Probiotics in the Complex Treatment of Various Diseases of the Gastrointestinal Tract

Aim. To present up-to-date information on the role of microbiota and its disorders in the development of various diseases of the gastrointestinal tract (GIT), including functional diseases, as well as to consider current methods of correction and maintenance of normal microbiota.

General findings. The human microbiome affects many organs at the biochemical, molecular and genetic levels. It has been confirmed that the microbiome participates in the development of inflammatory and functional diseases of the gastrointestinal tract, affects the immune system, central nervous system and mental status. An important problem of everyday medical practice consists in the management of patients with functional disorders of the gastrointestinal tract. The “7 × 7” questionnaire created in 2014 by a group of specialists from I.M. Sechenov First Moscow State Medical University in collaboration with Valenta Pharm allows dynamic evaluation of the clinical course of functional gastrointestinal diseases. The most frequent functional gastrointestinal disorder – irritable bowel syndrome (IBS) – is characterized by a quantitative and qualitative change in the intestinal microflora, which, together with inflammatory changes in the intestinal wall, may act as a trigger for the onset of symptoms, as well as lead to a functional change in the receptor apparatus of pain pathways. Over the
last decade, the number of studies on the use of probiotics for the treatment of various gastrointestinal diseases has increased significantly. The pathogenetic effect of the change in the normal ratio of microorganisms in the intestine proves the inclusion of probiotics in the complex treatment of functional disorders of the gastrointestinal tract to be reasonable.

Conclusion. Improved methods for assessing the microbiome state allows evaluation of the composition of the human intestine microflora in various diseases, thus facilitating the search for new approaches to correcting and maintaining the normal ratio of microorganisms for managing patients with various gastrointestinal diseases.

1. Prescott S.L. History of medicine: Origin of the term microbiome and why it matters. Human Microbiome Journal. 2017;4:24–5. DOI: 10.1016/j.humic.2017.05.004

2. Leffler D.A., Lamont T.J. Clostridium difficile Infection. N Engl J Med. 2015;372:1539–48. DOI: 10.1056/NEJMra1403772 (4)

3. Hvas C.L., Dahl Jørgensen S.M., Jørgensen S.P., Storgaard M., Lemming L., Hansen M.M., et al. Fecal Microbiota Transplantation Is Superior to Fidaxomicin

4. for Treatment of Recurrent Clostridium difficile Infection. Gastroenterology. 2019;156(5):1324–32.e3. DOI: 10.1053/j.gastro.2018.12.019

5. McCarthy J., O’Mahony L., Dunne C., Kelly P., Feeney M., Kiely B., et al. An open trial of a novel probiotic as an alternative to steroids in mild/moderately active Crohn’s disease. Gut. 2001;49: A2447.

6. Bousvaros A., Guandalini S., Baldassano R.N., Botelho C., Evans J., Ferry G.D., et al. A randomized, doubleblind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease. Inflamm Bowel Dis. 2005;11(9):833–9. DOI: 10.1097/01.mib.0000175905.00212.2c

7. Guslandi M., Mezzi G., Sorghi M., Testoni P.A. Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig Dis Sci. 2000;45(7):1462–4. DOI: 10.1023/a:1005588911207

8. Fedorak R.N., Feagan B.G., Hotte N., Leddin D., Dieleman L.A., Petrunia D.M., et al. The probiotic VSL#3 has anti-inflammatory effects and could reduce endoscopic recurrence after surgery for Crohn’s disease. Clin Gastroenterol Hepatol. 2015;13(5):928–35.e2. DOI: 10.1016/j.cgh.2014.10.031

9. Rohatgi S., Ahuja V., Makharia G.K., Rai T., Das P., Dattagupta S., et al. VSL#3 induces and maintains shortterm clinical response in patients with active microscopic colitis: a two-phase randomised clinical trial. BMJ Open Gastroenterol. 2015;2(1):e000018. DOI: 10.1136/bmjgast-2014-000018

10. Keller J., Wedel T., Seidl H., Kreis M.E., Andresen V., Preiss J.C., et al. S3 guideline of the German Society for Digestive and Metabolic Diseases (DGVS) and the German Society for Neurogastroenterology and Motility (DGNM)

11. to the definition, pathophysiology, diagnosis and treatment of intestinal motility. Z Gastroenterol. 2011;49(3):374–90. DOI: 10.1055/s-0029-1245993

12. Tursi A., Brandimarte G., Papa A., Giglio A., Elisei W., Giorgetti G.M., et al. Treatment of relapsing mild-tomoderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2010;105(10):2218–27. DOI: 10.1038/ajg.2010.218

13. Li Y. Sensory signal transduction in the vagal primary afferent neurons. Curr Med Chem. 2007;14(24):2554–63. DOI: 10.2174/092986707782023334

14. Feldman M., Friedman L.S., Brandt L.J. (ed.) Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 10th Edition. Philadelphia: Saunders/Elsevier. 2015:2616.

