SpringerLink
Log in

A Critical Review on Akkermansia muciniphila: Functional Mechanisms, Technological Challenges, and Safety Issues

  • Research
  • Published:
Probiotics and Antimicrobial Proteins Aims and scope Submit manuscript

Abstract

Due to its physiological benefits from in vitro and in vivo points of view, Akkermansia muciniphila, a common colonizer in the human gut mucous layer, has consistently been identified as an option for the next-generation probiotic. A. muciniphila is a significant bacterium that promotes host physiology. However, it also has a great deal of potential to become a probiotic due to its physiological advantages in a variety of therapeutic circumstances. Therefore, it can be established that the abundance of A. muciniphila in the gut environment, which is controlled by many genetic and dietary variables, is related to the biological behaviors of the intestinal microbiota and gut dysbiosis/eubiosis circumstances. Before A. muciniphila is widely utilized as a next-generation probiotic, regulatory obstacles, the necessity for significant clinical trials, and the sustainability of manufacturing must be eliminated. In this review, the outcomes of recent experimental and clinical reports are comprehensively reviewed, and common colonization patterns, main factors involved in the colonization of A. muciniphila in the gut milieu, their functional mechanisms in establishing homeostasis in the metabolic and energy pathways, the promising delivery role of microencapsulation, potential genetic engineering strategies, and eventually safety issues of A. muciniphila have been discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

No data was used for the research described in the article.

Abbreviations

IBD:

Inflammatory bowel disease

GIT:

Gastrointestinal tract

SHIME:

Simulator of the Human Intestinal Microbial Ecosystem

HFD:

High-fat diet

CR:

Caloric restriction

FODMAP:

Fermentable oligo-, di-, and monosaccharides and polyols

IBS:

Irritable bowel syndrome

SCFA:

Short-chain fatty acids

NAS:

Noncaloric artificial sweeteners

AMPK:

AMP-activated protein kinase

BHI:

Brain-heart infusion

PBS:

Phosphate-buffered saline

NOD:

Nonobese diabetic

Gpr43:

G protein-coupled receptor 43

GH:

Glycoside hydrolases

GlcNAc:

N-Acetylglucosamine

GalNAc:

N-Acetylgalactosamine

TLR2:

Toll-like receptor-2

2-OG:

2-Oleoylglycerol

DM:

Diabetes mellitus

T2DM:

Type 2 diabetes

GPCR:

G protein-coupled receptor

Ca2+ :

Calcium

GLP-1:

Glucagon-like peptide 1

BAT:

Brown adipose tissue

IL:

Interleukin

UC:

Ulcerative colitis

DSS:

Dextran sulfate sodium

TNF-alpha:

Necrotizing tumor factor-alpha

INF-gamma:

Interferon-gamma

CD:

Crohn’s disease

HC:

Healthy controls

CRC:

Colorectal cancer

Muc1:

Mucin 1

Muc 2:

Mucin 2

p53:

Protein 53

TRAIL:

Tumor-necrosis factor-associated apoptosis-inducing ligand

HCC:

Hepatocellular carcinoma

LPS:

Lipopolysaccharides

CVDs:

Cardiovascular diseases

TMAO:

Trimethylamine oxide

TMA:

Trimethylamine

FMOS:

Flavin monooxygenase

ASDs:

Autism spectrum disorders

MS:

Multiple sclerosis

CNS:

Central nervous system

APCs:

Antigen-presenting cells

Th1:

T helper type 1

FMT:

Fecal microbiota transplants

EAE:

Experimental autoimmune encephalomyelitis

PBMC:

Peripheral blood mononuclear cell

AhR:

Aryl hydrocarbon receptor

AD:

Alzheimer’s disease

Aβ:

Amyloid-β

γ-GABA:

Gamma-aminobutyric acid

GG:

Gamma-glutamylated

PS:

Peptone-sorbitol

ST:

Sucrose-trehalose

MGYM:

Skim milk-glucose-yeast-extract-mannitol

AS:

Agave syrup

a w :

Water activity

NICE:

Nisin-controlled gene expression

LAB:

Lactic acid bacteria

WMT:

Washed microbiota transplantation

SNPs:

Single nucleotide polymorphisms

MAGs:

Metagenome-assembled genomes

EVs:

Extracellular vesicles

OMVs:

Outer membrane vesicles

AmEVs:

Akkermansia muciniphila-Derived extracellular vesicles

ICAM-2:

Intercellular adhesion molecule-2

PLC:

Phospholipase C

CREB:

CAMP response element-binding protein

References

  1. Nishijima S et al (2022) Extensive gut virome variation and its associations with host and environmental factors in a population-level cohort. Nat Commun 13(1):1–14

