Mysterious Akkermansia muciniphila. What do we know about it? A review

Cover Page

Cite item

Full Text

Abstract

"Microbes and humans" is a topic that has been continuously studied over the past decade. Numerous recent studies show that quantitative and qualitative changes in the composition of the gastrointestinal tract microbiota have direct and indirect effects on metabolic changes in the host. Many countries are researching the microbiome and opportunities to influence health through environmental modification and introducing a probiotic, a metabiotic, or a synbiotic into the body. Considerable attention is paid to metabolic disorders and obesity, as these are issues that are becoming a progressive global epidemic. More than 2 billion people are overweight and obese, and many experts continue to look for promising methods to combat it. A special group of high risk for obesity is children. Statistics show a steady upward trend of obesity in children. Over the past 10 years, this trend has shown a rapid pace: from 6.7%, according to 2010, to 9.1% by 2020. In this context, Akkermansia muciniphila attracts special attention among all bacteria inhabiting the gastrointestinal tract due to its potential to treat insulin resistance, obesity, and diabetes mellitus. This article reviews new research on the A. muciniphila effects on the host and ways to correct metabolism using probiotics.

Full Text

Restricted Access

About the authors

Irina N. Zakharova

Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: zakharova-rmapo@yandex.ru
ORCID iD: 0000-0003-4200-4598

D. Sci. (Med.), Prof.

Russian Federation, Moscow

Irina V. Berezhnaya

Russian Medical Academy of Continuous Professional Education; Bashlyaeva Children`s City Clinical Hospital

Email: berezhnaya-irina26@yandex.ru
ORCID iD: 0000-0002-2847-6268

Cand. Sci. (Med.)

Russian Federation, Moscow; Moscow

Natalia F. Dubovets

Bashlyaeva Children`s City Clinical Hospital

Email: skorpionka_n@mail.ru

Pediatrician

Russian Federation, Moscow

Ekaterina V. Skorobogatova

Bashlyaeva Children`s City Clinical Hospital

Email: dgkb-bashlyaevoy@zdrav.mos.ru

Cand. Sci. (Med.)

Russian Federation, Moscow

Ekaterina A. Dubovets

Pirogov Russian National Research Medical University

Email: ekaterinka1501@gmail.com
ORCID iD: 0000-0002-1830-0357

Student

Russian Federation, Moscow

Alexandra A. Dubovets

Sechenov First Moscow State Medical University (Sechenov University)

