Pathophysiology, diagnostics and treatment of slow-transit constipation: a review

Introduction. The work is a review article that examines the pathophysiology, diagnostics and treatment options for slow-transit constipation.

Aim. The main goal of this study is to define slow-transit constipation, describe the primary pathophysiological mechanisms involved in its development, identify key aspects of diagnosing the condition, and thoroughly examine the existing treatment methods and their clinical efficacy.

Methods. A systematic search of the literature in electronic databases PubMed, EMBASE and Cochrane covering the past 20 years was conducted. Studies on clinical outcomes and pathophysiological mechanisms of slow-transit constipation were included in this review prepared in accordance with PRISMA guidelines.

Results. It has been established that, despite the widespread use of conservative therapy for idiopathic chronic constipation, its effectiveness in treating slow-transit constipation is low. Conversely, surgical treatment shows high effectiveness in improving symptoms and quality of life. This brings  up the question about making surgical approach the method of preference in treating slow-transit constipation. Yet, aspects related to the frequency of postoperative complications and the selection of the most appropriate surgical approach remain underexplored, leaving the question of the preferred option open for further investigation.

Conclusion. Despite the limited efficacy of conservative therapy for slow-transit constipation, radical surgical treatment shows significant improvement in symptoms and quality of life, requiring further studies to optimise treatment approaches and investigate postoperative complications.

1. Ivashkin VT, Shelygin YuA, Maev IV, Sheptulin AA, Aleshin DV, Achkasov SJ, Baranskaya EK, Kulikova ND, Lapina TL, Moskalev AI, Osipenko MF, Poluektova EA, Simanenkov VI, Trukhmanov AS, Fomenko OYu, Shifrin OS. Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia on Diagnosis and Treatment of Constipation in Adults. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(6):65—85 (in Russ.). https://doi.org/10.22416/1382-4376-2020-30-6-69-85

2. Barberio B, Judge C, Savarino EV, Ford AC. Global prevalence of functional constipation according to the Rome criteria: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(8):638—648. https://doi.org/10.1016/S2468-1253(21)00111-4

3. Bassotti G, Villanacci V. Slow transit constipation: a functional disorder becomes an enteric neuropathy. World J Gastroenterol. 2006;12(29):4609—4613. https://doi.org/10.3748/wjg.v12.i29.4609

4. Andrews CN, Storr M. The pathophysiology of chronic constipation. Can J Gastroenterol. 2011;25(Suppl B):16—21.

5. Törnblom H, Lang B, Clover L, Knowles CH, Vincent A, Lindberg G. Autoantibodies in patients with gut motility disorders and enteric neuropathy. Scand J Gastroenterol. 2007;42(11):1289—1293. https://doi.org/10.1080/00365520701396216

6. Prichard DO, Bharucha AE. Recent advances in understanding and managing chronic constipation. F1000Res. 2018;7:F1000 Faculty Rev-1640. https://doi.org/10.12688/f1000research.15900.1

7. Tillou J, Poylin V. Functional Disorders: Slow-Transit Constipation. Clin Colon Rectal Surg. 2017;30(1):76—86. https://doi.org/10.1055/s-0036-1593436

8. Isaev GB, Kerimova TM. Long-term outcomes of subtotal colectomy in patients with chronic colostasis. Bulletin of Surgery of Kazakhstan. 2018;1(54):30—33 (in Russ.).

9. Yang YP, Shi J, Zhao ZY, Yu LY, Liu TJ. Subtotal colectomy with antiperistaltic cecosigmoidal anastomosis may be another suitable option for slow transit constipation: Experiences from Chinese people. Medicine (Baltimore). 2020;99(7):e19065. https://doi.org/10.1097/MD.0000000000019065

10. Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol. 2011;106(9):1582—1592. https://doi.org/10.1038/ajg.2011.164

11. Milosavljevic T, Popovic DD, Mijac DD, Milovanovic T, Krstic S, Krstic MN. Chronic Constipation: Gastroenterohepatologist’s Approach. Dig Dis. 2022;40(2):175—180. https://doi.org/10.1159/000516976

12. Bassotti G, Iantorno G, Fiorella S, Bustos-Fernandez L, Bilder CR. Colonic motility in man: features in normal subjects and in patients with chronic idiopathic constipation. Am J Gastroenterol. 1999;94(7):1760—1770. https://doi.org/10.1111/j.1572-0241.1999.01203.x

13. Vlismas LJ, Wu W, Ho V. Idiopathic Slow Transit Constipation: Pathophysiology, Diagnosis, and Management. Medicina (Kaunas). 2024;60(1):108. https://doi.org/10.3390/medicina60010108

