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Роль нарушения проницаемости слизистой оболочки кишечника в генезе функциональных заболеваний желудочно-кишечного тракта
Роль нарушения проницаемости слизистой оболочки кишечника в генезе функциональных заболеваний желудочно-кишечного тракта
Андреев Д.Н. Роль нарушения проницаемости слизистой оболочки кишечника в генезе функциональных заболеваний желудочно-кишечного тракта. Consilium Medicum. 2019; 21 (8): 29–34. DOI: 10.26442/20751753.2019.8.190539
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Аннотация
Слизистая оболочка кишечника является своеобразным барьером, обеспечивая защитную функцию путем нивелирования поступления внутрипросветных антигенов во внутреннюю среду организма. На настоящий момент накапливается все больше научных сведений о роли нарушения проницаемости слизистой оболочки кишечника в генезе функциональных заболеваний желудочно-кишечного тракта (ЖКТ), включая синдром раздраженного кишечника (СРК) и функциональную диспепсию (ФД). При этих функциональных заболеваниях ЖКТ описана альтерация барьерной функции слизистой оболочки кишечника, связанная с компрометацией белков плотных контактов клеток, что приводит к повышению проницаемости и поступлению различных внутрипросветных факторов в собственную пластинку слизистой, а следовательно – к активации иммунокомпетентных клеток. В рамках модели патогенеза СРК главное место отводится активации тучных клеток в слизистой тонкой и толстой кишки, а при ФД – тучным клеткам и эозинофилам в слизистой двенадцатиперстной кишки. Данные эффекторные клетки иммунного ответа, вырабатывая ряд цитокинов, оказывают влияние на чувствительность нервных окончаний слизистой оболочки, тем самым индуцируя возникновение феномена висцеральной гиперчувствительности и альтерацию моторно-тонической функции ЖКТ, что приводит к развитию характерной симптоматики. Таким образом, повышенная проницаемость слизистой оболочки ЖКТ в настоящий момент потенциально является одной из приоритетных терапевтических мишеней в рамках лечения СРК и ФД.
Ключевые слова: функциональные заболевания желудочно-кишечного тракта, синдром раздраженного кишечника, функциональная диспепсия, кишечная проницаемость, кишечный барьер, плотные контакты.
Ключевые слова: функциональные заболевания желудочно-кишечного тракта, синдром раздраженного кишечника, функциональная диспепсия, кишечная проницаемость, кишечный барьер, плотные контакты.
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The intestinal mucosa is a kind of barrier that provides a protective function by preventing the passage of intraluminal antigens into the body internal milieu. Currently more and more of scientific information is accumulating on the role of an alterations in permeability of the intestinal mucosa in the genesis of functional gastrointestinal (GI) disorders, including irritable bowel syndrome (IBS) and functional dyspepsia (FD). In these functional GI disorders, alterations in the intestinal mucosa barrier function is described. This is linked to compromising proteins of tight contacts of intestinal cells, which leads to an increase in the permeability and to the passage of various intraluminal factors into the deep mucosa, and, consequently, to an activation of immunocompetent cells. Activation of mast cells in the small and large intestines mucosa plays a key role in a pathogenesis of IBS, and an activation of mast cells and eosinophils in the duodenal mucosa – in a pathogenesis of FD. These effector cells of the immune response produce a number of cytokines, which affect a sensitivity of nerve endings in the mucosa, thereby inducing the phenomenon of visceral hypersensitivity and alteration in the motility and tone function of the gastrointestinal tract, which leads to characteristic symptoms. Thus, increased permeability of the gastrointestinal mucosa is currently potentially one of the priority therapeutic targets in the treatment of IBS and FD.
Key words: functional gastrointestinal disorders, irritable bowel syndrome, functional dyspepsia, intestinal permeability, intestinal barrier, tight contacts.
Key words: functional gastrointestinal disorders, irritable bowel syndrome, functional dyspepsia, intestinal permeability, intestinal barrier, tight contacts.
Полный текст
Список литературы
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5. Ford AC, Marwaha A, Lim A, Moayyedi P. Systematic review and meta-analysis of the prevalence of irritable bowel syndrome in individuals with dyspepsia. Clin Gastroenterol Hepatol 2010; 8 (5): 401–9.
