Digestive System and Severe Acute Respiratory Syndrome Coronavirus 2: New Era of Microbiome Study and Gastrointestinal Tract Manifestations during the Coronavirus Disease-19 Pandemic

Alibek Kossumov; Karakoz Mussabay; Astghik Pepoyan; Vardan Tsaturyan; Ketevan Sidamonidze; David Tsereteli; Adil Supiyev; Samat Kozhakhmetov; Laura Chulenbayeva; Marat Dusmagambetov; Massimo Pignatelli; Zhaxybay Zhumadilov; Francesco Marotta; Almagul Kushugulova

doi:10.3889/oamjms.2021.7470

Authors

Alibek Kossumov Centre for Life Science, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan https://orcid.org/0000-0001-7827-6697
Karakoz Mussabay Department of Microbiology and Virology Named After Sh.I. Sarbasova, Astana Medical University, Nur-Sultan, Kazakhstan
Astghik Pepoyan Department of Food Safety and Biotechnology, Armenian National Agrarian University, Yerevan, Armenia; International Association for Human and Animals Health Improvement, Yerevan, Armenia
Vardan Tsaturyan International Association for Human and Animals Health Improvement, Yerevan, Armenia; Chair of Field Therapy, Yerevan State Medical University, Yerevan, Armenia
Ketevan Sidamonidze Department of Virology, Molecular Biology and Genome Research Communicable Diseases, National Centre for Disease Control and Public Health, Tbilisi, Georgia; Lugar Center for Public Health Research, Tbilisi, Georgia
David Tsereteli Communicable Diseases, National Centre for Disease Control and Public Health, Tbilisi, Georgia
Adil Supiyev Centre for Life Science, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan
Samat Kozhakhmetov Centre for Life Science, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan; Kazakhstan Association of Human Microbiome Researchers, Nur-Sultan, Kazakhstan
Laura Chulenbayeva Centre for Life Science, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan; Kazakhstan Association of Human Microbiome Researchers, Nur-Sultan, Kazakhstan
Marat Dusmagambetov Department of Microbiology and Virology Named After Sh.I. Sarbasova, Astana Medical University, Nur-Sultan, Kazakhstan
Massimo Pignatelli ReGenera R&D International for Aging Intervention, Milan, Italy
Zhaxybay Zhumadilov ReGenera R&D International for Aging Intervention, Milan, Italy
Francesco Marotta School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan
Almagul Kushugulova Centre for Life Science, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan; Kazakhstan Association of Human Microbiome Researchers, Nur-Sultan, Kazakhstan

DOI:

https://doi.org/10.3889/oamjms.2021.7470

Keywords:

Severe acute respiratory syndrome coronavirus 2, Virus-host interaction, Angiotensin-converting enzyme 2 receptor, Gut microbiome, Gastrointestinal tract, Probiotic

Abstract

Main focuses of the review were that during the pandemic of SARS-CoV-2 were gastrointestinal disorders were accompanying. Viral RNA and viral particles are found in feces for more than 30 days. Although SARS-CoV-2 primarily causes lung infection through binding to ACE2 receptors, intestinal epithelial cells, especially enterocytes of the small intestine, also express ACE2 receptors. It is also known that a respiratory viral infection causes disturbances in the gut microbiota. Diet, environmental factors, and genetics play an important role in the formation of gut microbiota, which can affect immunity. The diversity of gut microbiota diminishes in old age, and Covid-19 has been mostly fatal in older patients, further indicating the role that gut microbiota may play in this disease. It is therefore plausible that the gut microbiota could be a new therapeutic target and that probiotics could have a role in the management of these patients.

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References

Hasan N, Yang H. Factors affecting the composition of the gut microbiota, and its modulation. PeerJ. 2019;7:e7502. https://doi.org/10.7717/peerj.7502 PMid:31440436 DOI: https://doi.org/10.7717/peerj.7502

Chakaroun RM, Massier L, Kovacs P. Gut microbiome, intestinal permeability, and tissue bacteria in metabolic disease: Perpetrators or bystanders? Nutrients. 2020;12(4):1082. https://doi.org/10.3390/nu12041082 PMid:32295104 DOI: https://doi.org/10.3390/nu12041082

Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang RF. Impact of microbiota on central nervous system and neurological diseases: The gut-brain axis. J Neuroinflammation. 2019;16:53. https://doi.org/10.1186/s12974-019-1434-3 PMid:30823925 DOI: https://doi.org/10.1186/s12974-019-1434-3

Dhar D, Mohanty A. Gut microbiota and Covid-19- possible link and implications. Virus Res. 2020;285:198018. https://doi.org/10.1016/j.virusres.2020.198018 PMid:32430279 DOI: https://doi.org/10.1016/j.virusres.2020.198018

World Health Organization. WHO Coronavirus (COVID-19) Dashboard, With Vaccination Data. Geneva: World Health Organization; 2021.

