Хронический запор у коморбидного пациента - место лактулозы в терапии сложного пациента

Запор - часто встречающееся расстройство дефекации сложного генеза у пожилых людей, которое оказывает отрицательное влияние на качество жизни как самого пациента, так и увеличивает расходы на систему общественного здравоохранения. Хотя запор, как таковой, не является физиологическим следствием нормального старения, тем не менее, снижение физической активности, прием ряда лекарственных препаратов, влияющих на моторику толстой кишки, сопутствующие заболевания и ректальная сенсорно-моторная дисфункция могут способствовать его увеличению распространенности среди пожилых людей. Как правило, в этой возрастной категории обычно существует более одного этиологического механизма, что требует системного подхода к лечению. Большинство пациентов реагируют на диету и изменение образа жизни, подкрепленные мерами по тренировке кишечника. Однако, у тех, кто не реагирует на комплекс консервативных методов лечения, подход должен быть индивидуальным, учитывающим все сопутствующие заболевания. В этом случае препаратом выбора у коморбидных пациентов может являться лактулоза, обладающая как свойствами осмотического слабительного, так и выраженными пребиотическими свойствами. Безопасность лактулозы у коморбидных больных обусловлена ее метаболической нейтральностью и отсутствием влияния на систему цитохрома Р450, что минимизирует риски нежелательных лекарственных взаимодействий у пациентов, получающих полипрагмазию по поводу сердечно-сосудистых, эндокринных и других хронических заболеваний.

хронический запор, дисбиоз, короткоцепочечные жирные кислоты, лактулоза, эпителиальная проницаемость, коморбидность, сахарный диабет, ожирение, сердечно-сосудистая патология

1. Serkova M. Yu., Avalueva E.B., Sitkin S.I. Chronic constipation: focus on microbiome-targeted therapies with prebiotics, probiotics, and synbiotics. Almanac of Clinical Medicine. 2024;52(5):280-296. (in Russ.) doi: 10.18786/2072-0505-2024-52-026. @@ Серкова М.Ю., Авалуева Е.Б., Ситкин С.И. Хронический запор: фокус на микробиом-модулирующей терапии пребиотиками, про-биотиками и синбиотиками. Альманах клинической медицины. 2024;52(5):280-296. doi: 10.18786/2072-0505-2024-52-026.

2. Neri L, Basilisco G, Corazziari E. Constipation severity is associated with productivity losses and healthcare utilization in patients with chronic constipation. United European Gastroenterol J. 2014;2:138-47. doi: 10.1177/2050640614528175.

3. Menees S.B., Guentner A., Chey S.W., Saad R., Chey W.D. How Do US Gastroenterologists Use Over-the-Counter and Prescription Medications in Patients With Gastroesophageal Reflux and Chronic Constipation? Am J Gastroenterol. 2015 Nov;110(11):1516-25. doi: 10.1038/ajg.2015.156.

4. Mearin F., Lacy B.E., Chang L. et al. Bowel Disorders. Gastroenterology. 2016: S0016-5085(16)00222-5. doi: 10.1053/j.gastro.2016.02.031.

5. Harari D. Constipation. In: Halter JB, Ouslander JG, Tinetti ME, editors. Hazzard’s Geriatric Medicine and Gerontology. 6. New York, USA: McGraw-Hill Companies; 2009. pp. 1103-22.

6. Coyne KS, Cash B, Kopp Z, Murphy S, Smith GJ, Davidson GA. The prevalence of chronic constipation and fecal incontinence among men and women with symptoms of overactive bladder. BJU Int. 2011;107:254-61. doi: 10.1111/j.1464-410X.2010.09446.x.

7. Kinnunen O. Study of constipation in a geriatric hospital, day hospital, old people’s home and at home. Aging. 1991;3:161-70. doi: 10.1007/BF03323997.

8. Fominykh Yu.A., Pugachev P.V., Matveeva E.O., Shotik A.V. Features of chronic constipation in patients of older age groups. University Therapeutic Journal. 2025;7(4):92-103. (in Russ.) doi: 10.56871/UTJ.2025.67.77.005.@@ Фоминых Ю.А., Пугачев П.В., Матвеева Е.О., Шотик А.В. Особенности хронического запора у пациентов старших возрастных групп. University Therapeutic Journal. 2025;7(4):92-103. doi: 10.56871/UTJ.2025.67.77.005.