Email: alexa_sascha@mail.ru
ORCID iD: 0000-0002-9804-4364

Student

Russian Federation, Moscow

References

  1. O'Neill S, O'Driscoll L. Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev. 2015;16(1):1-12. doi: 10.1111/obr.12229
  2. Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy implications. Nat Rev Endocrinol. 2013;9(1):13-27. doi: 10.1038/nrendo.2012.199
  3. Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013;28;110(22):9066-71. doi: 10.1073/pnas.1219451110
  4. Zhao L. The gut microbiota and obesity: from correlation to causality. Nat Rev Microbiol. 2013;11(9):639-47. doi: 10.1038/nrmicro3089
  5. Plovier H, Everard A, Druart C, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107-13. doi: 10.1038/nm.4236
  6. Liang D, Leung RKK, Guan W, Au WW. Involvement of gut microbiome in human health and disease: Brief overview, knowledge gaps and research opportunities. Gut Pathog. 2018;10:3. doi: 10.1186/s13099-018-0230-4
  7. Gao Z, Yin J, Zhang J, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58(7):1509-17. doi: 10.2337/db08-1637
  8. Cani PD, Everard A, Duparc T. Gut microbiota, enteroendocrine functions and metabolism. Curr Opin Pharmacol. 2013;13(6):935-40. doi: 10.1016/j.coph.2013.09.008
  9. Gnauck A, Lentle RG, Kruger MC. The Characteristics and Function of Bacterial Lipopolysaccharides and Their Endotoxic Potential in Humans. Int Rev Immunol. 2015;35(3):189-218. doi: 10.3109/08830185.2015.1087518
  10. De Santis S, Ecavalcanti E, Emastronardi M, et al. Nutritional keys for intestinal barrier modulation. Front Immunol. 2015;6:612. doi: 10.3389/fimmu.2015.00612
  11. Jumpertz R, Le DS, Turnbaugh PJ, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011;94(1):58-65. doi: 10.3945/ajcn.110.010132
  12. Yoon HS, Cho CH, Yun MS, 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;6(5):563-73. doi: 10.1038/s41564-021-00880-5
  13. Shin NR, Lee JC, Lee HY, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63(5):727-35. doi: 10.1136/gutjnl-2012-303839
  14. Derrien M, Vaughan EE, Plugge CM, De Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-de- grading bacterium. Int J Syst Evol Microbiol. 2004;54(Pt. 5):1469-76. doi: 10.1099/ijs.0.02873-0
  15. Collado MC, Derrien M, Isolauri E, et al. Intestinal integrity and Akkermansia muciniphila, a mucin-degrad- ing member of the intestinal microbiota present in infants, adults, and the elderly. Appl Environ Microbiol. 2007;73(23):7767-70. doi: 10.1128/AEM.01477-07
  16. Derrien M, Collado MC, Ben-Amor K, et al. The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl Environ Microbiol. 2008;74(5):1646-8. doi: 10.1128/AEM.01226-07
  17. Ouwerkerk JP, Van der Ark KCH, Davids M, et al. Adaptation of Akkermansia muciniphila to the Oxic-Anoxic Interface of the Mucus Layer. Appl Environ Microbiol. 2016;82(23):6983-93. doi: 10.1128/AEM.01641-16
  18. Zhang T, Li Q, Cheng L, et al. Akkermansia muciniphila is a promising probiotic. Microb Biotechnol. 2019;12(1):1-17. doi: 10.1111/1751-7915.13410
  19. Ottman N, Geerlings SY, Aalvink S, et al. Action and function of Akkermansia muciniphila in microbiome ecology, health and disease. Best Pract Res Clin Gastroenterol. 2017;31(6):637-42. doi: 10.1016/j.bpg.2017.10.001
  20. Geerlings SY, Kostopoulos I, de Vos WM, Belzer C. Akkermansia muciniphila in the Human Gastrointestinal Tract: When, Where, and How? Microorganisms. 2018;6(3):75. DOI:10.3390/ microorganisms6030075
  21. Li J, Lin S, Vanhoutte PM, et al. Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe−/− Mice. Circulation. 2016;133(24):2434-46. doi: 10.1161/CIRCULATIONAHA.115.019645
  22. Cani PD, Knauf C. A newly identified protein from Akkermansia muciniphila stimulates GLP-1 secretion. Cell Metabolism. 2021;33(1):1073-75. doi: 10.1016/j.cmet.2021.05.004
  23. Бабенко А.Ю., Красильникова Е.И., Лихоносов Н.П., и др. Влияние различных групп сахароснижающих препаратов на вариабельность гликемии у больных сахарным диабетом 2 типа. Сахарный диабет. 2014;17(4):72-80 [Babenko AIu, Krasilnikova EI, Likhonosov NP, et al. Different antihyperglycaemic drug effects on glycaemic variability in Type 2 diabetic patients. Diabetes mellitus. 2014;17(4):72-80 (in Russian)]. doi: 10.14341/DM2014472-80
  24. Rodriquez de Fonseca F, Navarro M, Alvarez E, et al. Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats. Metabolism. 2000;49(6):709-17. doi: 10.1053/мета.2000.6251
