Pathogenesis factors of functional gastrointestinal disorders and overlap syndrome
S.S. Vyalov
LLC «GMS Clinic», Moscow
A role of motor disorders and hypersensitivity in the pathogenesis of functional gastrointestinal diseases is the most studied. In the literature, there are scattered data confirming and rebutting an involvement of pathogenesis of the intestinal bacterial flora disorders, an increase in the permeability of the epithelial barrier, immune activation, and microinflammation. In the works of recent years, the value of changes in the permeability of the mucous membrane of the gastrointestinal tract is studied, but reliable data are not enough. In studies on microscopic inflammation and immune activation, it was not possible to isolate significant markers of subclinical inflammation or a separate pool of cells associated with the pathogenesis of functional disorders. In the process of methodical complex microbiota studies, contradictory data were obtained on the effect of different types of bacteria on the pathogenesis of functional disorders or, on the contrary, on the absence of microbiota influence in general. There is also no data on the interrelation of the above pathogenesis factors among themselves and their interaction with the pathogenesis factors of organic diseases in the case of comorbidity, which requires a further search for new pathogenesis factors, as well as the confirmation of the influence of the factors discussed. An etiopathogenesis of combinations of functional disorders has not been studied; the factors of the pathogenesis of isolated functional disorders require confirmation.
Key words: pathogenesis, overlap syndrome, functional dyspepsia, irritable bowel syndrome, permeability, inflammation, microbiota.
For citation: Vyalov S.S. Pathogenesis factors of functional gastrointestinal disorders and overlap syndrome // RMJ. Medical Review. 2018. № 7(II). P. 68–71.
References
1. Boeckxstaens G., Camilleri M., Sifrim D. et al. Fundamentals of Neurogastroenterology: Physiology/Motility — Sensation // Gastroenterology. 2016. Vol. 150 (6). P.221–223.
2. Vanheel H., Vicario M., Vanuytsel T. et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia // Gut. 2014. Vol. 63 (2). P.262–271.
3. Du L., Shen J., Kim J.J. et al. Increased Duodenal Eosinophil Degranulation in Patients with Functional Dyspepsia: A Prospective Study // Sci Rep. 2016. Vol. 6. P.305.
4. Wang X., Li X., Ge W. et al. Quantitative evaluation of duodenal eosinophils and mast cells in adult patients with functional dyspepsia // Ann. Diagn. Pathol. 2015. Vol. 19 (2). P.50–56.
5. Binesh F., Akhondei M., Pourmirafzali H., Rajabzadeh Y. Determination of relative frequency of eosinophils and mast cells in gastric and duodenal mucosal biopsies in adults with non-ulcer dyspepsia // J. Coll. Physicians Surg. Pak. 2013. Vol. 23 (5). P.326–329.
6. Singh V., Singh M., Schurman J.V., Friesen C.A. Histopathological changes in the gastroduodenal mucosa of children with functional dyspepsia // Pathol. Res. Pract. 2018. Vol. 214 (8). P.1173–1178.
7. Du L., Chen B., Kim J.J. et al. Micro-inflammation in functional dyspepsia: A systematic review and meta-analysis // Neurogastroenterol. Motil. 2018. Vol. 30 (4). P.13304.
8. Emara M.H., Salama R.I., Salem A.A. Demographic, Endoscopic and Histopathologic Features Among Stool H. pylori Positive and Stool H. pylori Negative Patients With Dyspepsia // Gastroenterology Res. 2017. Vol. 10 (5). P.305–310.
9. Vanheel H., Vicario M., Boesmans W. et al. Activation of Eosinophils and Mast Cells in Functional Dyspepsia: an Ultrastructural Evaluation // Sci Rep. 2018. Vol. 8 (1). P.5383.
10. Ishigami H., Matsumura T., Kasamatsu S. et al. Endoscopy-Guided Evaluation of Duodenal Mucosal Permeability in Functional Dyspepsia // Clin Transl Gastroenterol. 2017. Vol. 8 (4). P.83.