9. Shemerovsky KA. Constipation as a risk factor for colorectal cancer. Clinical Medicine. 2005;83(12):60-64. (in Russ.)@@ Шемеровский КА. Запор - фактор риска колоректального рака. Клиническая медицина. 2005;83(12):60-64.

10. Chelakkot C., Ghim J., Ryu S.H. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp. Mol. Med. 2018;50:1-9. doi: 10.1038/s12276-018-0126-x.

11. Song C., Chai Z., Chen S., Zhang H., Zhang X., Zhou Y.Intestinal mucus components and secretion mechanisms: What we do and do not know. Exp. Mol. Med. 2023;55:681-691. doi: 10.1038/s12276-023-00960-y.

12. Horowitz A., Chanez-Paredes S.D., Haest X., Turner J.R. Paracellular permeability and tight junction regulation in gut health and disease. Nat. Rev. Gastroenterol. Hepatol. 2023;20:417-432. doi: 10.1038/s41575-023-00766-3.

13. Wu H., Hu T., Hao H., Hill M.A., Xu C., Liu Z. Inflammatory bowel disease and cardiovascular diseases: A concise review. Eur. Heart J. Open. 2021;2: oeab029. doi: 10.1093/ehjopen/oeab029.

14. Oikonomou I., Papageorgiou A., de Lastic A.L. et al. Gut barrier dysfunction, endotoxemia and inflammatory response in STEMI patients and effect of primary PCI. Am.J. Med Sci. 2024;368:485-493. doi: 10.1016/j.amjms.2024.07.004.

15. Zhao J., Zhang Q., Cheng W. et al. Heart-gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia/reperfusion. Cardiovasc. Res. 2023;119:1390. doi: 10.1093/cvr/cvad023.

16. Hillman E.T., Lu H., Yao T., Nakatsu C.H. Microbial Ecology along the Gastrointestinal Tract. Microbes Environ. 2017;32:300. doi: 10.1264/jsme2.ME17017.

17. Nicholson J.K., Holmes E., Kinross J., Burcelin R., Gibson G., Jia W., Pettersson S. Host-gut microbiota metabolic interactions. Science. 2012;336:1262-1267. doi: 10.1126/science.1223813.

18. Donaldson G.P., Lee S.M., Mazmanian S.K. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 2016;14:20-32. doi: 10.1038/nrmicro3552.

19. Pan R, Wang L, Xu X, Chen Y, Wang H, Wang G, Zhao J, Chen W. Crosstalk between the gut microbiome and colonic motility in chronic constipation: Potential mechanisms and microbiota modulation. Nutrients. 2022;14(18):3704. doi: 10.3390/nu14183704.

20. Chen W, Zhang S, Wu J, Ye T, Wang S, Wang P, et al. Butyrate-producing bacteria and the gut-heart axis in atherosclerosis. Clin Chim Acta. 2020; 507:236-41. 10.1016/j.cca.2020.04.037.

21. Tang W.H., Wang Z., Levison B.S. et al.Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575-84. 10.1056/NEJMoa1109400.

22. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al.Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19:576-85. 10.1038/nm.3145.

23. Rivera K, Gonzalez L, Bravo L, Manjarres L, Andia ME. The gut-heart axis: molecular perspectives and implications for myocardial infarction.Int J Mol Sci. 2024;25:12465. 10.3390/ijms252212465.

24. Judkins CP, Wang Y, Jelinic M, Bobik A, Vinh A, Sobey CG, et al. Association of constipation with increased risk of hypertension and cardiovascular events in elderly Australian patients. Sci Rep. 2023;13:10943. 10.1038/s41598-023-38068-y.

25. Hara K, Hirowatari Y, Yoshika M, Komiyama Y, Tsuka Y, Takahashi H. The ratio of plasma to whole-blood serotonin may be a novel marker of atherosclerotic cardiovascular disease. J Lab Clin Med. 2004;144:31-7. 10.1016/j.lab.2004.03.014.