  25. Depommier C, Everard A, Druart C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019;25(7):1096-103. doi: 10.1038/s41591-019-0495-2
  26. Derrien M, van Passel MW, van de Bovenkamp JH, et al. Mucin-bacterial interactions in the human oral cavity and digestive tract. Gut Microbes. 2010;1(4):254-68. doi: 10.4161/gmic.1.4.12778
  27. Jian H, Liu Y, Wang X, et al. Akkermansia muciniphila as a Next-Generation Probiotic in Modulating Human Metabolic Homeostasis and Disease Progression: A Role Mediated by Gut–Liver–Brain Axes? Int J Mol Sci. 2023;24(3900):1-32. doi: 10.3390/ijms24043900
  28. Caruso R, Lo BC, Núñez G. Host–microbiota interactions in inflammatory bowel disease. Nat Rev Immunol. 2020;20(7):411-26. doi: 10.1038/s41577-019-0268-7
  29. Kamitani Y, Kurumi H, Kanda T, et al. Comparative study between histochemical mucus volume, histopathological findings, and endocytoscopic scores in patients with ulcerative colitis. Medicine (Baltimore). 2023;102(9):e33033. doi: 10.1097/MD.0000000000033033
  30. Harel J, Fairbrother J, Forget K, et al. Virulence factors associated with F165-positive strains of Escherichia coli isolated from piglets and calves. Vet Microbiol. 1993;38(1-2):139-55. doi: 10.1016/0378-1135(93)90081-h
  31. Ouwerkerk JP, de Vos WM, Belzer K. Glycobiome: bacteria and mucus on the surface of the epithelium interface. Best Pract Res Clin Gastroenterol. 2013;27(1):25-38. doi: 10.1016/j.bpg.2013.03.001
  32. Martens EK, Chang HK, Gordon JI. The search for mucosal glycans improves the fitness and transmission of the human gut saccharolytic bacterial symbiont. Cellular Host Microbe. 2008;4(5):447-57. doi: 10.1016/j.chom.2008.09.007
  33. Jonker N, Skrypek N, Frenoy F, Van Seningen I. Membrane-associated modular mucin domains: from structure to function. Biochemistry. 2013;95(6):1077-86. doi: 10.1016/j.biochi.2012.11.005
  34. Shreiner AB, Kao JY, Young V. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015;31(1):69-75. doi: 10.1097/MOG.0000000000000139
  35. Le Poul E, Loison C, Struyf S, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem. 2003;278(28):25481-9. doi: 10.1074/jbc.M301403200
  36. Samuel BS, Shaito A, Motoike T, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008;105(43):16767-72. doi: 10.1073/pnas.0808567105
  37. Dao MC, Everard A, Aron-Wisnewsky J, et al. Akkermansia Muciniphila and Improved Metabolic Health During a Dietary Intervention in Obesity: Relationship With Gut Microbiome Richness and Ecology. Gut. 2016;65(3):426-36. doi: 10.1136/gutjnl-2014-308778
  38. Everard A, Lazarevic V, Derrien M, et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes. 2011;60(11):2775-86. doi: 10.2337/db11-0227
  39. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat med. 2012;18(3):363-74. doi: 10.1038/nm.2627
  40. Depommier C, Van Hul M, Everarda A, et al. Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice. Gut Microbes. 2020;11(5):1231-45. doi: 10.1080/19490976.2020.1737307
  41. Zhou Q, Zhang Y, Wang X, et al. Gut bacteria Akkermansia is associated with reduced risk of obesity: evidence from the American Gut Project. Nutr Metab (Lond). 2020;17:90. doi: 10.1186/s12986-020-00516-1
  42. Boix-Amorósa A, Puente-Sánchezhttps F, Du Toitd E, et al. Mycobiome Profiles in Breast Milk from Healthy Women Depend on Mode of Delivery, Geographic Location, and Interaction with Bacteria. Microbial Ecology. 2019;85(9):e02994-18. doi: 10.1128/AEM.02994-18
  43. Ma J, Li Z, Zhang W, et al. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: a study of 91 term infants. Sci Rep. 2020;10(1):15792. doi: 10.1038/s41598-020-72635-x
  44. Roger LS, Costabile A, Holland DT, et al. The study of fecal populations of bifidobacteria in children who are breastfed and artificially fed during the first 18 months of life. Microbiology (Reading). 2010;156(Pt. 11):3329-41. doi: 10.1099/mic.0.043224-0
  45. Lewis ZT. Fecal microbial community of infants from Armenia and Georgia. Sci Rep. 2017;7:40932. doi: 10.1038/srep40932
  46. Björksten B, Sepp E, Julge K, et al. Allergy development and gut microflora during the first year of life. J Allergy Clin Immunol. 2001;108(4):516-20. DOI:10.1067 /mai.2001.118130
