Пастеризованная форма бактерии Akkermansia muciniphila при ожирении и метаболическом синдроме: механизмы действия и клинический потенциал

Ожирение и метаболический синдром являются ведущими факторами риска развития сердечно-сосудистых заболеваний. В последние годы накоплены убедительные данные о важной роли дисбиоза кишечника в патогенезе этих состояний, что открывает возможности для разработки новых терапевтических стратегий. Пастеризованная форма бактерии Akkermansia muciniphila представляет интерес как перспективный постбиотик, способный сохранять эффекты живой бактерии при высоком профиле безопасности. Показано, что она оказывает многокомпонентное действие, включающее снижение проницаемости кишечного барьера, метаболической эндотоксемии и хронического низкоуровневого воспаления, а также модуляцию транспорта глюкозы в кишечнике, взаимодействие с осью «кишечник–мозг» и регуляцию энергетического обмена. Сведения об эффективности остаются ограниченными и основываются преимущественно на результатах доклинических исследований. На фоне приема A. muciniphila отмечалось снижение массы тела и жировой массы, улучшение гликемического контроля, повышение чувствительности к инсулину, а также уменьшение воспалительных и фибротических изменений в печени и жировой ткани. Вместе с тем сохраняется необходимость стандартизации постбиотических препаратов, включая режимы пастеризации и дозирования, а также проведения крупных долгосрочных рандомизированных исследований для определения их клинической эффективности и безопасности.

1. Sasidharan Pillai S, Gagnon CA, Foster C, Ashraf AP. Exploring the Gut Microbiota: Key Insights Into Its Role in Obesity, Metabolic Syndrome, and Type 2 Diabetes. J Clin Endocrinol Metab. 2024 Oct 15;109(11):2709–19. doi:10.1210/clinem/dgae499

2. Leonov G, Livantsova E, Varaeva Y, Starodubova A. Probiotics and Prebiotics in Post-Myocardial Infarction Rehabilitation: Mechanisms, Benefits, and Future Directions. Curr Nutr Rep. 2025 Jun 28;14(1):88. doi:10.1007/s13668-025-00679-4

3. Romantsova TI, Sych YuP. Immunometabolism and metaflammation in obesity. Ozhirenie i Metabolizm. 2019;16(4):3-17 (In Russ.) [Романцова Т.И., Сыч Ю.П. Иммунометаболизм и метавоспаление при ожирении. Ожирение и метаболизм. 2019;16(4):3-17].

4. Vetrani C, Di Nisio A, Paschou SA, Barrea L, Muscogiuri G, Graziadio C, et al. From Gut Microbiota through Low-Grade Inflammation to Obesity: Key Players and Potential Targets. Nutrients. 2022 May 18;14(10):2103. doi:10.3390/nu14102103

5. Hassan NE, El-Masry SA, El Shebini SM, Ahmed NH, Mohamed T F, Mostafa MI, et al. Gut dysbiosis is linked to metabolic syndrome in obese Egyptian women: potential treatment by probiotics and high fiber diets regimen. Sci Rep. 2024 Mar 5;14(1):5464. doi:10.1038/s41598-024-54285-5

6. Kang C, Wang B, Kaliannan K, Wang X, Lang H, Hui S, et al. Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet. mBio. 2017 May 23;8(3):10.1128/mbio.00470-17. doi:10.1128/mbio.00470-17

7. Koumpouli D, Koumpouli V, Koutelidakis AE. Functional Foods, Gut Microbiome and Association with Obesity and Metabolic Syndrome: A Literature Review. Appl Sci. 2024 Jun 26;14(13). doi:10.3390/app14135578

8. Kim YT, Mills DA. Exploring the gut microbiome: probiotics, prebiotics, synbiotics, and postbiotics as key players in human health and disease improvement. Food Sci Biotechnol. 2024 Jun 27;33(9):2065–80. doi:10.1007/s10068-024-01620-1

9. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506–14. doi:10.1038/nrgastro.2014.66

10. Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016 Mar;65(3):426–36. doi:10.1136/gutjnl-2014-308778

11. Yoon HS, Cho CH, Yun MS, Jang SJ, You HJ, Kim J hyeong, et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol. 2021 May;6(5):563–73. doi:10.1038/s41564-021-00880-5