6. Choung RS. Natural history and overlap of functional gastrointestinal disorders. Korean J Gastroenterol 2012; 60 (6): 345–8.
7. Keita ÅV, Söderholm JD. Mucosal permeability and mast cells as targets for functional gastrointestinal disorders. Curr Opin Pharmacol 2018; 43: 66–71.
8. Holtmann G, Shah A, Morrison M. Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview. Dig Dis 2017; 35 (Suppl. 1): 5–13.
9. Вялов С.С. Нарушение проницаемости слизистой оболочки как фактор патогенеза функциональных нарушений желудочно-кишечного тракта: обоснование и возможности коррекции. Consilium Medicum. 2018; 20 (12): 99–104. DOI: 10.26442/20751753.2018.12.180062
[Vialov S.S. Mucosal permeability disturbances as a pathogenesis factor of gastrointestinal tract functional disorders: rationale and correction possibilities. Consilium Medicum. 2018; 20 (12): 99–104. DOI: 10.26442/20751753.2018.12.180062 (in Russian).]
10. Farré R, Vicario M. Abnormal Barrier Function in Gastrointestinal Disorders. Handb Exp Pharmacol 2017; 239: 193–217.
11. Bischoff SC, Barbara G, Buurman W et al. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterol 2014; 14: 189.
12. Pascual S, Martínez J, Pérez-Mateo M. The intestinal barrier: functional disorders in digestive and non-digestive diseases. Gastroenterol Hepatol 2001; 24 (5): 256–67.
13. Shen L, Turner JR. Role of epithelial cells in initiation and propagation of intestinal inflammation. Eliminating the static: tight junction dynamics exposed. Am J Physiol Gastrointest Liver Physiol 2006; 290 (4): G577-82.
14. Camara-Lemarroy CR, Metz L, Meddings JB et al. The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics. Brain 2018; 141 (7): 1900–16.
15. Du L, Kim JJ, Shen J, Dai N. Crosstalk between Inflammation and ROCK/MLCK Signaling Pathways in Gastrointestinal Disorders with Intestinal Hyperpermeability. Gastroenterol Res Pract 2016; 2016: 7374197.
16. Bevins CL, Salzman NH. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 2011; 9 (5): 356–68.
17. Van der Flier LG, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 2009; 71: 241–60.
18. Zihni C, Mills C, Matter K, Balda MS. Tight junctions: from simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol 2016; 17 (9): 564–80.
19. Piche T. Tight junctions and IBS – the link between epithelial permeability, low-grade inflammation, and symptom generation? Neurogastroenterol Motil 2014; 26 (3): 296–302.
20. Niessen CM. Tight junctions/adherens junctions: basic structure and function. J Invest Dermatol 2007; 127 (11): 2525–32.
21. Hartsock A, Nelson WJ. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 2008; 1778 (3): 660–9.
22. Hammer AM, Morris NL, Earley ZM, Choudhry MA. The First Line of Defense: The Effects of Alcohol on Post-Burn Intestinal Barrier, Immune Cells, and Microbiome. Alcohol Res 2015; 37 (2): 209–22.
23. Park MY, Kim MY, Seo YR et al. High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity. J Cancer Prev 2016; 21 (2): 95–103.
24. Wilcz-Villega EM, McClean S, O'Sullivan MA. Mast cell tryptase reduces junctional adhesion molecule-A (JAM-A) expression in intestinal epithelial cells: implications for the mechanisms of barrier dysfunction in irritable bowel syndrome. Am J Gastroenterol 2013; 108 (7): 1140–51.
25. Gunnarsson J, Simrén M. Peripheral factors in the pathophysiology of irritable bowel syndrome. Dig Liver Dis 2009; 41: 788–93.
26. Camilleri M, Oduyebo I, Halawi H. Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions. Am J Physiol Gastrointest Liver Physiol 2016; 311 (5): G777-G784.
27. Ng QX, Soh AYS, Loke W et al. The role of inflammation in irritable bowel syndrome (IBS). J Inflamm Res 2018; 11: 345–9.
28. Самсонов А.А., Андреев Д.Н., Дичева Д.Т. Синдром раздраженного кишечника с позиций современной гастроэнтерологии. Фарматека. 2014; 18: 7–14.