  47. Dogra S, Sakwinska O, Ngom-Bru C, et al. Infant gut microbiota dynamics are influenced by mode of delivery and duration of pregnancy, which is associated with subsequent obesity. mBio. 2015;6(1):e02419-2514. doi: 10.1128/mBio.02419-14
  48. Huda MNM, Lewis Z, Kalanetra KM, et al. Stool microbiota and infant response to vaccine. Pediatrics. 2014;134(2):e362-72. DOI:10.1542/ peds.2013-3937
  49. Kostopoulos I, Elzinga J, Ottman N, et al. Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro. Sci Rep. 2020;10(1):14330. doi: 10.1038/s41598-020-71113-8
  50. Van den Abbeele P, Gérard P, Rabot S, et al. Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin-degradation in humanized rats. Environ Microbiol. 2011;13(10):2667-80. doi: 10.1111/j.1462-2920.2011.02533.x
  51. Anhe FF, Pilon G, Roy D, et al. Triggering Akkermansia with dietary polyphenols: a new weapon to combat the metabolic syndrome? Gut Microbes. 2016;7(2):146-53. doi: 10.1080/19490976.2016.1142036
  52. Zhao S, Liu W, Wang J, et al. Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice. J Mol Endocrinol. 2017;58(1):1-14. doi: 10.1530/jme-16-0054
  53. Wang Y, Xu Y, Liu Q, et al. Myosin IIA-related actomyosin contractility mediates oxidative stress-induced neuronal apoptosis. Front Mol Neurosci. 2017;10:75. doi: 10.3389/fnmol.2017.00075
  54. Hanninen A, Toivonen R, Poysti S, et al. Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice. Gut. 2017;67(8):1445-53. doi: 10.1136/gutjnl-2017-314508
  55. Etxeberria U, Arias N, Boque N, et al. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. J Nutr Biochem. 2015;26(6):651-60. doi: 10.1016/j.jnutbio.2015.01.002
  56. Shang Q, Wang Y, Pan L, et al. Dietary Polysaccharide from Enteromorpha Clathrata Modulates Gut Microbiota and Promotes the Growth of Akkermansia muciniphila, Bifidobacterium spp. and Lactobacillus spp. Mar Drugs. 2018;16(5):167. doi: 10.3390/md16050167
  57. Fukizawa S, Yamashita M, Wakabayashi KI, et al. Anti-obesity effect of a hop-derived prenylflavonoid isoxanthohumol in a high-fat diet-induced obese mouse model. Biosci Microbiota Food Health. 2020;39(3):175-82. doi: 10.12938/bmfh.2019-040
  58. Hamm AK, Manter DK, Kirkwood JS, et al. The effect of hops (Humulus lupulus L.) extract supplementation on weight gain, adiposity and intestinal function in ovariectomized mice. Nutrients. 2019;11(12):3004. doi: 10.3390/nu11123004
  59. Masumoto S, Terao A, Yamamoto Y, et al. Non-absorbable apple procyanidins prevent obesity associated with gut microbial. Sci Rep. 2016;6:31208. doi: 10.1038/srep31208
  60. De La Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V, et al. Metformin is associated with higher relative abundance of mucin-degrading Akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabetes Care. 2017;40(1):54-62. doi: 10.2337/dc16-1324
  61. Xu Y, Wang N, Tan HY, et al. Function of Akkermansia muciniphila in Obesity: Interactions With Lipid Metabolism, Immune Response and Gut Systems. Front Microbiol. 2020;11:219. doi: 10.3389/fmicb.2020.00219
  62. Schneeberger M, Everard A, Gómez-Valadés AG, et al. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep. 2015;13(5):16643. doi: 10.1038/srep16643
  63. Han MS, White A, Perry RJ, et al. Regulation of adipose tissue inflammation by interleukin 6. Proc Natl Acad Sci U S A. 2020;117(6):2751-60. doi: 10.1073/pnas.1920004117
  64. 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;7(8):281. doi: 10.3389/fcimb.2018.00281
  65. Llevenes P, Rodriguez-Dies R, Kros-Bruns L, et al. Beneficial effect of the multi-layered synbiotic Prodefen® Plus on systemic and vascular changes associated with metabolic syndrome in rats: the role of neuronal nitric oxide synthase and protein kinase A. Nutrients. 2020;1;12(1):117. doi: 10.3390/nu12010117
  66. Blanco-Rivero J. Beneficial effects of Prodefen® Plus multilayer synbiotic on systemic and vascular changes associated with metabolic syndrome in rats: the role of neuronal nitric oxide synthase and protein kinase A. Nutrients. 2020;12(1):117. doi: 10.3390/nu12010117

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Specific biomolecules produced by Akkermansia muciniphila and their mechanisms of action (Fig. adapted from P. Cani, et al) [22].

Download (94KB)

Copyright (c) 2023 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74329 от 19.11.2018 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies