THE ROLE OF THE INTESTINAL MICROBIOTA IN THE PATHOGENESIS OF BRONCHIAL ASTHMA

DOI: https://doi.org/https://doi.org/10.29296/24999490-2022-03-02

N.D. Potskherashvili, O. Yu. Zolnikova, V.T. Ivashkin
Sechenov First Moscow State University (Sechenov University), Russian Federation, ul. Trubetskaya 8, build. 2, Moscow, 119435

It is currently being discussed that the microbiota of the gastrointestinal tract and its metabolites affect the course of bronchial asthma (BA). The purpose to summarize the available data on the role of the intestinal microbiota in the pathogenesis of ВА. Material and methods. A analysis of the main foreign and domestic sources on PubMed / Medline, RSCI / elibrary databases over the last 25 years has been carried out. Results. In the course of the analysis of published works, the key links in the pathogenesis of ВА and changes arising from disturbance of intestinal microbiota composition (hygienic hypothesis, early prescription of antibacterial drugs) were compared. The results of studies on the role of bacterial overgrowth syndrome in the small intestine are analyzed. The results of studies where microbiota correction by prescribing probiotics and prebiotics resulted in positive effects on the course and prognosis in ВА are presented. Conclusion. A lot of data has been accumulated confirming the significant pathogenetic role of the microbiota. The positive effects of pro- and prebiotics both on the microbial composition of the intestine and on the course and prognosis in ВА allow us to consider the microbiome as a marker and a possible target in ВА therapy. All of the above dictates the need for further research in this area.
Keywords: 
intestinal microbiota, bronchial asthma, probiotics, cytokines
Список литературы: 
  1. Thursby E., Nathalie J. Introduction to the human gut microbiota. Biochemical J. 2017; 474: 1823–36. https://doi.org/10.1042/BCJ20160510
  2. Aagaard K., Riehle K., Ma J., Segata N., Mistretta T.-A., Coarfa C. Ametagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS ONE. 2012; 7: 36–46. https://doi.org/10.1371/journal.pone.0036466
  3. Backhed F., Roswall J., Peng Y., Feng Q., Jia H., Kovatcheva-Datchary P. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015; 17: 5. https://doi.org/10.1016/j.chom.2015.04.004
  4. Jakobsson H.E., Abrahamsson T.R., Jenmalm M.C., Harris K., Quince C., Jernberg C. Decreased gut microbiota diversity, delayed Bacteroidetescolonisation and reduced Th1 responses in infants delivered by caesarean section. Gut. 2012; 63: 559–66. https://doi.org/10.1136/gutjnl-2012-303249
  5. Avershina E., Storrø O., Øien T., Johnsen R., Pope P., Rudi K. Major faecal microbiota shifts in composition and diversity with age in a geographically restricted cohort of mothers and their children. FEMS Microbiol. Ecol. 2014; 87: 280–90. https://doi.org/10.1111/1574-6941.12223
  6. Koenig J.E., Spor A., Scalfone N., Fricker A.D., Stombaugh J. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 4578–85. https://doi.org/10.1073/pnas.1000081107
  7. Aagaard K., Ma J., Antony K.M., Ganu R., Petrosino J., Versalovic J. The placenta harbors a unique microbiome. Sci. Transl. Med. 2014; 6: 237. https://doi.org/10.1126/scitranslmed.3008599
  8. David L.A., Maurice C.F., Carmody R.N., Gootenberg D.B., Button J.E., Wolfe B.E. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2012; 505: 559–63. https://doi.org/10.1038/nature12820
  9. De Filippo C., Cavalieri D., Di Paola M., Ramazzotti M., Poullet J.B., Massart S. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 14691–6. https://doi.org/10.1073/pnas.1005963107
  10. Integrative HMP (iHMP) Research Network Consortium. The Integrative Human Microbiome Project Nature. 2019; 569 (7758): 641–8. https://doi.org/10.1038/s41586-019-1238-8
  11. Bouhnik Y., Alain S., Attar A., Flourié B., Raskine L., Sanson-Le Pors M.J., Rambaud J.C. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol. 1999; 94: 1327–31. https://doi.org/10.1111/j.1572-0241.1999.01016.x
  12. Grace E., Shaw C., Whelan K., Andreyev H.J. Review article: small intestinal bacterial overgrowth prevalence, clinical features, current and developing diagnostic tests, and treatment. Aliment Pharmacol Ther. 2013; 38 (7): 88. https://doi.org/10.1111/apt.12456
  13. Sachdev, A.H. Gastrointestinal Bacterial Overgrowth Pathogenesis and Clinical Significance. Ther. Adv. Chronic Dis. 2013; 4 (5): 223–31. https://doi.org/10.1177/2040622313496126
  14. Quigley E.M. Small Intestinal Bacterial Overgrowth: What It Is and What It Is Not Current Opinion in Gastroenterology. 2014; 30 (2): 141–6. https://doi.org/10.1097/MOG.0000000000000040
  15. Hoog C.M., Lindberg G., Sjoqvist U. Findings in patients with chronic intestinal dysmotility investigated by capsule endoscopy. BMC Gastroenterol. 2007; 7: 29. https://doi.org/10.1186/1471-230X-7-29
  16. Dibaise J.K., Young R.J., Vanderhoof J.A. Enteric microbial flora, bacterial overgrowth, and short-bowel syndrome. Clin Gastroenterol Hepatol. 2006; 4: 11–20. https://doi.org/10.1016/j.cgh.2005.10.020
  17. Nelis G.F., Vermeeren M.A., Jansen W. Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. Gastroenterology. 1990; 99: 1016–20. https://doi.org/10.1016/0016-5085(90)90621-7
  18. Nucera G., Gabrielli M., Lupascu A., Lauritano E.C., Santoliquido A., Cremonini F., Cammarota G., Tondi P., Pola P., Gasbarrini G., Gasbarrini A. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2005; 21: 1391–5. https://doi.org/10.1111/j.1365-2036.2005.02493.x.