[Samsonov A.A., Andreev D.N., Dicheva D.T. Sindrom razdrazhennogo kishechnika s pozitsii sovremennoi gastroenterologii. Farmateka. 2014; 18: 7–14 (in Russian).]
29. Дичева Д.Т., Андреев Д.Н., Щегланова М.П., Парцваниа-Виноградова Е.В. Синдром раздраженного кишечника в свете Римских критериев IV пересмотра (2016 г.). Мед. совет. 2018; 3: 60–6.
[Dicheva D.T., Andreev D.N., Shcheglanova M.P., Partsvania-Vinogradova E.V. Sindrom razdrazhennogo kishechnika v svete Rimskikh kriteriev IV peresmotra (2016 g.). Med. sovet. 2018; 3: 60–6 (in Russian).]
30. Barbara G, Grover M, Bercik P et al. Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome. Gastroenterology 2019; 156 (1): 46-58.e7.
31. Spiller RC, Jenkins D, Thornley JP et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000; 47: 804.
32. Marshall JK, Thabane M, Garg AX et al. Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario. Aliment Pharmacol Ther 2004; 20: 1317–22.
33. Vazquez-Roque MI, Camilleri M, Smyrk T et al. Association of HLA-DQ gene with bowel transit, barrier function, and inflammation in irritable bowel syndrome with diarrhea. Am J Physiol Gastrointest Liver Physiol 2012; 303 (11): G1262-9.
34. Shulman RJ, Jarrett ME, Cain KC et al. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome. J Gastroenterol 2014; 49 (11): 1467–76.
35. Coëffier M, Gloro R, Boukhettala N et al. Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol 2010; 105 (5): 1181–8.
36. Piche T, Barbara G, Aubert P et al. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 2009; 58 (2): 196–201.
37. Bertiaux-Vandaële N, Youmba SB, Belmonte L et al. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol 2011; 106 (12): 2165–73.
38. Bonfiglio F, Henström M, Nag A et al. A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome. Neurogastroenterol Motil 2018; 30 (9): e13358.
39. Chadwick VS, Chen W, Shu D et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology 2002; 122: 1778.
40. Liebregts T, Adam B, Bredack C et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology 2007; 132: 913.
41. Törnblom H, Lindberg G, Nyberg B, Veress B. Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology 2002; 123: 1972.
42. Ait-Belgnaoui A, Bradesi S, Fioramonti J et al. Acute stress-induced hypersensitivity to colonic distension depends upon increase in paracellular permeability: role of myosin light chain kinase. Pain 2005; 113 (1–2): 141–7.
43. Barbaro MR, Di Sabatino A, Cremon C et al. Interferon-y is increased in the gut of patients with irritable bowel syndrome and modulates serotonin metabolism. Am J Physiol Gastrointest Liver Physiol 2016; 310 (6): G439-47.
44. Chen J, Zhang Y, Deng Z. Imbalanced shift of cytokine expression between T helper 1 and T helper 2 (Th1/Th2) in intestinal mucosa of patients with post-infectious irritable bowel syndrome. BMC Gastroenterol 2012; 12: 91.
45. Lee KN, Lee OY. The Role of Mast Cells in Irritable Bowel Syndrome. Gastroenterol Res Pract 2016; 2016: 2031480.
46. Guilarte M, Santos J, de Torres I et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 2007; 56: 203.
47. Barbara G, Stanghellini V, De Giorgio R et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004; 126: 693.
48. Buhner S, Li Q, Vignali S et al. Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome. Gastroenterology 2009; 137 (4): 1425–34.
49. Barbara G, Wang B, Stanghellini V et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology 2007; 132 (1): 26–37.
50. Schemann M, Camilleri M. Functions and imaging of mast cell and neural axis of the gut. Gastroenterology 2013; 144 (4): 698–704.e4.
51. Bueno L. Protease activated receptor 2: a new target for IBS treatment. Eur Rev Med Pharmacol Sci 2008; 12 (Suppl. 1): 95.
52. Gecse K, Róka R, Ferrier L et al. Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity. Gut 2008; 57: 591.
53. Edogawa S, Edwinson AL, Peters SA et al. Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS. Gut 2019 Mar 28. pii: gutjnl-2018-317416.