26. Vikenes K, Farstad M, Nordrehaug JE. Serotonin is associated with coronary artery disease and cardiac events. Circulation. 1999;100:483-9. 10.1161/01.CIR.100.5.483.

27. Meng S., Pan Y., Deng Q., Wang L., Chang Q. Efficacy and safety of lactulose on the treatment of puerperal constipation. Zhonghua Yi Xue Za Zhi. 2015; 95 (28): 2288-2890.

28. Bouhnik Y, Neut C, Raskine L, Michel C, Riottot M, Andrieux C, Guillemot F, Dyard F, Flourié B. Prospective, randomized, parallel-group trial to evaluate the effects of lactulose and polyethylene glycol-4000 on colonic flora in chronic idiopathic constipation. Aliment Pharmacol Ther. 2004 Apr 15;19(8):889-99. doi: 10.1111/j.1365-2036.2004.01918.x.

29. Timofeeva A.V., Moiseeva Yu.N., Libov I.A. Duphalac in the treatment of constipation in elderly patients suffering from cardiovascular diseases. RMJ. 2007;6:464. (in Russ.)@@ Тимофеева А.В., Моисеева Ю.Н., Либов И.А. Дюфалак в лечении запора у пожилых пациентов, страдающих сердечно-сосудистыми заболеваниями. РМЖ. 2007;6:464.

30. Prasad V.G., Abraham P. Management of chronic constipation in patients with diabetes mellitus. Indian J Gastroenterol. 2017;36:11-22. doi: 10.1007/s12664-016-0724-2.

31. Fritz E, Hammer HF, Lipp RW, Högenauer C, Stauber R, Hammer J. Effects of lactulose and polyethylene glycol on colonic transit. Aliment Pharmacol Ther. 2005;21:259-268. doi: 10.1111/j.1365-2036.2005.02244.x.

32. Bouhnik Y, Neut C, Raskine L, Michel C, Riottot M, Andrieux C, Guillemot F, Dyard F, Flourié B. Prospective, randomized, parallel-group trial to evaluate the effects of lactulose and polyethylene glycol-4000 on colonic flora in chronic idiopathic constipation. Aliment Pharmacol Ther. 2004;19:889-899. doi: 10.1111/j.1365-2036.2004.01918.x.

33. Rayner CK, Samsom M, Jones KL, Horowitz M. Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care. 2001;24:371-381. doi: 10.2337/diacare.24.2.371.

34. Piper MS, Saad RJ. Diabetes Mellitus and the Colon. Curr Treat Options Gastroenterol. 2017;15:460-474. doi: 10.1007/s11938-017-0151-1.

35. Wei L., Ji L., Miao Y. et al. Constipation in DM are associated with both poor glycemic control and diabetic complications: Current status and future directions. Biomed Pharmacother. 2023;165:115202. doi: 10.1016/j.biopha.2023.115202.

36. Overduin J, Tylee TS, Frayo RS, Cummings DE. Hyperosmolarity in the small intestine contributes to postprandial ghrelin suppression. Am J Physiology-Gastrointestinal Liver Physiol. 2014;306(12): G1108-G16. doi: 10.1152/ajpgi.00072.2014.

37. Ropert A, Cherbut C, Rozé C, Le Quellec A, Holst J, Fu-Cheng X. et al. Colonic fermentation and proximal gastric tone in humans. Gastroenterology. 1996;111(2):289-96. doi: 10.1053/gast.1996.v111.pm8690193.

38. Kellow NJ, Coughlan MT, Reid CM. Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials. Br J Nutr. 2014;111(7):1147-61. doi: 10.1017/S0007114513003607.

39. Chu N, Ling J, Jie H, Leung K, Poon E. The potential role of lactulose pharmacotherapy in the treatment and prevention of diabetes. Front Endocrinol (Lausanne). 2022 Sep 15;13:956203. doi: 10.3389/fendo.2022.956203.

40. Mizota T, Mori T, Yaeshima T, Yanagida T, Iwatsuki K, Ishibashi N, et al. Effects of low dosages of lactulose on the intestinal function of healthy adults. Milchwissenschaft. 2002;57(6):312-5.