11. Keita А.V., Söderholm J.D. Mucosal permeability and mast cells as targets for functional gastrointestinal disorders // Curr Opin Pharmacol. 2018. Vol. 43. P.66–71.
12. Vakil N. Editorial: functional dyspepsia-a disorder of duodenal permeability? // Aliment Pharmacol Ther. 2017. Vol. 46 (1). P.70–71.
13. Neilan N.A., Garg U.C., Schurman J.V., Friesen C.A. Intestinal permeability in children/adolescents with functional dyspepsia // BMC Res Notes. 2014. Vol. 7. P.275.
14. Masci E., Pellicano R., Mangiavillano B. et al. GastroPanel test for non-invasive diagnosis of atrophic gastritis in patients with dyspepsia // Minerva Gastroenterol Dietol. 2014. Vol. 60 (1). P.79–83.
15. Daugule I., Ruskule A., Moisejevs G. et al. Long-term dynamics of gastric biomarkers after eradication of Helicobacter pylori infection // Eur. J. Gastroenterol. Hepatol. 2015. Vol. 27 (5). P.501–505.
16. Petersen K.U. Pepsin and Its Importance for Functional Dyspepsia: Relic, Regulator or Remedy? // Dig. Dis. 2018. Vol. 36 (2). P.98–105.
17. Tomita T., Oshima T., Fukui H. et al. Role of acid in functional dyspepsia // Nihon. Rinsho. 2015. Vol. 73 (7). P.1202–1208.
18. Tack J., Carbone F. Functional dyspepsia and gastroparesis // Curr. Opin. Gastroenterol. 2017. Vol. 33 (6). P.446–454.
19. Tahara T., Shibata T., Okubo M. et al. Association between interleukin-1β and tumor necrosis factor-α polymorphisms and symptoms of dyspepsia // Mol. Med. Rep. 2015. Vol. 11 (5). P.3888–3893.
20. Lee K.N., Lee O.Y. The Role of Mast Cells in Irritable Bowel Syndrome // Gastroenterol. Res. Pract. 2016. Vol. 2016. P.2031480.
21. Zhang L., Song J., Hou X. Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside // J. Neurogastroenterol. Motil. 2016. Vol. 22 (2). P.181–192.
22. Bashashati M., Moossavi S., Cremon C. et al. Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis // Neurogastroenterol. Motil. 2018. Vol. 30 (1). P.13192.
23. Boyer J., Saint-Paul M.C., Dadone B. et al. Inflammatory cell distribution in colon mucosa as a new tool for diagnosis of irritable bowel syndrome: A promising pilot study // Neurogastroenterol. Motil. 2018. Vol. 30 (1). P 13223.
24. Adamsson J., Ottsjö L.S., Lundin S.B. et al. Gastric expression of IL-17A and IFNγ in Helicobacter pylori infected individuals is related to symptoms // Cytokine. 2017. Vol. 99. P.30–34.
25. Tran L.S., Chonwerawong M., Ferrero R.L. Regulation and functions of inflammasome-mediated cytokines in Helicobacter pylori infection // Microbes Infect. 2017. Vol. 19 (9–10). P.449–458.
26. Murni A.W., Darwin E., Zubir N., Nurdin A.E. Analyzing Determinant Factors for Pathophysiology of Functional Dyspepsia Based on Plasma Cortisol Levels, IL-6 and IL-8 Expressions and H. pylori Activity // Acta Med. Indones. 2018. Vol. 50 (1). P.38–45.
27. Darwin E., Murni A.W., Nurdin A.E. The Effect of Psychological Stress on Mucosal IL-6 and Helicobacter pylori Activity in Functional Dyspepsia // Acta Med. Indones. 2017. Vol. 49 (2). P.99–104.
28. Vara E.J., Brokstad K.A., Hausken T., Lied G.A. Altered levels of cytokines in patients with irritable bowel syndrome are not correlated with fatigue // Int. J. Gen. Med. 2018. Vol. 6 (11). P.285–291.