54. Liang WJ, Zhang G, Luo HS et al. Tryptase and Protease-Activated Receptor 2 Expression Levels in Irritable Bowel Syndrome. Gut Liver 2016; 10 (3): 382–90.
55. Du L, Long Y, Kim JJ et al. Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice. Dig Dis Sci. 2019; 64 (3): 729–739.
56. Stanghellini V, Chan FK, Hasler WL et al. Gastroduodenal Disorders. Gastroenterology 2016; 150 (6): 1380–92.
57. Маев И.В., Андреев Д.Н., Кучерявый Ю.А. Функциональная диспепсия. М.: Ремедиум, 2019.
[Maev I.V., Andreev D.N., Kucheriavyi Iu.A. Functional dyspepsia. Moscow: Remedium, 2019 (in Russian).]
58. Jung HK, Talley NJ. Role of the Duodenum in the Pathogenesis of Functional Dyspepsia: A Paradigm Shift. J Neurogastroenterol Motil 2018; 24 (3): 345–54.
59. Vanheel H, Vicario M, Vanuytsel T et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 2014; 63 (2): 262–71.
60. Vanheel H, Vicario M, Boesmans W et al. Activation of Eosinophils and Mast Cells in Functional Dyspepsia: an Ultrastructural Evaluation. Sci Rep 2018; 8 (1): 5383.
61. Du L, Chen B, Kim JJ et al. Micro-inflammation in functional dyspepsia: A systematic review and meta-analysis. Neurogastroenterol Motil 2018; 30 (4): e13304.
62. Маев И.В., Андреев Д.Н., Кучерявый Ю.А. и др. Современные представления о патофизиологических основах синдрома функциональной диспепсии. РЖГГК. 2015; 4: 15–22.
[Maev I.V., Andreev D.N., Kucheriavyi Iu.A.et al. Sovremennye predstavleniia o patofiziologicheskikh osnovakh sindroma funktsional'noi dispepsii. RZhGGK. 2015; 4: 15–22. (in Russian).]
63. Дичева Д.Т., Субботина Ю.С., Бектемирова Л.Г., Андреев Д.Н. Функциональная диспепсия: от патогенеза к терапевтическим аспектам. Мед. совет. 2019; 3: 18–25.
[Dicheva D.T., Subbotina Iu.S., Bektemirova L.G., Andreev D.N. Funktsional'naia dispepsiia: ot patogeneza k terapevticheskim aspektam. Med. sovet. 2019; 3: 18–25 (in Russian).]
64. Miwa H, Oshima T, Tomita T et al. Recent understanding of the pathophysiology of functional dyspepsia: role of the duodenum as the pathogenic center. J Gastroenterol 2019; 54 (4): 305–11.
65. Leech B, Schloss J, Steel A. Treatment Interventions for the Management of Intestinal Permeability: A Cross-Sectional Survey of Complementary and Integrative Medicine Practitioners. J Altern Complement Med 2019; 25 (6): 623–36.
66. Leech B, McIntyre E, Steel A, Sibbritt D. Risk factors associated with intestinal permeability in an adult population: A systematic review. Int J Clin Pract 2019: e13385. DOI: 10.1111/ijcp.13385
67. Sturniolo GC, Di Leo V, Ferronato A et al. Zinc supplementation tightens ‘leaky gut’ in Crohn's disease. Inflamm Bowel Dis 2001; 7 (2): 94–8.
68. Sturniolo GC, Fries W, Mazzon E et al. Effect of zinc supplementation on intestinal permeability in experimental colitis. J Lab Clin Med 2002; 139 (5): 311–5.
69. Zhou Q, Verne ML, Fields JZ et al. Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. Gut 2019; 68 (6): 996–1002.
70. Bertrand J, Ghouzali I, Guérin C et al. Glutamine Restores Tight Junction Protein Claudin-1 Expression in Colonic Mucosa of Patients With Diarrhea-Predominant Irritable Bowel Syndrome. JPEN J Parenter Enteral Nutr 2016; 40 (8): 1170–6.
71. Kelly CP, Green PH, Murray JA et al. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther 2013; 37 (2): 252–62.
72. Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol 2010; 4 (3): 261–70.
73. Song DU, Ryu MH, Chay KO et al. Effect of rebamipide on the glycosaminoglycan content of the ulcerated rat stomach. Fundam Clin Pharmacol 1998; 12 (5): 546–52.
74. Suzuki T, Yoshida N, Nakabe N et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. J Pharmacol Sci 2008; 106 (3): 469–77.
75. Tarnawski AS, Chai J, Pai R, Chiou SK. Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action? Dig Dis Sci 2004; 49 (2): 202–9.
76. Jaafar MH, Safi SZ, Tan MP et al. Efficacy of Rebamipide in Organic and Functional Dyspepsia: A Systematic Review and Meta-Analysis. Dig Dis Sci 2018; 63 (5): 1250–60.
77. Miwa H, Osada T, Nagahara A et al. Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan. J Gastroenterol Hepatol 2006; 21 (12): 1826–31.
78. Matysiak-Budnik T, Heyman M, Mégraud F. Review article: rebamipide and the digestive epithelial barrier. Aliment Pharmacol Ther 2003; 18 (Suppl. 1): 55–62.
79. Pittayanon R, Leelakusolvong S, Vilaichone RK et al. Thailand Dyspepsia Guidelines: 2018. J Neurogastroenterol Motil 2019; 25 (1): 15–26.
________________________________________________
2. Andreev D.N., Zaborovskii A.V., Trukhmanov A.S. et al. Evoliutsiia predstavlenii o funktsional'nykh zabolevaniiakh zheludochno-kishechnogo trakta v svete Rimskikh kriteriev IV peresmotra (2016 g.). RZhGGK. 2017; 1: 4–11 (in Russian).
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14. Camara-Lemarroy CR, Metz L, Meddings JB et al. The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics. Brain 2018; 141 (7): 1900–16.
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19. Piche T. Tight junctions and IBS – the link between epithelial permeability, low-grade inflammation, and symptom generation? Neurogastroenterol Motil 2014; 26 (3): 296–302.
20. Niessen CM. Tight junctions/adherens junctions: basic structure and function. J Invest Dermatol 2007; 127 (11): 2525–32.
21. Hartsock A, Nelson WJ. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 2008; 1778 (3): 660–9.
22. Hammer AM, Morris NL, Earley ZM, Choudhry MA. The First Line of Defense: The Effects of Alcohol on Post-Burn Intestinal Barrier, Immune Cells, and Microbiome. Alcohol Res 2015; 37 (2): 209–22.
23. Park MY, Kim MY, Seo YR et al. High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity. J Cancer Prev 2016; 21 (2): 95–103.
24. Wilcz-Villega EM, McClean S, O'Sullivan MA. Mast cell tryptase reduces junctional adhesion molecule-A (JAM-A) expression in intestinal epithelial cells: implications for the mechanisms of barrier dysfunction in irritable bowel syndrome. Am J Gastroenterol 2013; 108 (7): 1140–51.
25. Gunnarsson J, Simrén M. Peripheral factors in the pathophysiology of irritable bowel syndrome. Dig Liver Dis 2009; 41: 788–93.
26. Camilleri M, Oduyebo I, Halawi H. Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions. Am J Physiol Gastrointest Liver Physiol 2016; 311 (5): G777-G784.
27. Ng QX, Soh AYS, Loke W et al. The role of inflammation in irritable bowel syndrome (IBS). J Inflamm Res 2018; 11: 345–9.
28. Samsonov A.A., Andreev D.N., Dicheva D.T. Sindrom razdrazhennogo kishechnika s pozitsii sovremennoi gastroenterologii. Farmateka. 2014; 18: 7–14 (in Russian).
29. Dicheva D.T., Andreev D.N., Shcheglanova M.P., Partsvania-Vinogradova E.V. Sindrom razdrazhennogo kishechnika v svete Rimskikh kriteriev IV peresmotra (2016 g.). Med. sovet. 2018; 3: 60–6 (in Russian).
30. Barbara G, Grover M, Bercik P et al. Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome. Gastroenterology 2019; 156 (1): 46-58.e7.