  19. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, auto immunity and cancer. Physiol Rev. 2011; 91: 151–75. https://doi.org/10.1152/physrev.00003.2008
  20. Garate I., Garcia-Bueno В., Madrigal J.L.M. Origin and consequences of brain toll-like receptor 4 pathway stimulation in an experimental model of depression. J. Neuroinflamm. 2011; 8: 1–31. https://doi.org/10.1186/1742-2094-8-151.
  21. Gasbarrini A., Lauritano E.C., Gabrielli M., Scarpellini E., Lupascu A., Ojetti V., Gasbarrini G. Small intestinal bacterial overgrowth: diagnosis and treatment. Dig Dis. 2007; 25: 237–40. https://doi.org/10.1159/000103892.
  22. Fan X., Sellin J.H. Review article: Small intestinal bacterialovergrowth, bile acid malabsorption and gluten intolerance as possible causes of chronic watery diarrhoea. Aliment Pharmacol Ther. 2009; 29: 1069–77. https://doi.org/10.1111/j.1365-2036.2009.03970.x.
  23. Vanderhoof J.A., Young R.J. Etiology and pathogenesis of bacterial overgrowth. J. Pediatr Gastroenterol Nutr. 2010; 50 (6): 88–90. https://doi.org/10.1097/MPG.0b013e3181c15f60
  24. Quera R.P. Small intestinal bacterial overgrowth. Rev. Med. Chil. 2005; 133: 1361–70. https://doi.org/10.4067/s0034-98872005001100013.
  25. Riordan S.M., McIver C.J., Walker B.M., Duncombe V.M., Bolin T.D., Thomas M.C. The lactulose breath hydrogen test and small intestinal bacterial overgrowth. Am. J. Gastroenterol. 1996; 91: 1795–803. PMID: 8792701
  26. Kerlin P., Wong L. Breath hydrogen testing in bacterial overgrowth of the small intestine. Gastroenterology. 1988; 95: 982–8. https://doi.org/10.1016/0016-5085(88)90173-4.
  27. Gasbarrini A. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference Aliment. Pharmacol. Ther. 2009; 29 (1): 1–49. https://doi.org/10.1111/j.1365-2036.2009.03951.x
  28. Shah S.C. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth Aliment. Pharmacol. Ther. 2013; 38 (8): 925–34. https://doi.org/10.1111/apt.12479
  29. Lauritano E.C., Gabrielli M., Scarpellini E., Lupascu A., Novi M., Sottili S., Vitale G., Cesario V., Serricchio M., Cammarota G., Gasbarrini G., Gasbarrini A. Small intestinal bacterial overgrowth recurrence after antibiotic therapy. Am. J. Gastroenterol. 2008; 103 (8): 2031–5. https://doi.org/10.1111/j.1572-0241.2008.02030.x.
  30. Barclay L. Benefits of probiotics reviewed. Am. Fam Physician. 2008; 78: 1073e8. PMID: 19007054
  31. Lin H.V., Frassetto A., Kowalik EJ. Jr., Nawrocki A.R., Lu M.M., Kosinski J.R., Hubert J.A., Szeto D., Yao X., Forrest G., Marsh D.J. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012; 7 (4): 35240. https://doi.org/10.1371/journal.pone.0035240
  32. Samuelson D.R., Welsh D.A. and Shellito J.E. Regulation of lung immunity and host defense by the intestinal microbiota. Front. Microbiol. 2015; 6: 1085. https://doi.org/10.3389/fmicb.2015.01085
  33. 33. Brown A.J. The Orphan G protein-coupled receptors GPR41 and GPR43 are activatedby propionate and other short chain carboxylic acids. J. Biol. Chem. 2003; 278 (13): 11312–9. https://doi.org/10.1074/jbc.M211609200
  34. Ang Z., Ding J. GPR41 and GPR43 in Obesity and Inflammation –Protective or Causative? Front Immunol. 2016; 7: 28. https://doi.org/10.3389/fimmu.2016.00028
  35. Larsen J.M., Steen-Jensen D.B., Laursen J.M. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota. PLoS One. 2012; 7 (2): 31976. https://doi.org/10.1371/journal.pone.0031976
  36. Arrieta M., Leah T. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Translational Medicine. 2015; 7: 307ra152. https://doi.org/10.1126/scitranslmed.aab2271
  37. Abrahamsson T.R., Jakobsson H.E., Andersson A.F., Björkstén B., Engstrand L., Jenmalm M.C. Low gut microbiota diversity in early infancy precedes asthma at school age. ClinExp Allergy. 2014; 44 (6): 842–50. https://doi.org/10.1111/cea.12253
  38. Kalliomäki M., Kirjavainen P., Eerola E., Kero P., Salmi-nen S., Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J. Allergy ClinImmunol. 2001; 1: 129–34. https://doi.org/10.1067/mai.2001.111237.
  39. Gerrard J.W., Vickers P., Gerrard C.D. The familial incidence of allergic disease. Ann Allergy. 1976; 36: 10–5. PMID: 1247187
  40. Strachan D.P. Family size, infection and atopy: the first decade of the «hygiene hypothesis» Thorax. 2000; 55: 2–10. https://doi.org/10.1136/thorax.55.suppl_1.s2.
  41. Winkler P., Ghadimi D., Schrezenmeir J., Kraehenbuhl J.P. Molecular and cellular basis of microfloraehostinteractions. J. Nutr. 2007; 137: 756–72. https://doi.org/10.1093/jn/137.3.756S
  42. Tang R.B., Chen S.J. Soluble interleukin 2 receptor and interleukin 4 in sera of asthmatic children before and after a prednisolone course. Ann Allergy Asthma Immunol. 2001; 86 (3): 314–7. https://doi.org/10.1016/S1081-1206(10)63305-4.
  43. Herbst T., Sichelstiel A., Schar C., Yadava K., Burki K., Cahenzli J., McCoy K., Marsland B.J., Harris N.L. Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am. J. Respir Crit Care Med. 2011; 184 (2): 198–205. https://doi.org/10.1164/rccm.201010-1574OC
  44. De Kivit S., Tobin M.C., DeMeo M.T. In vitro evaluation of intestinal epithelial TLR activation in preventing food allergic responses. Clin. Immunol. 2014; 154 (2): 91–9. https://doi.org/10.1016/j.clim.2014.07.002
  45. Bjorksten B., Naaber P., Sepp E., Mikelsaar M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin. Exp Allergy. 1999; 29: 342–6. https://doi.org/10.1046/j.1365-2222.1999.00560.x.
  46. Toh Z.Q., Anzela A., Tang M.L., Licciardi P.V. Probiotic therapy as a novel approach for allergic disease. Front Pharmacol. 2012; 3: 171. https://doi.org/10.3389/fphar.2012.00171
  47. Ventura M., Turroni F., Canchaya C., Vaughan E.E., O'Toole P.W., van Sinderen D. Microbial diversity in the human intestine and novel insights from metagenomics. Front Biosci (Landmark Ed). 2009; 14: 3214–21. https://doi.org/10.2741/3445
  48. Hevia A., Milani Ch., López P., DonadoC. D. Allergic Patients with Long-Term Asthma Display Low Levels of Bifidobacterium adolescentis. PLoS ONE. 2011; 11 (2): e0147809. https://doi.org/10.1371/journal.pone.0147809
  49. Rogers G.B., Wesselingh S. Precision respiratory medicine and the microbiome. Lancet Respir Med. 2016; 4 (1): 73–82. https://doi.org/10.1016/S2213-2600(15)00476-2.
  50. Venkataraman A., BassisCh.M., Beck J.M., Young V. B. Application of a Neutral Community Model To Assess Structuring of the Human Lung Microbiome. mBio. 2015; 6: 02284–14. https://doi.org/10.1128/mBio.02284-14.
  51. Trompette A., Gollwitzer E. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nature Medicine. 2014; 20: 159–66. https://doi.org/10.1038/nm.3444
  52. Ganesh В.Р., Versalovic J. Luminal Conversion and Immunoregulation by Probiotics. Front Pharmacol. 2015; 6: 269. https://doi.org/10.3389/fphar.2015.00269
  53. Isolauri E, Joensuu J, Suomalainen H, Luomala M, Vesikari T. Improved immunogenicity of oral DxRRVreassortant rotavirus vaccine by Lactobacillus casei GG. Vaccine. 1995; 13: 310–2. https://doi.org/10.1016/0264-410x(95)93319-5.
  54. Smolinska S., Jutel M., Crameri R., O’Mahony L. Histamine and gut mucosal immune regulation. Allergy. 2014; 6: 273–81. https://doi.org/10.1111/all.12330
  55. Barcik W., Wawrzyniak M., Akdis C., O’Mahony L. Immune regulation by histamine and histamine-secreting bacteria. Current Opinion in Immunology. 2017; 48: 108–13. https://doi.org/10.1016/j.coi.2017.08.011
  56. Jutel M., Akdis M., Akdis C.A. Histamine, histamine receptors and their role in immune pathology. Clin. Exp Allergy. 2009; 39: 1786–800. https://doi.org/10.1111/j.1365-2222.2009.03374.x
  57. Liang X., Bushman FD., Fitz Gerald GA. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proc Natl Acad Sci USA. 2015; 112 (33): 10479–84. https://doi.org/10.1073/pnas.1501305112
  58. Salyers A.A. Bacteroides of the human lower intestinaltract. Annu Rev Microbiol. 1984; 38: 293–313. https://doi.org/10.1146/annurev.mi.38.100184.001453
  59. Hol J., van Leer E.H., Elink-Schuurman B.E., de Ruiter L.F., Samsom J.N., Hop W. et al. The acquisition of tolerance toward cow's milk through probiotic supplementation: a randomized, controlled trial. J. Allergy ClinImmunol. 2008; 121 (6): 1448–54. https://doi.org/10.1016/j.jaci.2008.03.018
  60. The Human Microbiome Project Consortium Structure, function and diversity of the healthy human microbiome. Nature. 2012; 486: 207–14. https://doi.org/10.1038/nature11234.
  61. Kirjavainen P.V., Gibson G.R. Healthy gut microflora and allergy: factors influencing development of the microbiota. Ann Med. 1999; 31 (2): 88–92. https://doi.org/10.3109/07853899908995892
  62. Pande C., Kumar A., Sarin Pande S. K., C. Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease. Aliment. Pharmacol. Ther. 2009; 29 (12): 1273–81. https://doi.org/10.1111/j.1365-2036.2009.03994.x.
  63. Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A. World Allergy Organization-McMaster University Guidelines for allergic disease prevention (GLAD-P): probiotics. World Allergy Organ J. 2015; 8 (1): 4–10. https://doi.org/10.1186/s40413-015-0055-2
  64. Helin T., Haahtela S., Haahtela T. No effect of oral treatment with an intestinal bacterial strain, Lactobacillus rhamnosus (ATCC 53103), on birch-pollen allergy: a placebo-controlled double-blind study. Allergy. 2002; 5: 243–6. https://doi.org/10.1034/j.1398-9995.2002.1s3299.x.
  65. Turnbaugh P., Ley R., Hamady M., Fraser-Liggett C., Knight R., Gordon J. Gordon Nature The human microbiome project: exploring the microbial part of ourselves in a changing world. PMC. 2013; 449 (7164): 804–10. https://doi.org/10.1038/nature06244
  66. Cabana M., McKean M., Caughey A., Fong L., Lynch L., Wong A., Leong R., Boushey H., Hiltonn J. Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial. Pediatrics. 2017; 140 (3): e20163000. https://doi.org/10.1542/peds.2016-3000
  67. Michail S. The role of probiotics in allergic diseases. Allergy Asthma ClinImmunol. 2009; 5 (1): 5. 10.1186/1710-1492-5-5.
  68. Giovannini M., Agostoni C., Riva E., Salvini F., Ruscitto A., Zuccotti G.V. A randomized prospective double blind controlled trial on effects of long-term consumption of fermented milk containing Lactobacillus casei in pre-school children with allergic asthma and/or rhinitis. Pediatr Res. 2007; 62 (2): 15–20. https://doi.org/10.1203/PDR.0b013e3180a76d94
  69. Ismai I.H., Licciardi P.V., Tang M.L.K. Probiotic effects in allergic disease. J. Paediatr Child Health. 2013; 49 (9): 709–15. https://doi.org/10.1111/jpc.12175
  70. Del Giudice M.M., Leonardi S., Maiello N., Brunese F.P. Food allergy and probiotics in childhood. J. Clin. Gastroenterol. 2010; 44: 22–5. https://doi.org/10.1097/MCG.0b013e3181e102a7
  71. Van de Pol M.A., Lutter R., Smids B.S., Weersink E.J., van der Zee J.S. Synbiotics reduce allergen-induced T-helper 2 response and improve peak expiratory flow in allergic asthmatics Allergy. 2010; 66 (1): 39–47. https://doi.org/10.1111/j.1398-9995.2010.02454.x