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(9):843-51. https://doi.org/10.1111/apt.15731 PMid:32222988 DOI: https://doi.org/10.1111/apt.15731

Zhiwei Y, Ganwen L, Xiaoling D, Guirong L, Gang L, Yusheng J. Three cases of novel coronavirus pneumonia with viral nucleic acids still positive in stool after throat swab detection turned negative. Chinese J Dig. 2020;12:E002.

Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H, et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020158(6):1831-3.e3. https://doi.org/10.1053/j.gastro.2020.02.055 PMid:32142773 DOI: https://doi.org/10.1053/j.gastro.2020.02.055

Donati Zeppa S, Agostini D, Piccoli G, Stocchi V, Sestili P. Gut microbiota status in COVID-19: An unrecognized player? Front Cell Infect Microbiol. 2020;10:576551. https://doi.org/10.3389/fcimb.2020.576551 PMid:33324572 DOI: https://doi.org/10.3389/fcimb.2020.576551

Vaiserman AM, Koliada AK, Marotta F. Gut microbiota: A player in aging and a target for anti-aging intervention. Ageing Res Rev. 2017;35:36-45. https://doi.org/10.1016/j.arr.2017.01.001 PMid:28109835 DOI: https://doi.org/10.1016/j.arr.2017.01.001

Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol. 2019;10:277. https://doi.org/10.3389/fimmu.2019.00277 PMid:30915065 DOI: https://doi.org/10.3389/fimmu.2019.01486

Taylor SA, Green RM. Bile acids, microbiota, and metabolism. Hepatology. 2018;68(4):1229-31. https://doi.org/10.1002/hep.30078 PMid:29729182 DOI: https://doi.org/10.1002/hep.30078

Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157(1):121-41. https://doi.org/10.1016/j.cell.2014.03.011 PMid:24679531 DOI: https://doi.org/10.1016/j.cell.2014.03.011

Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster. Lancet. 2020;395(10223):514-23. https://doi.org/10.1016/S0140-6736(20)30154-9 PMid:31986261 DOI: https://doi.org/10.1016/S0140-6736(20)30154-9

Zhang J, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARSCoV-2 in Wuhan, China. Allergy. 2020;75(7):1730-41. https://doi.org/10.1111/all.14238 PMid:32077115 DOI: https://doi.org/10.1111/all.14238

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical

course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020;395(10229):1054-62. https://doi.org/10.1016/S0140-6736(20)30566-3 PMid:32171076 DOI: https://doi.org/10.1016/S0140-6736(20)30566-3

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 2020;395(10223):507-13. https://doi.org/10.1016/S0140-6736(20)30211-7 PMid:32007143 DOI: https://doi.org/10.1016/S0140-6736(20)30211-7

Guan W, Ni Z, Hu Y. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-20. https://doi.org/10.1016/j.jemermed.2020.04.004 DOI: https://doi.org/10.1016/j.jemermed.2020.04.004

Liang W, Feng Z, Rao S, Xiao C, Xue X, Lin Z, et al. Diarrhoea may be underestimated: A missing link in 2019 novel coronavirus. Gut. 2020;69(6):1141. https://doi.org/10.1136/gutjnl-2020-320832 PMid:32102928 DOI: https://doi.org/10.1136/gutjnl-2020-320832

Lin L, Meng AT, Ma D. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020;69:997-1001. DOI: https://doi.org/10.1136/gutjnl-2020-321013

Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: A systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(7):667-8. https://doi.org/10.1016/S2468-1253(20)30126-6 PMid:32405603 DOI: https://doi.org/10.1016/S2468-1253(20)30126-6

Gao QY. Chen YX, Fang JY. 2019 Novel coronavirus infection and gastrointestinal tract. J Dig Dis. 2020;21:125-6. https://doi.org/10.1111/1751-2980.12851 PMid:32096611 DOI: https://doi.org/10.1111/1751-2980.12851

Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. N Engl J Med. 2020;382(17):1663-5. https://doi.org/10.1056/NEJMc2005073 PMid:32187458 DOI: https://doi.org/10.1056/NEJMc2005073