    Article  Google Scholar 

  2. Tan AH, Lim SY, Lang AE (2022) The microbiome–gut–brain axis in Parkinson disease—from basic research to the clinic. Nat Rev Neurol 18(8):476–495

    Article  PubMed  Google Scholar 

  3. Sharma R (2022) Emerging interrelationship between the gut microbiome and cellular senescence in the context of aging and disease: perspectives and therapeutic opportunities. Probiotics and Antimicrobial Proteins 14(4):648–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mulpuru V, Mishra N (2022) Antimicrobial peptides from human microbiome against multidrug efflux pump of Pseudomonas aeruginosa: a computational study. Probiotics and Antimicrobial Proteins 14(1):180–188

    Article  CAS  PubMed  Google Scholar 

  5. Zhang B et al (2022) Human milk oligosaccharides and infant gut microbiota: molecular structures, utilization strategies and immune function. Carbohyd Polym 276:118738

    Article  CAS  Google Scholar 

  6. Duncan SH, Louis P, Flint HJ (2004) Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. Appl Environ Microbiol 70(10):5810–5817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Allen-Vercoe E et al (2012) Anaerostipes hadrus comb. nov., a dominant species within the human colonic microbiota; reclassification of Eubacterium hadrum Moore et al. 1976. Anaerobe 18(5):523–529

  8. Machiels K et al (2014) A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63(8):1275–1283

    Article  CAS  PubMed  Google Scholar 

  9. Louis P, Flint HJ (2009) Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett 294(1):1–8

    Article  CAS  PubMed  Google Scholar 

  10. Cani PD, de Vos WM (2017) Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front Microbiol 8:1765

    Article  PubMed  PubMed Central  Google Scholar 

  11. Heinken A et al (2014) Functional metabolic map of Faecalibacterium prausnitzii, a beneficial human gut microbe. J Bacteriol 196(18):3289–3302

    Article  PubMed  PubMed Central  Google Scholar 

  12. Venkataraman A et al (2016) Variable responses of human microbiomes to dietary supplementation with resistant starch. Microbiome 4:1–9

    Article  Google Scholar 

  13. Konikoff T, Gophna U (2016) Oscillospira: a central, enigmatic component of the human gut microbiota. Trends Microbiol 24(7):523–524

    Article  CAS  PubMed  Google Scholar 

  14. Lopez-Siles M et al (2012) Cultured representatives of two major phylogroups of human colonic Faecalibacterium prausnitzii can utilize pectin, uronic acids, and host-derived substrates for growth. Appl Environ Microbiol 78(2):420–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Belzer C et al (2017) Microbial metabolic networks at the mucus layer lead to diet-independent butyrate and vitamin B12 production by intestinal symbionts. MBio 8(5):e00770-e817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rivière A et al (2015) Mutual cross-feeding interactions between Bifidobacterium longum subsp. longum NCC2705 and Eubacterium rectale ATCC 33656 explain the bifidogenic and butyrogenic effects of arabinoxylan oligosaccharides. Appl Environ Microbiol 81(22):7767–7781

  17. Goodrich JK et al (2014) Human genetics shape the gut microbiome. Cell 159(4):789–799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang T et al (2019) Akkermansia muciniphila is a promising probiotic. Microb Biotechnol 12(6):1109–1125

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ghaffari S et al (2022) Akkermansia muciniphila: from its critical role in human health to strategies for promoting its abundance in human gut microbiome. Crit Rev Food Sci Nutr 1–21

  20. Keshavarz Azizi Raftar S et al (2021) The anti-fibrotic effects of heat-killed Akkermansia muciniphila MucT on liver fibrosis markers and activation of hepatic stellate cells. Probiotics Antimicrob Proteins 13:776–787

  21. Wang L et al (2011) Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Appl Environ Microbiol 77(18):6718–6721

  22. Anhê FF et al (2015) A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut 64(6):872–883

  23. Derrien M et al (2011) Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front Microbiol 2:166

    Article  PubMed  PubMed Central  Google Scholar 

  24. Everard A et al (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci 110(22):9066–9071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Byrd JC, Bresalier RS (2004) Mucins and mucin binding proteins in colorectal cancer. Cancer Metastasis Rev 23(1):77–99

    Article  CAS  PubMed  Google Scholar 

  26. Cheng D, **e M (2021) A review of a potential and promising probiotic candidate—Akkermansia muciniphila. J Appl Microbiol 130(6):1813–1822