29. Bashashati M., Moradi M., Sarosiek I. Interleukin-6 in irritable bowel syndrome: A systematic review and meta-analysis of IL-6 (-G174C) and circulating IL-6 levels // Cytokine. 2017. Vol. 99. P.132–138.
30. Choghakhori R., Abbasnezhad A., Hasanvand A., Amani R. Inflammatory cytokines and oxidative stress biomarkers in irritable bowel syndrome: Association with digestive symptoms and quality of life // Cytokine. 2017. Vol. 93. P.34–43.
31. Bennet S.M., Polster A., Törnblom H. et al. Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome // Am J. Gastroenterol. 2016. Vol. 111 (8). P.1165–1176.
32. Rodiño-Janeiro B.K., Vicario M., Alonso-Cotoner C. et al. A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies // Adv. Ther. 2018. Vol. 35 (3). P.289–310.
33. Hadizadeh F., Bonfiglio F., Belheouane M. et al. Faecal microbiota composition associates with abdominal pain in the general population // Gut. 2018. Vol. 67 (4). P.778–779.
34. Chen Y.J., Wu H., Wu S.D. et al. Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation // J. Gastroenterol. Hepatol. 2018. Vol. 33 (11). P.1844–1852.
35. Lopez-Siles M., Enrich-Capó N., Aldeguer X. et al. Alterations in the Abundance and Co-occurrence of Akkermansia muciniphila and Faecalibacterium prausnitzii in the Colonic Mucosa of Inflammatory Bowel Disease Subjects // Front Cell Infect Microbiol. 2018. Vol. 8. P.281.
36. Tap J., Derrien M., Törnblom H. et al. Identification of an intestinal microbiota signature associated with Severity of irritable bowel syndrome // Gastroenterology. 2017. Vol. 152. P.111–123.
37. Hod K., Dekel R., Aviv Cohen N. et al. The effect of a multispecies probiotic on microbiota composition in a clinical trial of patients with diarrhea-predominant irritable bowel syndrome // Neurogastroenterol. Motil. 2018. Vol. 23. P. 13456.
38. Chang C. Short-course therapy for diarrhea-predominant irritable bowel syndrome: understanding the mechanism, impact on gut microbiota, and safety and tolerability of rifaximin // Clin. Exp. Gastroenterol. 2018. Vol. 11. P.335–345.
39. Maharshak N., Ringel Y., Katibian D. et al. Fecal and Mucosa-Associated Intestinal Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome // Dig. Dis. Sci. 2018. Vol. 63 (7). P.1890–1899.
40. Halkhaer S.I., Christensen A.H., Lo B.Z.S. et al. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study // Gut. 2018. Vol. 67 (12). P.2107–2115.
2. Vanheel H., Vicario M., Vanuytsel T. et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia // Gut. 2014. Vol. 63 (2). P.262–271.
3. Du L., Shen J., Kim J.J. et al. Increased Duodenal Eosinophil Degranulation in Patients with Functional Dyspepsia: A Prospective Study // Sci Rep. 2016. Vol. 6. P.305.
4. Wang X., Li X., Ge W. et al. Quantitative evaluation of duodenal eosinophils and mast cells in adult patients with functional dyspepsia // Ann. Diagn. Pathol. 2015. Vol. 19 (2). P.50–56.
5. Binesh F., Akhondei M., Pourmirafzali H., Rajabzadeh Y. Determination of relative frequency of eosinophils and mast cells in gastric and duodenal mucosal biopsies in adults with non-ulcer dyspepsia // J. Coll. Physicians Surg. Pak. 2013. Vol. 23 (5). P.326–329.
6. Singh V., Singh M., Schurman J.V., Friesen C.A. Histopathological changes in the gastroduodenal mucosa of children with functional dyspepsia // Pathol. Res. Pract. 2018. Vol. 214 (8). P.1173–1178.
7. Du L., Chen B., Kim J.J. et al. Micro-inflammation in functional dyspepsia: A systematic review and meta-analysis // Neurogastroenterol. Motil. 2018. Vol. 30 (4). P.13304.
8. Emara M.H., Salama R.I., Salem A.A. Demographic, Endoscopic and Histopathologic Features Among Stool H. pylori Positive and Stool H. pylori Negative Patients With Dyspepsia // Gastroenterology Res. 2017. Vol. 10 (5). P.305–310.
9. Vanheel H., Vicario M., Boesmans W. et al. Activation of Eosinophils and Mast Cells in Functional Dyspepsia: an Ultrastructural Evaluation // Sci Rep. 2018. Vol. 8 (1). P.5383.
10. Ishigami H., Matsumura T., Kasamatsu S. et al. Endoscopy-Guided Evaluation of Duodenal Mucosal Permeability in Functional Dyspepsia // Clin Transl Gastroenterol. 2017. Vol. 8 (4). P.83.
11. Keita А.V., Söderholm J.D. Mucosal permeability and mast cells as targets for functional gastrointestinal disorders // Curr Opin Pharmacol. 2018. Vol. 43. P.66–71.
12. Vakil N. Editorial: functional dyspepsia-a disorder of duodenal permeability? // Aliment Pharmacol Ther. 2017. Vol. 46 (1). P.70–71.
13. Neilan N.A., Garg U.C., Schurman J.V., Friesen C.A. Intestinal permeability in children/adolescents with functional dyspepsia // BMC Res Notes. 2014. Vol. 7. P.275.
14. Masci E., Pellicano R., Mangiavillano B. et al. GastroPanel test for non-invasive diagnosis of atrophic gastritis in patients with dyspepsia // Minerva Gastroenterol Dietol. 2014. Vol. 60 (1). P.79–83.
15. Daugule I., Ruskule A., Moisejevs G. et al. Long-term dynamics of gastric biomarkers after eradication of Helicobacter pylori infection // Eur. J. Gastroenterol. Hepatol. 2015. Vol. 27 (5). P.501–505.
16. Petersen K.U. Pepsin and Its Importance for Functional Dyspepsia: Relic, Regulator or Remedy? // Dig. Dis. 2018. Vol. 36 (2). P.98–105.
17. Tomita T., Oshima T., Fukui H. et al. Role of acid in functional dyspepsia // Nihon. Rinsho. 2015. Vol. 73 (7). P.1202–1208.
18. Tack J., Carbone F. Functional dyspepsia and gastroparesis // Curr. Opin. Gastroenterol. 2017. Vol. 33 (6). P.446–454.
19. Tahara T., Shibata T., Okubo M. et al. Association between interleukin-1β and tumor necrosis factor-α polymorphisms and symptoms of dyspepsia // Mol. Med. Rep. 2015. Vol. 11 (5). P.3888–3893.
20. Lee K.N., Lee O.Y. The Role of Mast Cells in Irritable Bowel Syndrome // Gastroenterol. Res. Pract. 2016. Vol. 2016. P.2031480.
21. Zhang L., Song J., Hou X. Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside // J. Neurogastroenterol. Motil. 2016. Vol. 22 (2). P.181–192.
22. Bashashati M., Moossavi S., Cremon C. et al. Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis // Neurogastroenterol. Motil. 2018. Vol. 30 (1). P.13192.
23. Boyer J., Saint-Paul M.C., Dadone B. et al. Inflammatory cell distribution in colon mucosa as a new tool for diagnosis of irritable bowel syndrome: A promising pilot study // Neurogastroenterol. Motil. 2018. Vol. 30 (1). P 13223.
24. Adamsson J., Ottsjö L.S., Lundin S.B. et al. Gastric expression of IL-17A and IFNγ in Helicobacter pylori infected individuals is related to symptoms // Cytokine. 2017. Vol. 99. P.30–34.