Wan Y, Li J, Shen L, Zou Y, Hou L, Zhu L, et al. Enteric involvement in hospitalised patients with COVID-19 outside Wuhan. Lancet Gastroenterol Hepatol. 2020;5(6):534-5. https://doi.org/10.1016/S2468-1253(20)30118-7 PMid:32304638 DOI: https://doi.org/10.1016/S2468-1253(20)30118-7

Jin X, Lian JS, Hu JH, Gao J, Zheng L, Zhang YM, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020;69(6):1002-9. DOI: https://doi.org/10.1136/gutjnl-2020-320926

Cheung KS, Hung IF, Chan PP, Lung KC, Tso E, Liu R, et al. Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from a hong kong cohort: Systematic review and meta-analysis. Gastroenterology. 2020;159(1):81-95. https://doi.org/10.1053/j.gastro.2020.03.065 PMid:32251668 DOI: https://doi.org/10.1053/j.gastro.2020.03.065

Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10):929-36. https://doi.org/10.1056/NEJMoa2001191 PMid:32004427 DOI: https://doi.org/10.1056/NEJMoa2001191

Nobel YR, Phipps M, Zucker J, Lebwohl B, Wang TC, Sobieszczyk ME, et al. Gastrointestinal symptoms and coronavirus disease 2019: A case-control study from the United States. Gastroenterology. 2020;159:373-5.e2. https://doi.org/10.1053/j.gastro.2020.04.017 PMid:32294477 DOI: https://doi.org/10.1053/j.gastro.2020.04.017

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England). 2020;395:497-506. https://doi.org/10.1016/S0140-6736(20)30183-5 PMid:31986264 DOI: https://doi.org/10.1016/S0140-6736(20)30183-5

Pazgan-Simon M, Rorat M, Buczyńska I, Zińczuk A, Simon K. Gastrointestinal symptoms as the first, atypical indication of severe acute respiratory syndrome coronavirus 2 infection. Pol Arch Intern Med. 2020;130(4):338-9. https://doi.org/10.20452/pamw.15278 PMid:32250094 DOI: https://doi.org/10.20452/pamw.15278

Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-81. https://doi.org/10.1016/S2213-2600(20)30079-5. DOI: https://doi.org/10.1016/S2213-2600(20)30079-5

Keely S, Talley NJ, Hansbro PM. Pulmonary-intestinal crosstalk in mucosal inflammatory disease. Mucosal Immunol. 2012;5(1):7-18. https://doi.org/10.1038/mi.2011.55 PMid:22089028 DOI: https://doi.org/10.1038/mi.2011.55

Zhang D, Li S, Wang N, Tan HY, Zhang Z, Feng Y. The cross-talk between gut microbiota and lungs in common lung diseases. Front Microbiol. 2020;11:301. https://doi.org/10.3389/fmicb.2020.00301 PMid:32158441 DOI: https://doi.org/10.3389/fmicb.2020.00301

Dumas A, Bernard L, Poquet Y, Lugo-Villarino G, Neyrolles O. The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases. Cell Microbiol. 2018;20(12):e12966. https://doi.org/10.1111/cmi.12966 PMid:30329198 DOI: https://doi.org/10.1111/cmi.12966

Groves HT, Higham SL, Moffatt MF, Cox MJ, Tregoning JS. Respiratory Viral Infection Alters the Gut Microbiota by Inducing Inappetence. mBio. 2020;11(1):e03236-19. https://doi.org/10.1128/mBio.03236-19 PMid:32071269 DOI: https://doi.org/10.1128/mBio.03236-19

Lake MA. What we know so far: COVID-19 current clinical knowledge and research. Clin Med. 2020;20(2):124-7. https://doi.org/10.7861/clinmed.2019-coron PMid:32139372 DOI: https://doi.org/10.7861/clinmed.2019-coron

Dickson RP. The microbiome and critical illness. Lancet Respir Med. 2016;4(1):59-72. https://doi.org/10.1016/S2213-2600(15)00427-0 PMid:26700442 DOI: https://doi.org/10.1016/S2213-2600(15)00427-0

Ma C, Cong Y, Zhang H. COVID-19 and the digestive system. Am J Gastroenterol. 2020;115(7):1003-6. https://doi.org/10.14309/ajg.0000000000000691 PMid:32618648 DOI: https://doi.org/10.14309/ajg.0000000000000691