41. Venema K, van Nuenen MH, van den Heuvel EG, Pool W, van der Vossen JM. The effect of lactulose on the composition of the intestinal microbiota and short-chain fatty acid production in human volunteers and a computer-controlled model of the proximal large intestine. Microbial Ecol Health Dis. 2003;15(2-3):94-105. doi: 10.1080/08910600310019895.

42. Schönfeld P, Wojtczak L. Short-and medium-chain fatty acids in energy metabolism: the cellular perspective. J Lipid Res. 2016;57(6):943-54. doi: 10.1194/jlr.R067629.

43. Chambers ES, Preston T, Frost G, Morrison DJ. Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health. Curr Nutr Rep. 2018;7(4):198-206. doi: 10.1007/s13668-018-0248-8.

44. Mooranian A, Zamani N, Takechi R, Luna G, Mikov M, Goločorbin-Kon S, et al. Modulatory nano/micro effects of diabetes development on pharmacology of primary and secondary bile acids concentrations. Curr Diabetes Rev. 2020;16(8):900-9. doi: 10.2174/1389450121666200204115121.

45. Mooranian A, Zamani N, Takechi R, Al-Sallami H, Mikov M, Goločorbin-Kon S, et al. Pharmacological effects of nanoencapsulation of human-based dosing of probucol on ratio of secondary to primary bile acids in gut, during induction and progression of type 1 diabetes. Artif Cells Nanomedicine Biotechnol. 2018;46(sup3): S748-S54. doi: 10.1080/21691401.2018.1511572.

46. Lu J, Wang S, Li M, Gao Z, Xu Y, Zhao X, et al. Association of serum bile acids profile and pathway dysregulation with the risk of developing diabetes among normoglycemic chinese adults: Findings from the 4C study. Diabetes Care. 2021;44(2):499-510. doi: 10.2337/dc20-0884.

47. Pieber T.R., Svehlikova E., Mursic I. et al. Blood glucose response after oral lactulose intake in type 2 diabetic individuals. World J Diabetes. 2021;12(6):893-907. doi: 10.4239/WJD.V12.I6.893.

48. Vincent AD, Wang XY, Parsons SP, Khan WI, Huizinga JD. Abnormal absorptive colonic motor activity in germ-free mice is rectified by butyrate, an effect possibly mediated by mucosal serotonin. Am J Physiol Gastrointest Liver Physiol. 2018;315(5): G896-G907. doi: 10.1152/ajpgi.00237.2017.

49. Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013;93(1):359-404. doi: 10.1152/physrev.00033.2011.

50. Alsheridah N, Akhtar S. Diet, obesity and colorectal carcinoma risk: results from a national cancer registry-based middle-eastern study. BMC Cancer. 2018;18:1-10. doi: 10.1186/s12885-018-5132-9.

51. Delgado-Aros S, Locke GR, 3rd, Camilleri M, Talley NJ, Fett S, Zinsmeister AR, Melton LJ., 3rd Obesity is associated with increased risk of gastrointestinal symptoms: a population-based study. Am J Gastroenterol. 2004;99(9):1801-1806. doi: 10.1111/j.1572-0241.2004.30887.x.

52. Talley NJ, Howell S, Poulton R. Obesity and chronic gastrointestinal tract symptoms in young adults: a birth cohort study. Am Coll Gastroenterol. 2004;99(9):1807-1814. doi: 10.1111/j.1572-0241.2004.30388.x.

53. Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci. 2013; 9:191-200. 10.5114/aoms.2013.33181.

54. Di Vincenzo F., Del Gaudio A., Petito V. et al. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review.Intern Emerg Med. 2023;19(20:275-293. doi: 10.1007/S11739-023-03374-W.

55. Bergman EN. Energy contributions of volatile fatty acids from the gastrointestinal tract in various s species. Physiol Rev. 1990;70:567-590. doi: 10.1152/physrev.1990.70.2.567.

56. Blaak E.E., Canfora E.E., Theis S. et al. Short chain fatty acids in human gut and metabolic health. Benef Microbes. 2020;11:411-455. doi: 10.3920/BM2020.0057.

57. Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019;16:461-478. doi: 10.1038/s41575-019-0157-3.