25. Tran L.S., Chonwerawong M., Ferrero R.L. Regulation and functions of inflammasome-mediated cytokines in Helicobacter pylori infection // Microbes Infect. 2017. Vol. 19 (9–10). P.449–458.
26. Murni A.W., Darwin E., Zubir N., Nurdin A.E. Analyzing Determinant Factors for Pathophysiology of Functional Dyspepsia Based on Plasma Cortisol Levels, IL-6 and IL-8 Expressions and H. pylori Activity // Acta Med. Indones. 2018. Vol. 50 (1). P.38–45.
27. Darwin E., Murni A.W., Nurdin A.E. The Effect of Psychological Stress on Mucosal IL-6 and Helicobacter pylori Activity in Functional Dyspepsia // Acta Med. Indones. 2017. Vol. 49 (2). P.99–104.
28. Vara E.J., Brokstad K.A., Hausken T., Lied G.A. Altered levels of cytokines in patients with irritable bowel syndrome are not correlated with fatigue // Int. J. Gen. Med. 2018. Vol. 6 (11). P.285–291.
29. Bashashati M., Moradi M., Sarosiek I. Interleukin-6 in irritable bowel syndrome: A systematic review and meta-analysis of IL-6 (-G174C) and circulating IL-6 levels // Cytokine. 2017. Vol. 99. P.132–138.
30. Choghakhori R., Abbasnezhad A., Hasanvand A., Amani R. Inflammatory cytokines and oxidative stress biomarkers in irritable bowel syndrome: Association with digestive symptoms and quality of life // Cytokine. 2017. Vol. 93. P.34–43.
31. Bennet S.M., Polster A., Törnblom H. et al. Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome // Am J. Gastroenterol. 2016. Vol. 111 (8). P.1165–1176.
32. Rodiño-Janeiro B.K., Vicario M., Alonso-Cotoner C. et al. A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies // Adv. Ther. 2018. Vol. 35 (3). P.289–310.
33. Hadizadeh F., Bonfiglio F., Belheouane M. et al. Faecal microbiota composition associates with abdominal pain in the general population // Gut. 2018. Vol. 67 (4). P.778–779.
34. Chen Y.J., Wu H., Wu S.D. et al. Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation // J. Gastroenterol. Hepatol. 2018. Vol. 33 (11). P.1844–1852.
35. Lopez-Siles M., Enrich-Capó N., Aldeguer X. et al. Alterations in the Abundance and Co-occurrence of Akkermansia muciniphila and Faecalibacterium prausnitzii in the Colonic Mucosa of Inflammatory Bowel Disease Subjects // Front Cell Infect Microbiol. 2018. Vol. 8. P.281.
36. Tap J., Derrien M., Törnblom H. et al. Identification of an intestinal microbiota signature associated with Severity of irritable bowel syndrome // Gastroenterology. 2017. Vol. 152. P.111–123.
37. Hod K., Dekel R., Aviv Cohen N. et al. The effect of a multispecies probiotic on microbiota composition in a clinical trial of patients with diarrhea-predominant irritable bowel syndrome // Neurogastroenterol. Motil. 2018. Vol. 23. P. 13456.
38. Chang C. Short-course therapy for diarrhea-predominant irritable bowel syndrome: understanding the mechanism, impact on gut microbiota, and safety and tolerability of rifaximin // Clin. Exp. Gastroenterol. 2018. Vol. 11. P.335–345.
39. Maharshak N., Ringel Y., Katibian D. et al. Fecal and Mucosa-Associated Intestinal Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome // Dig. Dis. Sci. 2018. Vol. 63 (7). P.1890–1899.
40. Halkhaer S.I., Christensen A.H., Lo B.Z.S. et al. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study // Gut. 2018. Vol. 67 (12). P.2107–2115.

This work is licensed under a Creative Commons «Attribution» 4.0 License.
Previous article
Next article
