14. Bassotti G, Chiarioni G, Imbimbo BP, Betti C, Bonfante F, Vantini I, Morelli A, Whitehead WE. Impaired colonic motor response to cholinergic stimulation in patients with severe chronic idiopathic (slow transit type) constipation. Dig Dis Sci. 1993;38(6):1040—1045. https://doi.org/10.1007/BF01295719

15. Bassotti G, Chistolini F, Nzepa FS, Morelli A. Colonic propulsive impairment in intractable slow-transit constipation. Arch Surg. 2003;138(12):1302—1304. https://doi.org/10.1001/archsurg.138.12.1302

16. Sharma A, Rao S. Constipation: Pathophysiology and Current Therapeutic Approaches. Handbook of Experimental Pharmacology. 2017;239:59—74. https://doi.org/10.1007/164_2016_111

17. He CL, Burgart L, Wang L, Pemberton J, Young-Fadok T, Szurszewski J, Farrugia G. Decreased interstitial cell of cajal volume in patients with slow-transit constipation. Gastroenterology. 2000;118(1):14—21. https://doi.org/10.1016/s0016-5085(00)70409-4

18. Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, Lindberg G, Martin JE, Meier- Ruge WA, Milla PJ, Smith VV, Vandervinden JM, Veress B, Wedel T. The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group. Gut. 2010;59(7):882—887. https://doi.org/10.1136/gut.2009.200444

19. Pimentel M, Lin HC, Enayati P, van den Burg B, Lee HR, Chen JH, Park S, Kong Y, Conklin J. Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity. Am J Physiol Gastrointest Liver Physiol. 2006;290(6):G1089—1095. https://doi.org/10.1152/ajpgi.00574.2004

20. Bassotti G, Villanacci V, Nascimbeni R, Cadei M, Manenti S, Sabatino G, Maurer CA, Cathomas G, Salerni B. Colonic mast cells in controls and slow transit constipation patients. Aliment Pharmacol Ther. 2011;34(1):92—99. https://doi.org/10.1111/j.1365-2036.2011.04684.x

21. Liu W, Zhang Q, Li S, Li L, Ding Z, Qian Q, Fan L, Jiang C. The Relationship Between Colonic Macrophages and MicroRNA-128 in the Pathogenesis of Slow Transit Constipation. Dig Dis Sci. 2015;60(8):2304—2315. https://doi.org/10.1007/s10620-015-3612-1

22. Roe AM, Bartolo DC, Mortensen NJ. Slow transit constipation. Comparison between patients with or without previous hysterectomy. Dig Dis Sci. 1988;33(9):1159—1163. https://doi.org/10.1007/BF01535794

23. Scott SM, Knowles CH, Newell M, Garvie N, Williams NS, Lunniss PJ. Scintigraphic assessment of colonic transit in women with slow-transit constipation arising de novo and following pelvic surgery or childbirth. Br J Surg. 2001;88(3):405—411. https://doi.org/10.1046/j.1365-2168.2001.01699.x

24. Camilleri M, Ford AC, Mawe GM, Dinning PG, Rao SS, Chey WD, Simrén M, Lembo A, Young-Fadok TM, Chang L. Chronic constipation. Nat Rev Dis Primers. 2017;3:17095. https://doi.org/10.1038/nrdp.2017.95

25. Black CJ, Ford AC. Chronic idiopathic constipation in adults: epidemiology, pathophysiology, diagnosis and clinical management. Med J Aust. 2018;209(2):86—91. https://doi.org/10.5694/mja18.00241

26. Frattini JC, Nogueras JJ. Slow transit constipation: a review of a colonic functional disorder. Clin Colon Rectal Surg. 2008;21(2):146—152. https://doi.org/10.1055/s-2008-1075864

27. Yang Y, Yim J, Choi W, Lee S. Improving slow-transit constipation with transcutaneous electrical stimulation in women: A randomized, comparative study. Women Health. 2017;57(4):494—507. https://doi.org/10.1080/03630242.2016.1176098

28. Chiarioni G, Salandini L, Whitehead WE. Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit constipation. Gastroenterology. 2005;129(1):86—97. https://doi.org/10.1053/j.gastro.2005.05.015

29. Emmanuel AV, Kamm MA. Response to a behavioural treatment, biofeedback, in constipated patients is associated with improved gut transit and autonomic innervation. Gut. 2001;49(2):214—219. https://doi.org/10.1136/gut.49.2.214

30. Staller K, Barshop K, Ananthakrishnan AN, Kuo B. Number of retained radiopaque markers on a colonic transit study does not correlate with symptom severity or quality of life in chronic constipation. Neurogastroenterol Motil. 2018;30(5):e13269. https://doi.org/10.1111/nmo.13269

31. Kim NY, Kim DH, Pickhardt PJ, Carchman EH, Wald A, Robbins JB. Defecography: An Overview of Technique, Interpretation, and Impact on Patient Care. Gastroenterol Clin North Am. 2018;47(3):553—568. https://doi.org/10.1016/j.gtc.2018.04.006

32. Christodoulides S, Dimidi E, Fragkos KC, Farmer AD, Whelan K, Scott SM. Systematic review with meta- analysis: effect of fibre supplementation on chronic idiopathic constipation in adults. Aliment Pharmacol Ther. 2016;44(2):103—116. https://doi.org/10.1111/apt.13662

33. Prichard DO, Bharucha AE. Recent advances in understanding and managing chronic constipation. F1000Res. 2018;7:F1000 Faculty Rev-1640. https://doi.org/10.12688/f1000research.15900.1

34. Suares NC, Ford AC. Systematic review: the effects of fibre in the management of chronic idiopathic constipation. Aliment Pharmacol Ther. 2011;33(8):895—901. https://doi.org/10.1111/j.1365-2036.2011.04602.x

35. Voderholzer WA, Schatke W, Mühldorfer BE, Klauser AG, Birkner B, Müller-Lissner SA. Clinical response to dietary fiber treatment of chronic constipation. Am J Gastroenterol. 1997;92(1):95—98.

36. Meshkinpour H, Selod S, Movahedi H, Nami N, James N, Wilson A. Effects of regular exercise in management of chronic idiopathic constipation. Dig Dis Sci. 1998;43(11):2379—2383. https://doi.org/10.1023/a:1026609610466

37. Wald A. Slow Transit Constipation. Curr Treat Options Gastroenterol. 2002;5(4):279—283. https://doi.org/10.1007/s11938-002-0050-x

38. Johanson JF, Ueno R. Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety. Aliment Pharmacol Ther. 2007;25(11):1351—1361. https://doi.org/10.1111/j.1365-2036.2007.03320.x

39. Chang L, Chey WD, Imdad A, Almario CV, Bharucha AE, Diem S, Greer KB, Hanson B, Harris LA, Ko C, Murad MH, Patel A, Shah ED, Lembo AJ, Sultan S. American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation. Gastroenterology. 2023;164(7):1086—1106. https://doi.org/10.1053/j.gastro.2023.03.214

40. Emmanuel AV, Roy AJ, Nicholls TJ, Kamm MA. Prucalopride, a systemic enterokinetic, for the treatment of constipation. Aliment Pharmacol Ther. 2002;16(7):1347—1356. https://doi.org/10.1046/j.1365-2036.2002.01272.x

41. Ahuja NK, Mische L, Clarke JO, Wigley FM, McMahan ZH. Pyridostigmine for the treatment of gastrointestinal symptoms in systemic sclerosis. Semin Arthritis Rheum. 2018;48(1):111—116. https://doi.org/10.1016/j.semarthrit.2017.12.007

42. Tian H, Ge X, Nie Y, Yang L, Ding C, McFarland LV, Zhang X, Chen Q, Gong J, Li N. Fecal microbiota transplantation in patients with slow-transit constipation: A randomized, clinical trial. PLoS One. 2017;12(2):e0171308. https://doi.org/10.1371/journal.pone.0171308

43. Ding C, Fan W, Gu L, Tian H, Ge X, Gong J, Nie Y, Li N. Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: results from a prospective study with long-term follow-up. Gastroenterol Rep (Oxf). 2018;6(2):101—107. https://doi.org/10.1093/gastro/gox036

44. Patton V, Stewart P, Lubowski DZ, Cook IJ, Dinning PG. Sacral Nerve Stimulation Fails to Offer Longterm Benefit in Patients With Slow-Transit Constipation. Dis Colon Rectum. 2016;59(9):878—885. https://doi.org/10.1097/DCR.0000000000000653

45. Wang L, Xu M, Zheng Q, Zhang W, Li Y. The Effectiveness of Acupuncture in Management of Functional Constipation: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2020;2020:6137450. https://doi.org/10.1155/2020/6137450

46. Wang X, Yin J. Complementary and Alternative Therapies for Chronic Constipation. Evid Based Complement Alternat Med. 2015;2015:396396. https://doi.org/10.1155/2015/396396

47. Emmett CD, Close HJ, Yiannakou Y, Mason JM. Trans-anal irrigation therapy to treat adult chronic functional constipation: systematic review and meta-analysis. BMC Gastroenterol. 2015;15:139. https://doi.org/10.1186/s12876-015-0354-7