12. Zhang Y, Liu R, Chen Y, Cao Z, Liu C, Bao R, et al. Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut. Cell Metab. 2025 Mar 4;37(3):592-605.e6. doi:10.1016/j.cmet.2024.12.010

13. Wegh CAM, Geerlings SY, Knol J, Roeselers G, Belzer C. Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond. Int J Mol Sci. 2019 Sep 20;20(19):4673. doi:10.3390/ijms20194673

14. Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. 2021 Sep;18(9):649–67. doi:10.1038/s41575-021-00440-6

15. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004 Sep;54(Pt 5):1469–76. doi:10.1099/ijs.0.02873-0

16. Chiantera V, Laganà AS, Basciani S, Nordio M, Bizzarri M. A Critical Perspective on the Supplementation of Akkermansia muciniphila: Benefits and Harms. Life. 2023 May 24;13(6):1247. doi:10.3390/life13061247

17. Mierlan OL, Busila C, Amaritei O, Elena D, Raileanu CR, Maftei NM, et al. Akkermansia muciniphila in Metabolic Disease: Far from Perfect. Int J Mol Sci. 2025 Jan;26(23):11602. doi:10.3390/ijms262311602

18. Trastoy B, Naegeli A, Anso I, Sjögren J, Guerin ME. Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila. Nat Commun. 2020 Sep 24;11(1):4844. doi:10.1038/s41467-020-18696-y

19. Mo C, Lou X, Xue J, Shi Z, Zhao Y, Wang F, et al. The influence of Akkermansia muciniphila on intestinal barrier function. Gut Pathog. 2024 Aug 3;16(1):41. doi:10.1186/s13099-024-00635-7

20. Martin-Gallausiaux C, Garcia-Weber D, Lashermes A, Larraufie P, Marinelli L, Teixeira V, et al. Akkermansia muciniphila upregulates genes involved in maintaining the intestinal barrier function via ADP-heptose-dependent activation of the ALPK1/TIFA pathway. Gut Microbes. 2022;14(1):2110639. doi:10.1080/19490976.2022.2110639

21. Wade H, Pan K, Duan Q, Kaluzny S, Pandey E, Fatumoju L, et al. Akkermansia muciniphila and its membrane protein ameliorates intestinal inflammatory stress and promotes epithelial wound healing via CREBH and miR-143/145. J Biomed Sci. 2023 Jun 7;30(1):38. doi:10.1186/s12929-023-00935-1

22. Costa RL, Moreira J, Lorenzo A, Lamas CC. Infectious complications following probiotic ingestion: a potentially underestimated problem? A systematic review of reports and case series. BMC Complement Altern Med. 2018 Dec 12;18:329. doi:10.1186/s12906-018-2394-3

23. D’Agostin M, Squillaci D, Lazzerini M, Barbi E, Wijers L, Da Lozzo P. Invasive Infections Associated with the Use of Probiotics in Children: A Systematic Review. Children. 2021 Oct 16;8(10):924. doi:10.3390/children8100924

24. Mg B, Hc van S, E B, Ma B, H van G, Hm T, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet Lond Engl. 2008 Feb 23;371(9613). doi:10.1016/S0140-6736(08)60207-X

25. Choi Y, Bose S, Seo J, Shin JH, Lee D, Kim Y, et al. Effects of Live and Pasteurized Forms of Akkermansia from the Human Gut on Obesity and Metabolic Dysregulation. Microorganisms. 2021 Sep 27;9(10):2039. doi:10.3390/microorganisms9102039

26. Karbowiak M, Gałek M, Szydłowska A, Zielińska D. The Influence of the Degree of Thermal Inactivation of Probiotic Lactic Acid Bacteria and Their Postbiotics on Aggregation and Adhesion Inhibition of Selected Pathogens. Pathogens. 2022 Oct 29;11(11):1260. doi:10.3390/pathogens11111260

27. Turck D, Bohn T, Castenmiller J, De Henauw S, Hirsch‐Ernst KI, Maciuk A, et al. Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2021 Sep 1;19(9):e06780. doi:10.2903/j.efsa.2021.6780