    Article  CAS  PubMed  Google Scholar 

  27. Heiss CN, Olofsson LE (2018) Gut microbiota-dependent modulation of energy metabolism. J Innate Immun 10(3):163–171

    Article  CAS  PubMed  Google Scholar 

  28. Zhao S et al (2017) Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice. J Mol Endocrinol 58(1):1–14

    Article  PubMed  Google Scholar 

  29. Samuel VT, Shulman GI (2016) The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Investig 126(1):12–22

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rad AH et al (2020) Potential pharmaceutical and food applications of postbiotics: a review. Curr Pharm Biotechnol 21(15):1576–1587

    Article  CAS  PubMed  Google Scholar 

  31. Muccioli GG et al (2010) The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol 6(1):392

    Article  PubMed  PubMed Central  Google Scholar 

  32. Homayouni Rad A et al (2021) Postbiotics: a novel strategy in food allergy treatment. Crit Rev Food Sci Nutr 61(3):492–499

    Article  CAS  PubMed  Google Scholar 

  33. Hansen KB et al (2011) 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J Clin Endocrinol Metab 96(9):E1409–E1417

    Article  CAS  PubMed  Google Scholar 

  34. Cani PD et al (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58(8):1091–1103

    Article  CAS  PubMed  Google Scholar 

  35. Depommier C et al (2019) Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med 25(7):1096–1103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Xu Y et al (2020) Function of Akkermansia muciniphila in obesity: interactions with lipid metabolism, immune response and gut systems. Front Microbiol 11:219

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ashrafian F et al (2019) Akkermansia muciniphila-derived extracellular vesicles as a mucosal delivery vector for amelioration of obesity in mice. Front Microbiol 10:2155

    Article  PubMed  PubMed Central  Google Scholar 

  38. Martin-Gallausiaux C et al (2022) Akkermansia muciniphila upregulates genes involved in maintaining the intestinal barrier function via ADP-heptose-dependent activation of the ALPK1/TIFA pathway. Gut microbes 14(1):2110639

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ince D, Lucas TM, Malaker SA (2022) Current strategies for characterization of mucin-domain glycoproteins. Curr Opin Chem Biol 69:102174

    Article  CAS  PubMed  Google Scholar 

  40. Liu X et al (2021) Transcriptomics and metabolomics reveal the adaption of Akkermansia muciniphila to high mucin by regulating energy homeostasis. Sci Rep 11(1):1–13

    Google Scholar 

  41. Crost EH et al (2016) The mucin-degradation strategy of Ruminococcus gnavus: the importance of intramolecular trans-sialidases. Gut microbes 7(4):302–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kosciow K, Deppenmeier U (2020) Characterization of three novel β-galactosidases from Akkermansia muciniphila involved in mucin degradation. Int J Biol Macromol 149:331–340

    Article  CAS  PubMed  Google Scholar 

  43. Zhang S et al (2018) The stem cell factor Sox2 is a positive timer of oligodendrocyte development in the postnatal murine spinal cord. Mol Neurobiol 55(12):9001–9015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kemperman RA et al (2013) Impact of polyphenols from black tea and red wine/grape juice on a gut model microbiome. Food Res Int 53(2):659–669

    Article  CAS  Google Scholar 

  45. Ottman N et al (2017) Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS ONE 12(3):e0173004

    Article  PubMed  PubMed Central  Google Scholar 

  46. Cani PD et al (2016) Endocannabinoids—at the crossroads between the gut microbiota and host metabolism. Nat Rev Endocrinol 12(3):133

    Article  CAS  PubMed  Google Scholar 

  47. Li G et al (2015) Diversity of duodenal and rectal microbiota in biopsy tissues and luminal contents in healthy volunteers. J Microbiol Biotechnol 25(7):1136–1145

    Article  CAS  PubMed  Google Scholar 

  48. Rogers MB et al (2017) Disturbances of the perioperative microbiome across multiple body sites in patients undergoing pancreaticoduodenectomy. Pancreas 46(2):260

    Article  PubMed  PubMed Central  Google Scholar 

  49. Wang M et al (2005) Comparison of bacterial diversity along the human intestinal tract by direct cloning and sequencing of 16S rRNA genes. FEMS Microbiol Ecol 54(2):219–231

    Article  CAS  PubMed  Google Scholar 

  50. Lysgård Madsen J (1992) Effects of gender, age, and body mass index on gastrointestinal transit times. Dig Dis Sci 37(10):1548–1553

    Article  Google Scholar 

  51. Johansson ME et al (2011) Composition and functional role of the mucus layers in the intestine. Cell Mol Life Sci 68(22):3635–3641