58. Pokrovskaya E.V., Shamkhalova M. Sh., Shestakova M.V. New views on the state of intestinal microbiota in obesity and type 2 diabetes mellitus. Diabetes mellitus. 2019; 22:253-262. doi: 10.14341/DM10194-9234.@@ Покровская Е.В., Шамхалова М.Ш., Шестакова М.В. Новые взгляды на состояние кишечной микробиоты при ожирении и сахарном диабете 2 типа. Сахарный диабет. 2019;22:253-262. doi: 10.14341/DM10194-9234.

59. Iqbal M, Yu Q, Tang J, Xiang J. Unraveling the gut microbiota’s role in obesity: key metabolites, microbial species, and therapeutic insights. J Bacteriol. 2025 May 22;207(5): e0047924. doi: 10.1128/jb.00479-24.

60. Shen C, Cai C, Zhang Y, Xu H, Wu Y, Xu T, Mao Y. Global burden of colorectal cancer and associated risk factors in young-older adults: Trends from 1990 to 2021 with projections to 2050. Medicine (Baltimore). 2026 Feb 6;105(6): e47448. doi: 10.1097/MD.0000000000047448.

61. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834.

62. He Y, Wang X, Zhou M, Li L, Han T, He J, Mai W, Li X. Global, regional and national burden of colon and rectum cancer: a systematic analysis of prevalence, incidence, deaths and DALYs from 1990 to 2021 using data from the Global Burden of Disease Study 2021 with projections to 2036. BMJ Open. 2025 Oct 6;15(10): e100042. doi: 10.1136/bmjopen-2025-100042.

63. Aierken A, Aizezi Y, Atabieke F, Rehaman M, Aierken M, Li SX. No bidirectional relationship between constipation and colorectal cancer in European and Asian populations: A Mendelian randomization study. Medicine (Baltimore). 2024 Oct 25;103(43): e40206. doi: 10.1097/MD.0000000000040206.

64. Parthasarathy G, Chen J, Chen X, Chia N, O’Connor HM, Wolf PG, Gaskins HR, Bharucha AE. Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation. Gastroenterology. 2016;150:367-79.e1. doi: 10.1053/j.gastro.2015.10.005.

65. Yang L, Wang Y, Zhang Y, Li W, Jiang S, Qian D, Duan J. Gut microbiota: a new avenue to reveal pathological mechanisms of constipation. Appl Microbiol Biotechnol. 2022;106:6899-6913. doi: 10.1007/s00253-022-12197-2.

66. Galan-Ros J, Ramos-Arenas V, Conesa-Zamora P. Predictive values of colon microbiota in the treatment response to colorectal cancer. Pharmacogenomics. 2020;21:1045-1059. doi: 10.2217/pgs-2020-0044.

67. O’Keefe SJ. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol. 2016;13:691-706. doi: 10.1038/nrgastro.2016.165.

68. Livzan M.A., Bordin D.S., Abdulkhakov S.R. Constipation, intestinal microbiota and comorbid pathology: the search for an optimal approach to patient management.Russian Medical Inquiry. 2025;9(9):596-605 (in Russ.) doi: 10.32364/2587-6821-2025-9-9-9.@@ Ливзан М.А., Бордин Д.С., Абдулхаков С.Р. Запор, кишечная микробиота и коморбидная патология: поиск оптимального подхода к ведению пациента. РМЖ. Медицинское обозрение. 2025;9(9):596-605. doi: 10.32364/2587-6821-2025-9-9-9.

69. Hefny AF, Ayad AZ, Matev N, Bashir MO.Intestinal obstruction caused by a laxative drug (Psyllium): A case report and review of the literature.Int J Surg Case Rep. 2018;52:59-62. doi: 10.1016/j.ijscr.2018.10.001.

70. General characteristics of the medicinal product Mukofalk®, granules for the preparation of an oral suspension (orange flavor), LP-No. (009297)-(RG-RU) dated 18.05.2026. (in Russ.)@@ Общая характеристика лекарственного препарата Мукофальк®, гранулы для приготовления суспензии для приема внутрь (со вкусом апельсина), ЛП-№ (009297)-(РГ-RU) от 18.05.2026.