15. An S., Zong G., Wang Z., Shi J., Du H., Hu J. Expression of inducible nitric oxide synthase in mast cells contributes to the regulation of inflammatory cytokines in irritable bowel syndrome with diarrhea. Neurogastroenterol Motil. 2016;28(7):1083–93. DOI: 10.1111/nmo.12811

16. Goyal R.K., Hirano I. The enteric nervous system. N Engl J Med. 1996;334(17):1106–15. DOI: 10.1056/NEJM199604253341707

17. Ivashkin V.T., Poluektova Ye.A. Irritable bowel syndrome: pathophysiological and clinical issues. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2015;25(1):4–16 (In Russ.).

18. Pyleris E., Giamarellos-Bourboulis E.J., Tzivras D., Koussoulas V., Barbatzas C., Pimentel M. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012;57(5):1321–9. DOI: 10.1007/s10620-012-2033-7

19. An S., Zong G., Wang Z., Shi J., Du H., Hu J. Expression of inducible nitric oxide synthase in mast cells contributes to the regulation of inflammatory cytokines in irritable bowel syndrome with diarrhea. Neurogastroenterol Motil. 2016;28(7):1083–93. DOI: 10.1111/nmo.12811

20. Cremon C., Gargano L., Morselli-Labate A.M., Santini D., Cogliandro R.F., De Giorgio R., et al. Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms. Am J Gastroenterol. 2009;104(2):392–400. DOI: 10.1038/ajg.2008.94

21. Piche T., Saint-Paul M.C., Dainese R., Marine-Barjoan E., Iannelli A., Montoya M.L., et al. Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut. 2008;57(4):468–73. DOI: 10.1136/gut.2007.127068

22. O’Malley D. Neuroimmune Cross Talk in the Gut. Neuroendocrine and neuroimmune pathways contribute to the pathophysiology of irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2016;311(5):G934–41. DOI: 10.1152/ajpgi.00272.2016

23. Ivashkin V. T. Basic concepts and statements of fundamental immunology. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2008;18(4):4–14 (In Russ.).

24. Walczak A., Przybylowska K., Dziki L., Sygut A., Chojnacki C., Chojnacki J., et al. The lL-8 and IL-13 gene polymorphisms in inflammatory bowel disease and colorectal cancer. DNA Cell Biol. 2012;31(8):1431–8. DOI: 10.1089/dna.2012.1692

25. Poluektova E.A. Irritable bowel syndrome: pathophysiological, clinical and social aspects of the problem. Doctoral thesis. Moscow, 2019 (In Russ.).

26. Shulpekova Y.O., Sheptulin D.A., Shulpekova N.V. Principles of Rational Nutrition for Managing Constipation. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018;28(5):117–25 (In Russ.). DOI: 10.22416/1382-4376-2018-28-5-117-12

27. Ivashkin V., Drapkina O., Poluektova Ye., Kuchumova S., Sheptulin A., Shifrin O. The Effect of a Multistrain Probiotic on the Symptoms and Small Intestinal Bacterial Overgrowth in Constipation-predominant Irritable Bowel Syndrome: A Randomized, Simple-blind, Placebo-controlled Trial. American Journal of Clinical Medicine Research. 2015;3(2):18–23. DOI: 10.12691/ajcmr-3-2-1

28. Ivashkin V.T., Ivashkin K.V. Psychobiotic effects of probiotics and prebiotics. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018;28(1):4–12 (In Russ.). DOI: 10.22416/1382-4376-2018-28-1-4-12

29. Ivashkin V.T., Ivashkin K.V. Intestinal microbiome as effective regulator of enteral and central nervous system activity. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2017;27(5):11–19 (In Russ.). DOI: 10.22416/1382-4376-2017-27-5-11-19

30. Ivashkin V.T., Ivashkin K.V. Human microbiome, applied to clinical practice. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2017;27(6):4–13 (In Russ.). DOI: 10.22416/1382-4376-2017-27-6-4-13