    Article  CAS  PubMed  Google Scholar 

  52. Van den Abbeele P et al (2011) Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin-degradation in humanized rats. Environ Microbiol 13(10):2667–2680

    Article  PubMed  Google Scholar 

  53. Kubasova T et al (2019) Gut anaerobes capable of chicken caecum colonisation. Microorganisms 7(12):597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lyra A et al (2012) Comparison of bacterial quantities in left and right colon biopsies and faeces. World J Gastroenterol: WJG 18(32):4404

    Article  PubMed  PubMed Central  Google Scholar 

  55. Ringel Y et al (2015) High throughput sequencing reveals distinct microbial populations within the mucosal and luminal niches in healthy individuals. Gut microbes 6(3):173–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Evans D et al (1988) Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 29(8):1035–1041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Van Herreweghen F et al (2017) In vitro colonisation of the distal colon by Akkermansia muciniphila is largely mucin and pH dependent. Beneficial microbes 8(1):81–96

    Article  PubMed  Google Scholar 

  58. Bäckhed F et al (2015) Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17(5):690–703

    Article  PubMed  Google Scholar 

  59. Guo M et al (2020) Developmental differences in the intestinal microbiota of Chinese 1-year-old infants and 4-year-old children. Sci Rep 10(1):1–9

    Article  Google Scholar 

  60. Kong F et al (2016) Gut microbiota signatures of longevity. Curr Biol 26(18):R832–R833

    Article  CAS  PubMed  Google Scholar 

  61. Biagi E et al (2016) Gut microbiota and extreme longevity. Curr Biol 26(11):1480–1485

    Article  CAS  PubMed  Google Scholar 

  62. Rampelli S et al (2020) Shotgun metagenomics of gut microbiota in humans with up to extreme longevity and the increasing role of xenobiotic degradation. Msystems 5(2):e00124-e220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhang X et al (2021) Age-related compositional changes and correlations of gut microbiome, serum metabolome, and immune factor in rats. GeroScience 43(2):709–725

    Article  CAS  PubMed  Google Scholar 

  64. Neyrinck AM et al (2017) Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake, an effect related to the modulation of the gut microbiota. Mol Nutr Food Res 61(1):1500899

    Article  Google Scholar 

  65. Power KA et al (2016) Dietary flaxseed modulates the colonic microenvironment in healthy C57Bl/6 male mice which may alter susceptibility to gut-associated diseases. J Nutr Biochem 28:61–69

    Article  CAS  PubMed  Google Scholar 

  66. Dakic T et al (2022) The less we eat, the longer we live: can caloric restriction help us become centenarians? Int J Mol Sci 23(12):6546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Preidis GA et al (2015) Composition and function of the undernourished neonatal mouse intestinal microbiome. J Nutr Biochem 26(10):1050–1057

    Article  CAS  PubMed  Google Scholar 

  68. Dao MC et al (2016) Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65(3):426–436

    Article  CAS  PubMed  Google Scholar 

  69. Martin AM et al (2019) The influence of the gut microbiome on host metabolism through the regulation of gut hormone release. Front Physiol 10:428

    Article  PubMed  PubMed Central  Google Scholar 

  70. Davis JA et al (2020) Obesity, Akkermansia muciniphila, and proton pump inhibitors: is there a link? Obes Res Clin Pract 14(6):524–530

    Article  PubMed  Google Scholar 

  71. Murphy E et al (2010) Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59(12):1635–1642

    Article  CAS  PubMed  Google Scholar 

  72. Kaczmarek JL, Musaad SM, Holscher HD (2017) Time of day and eating behaviors are associated with the composition and function of the human gastrointestinal microbiota. Am J Clin Nutr 106(5):1220–1231

    Article  CAS  PubMed  Google Scholar 

  73. Zarrinpar A et al (2014) Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab 20(6):1006–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Özkul C, Yalınay M, Karakan T (2019) Islamic fasting leads to an increased abundance of Akkermansia muciniphila and Bacteroides fragilis group: a preliminary study on intermittent fasting. Turk J Gastroenterol 30(12):1030

    Article  PubMed  PubMed Central  Google Scholar 

  75. Fu Y-P et al (2018) Characterization and prebiotic activity in vitro of inulin-type fructan from Codonopsis pilosula roots. Carbohyd Polym 193:212–220

    Article  CAS  Google Scholar 

  76. Ghorbani Tajani A, Bisha B (2023) Effect of food matrix and treatment time on the effectiveness of grape seed extract as an antilisterial treatment in fresh produce. Microorganisms 11(4):1029

  77. Lane JA et al (2012) Methodologies for screening of bacteria–carbohydrate interactions: anti-adhesive milk oligosaccharides as a case study. J Microbiol Methods 90(1):53–59

    Article  CAS  PubMed  Google Scholar 

  78. Shoaf K et al (2006) Prebiotic galactooligosaccharides reduce adherence of enteropathogenic Escherichia coli to tissue culture cells. Infect Immun 74(12):6920–6928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Everard A et al (2014) Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J 8(10):2116–2130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Somerville V, Bringans C, Braakhuis A (2017) Polyphenols and performance: a systematic review and meta-analysis. Sports Med 47(8):1589–1599

    Article  PubMed  Google Scholar 

  81. Van Dorsten F et al (2012) Gut microbial metabolism of polyphenols from black tea and red wine/grape juice is source-specific and colon-region dependent. J Agric Food Chem 60(45):11331–11342

    Article  PubMed  Google Scholar 

  82. Axling U et al (2012) Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice. Nutr Metab 9(1):1–18

    Article  Google Scholar 

  83. Roopchand DE et al (2015) Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet–induced metabolic syndrome. Diabetes 64(8):2847–2858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Reid DT et al (2016) Postnatal prebiotic fibre intake mitigates some detrimental metabolic outcomes of early overnutrition in rats. Eur J Nutr 55(8):2399–2409

    Article  CAS  PubMed  Google Scholar 

  85. Yang J et al (2016) Disparate metabolic responses in mice fed a high-fat diet supplemented with maize-derived non-digestible feruloylated oligo-and polysaccharides are linked to changes in the gut microbiota. PLoS One 11(1):e0146144

    Article  PubMed  PubMed Central  Google Scholar 

  86. Vandeputte D, Joossens M (2020) Effects of low and high FODMAP diets on human gastrointestinal microbiota composition in adults with intestinal diseases: a systematic review. Microorganisms 8(11):1638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Gibson PR, Shepherd SJ (2010) Evidence-based dietary management of functional gastrointestinal symptoms: the FODMAP approach. J Gastroenterol Hepatol 25(2):252–258

    Article  PubMed  Google Scholar 

  88. So D, Loughman A, Staudacher HM (2022) Effects of a low FODMAP diet on the colonic microbiome in irritable bowel syndrome: a systematic review with meta-analysis. Am J Clin Nutr 116(4):943–952

    Article  PubMed  PubMed Central  Google Scholar 

  89. Halmos EP et al (2015) Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut 64(1):93–100

    Article  CAS  PubMed  Google Scholar 

  90. Halmos EP et al (2016) Consistent prebiotic effect on gut microbiota with altered FODMAP intake in patients with Crohn’s disease: a randomised, controlled cross-over trial of well-defined diets. Clin Transl Gastroenterol 7(4):e164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Gibson PR, Shepherd SJ (2005) Personal view: food for thought–western lifestyle and susceptibility to Crohn’s disease. The FODMAP hypothesis. Aliment Pharmacol Ther 21(12):1399–1409

  92. Halmos EP et al (2014) A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology 146(1):67–75. e5

  93. Shin N-R et al (2014) An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63(5):727–735

  94. Cui H-X et al (2019) A purified anthraquinone-glycoside preparation from rhubarb ameliorates type 2 diabetes mellitus by modulating the gut microbiota and reducing inflammation. Front Microbiol 10:1423

    Article  PubMed  PubMed Central  Google Scholar 

  95. Suez J et al (2014) Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514(7521):181–186

    Article  CAS  PubMed  Google Scholar 

  96. Shi Z et al (2021) Impaired intestinal Akkermansia muciniphila and aryl hydrocarbon receptor ligands contribute to nonalcoholic fatty liver disease in mice. Msystems 6(1):e00985-e1020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Chang C-J et al (2015) Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun 6(1):1–19

    Article  Google Scholar 

  98. Zhong Y, Nyman M, Fåk F (2015) Modulation of gut microbiota in rats fed high-fat diets by processing whole-grain barley to barley malt. Mol Nutr Food Res 59(10):2066–2076

    Article  CAS  PubMed  Google Scholar 

  99. Jakobsdottir G et al (2013) High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects. PLoS One 8(11):e80476

    Article  PubMed  PubMed Central  Google Scholar 

  100. Everard A et al (2011) Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60(11):2775–2786

  101. Lee H, Ko G (2014) Effect of metformin on metabolic improvement and gut microbiota. Appl Environ Microbiol 80(19):5935–5943

    Article  PubMed  PubMed Central  Google Scholar 

  102. Alesaeidi S et al (2023) Soy protein isolate/sodium alginate hybrid hydrogel embedded with hydroxyapatite for tissue engineering. J Polym Environ 31(1):396–405