28. Piqué N, Berlanga M, Miñana-Galbis D. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci. 2019 May 23;20(10):2534. doi:10.3390/ijms20102534

29. Abraham L, Raise A, Beney L, Lapaquette P, Rieu A. Membrane vesicles produced by next-generation probiotics from the gut as innovative tools for human health. Gut Microbes. 2025 Dec 31;17(1):2552344. doi:10.1080/19490976.2025.2552344

30. Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017 Jan;23(1):107–13. doi:10.1038/nm.4236

31. Wachsmuth HR, Weninger SN, Duca FA. Role of the gut–brain axis in energy and glucose metabolism. Exp Mol Med. 2022 Apr 26;54(4):377–92. doi:10.1038/s12276-021-00677-w

32. Abot A, Brochot A, Pomié N, Astre G, Druart C, de Vos WM, et al. Pasteurized Akkermansia muciniphila improves glucose metabolism is linked with increased hypothalamic nitric oxide release. Heliyon. 2023 Jul 13;9(7):e18196. doi:10.1016/j.heliyon.2023.e18196

33. Depommier C, Van Hul M, Everard A, Delzenne NM, De Vos WM, Cani PD. Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice. Gut Microbes. 2020 Sep 2;11(5):1231–45. doi:10.1080/19490976.2020.1737307

34. Wu Z, Xiao Y, Zhou F, Chen J, Chen X, Hou A, et al. Pasteurized Akkermansia muciniphila Reduces Fat Accumulation via nhr-49-Mediated Nuclear Hormone Signaling Pathway in Caenorhabditis elegans. Molecules. 2022 Sep 20;27(19):6159. doi:10.3390/molecules27196159

35. Keshavarz Azizi Raftar S, Ashrafian F, Yadegar A, Lari A, Moradi HR, Shahriary A, et al. The Protective Effects of Live and Pasteurized Akkermansia muciniphila and Its Extracellular Vesicles against HFD/CCl4-Induced Liver Injury. Microbiol Spectr. 2021 Oct 31;9(2):e0048421. doi:10.1128/Spectrum.00484-21

36. Zhang M, Wang Y, Gan Y. The potential role of Akkermansia muciniphila in liver health. Future Microbiol. 19(12):1081–96. doi:10.2217/fmb-2023-0220

37. Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019 Jul;25(7):1096–103. doi:10.1038/s41591-019-0495-2

38. Li J, Lin S, Vanhoutte PM, Woo CW, Xu A. Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-/- Mice. Circulation. 2016 Jun 14;133(24):2434–46. doi:10.1161/CIRCULATIONAHA.115.019645

39. Kim JY, Kim CW, Oh SY, Jang S, Yetunde OZ, Kim BA, et al. Akkermansia muciniphila extracellular vesicles have a protective effect against hypertension. Hypertens Res. 2024 Jun;47(6):1642–53. doi:10.1038/s41440-024-01627-5

40. Zhang Y, Liu R, Chen Y, Cao Z, Liu C, Bao R, et al. Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut. Cell Metab. 2025 Mar 4;37(3):592-605.e6. doi:10.1016/j.cmet.2024.12.010

41. Roshanravan N, Mahdavi R, Alizadeh E, Ghavami A, Rahbar Saadat Y, Mesri Alamdari N, et al. The effects of sodium butyrate and inulin supplementation on angiotensin signaling pathway via promotion of Akkermansia muciniphila abundance in type 2 diabetes; A randomized, double-blind, placebo-controlled trial. J Cardiovasc Thorac Res. 2017;9(4):183–90. doi:10.15171/jcvtr.2017.32

42. Druart C, Plovier H, Van Hul M, Brient A, Phipps KR, de Vos WM, et al. Toxicological safety evaluation of pasteurized Akkermansia muciniphila. J Appl Toxicol JAT. 2021 Feb;41(2):276–90. doi:10.1002/jat.4044

43. Niu H, Zhou M, Zogona D, Xing Z, Wu T, Chen R, et al. Akkermansia muciniphila: a potential candidate for ameliorating metabolic diseases. Front Immunol. 2024;15:1370658. doi:10.3389/fimmu.2024.1370658