Wang X, Zheng J, Guo L, Yao H, Wang L, Xia XD, et al. Fecal viral shedding in COVID-19 patients: Clinical significance, viral load dynamics and survival analysis. Virus Res. 2020;289:198147. https://doi.org/10.1016/j.virusres.2020.198147 PMid:32866537 DOI: https://doi.org/10.1016/j.virusres.2020.198147

Yeoh YK, Zuo T, Lui GC, Zhang F, Liu A, Li AY, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70(4):698-706. https://doi.org/10.1136/gutjnl-2020-323020 PMid:33431578 DOI: https://doi.org/10.1136/gutjnl-2020-323020

Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323:1843-4. https://doi.org/10.1001/jama.2020.3786 PMid:32159775 DOI: https://doi.org/10.1001/jama.2020.3786

Wu Y, Guo C, Tang L, Hong Z, Zhou J, Dong X, et al. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol. 2020;5(5):434-5. https://doi.org/10.1016/S2468-1253(20)30083-2 PMid:32199469 DOI: https://doi.org/10.1016/S2468-1253(20)30083-2

Xu Y, Li X, Zhu B, Liang H, Fang C, Gong Y, et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020;26(4):502-5. https://doi.org/10.1038/s41591-020-0817-4 PMid:32284613 DOI: https://doi.org/10.1038/s41591-020-0817-4

Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220-30. https://doi.org/10.1038/nature11550 PMid:22972295 DOI: https://doi.org/10.1038/nature11550

Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: Mechanisms of intestinal immunomodulation and neuromodulation. Ther Adv Gastroenterol. 2013;6(1):39-51. https://doi.org/10.1177/1756283X12459294 PMid:23320049 DOI: https://doi.org/10.1177/1756283X12459294

Mak JW, Chan FK, Ng SC. Probiotics and COVID-19: One size does not fit all. Lancet Gastroenterol Hepatol. 2020;5(7):644-5. https://doi.org/10.1016/S2468-1253(20)30122-9 PMid:32339473 DOI: https://doi.org/10.1016/S2468-1253(20)30122-9

Lazar V, Ditu LM, Pircalabioru GG, Gheorghe I, Curutiu C, Holban AM, et al. Aspects of gut microbiota and immune system interactions in infectious diseases, immunopathology, and cancer. Front Immunol. 2018;9:1830. https://doi.org/10.3389/fimmu.2018.01830 PMid:30158926 DOI: https://doi.org/10.3389/fimmu.2018.01830

Shinde T, Hansbro PM, Sohal SS, Dingle P, Eri R, Stanley R, et al. Microbiota modulating nutritional approaches to countering the effects of viral respiratory infections including SARS-CoV-2 through promoting metabolic and immune fitness with probiotics and plant bioactives. Microorganisms. 2020;8(6):921. https://doi.org/10.3390/microorganisms8060921 PMid:32570850 DOI: https://doi.org/10.3390/microorganisms8060921

Snyder J. Oral therapy for acute diarrhea. Rep Pediatr Infect Dis. 1993;3:6-7.

Bartlett JG. Antibiotic-associated diarrhea. N Engl J Med. 2002;346:334-9. DOI: https://doi.org/10.1056/NEJMcp011603

Logan C, Beadsworth MB, Beeching NJ. HIV and diarrhoea: What is new? Curr Opin Infect Dis. 2016;29(5):486-94. https://doi.org/10.1097/QCO.0000000000000305 PMid:27472290 DOI: https://doi.org/10.1097/QCO.0000000000000305

Bradley KC, Finsterbusch K, Schnepf D, Crotta S, Llorian M, Davidson S, et al. Microbiota-driven tonic interferon signals in lung stromal cells protect from influenza virus infection. Cell Rep. 2019;28(1):245-56.e4. https://doi.org/10.1016/j.celrep.2019.05.105 PMid:31269444 DOI: https://doi.org/10.1016/j.celrep.2019.05.105

Bagherpour G, Ghasemi H, Zand B, Zarei N, Roohvand F, Ardakani EM, et al. Oral administration of recombinant Saccharomyces boulardii expressing ovalbumin-CPE fusion protein induces antibody response in mice. Front Microbiol. 2018;9:723. https://doi.org/10.3389/fmicb.2018.00723 PMid:29706942 DOI: https://doi.org/10.3389/fmicb.2018.00723

Pepoyan AZ, Balayan MH, Manvelyan AM, Mamikonyan V, Isajanyan M, Tsaturyan VV, et al. Lactobacillus acidophilus INMIA 9602 Er-2 strain 317/402 probiotic regulates growth of commensal Escherichia coli in gut microbiota of familial Mediterranean fever disease subjects. Lett Appl Microbiol. 2017;64(4):254-60. https://doi.org/10.1111/lam.12722 PMid:28140472 DOI: https://doi.org/10.1111/lam.12722