    Article  CAS  Google Scholar 

  103. Alard J et al (2016) Beneficial metabolic effects of selected probiotics on diet-induced obesity and insulin resistance in mice are associated with improvement of dysbiotic gut microbiota. Environ Microbiol 18(5):1484–1497

    Article  CAS  PubMed  Google Scholar 

  104. Dubourg G et al (2013) High-level colonisation of the human gut by Verrucomicrobia following broad-spectrum antibiotic treatment. Int J Antimicrob Agents 41(2):149–155

    Article  CAS  PubMed  Google Scholar 

  105. Hansen C et al (2012) Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia 55(8):2285–2294

    Article  CAS  PubMed  Google Scholar 

  106. Marcial-Coba MS et al (2018) Viability of microencapsulated Akkermansia muciniphila and Lactobacillus plantarum during freeze-drying, storage and in vitro simulated upper gastrointestinal tract passage. Food Funct 9(11):5868–5879

    Article  CAS  PubMed  Google Scholar 

  107. Tripathi MK, Giri SK (2014) Probiotic functional foods: survival of probiotics during processing and storage. J Funct Foods 9:225–241

    Article  CAS  Google Scholar 

  108. Morgan CA et al (2006) Preservation of micro-organisms by drying; a review. J Microbiol Methods 66(2):183–193

    Article  CAS  PubMed  Google Scholar 

  109. Chen M, Mustapha A (2012) Survival of freeze-dried microcapsules of α-galactosidase producing probiotics in a soy bar matrix. Food Microbiol 30(1):68–73

    Article  PubMed  Google Scholar 

  110. Laličić-Petronijević J et al (2015) Viability of probiotic strains Lactobacillus acidophilus NCFM® and Bifidobacterium lactis HN019 and their impact on sensory and rheological properties of milk and dark chocolates during storage for 180 days. J Funct Foods 15:541–550

    Article  Google Scholar 

  111. Marcial-Coba MS et al (2019) Dark chocolate as a stable carrier of microencapsulated Akkermansia muciniphila and Lactobacillus casei. FEMS Microbiol Lett 366(2):fny290

  112. van der Ark KC et al (2017) Encapsulation of the therapeutic microbe Akkermansia muciniphila in a double emulsion enhances survival in simulated gastric conditions. Food Res Int 102:372–379

    Article  PubMed  Google Scholar 

  113. Van Passel MW et al (2011) The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS One 6(3):e16876

    Article  PubMed  PubMed Central  Google Scholar 

  114. Caputo A et al (2015) Whole-genome assembly of Akkermansia muciniphila sequenced directly from human stool. Biol Direct 10(1):1–11

    Article  Google Scholar 

  115. Guo X et al (2017) Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population structure, genomic and functional diverisity, and global distribution in mammalian gut microbiotas. BMC Genomics 18(1):1–12

    Article  Google Scholar 

  116. Ouwerkerk J et al (2017) Preparation and preservation of viable Akkermansia muciniphila cells for therapeutic interventions. Benef Microbes 8(2):163–169

    Article  CAS  PubMed  Google Scholar 

  117. Ouwerkerk JP et al (2016) Adaptation of Akkermansia muciniphila to the oxic-anoxic interface of the mucus layer. Appl Environ Microbiol 82(23):6983–6993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Baban CK et al (2010) Bacteria as vectors for gene therapy of cancer. Bioeng Bugs 1(6):385–394

    Article  PubMed  PubMed Central  Google Scholar 

  119. Pedrolli DB et al (2019) Engineering microbial living therapeutics: the synthetic biology toolbox. Trends Biotechnol 37(1):100–115

    Article  CAS  PubMed  Google Scholar 

  120. Waller MC et al (2017) Toward a genetic tool development pipeline for host-associated bacteria. Curr Opin Microbiol 38:156–164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Welker DL et al (2015) High efficiency electrotransformation of Lactobacillus casei. FEMS Microbiol Lett 362(2):1–6

    Article  CAS  PubMed  Google Scholar 

  122. Kleerebezem M et al (2004) Autoregulation of subtilin biosynthesis in Bacillus subtilis: the role of the spa-box in subtilin-responsive promoters. Peptides 25(9):1415–1424

    Article  CAS  PubMed  Google Scholar 

  123. Dora C et al (2015) Indicators linking health and sustainability in the post-2015 development agenda. The Lancet 385(9965):380–391

    Article  Google Scholar 

  124. Kaiser AD (1955) A genetic study of the temperate coliphage. Virology 1(4):424–443

    Article  CAS  PubMed  Google Scholar 

  125. Carter DM, Radding CM (1971) The role of exonuclease and beta protein of phage lambda in genetic recombination. II. Substrate specificity and the mode of action of lambda exonuclease. J Biol Chem 246(8):2502–12

  126. Murphy KC (1991) Lambda Gam protein inhibits the helicase and chi-stimulated recombination activities of Escherichia coli RecBCD enzyme. J Bacteriol 173(18):5808–5821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Murphy Kenan C, Slauch James M (2016) λ recombination and recombineering. EcoSal Plus 7(1)

  128. Deltcheva E et al (2011) CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471(7340):602–607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Tong Y et al (2015) CRISPR-Cas9 based engineering of actinomycetal genomes. ACS Synth Biol 4(9):1020–1029

    Article  CAS  PubMed  Google Scholar 

  130. van der Els S et al (2018) Versatile Cas9-driven subpopulation selection toolbox for Lactococcus lactis. Appl Environ Microbiol 84(8):e02752-e2817

    PubMed  PubMed Central  Google Scholar 

  131. Crawley AB, Henriksen JR, Barrangou R (2018) CRISPRdisco: an automated pipeline for the discovery and analysis of CRISPR-Cas systems. CRISPR J 1(2):171–181

    Article  PubMed  PubMed Central  Google Scholar 

  132. Lakshmanan AP et al (2021) Akkermansia, a possible microbial marker for poor glycemic control in Qataris children consuming Arabic diet—a pilot study on pediatric T1DM in Qatar. Nutrients 13(3):836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Zhang X-S et al (2018) Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity. Elife 7

  134. Seregin SS et al (2017) NLRP6 protects Il10−/− mice from colitis by limiting colonization of Akkermansia muciniphila. Cell Rep 19(4):733–745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Håkansson Å et al (2015) Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. Clin Exp Med 15(1):107–120

    Article  PubMed  Google Scholar 

  136. Ganesh B et al (2012) Enterococcus faecium NCIMB 10415 does not protect interleukin-10 knock-out mice from chronic gut inflammation. Benef Microbes 3(1):43–50

    Article  CAS  PubMed  Google Scholar 

  137. **ao X, Wu Z-C, Chou K-C (2011) A multi-label classifier for predicting the subcellular localization of gram-negative bacterial proteins with both single and multiple sites. PLoS One 6(6):e20592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Hill-Burns EM et al (2017) Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome. Mov Disord 32(5):739–749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Vallino A et al (2020) Gut bacteria Akkermansia elicit a specific IgG response in CSF of patients with MS. Neurol-Neuroimmunol Neuroinflammation 7(3)

  140. Cekanaviciute E et al (2017) Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci 114(40):10713–10718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Dingemanse C et al (2015) Akkermansia muciniphila and Helicobacter typhlonius modulate intestinal tumor development in mice. Carcinogenesis 1388–1396

  142. Zackular JP et al (2013) The gut microbiome modulates colon tumorigenesis. MBio 4(6):e00692-e713

    Article  PubMed  PubMed Central  Google Scholar 

  143. Baxter NT et al (2014) Structure of the gut microbiome following colonization with human feces determines colonic tumor burden. Microbiome 2(1):1–11

    Article  CAS  Google Scholar 

  144. Ganesh BP et al (2013) Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella Typhimurium-infected gnotobiotic mice. PLoS One 8(9):e74963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Argüello H et al (2018) Early Salmonella Typhimurium infection in pigs disrupts microbiome composition and functionality principally at the ileum mucosa. Sci Rep 8(1):1–12

    Article  Google Scholar 

  146. Desai MS et al (2016) A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167(5):1339–1353. e21

  147. Jang YJ et al (2019) Lactobacillus fermentum species ameliorate dextran sulfate sodium-induced colitis by regulating the immune response and altering gut microbiota. Gut Microbes 10(6):696–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Becken B et al (2021) Genotypic and phenotypic diversity among human isolates of Akkermansia muciniphila. MBio 12(3):e00478–e521

    Article  PubMed  PubMed Central  Google Scholar 

  149. Ottman N et al (2017) Genome-scale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle. Appl Environ Microbiol 83(18):e01014-e1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Liu Y et al (2021) Long-term and continuous administration of Bacillus subtilis during remission effectively maintains the remission of inflammatory bowel disease by protecting intestinal integrity, regulating epithelial proliferation, and resha** microbial structure and function. Food Funct 12(5):2201–2210

    Article  CAS  PubMed  Google Scholar 

  151. Bian X et al (2019) Administration of Akkermansia muciniphila ameliorates dextran sulfate sodium-induced ulcerative colitis in mice. Front Microbiol 10:2259