31. Spiller RC, Jenkins D, Thornley JP et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000; 47: 804.
32. Marshall JK, Thabane M, Garg AX et al. Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario. Aliment Pharmacol Ther 2004; 20: 1317–22.
33. Vazquez-Roque MI, Camilleri M, Smyrk T et al. Association of HLA-DQ gene with bowel transit, barrier function, and inflammation in irritable bowel syndrome with diarrhea. Am J Physiol Gastrointest Liver Physiol 2012; 303 (11): G1262-9.
34. Shulman RJ, Jarrett ME, Cain KC et al. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome. J Gastroenterol 2014; 49 (11): 1467–76.
35. Coëffier M, Gloro R, Boukhettala N et al. Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol 2010; 105 (5): 1181–8.
36. Piche T, Barbara G, Aubert P et al. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 2009; 58 (2): 196–201.
37. Bertiaux-Vandaële N, Youmba SB, Belmonte L et al. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol 2011; 106 (12): 2165–73.
38. Bonfiglio F, Henström M, Nag A et al. A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome. Neurogastroenterol Motil 2018; 30 (9): e13358.
39. Chadwick VS, Chen W, Shu D et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology 2002; 122: 1778.
40. Liebregts T, Adam B, Bredack C et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology 2007; 132: 913.
41. Törnblom H, Lindberg G, Nyberg B, Veress B. Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology 2002; 123: 1972.
42. Ait-Belgnaoui A, Bradesi S, Fioramonti J et al. Acute stress-induced hypersensitivity to colonic distension depends upon increase in paracellular permeability: role of myosin light chain kinase. Pain 2005; 113 (1–2): 141–7.
43. Barbaro MR, Di Sabatino A, Cremon C et al. Interferon-y is increased in the gut of patients with irritable bowel syndrome and modulates serotonin metabolism. Am J Physiol Gastrointest Liver Physiol 2016; 310 (6): G439-47.
44. Chen J, Zhang Y, Deng Z. Imbalanced shift of cytokine expression between T helper 1 and T helper 2 (Th1/Th2) in intestinal mucosa of patients with post-infectious irritable bowel syndrome. BMC Gastroenterol 2012; 12: 91.
45. Lee KN, Lee OY. The Role of Mast Cells in Irritable Bowel Syndrome. Gastroenterol Res Pract 2016; 2016: 2031480.
46. Guilarte M, Santos J, de Torres I et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 2007; 56: 203.
47. Barbara G, Stanghellini V, De Giorgio R et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004; 126: 693.
48. Buhner S, Li Q, Vignali S et al. Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome. Gastroenterology 2009; 137 (4): 1425–34.
49. Barbara G, Wang B, Stanghellini V et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology 2007; 132 (1): 26–37.
50. Schemann M, Camilleri M. Functions and imaging of mast cell and neural axis of the gut. Gastroenterology 2013; 144 (4): 698–704.e4.
51. Bueno L. Protease activated receptor 2: a new target for IBS treatment. Eur Rev Med Pharmacol Sci 2008; 12 (Suppl. 1): 95.
52. Gecse K, Róka R, Ferrier L et al. Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity. Gut 2008; 57: 591.
53. Edogawa S, Edwinson AL, Peters SA et al. Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS. Gut 2019 Mar 28. pii: gutjnl-2018-317416.
54. Liang WJ, Zhang G, Luo HS et al. Tryptase and Protease-Activated Receptor 2 Expression Levels in Irritable Bowel Syndrome. Gut Liver 2016; 10 (3): 382–90.
55. Du L, Long Y, Kim JJ et al. Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice. Dig Dis Sci. 2019; 64 (3): 729–739.
56. Stanghellini V, Chan FK, Hasler WL et al. Gastroduodenal Disorders. Gastroenterology 2016; 150 (6): 1380–92.
57. Maev I.V., Andreev D.N., Kucheriavyi Iu.A. Functional dyspepsia. Moscow: Remedium, 2019 (in Russian).
58. Jung HK, Talley NJ. Role of the Duodenum in the Pathogenesis of Functional Dyspepsia: A Paradigm Shift. J Neurogastroenterol Motil 2018; 24 (3): 345–54.