Pepoyan AZ, Manvelyan AM, Balayan MH, McCabe G, Tsaturyan VV, Melnikov VG, et al. The effectiveness of potential probiotics Lactobacillus rhamnosus Vahe and Lactobacillus delbrueckii IAHAHI in irradiated rats depends on the nutritional stage of the host. Probiotics Antimicrob Proteins. 2020;12(4):1439-50. https://doi.org/10.1007/s12602-020-09662-7 PMid:32462507 DOI: https://doi.org/10.1007/s12602-020-09662-7

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):4812. https://doi.org/10.1038/s41598-019-39602-7 PMid:30886158 DOI: https://doi.org/10.1038/s41598-019-39602-7

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(6):710-7. https://doi.org/10.2174/1381612824666180116163411 PMid:29345577 DOI: https://doi.org/10.2174/1381612824666180116163411

Al Kassaa I. New Insights on Antiviral Probiotics: From Research to Applications. New Insights on Antiviral Probiotics: From Research to Applications. Berlin, Germany: Springer International Publishing; 2016. https://doi.org/10.1007/978-3-319-49688-7 DOI: https://doi.org/10.1007/978-3-319-49688-7

Lehtoranta L, Pitkäranta A, Korpela R. Probiotics in respiratory virus infections. Eur J Clin Microbiol Infect Dis. 2014;33(8):1289-302. https://doi.org/10.1007/s10096-014-2086-y PMid:24638909 DOI: https://doi.org/10.1007/s10096-014-2086-y

Rautava S, Salminen S, Isolauri E. Specific probiotics in reducing the risk of acute infections in infancy-a randomised, doubleblind, placebo-controlled study. Br J Nutr. 2009;101:1722-6. DOI: https://doi.org/10.1017/S0007114508116282

Chong HX, Yusoff NA, Hor YY, Lew LC, Jaafar MH, Choi SB, et al. Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: A randomised, double-blind, placebo-controlled study. Benef Microbes. 2019;10:355-73. https://doi.org/10.3920/BM2018.0135 PMid:30882244 DOI: https://doi.org/10.3920/BM2018.0135

Sanders ME, Merenstein DJ, Ouwehand AC, Reid G, Salminen S, Cabana MD, et al. Probiotic use in at-risk populations. J Am Pharm Assoc. 2016;56(6):680-6. https://doi.org/10.1016/j.japh.2016.07.001 PMid:27836128 DOI: https://doi.org/10.1016/j.japh.2016.07.001

Xiao L, Gong C, Ding Y, Ding G, Xu X, Deng C, et al. Probiotics maintain intestinal secretory immunoglobulin A levels in healthy formula-fed infants: A randomised, double-blind, placebocontrolled study. Benef Microbes 2019;10(7):729-39. https://doi.org/10.3920/BM2019.0025 PMid:31965842 DOI: https://doi.org/10.3920/BM2019.0025

Wang IK, Wu YY, Yang YF, Ting IW, Lin CC, Yen TH, et al. The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: A randomised, double-blind, placebo-controlled trial. Benef Microbes. 2015;6(4):423-30. https://doi.org/10.3920/BM2014.0088 PMid:25609654 DOI: https://doi.org/10.3920/BM2014.0088

Cosseau C, Devine DA, Dullaghan E, Gardy JL, Chikatamarla A, Gellatly S, et al. The commensal Streptococcus salivarius K12 downregulates the innate immune responses of human epithelial cells and promotes host-microbe homeostasis. Infect Immun. 2008;76(9):4163-75. https://doi.org/10.1128/IAI.00188-08 PMid:18625732 DOI: https://doi.org/10.1128/IAI.00188-08

Imaoka A, Shima T, Kato K, Mizuno S, Uehara T, Matsumoto S, et al. Anti-inflammatory activity of probiotic bifidobacterium: Enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells. World J Gastroenterol. 2008;14(16):2511-6. https://doi.org/10.3748/wjg.14.2511 PMid:18442197 DOI: https://doi.org/10.3748/wjg.14.2511

Kushugulova A, Kozhakhmetov S, Supiyev A, Shakhabayeva G, Saduakhasova S, Sabitkyzy S, et al. Isolation and characterization of lactobacilli from traditional Kazakh dairy products. Int J Probiotics Prebiotics. 2013;8(2-3):95-9.