. 249–252. doi: 10.1007/s10389-020-01294-z
  38. Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y., Xie C., Ma K., Shang K., Wang W., Tian D.S. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin. Infect. Dis., 2020, vol. 71, no. 15, pp. 762–768. doi: 10.1093/cid/ciaa248
  39. Song W., Li J., Zou N., Guan W., Pan J., Xu W. Clinical features of pediatric patients with coronavirus disease (COVID-19). J. Clin. Virol., 2020, vol. 127: 104377. doi: 10.1016/j.jcv.2020.104377
  40. Tan J.Y., Tang Y.C., Huang J. Gut Microbiota and Lung Injury. Adv. Exp. Med. Biol., 2020, vol. 1238, pp. 55–72. doi: 10.1007/978-981-15-2385-4_5
  41. 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, vol. 51, no. 9, pp. 843–851. doi: 10.1111/apt.15731
  42. Wang H., Gao K., Wen K., Allen I.C., Li G., Zhang W., Kocher J., Yang X., Giri-Rachman E., Li G.H., Clark-Deener S., Yuan L. Lactobacillus rhamnosus GG modulates innate signaling pathway and cytokine responses to rotavirus vaccine in intestinal mononuclear cells of gnotobiotic pigs transplanted with human gut microbiota. BMC Microbiol., 2016, vol. 16, no. 1: 109. doi: 10.1186/s12866-016-0727-2
  43. West C.E., Jenmalm M.C., Prescott S.L. The gut microbiota and its role in the development of allergic disease: a wider perspective. Clin. Exp. Allergy, 2015, vol. 45, no. 1, pp. 43–53. doi: 10.1111/cea.12332
  44. World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report – 51. 11 March 2020. WHO, 2020, vol. 51, pp. 1–10. URL: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10
  45. World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report – 146. 14 June 2020. WHO, 2020, vol. 146, pp. 1–15. URL: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200614-covid-19-sitrep-146.pdf?sfvrsn=5b89bdad_6
  46. Wong S.H., Lui R.N., Sung J.J. Covid-19 and the digestive system. J. Gastroenterol. Hepatol., 2020, vol. 35, no. 5, pp. 744–748. doi: 10.1111/jgh.15047
  47. Xiao F., Tang M., Zheng X., Liu Y., Li X., Shan H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology, 2020, vol. 158, no. 6, pp. 1831–1833.e3: doi: 10.1053/j.gastro.2020.02.055
  48. Xu X.W., Wu X.X., Jiang X.G., Xu K.J., Ying L.J., Ma C.L., Li S.B., Wang H.Y., Zhang S., Gao H.N., Sheng J.F., Cai H.L., Qiu Y.Q., Li L.J. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ, 2020, vol. 368: m606. doi: 10.1136/bmj.m606
  49. Xu Y., Li X., Zhu B., Liang H., Fang C., Gong Y., Guo Q., Sun X., Zhao D., Shen J., Zhang H., Liu H., Xia H., Tang J., Zhang K., Gong S. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat. Med., 2020, vol. 26, no. 4, pp. 502–505. doi: 10.1038/s41591-020-0817-4
  50. Yadav A.K., Tyagi A., Kumar A., Panwar S., Grover S., Saklani A.C., Hemalatha R., Batish V.K. Adhesion of Lactobacilli and their anti-infectivity potential. Crit. Rev. Food Sci. Nutr., 2017, vol. 57, no. 10, pp. 2042–2056. doi: 10.1080/10408398.2014.918533
  51. Young B.E., Ong S.W.X., Kalimuddin S., Low J.G., Tan S.Y., Loh J., Ng O.T., Marimuthu K., Ang L.W., Mak T.M., Lau S.K., Anderson D.E., Chan K.S., Tan T.Y., Ng T.Y., Cui L., Said Z., Kurupatham L., Chen M.I., Chan M., Vasoo S., Wang L.F., Tan B.H., Lin R.T.P., Lee V.J.M., Leo Y.S., Lye D.C.; Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA, 2020, vol. 323, no. 15, pp. 1488–1494. doi: 10.1001/jama.2020.3204
  52. Yuki K., Fujiogi M., Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin. Immunol., 2020, vol. 215: 108427. doi: 10.1016/j.clim.2020.108427
  53. Zaim S., Chong J.H., Sankaranarayanan V., Harky A. COVID-19 and Multiorgan Response. Curr. Probl. Cardiol., 2020, vol. 45, no. 8: 100618. doi: 10.1016/j.cpcardiol.2020.100618
  54. Zhang D., Li S., Wang N., Tan H.Y., Zhang Z., Feng Y. The Cross-Talk Between Gut Microbiota and Lungs in Common Lung Diseases. Front. Microbiol., 2020, vol. 11: 301. doi: 10.3389/fmicb.2020.00301
  55. Zhang H., Kang Z., Gong H., Xu D., Wang J., Li Z., Li Z., Cui X., Xiao J., Zhan J., Meng T., Zhou W., Liu J., Xu H. Digestive system is a potential route of COVID-19: an analysis of single-cell co-expression pattern of key proteins in viral entry process. Gut, 2020, vol. 69, no. 6, pp. 1010–1018. doi: 10.1136/gutjnl-2020-320953
  56. Zhang W., Du R.H., Li B., Zheng X.S., Yang X.L., Hu B., Wang Y.Y., Xiao G.F., Yan B., Shi Z.L., Zhou P. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg. Microbes Infect., 2020, vol. 9, no. 1, pp. 386–389. doi: 10.1080/22221751.2020.1729071
  57. Zhou Y., Fu B., Zheng X., Wang D., Zhao C., Qi Y., Sun R., Tian Z., Xu X., Wei H. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl. Sci. Rev., 2020, vol. 7, no. 6, pp. 998–1002. doi: 10.1093/nsr/nwaa041
  58. Zuo T., Zhang F., Lui G.C.Y., Yeoh Y.K., Li A.Y.L., Zhan H., Wan Y., Chung A.C.K., Cheung C.P., Chen N., Lai C.K.C., Chen Z., Tso E.Y.K., Fung K.S.C., Chan V., Ling L., Joynt G., Hui D.S.C., Chan F.K.L., Chan P.K.S., Ng S.C. Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology, 2020, vol. 159, no. 3, pp. 944–955.e8: doi: 10.1053/j.gastro.2020.05.048

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Budiyono D., Intan A.M., Nurhasan P.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).