48. Sakulin KA, Karpukhin OYu. Therapeutic and diagnostic algorithm for resistant forms of cologenous constipation in adults. Bulletin of Modern Clinical Medicine. 2021;14(3):38—43 (in Russ.). https://doi.org/10.20969/VSKM.2021

49. Rongen MJ, van der Hoop AG, Baeten CG. Cecal access for antegrade colon enemas in medically refractory slow-transit constipation: a prospective study. Dis Colon Rectum. 2001;44(11):1644—1649. https://doi.org/10.1007/BF02234385

50. Lees NP, Hodson P, Hill J, Pearson RC, MacLennan I. Long-term results of the antegrade continent enema procedure for constipation in adults. Colorectal Dis. 2004;6(5):362—368. https://doi.org/10.1111/j.1463-1318.2004.00669.x

51. Chen W, Jiang CQ, Qian Q, Ding Z, Liu ZS. Antiperistaltic Side-to-Side Ileorectal Anastomosis is Associated with a Better Short-Term Fecal Continence and Quality of Life in Slow Transit Constipation Patients. Dig Surg. 2015;32(5):367—374. https://doi.org/10.1159/000437234

52. Knowles CH, Grossi U, Horrocks EJ, Pares D, Vollebregt PF, Chapman M, Brown S, Mercer-Jones M, Williams AB, Yiannakou Y, Hooper RJ, Stevens N, Mason J; NIHR CapaCiTY working group; Pelvic floor Society and; European Society of Coloproctology. Surgery for constipation: systematic review and practice recommendations: Graded practice and future research recommendations. Colorectal Dis. 2017;19 Suppl 3:101—113. https://doi.org/10.1111/codi.13775

53. Hassan I, Pemberton JH, Young-Fadok TM, You YN, Drelichman ER, Rath-Harvey D, Schleck CD, Larson DR. Ileorectal anastomosis for slow transit constipation: long-term functional and quality of life results. J Gastrointest Surg. 2006;10(10):1330—1337. https://doi.org/10.1016/j.gassur.2006.09.006

54. Tian Y, Wang L, Ye JW, Zhang Y, Zheng HC, Shen HD, Li F, Liu BH, Tong, WD. Defecation function and quality of life in patients with slow-transit constipation after colectomy. World journal of clinical cases. 2020;8(10):1897—1907. https://doi.org/10.12998/wjcc.v8.i10.1897

55. Giorgio V, Borrelli O, Smith VV, Rampling D, Köglmeier J, Shah N, Thapar N, Curry J, Lindley KJ. High-resolution colonic manometry accurately predicts colonic neuromuscular pathological phenotype in pediatric slow transit constipation. Neurogastroenterol Motil. 2013;25(1):70-8.e8—9. https://doi.org/10.1111/nmo.12016

56. Tsimogiannis KE, Karlbom U, Lundin E, Graf W. Long-term outcome after segmental colonic resection for slow transit constipation. Int J Colorectal Dis. 2019;34(6):1013—1019. https://doi.org/10.1007/s00384-019-03283-5

57. Xie XY, Sun KL, Chen WH, Zhou Y, Chen BX, Ding Z, Yu XQ, Wu YH, Qian Q, Jiang CQ, Liu WC. Surgical outcomes of subtotal colectomy with antiperistaltic caecorectal anastomosis vs total colectomy with ileorectal anastomosis for intractable slow-transit constipation. Gastroenterol Rep (Oxf). 2019;7(6):449—454. https://doi.org/10.1093/gastro/goz014

58. Romashchenko PN, Maistrenko NA, Samedov VB. Chronic slow-transit constipation: aspects of diagnosis and surgical treatment. TMBV. 2022;25(2):90—97 (in Russ.). https://doi.org/10.37279/2070-8092-2022-25-2-90-97

59. Deng XM, Zhu TY, Wang GJ, Gao BL, Li RX, Wang JT. Laparoscopic total colectomy with ileorectal anastomosis and subtotal colectomy with antiperistaltic cecorectal anastomosis for slow transit constipation. Updates Surg. 2023;75(4):871—880. https://doi.org/10.1007/s13304-023-01458-y

60. Patton V, Balakrishnan V, Pieri C, Doherty P, Phan-Thien KC, King DW, Lubowski DZ. Subtotal colectomy and ileorectal anastomosis for slow transit constipation: clinical follow-up at median of 15 years. Tech Coloproctol. 2020;24(2):173—179. https://doi.org/10.1007/s10151-019-02140-5