59. Vanheel H, Vicario M, Vanuytsel T et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 2014; 63 (2): 262–71.
60. Vanheel H, Vicario M, Boesmans W et al. Activation of Eosinophils and Mast Cells in Functional Dyspepsia: an Ultrastructural Evaluation. Sci Rep 2018; 8 (1): 5383.
61. Du L, Chen B, Kim JJ et al. Micro-inflammation in functional dyspepsia: A systematic review and meta-analysis. Neurogastroenterol Motil 2018; 30 (4): e13304.
62. Maev I.V., Andreev D.N., Kucheriavyi Iu.A.et al. Sovremennye predstavleniia o patofiziologicheskikh osnovakh sindroma funktsional'noi dispepsii. RZhGGK. 2015; 4: 15–22. (in Russian).
63. Dicheva D.T., Subbotina Iu.S., Bektemirova L.G., Andreev D.N. Funktsional'naia dispepsiia: ot patogeneza k terapevticheskim aspektam. Med. sovet. 2019; 3: 18–25 (in Russian).
64. Miwa H, Oshima T, Tomita T et al. Recent understanding of the pathophysiology of functional dyspepsia: role of the duodenum as the pathogenic center. J Gastroenterol 2019; 54 (4): 305–11.
65. Leech B, Schloss J, Steel A. Treatment Interventions for the Management of Intestinal Permeability: A Cross-Sectional Survey of Complementary and Integrative Medicine Practitioners. J Altern Complement Med 2019; 25 (6): 623–36.
66. Leech B, McIntyre E, Steel A, Sibbritt D. Risk factors associated with intestinal permeability in an adult population: A systematic review. Int J Clin Pract 2019: e13385. DOI: 10.1111/ijcp.13385
67. Sturniolo GC, Di Leo V, Ferronato A et al. Zinc supplementation tightens ‘leaky gut’ in Crohn's disease. Inflamm Bowel Dis 2001; 7 (2): 94–8.
68. Sturniolo GC, Fries W, Mazzon E et al. Effect of zinc supplementation on intestinal permeability in experimental colitis. J Lab Clin Med 2002; 139 (5): 311–5.
69. Zhou Q, Verne ML, Fields JZ et al. Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. Gut 2019; 68 (6): 996–1002.
70. Bertrand J, Ghouzali I, Guérin C et al. Glutamine Restores Tight Junction Protein Claudin-1 Expression in Colonic Mucosa of Patients With Diarrhea-Predominant Irritable Bowel Syndrome. JPEN J Parenter Enteral Nutr 2016; 40 (8): 1170–6.
71. Kelly CP, Green PH, Murray JA et al. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther 2013; 37 (2): 252–62.
72. Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol 2010; 4 (3): 261–70.
73. Song DU, Ryu MH, Chay KO et al. Effect of rebamipide on the glycosaminoglycan content of the ulcerated rat stomach. Fundam Clin Pharmacol 1998; 12 (5): 546–52.
74. Suzuki T, Yoshida N, Nakabe N et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. J Pharmacol Sci 2008; 106 (3): 469–77.
75. Tarnawski AS, Chai J, Pai R, Chiou SK. Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action? Dig Dis Sci 2004; 49 (2): 202–9.
76. Jaafar MH, Safi SZ, Tan MP et al. Efficacy of Rebamipide in Organic and Functional Dyspepsia: A Systematic Review and Meta-Analysis. Dig Dis Sci 2018; 63 (5): 1250–60.
77. Miwa H, Osada T, Nagahara A et al. Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan. J Gastroenterol Hepatol 2006; 21 (12): 1826–31.
78. Matysiak-Budnik T, Heyman M, Mégraud F. Review article: rebamipide and the digestive epithelial barrier. Aliment Pharmacol Ther 2003; 18 (Suppl. 1): 55–62.
79. Pittayanon R, Leelakusolvong S, Vilaichone RK et al. Thailand Dyspepsia Guidelines: 2018. J Neurogastroenterol Motil 2019; 25 (1): 15–26.
Авторы
Д.Н. Андреев
ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия
*dna-mit8@mail.ru
ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия
*dna-mit8@mail.ru
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Dmitrii N. Andreev
Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
*dna-mit8@mail.ru
Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
*dna-mit8@mail.ru
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