    Article  PubMed  PubMed Central  Google Scholar 

  152. Asnicar F et al (2021) Blue poo: impact of gut transit time on the gut microbiome using a novel marker. Gut 70(9):1665–1674

    Article  CAS  PubMed  Google Scholar 

  153. Chelakkot C et al (2018) Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp Mol Med 50(2):e450–e450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Wang L et al (2020) A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice. Gut 69(11):1988–1997

    Article  CAS  PubMed  Google Scholar 

  155. Blikslager AT et al (2007) Restoration of barrier function in injured intestinal mucosa. Physiol Rev 87(2):545–564

    Article  CAS  PubMed  Google Scholar 

  156. Shin J et al (2019) Elucidation of Akkermansia muciniphila probiotic traits driven by mucin depletion. Front Microbiol 10:1137

    Article  PubMed  PubMed Central  Google Scholar 

  157. Li J et al (2016) Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe−/− mice. Circulation 133(24):2434–2446

    Article  CAS  PubMed  Google Scholar 

  158. Crespo-Piazuelo D et al (2019) Association between the pig genome and its gut microbiota composition. Sci Rep 9(1):1–11

    Article  CAS  Google Scholar 

  159. Zhu L et al (2020) Akkermansia muciniphila protects intestinal mucosa from damage caused by S. pullorum by initiating proliferation of intestinal epithelium. Vet Res 51(1):1–9

  160. Hiraoka N et al (2000) Molecular cloning and expression of two distinct human chondroitin 4-O-sulfotransferases that belong to the HNK-1 sulfotransferase gene family. J Biol Chem 275(26):20188–20196

    Article  CAS  PubMed  Google Scholar 

  161. Png CW et al (2010) Mucolytic bacteria with increased prevalence in IBD mucosa augmentin vitroutilization of mucin by other bacteria. Offic J Am Col Gastroenterol| ACG 105(11):2420–2428

  162. Ouwerkerk JP, De Vos WM, Belzer C (2013) Glycobiome: bacteria and mucus at the epithelial interface. Best Pract Res Clin Gastroenterol 27(1):25–38

    Article  CAS  PubMed  Google Scholar 

  163. Fan L et al B (2021) adolescentis ameliorates chronic colitis by regulating Treg/Th2 response and gut microbiota remodeling. Gut Microbes 13(1):1826746

  164. Wu X et al (2021) A Korean-style balanced diet has a potential connection with Ruminococcaceae enterotype and reduction of metabolic syndrome incidence in Korean adults. Nutrients 13(2):495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Cozzolino A et al (2020) Preliminary evaluation of the safety and probiotic potential of Akkermansia muciniphila DSM 22959 in comparison with Lactobacillus rhamnosus GG. Microorganisms 8(2):189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Van Der Lugt B et al (2019) Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1−/Δ7 mice. Immun Ageing 16(1):1–17

    Google Scholar 

  167. Vandeputte D et al (2016) Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut 65(1):57–62

    Article  CAS  PubMed  Google Scholar 

  168. Kong C et al (2021) Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome. Signal Transduct Target Ther 6(1):1–12

    Google Scholar 

  169. Li L et al (2020) The effects of daily fasting hours on sha** gut microbiota in mice. BMC Microbiol 20(1):1–8

    Article  Google Scholar 

  170. Zheng J et al (2020) Dietary inflammatory potential in relation to the gut microbiome: results from a cross-sectional study. Br J Nutr 124(9):931–942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Yoon HS et al (2021) Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol 6(5):563–573

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study is related to the project no. 1400/62973 from Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran. We also appreciate the “Student Research Committee” and “Research & Technology Chancellor” in Shahid Beheshti University of Medical Sciences for their financial support of this study.

Author information

Authors and Affiliations

  1. Student Research Committee, Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Amin Abbasi

  2. Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sara Bazzaz, Nasim Khorshidian & Amir M. Mortazavian

  3. Department of Food Processing, Federal Institute of Science and Technology Education of Rio de Janeiro (IFRJ) – Campus Maracanã, Rio de Janeiro, Rio de Janeiro, Brazil

    Adriano G. Da Cruz

  4. Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Yalda Rahbar Saadat

  5. Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Sahar Sabahi

  6. Department of Medical Bacteriology and Virology, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahdi Asghari Ozma

  7. Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

    Masoud Lahouty

  8. Food Safety and Hygiene Division, Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Ramin Aslani

Authors
  1. Amin Abbasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Bazzaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adriano G. Da Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nasim Khorshidian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yalda Rahbar Saadat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sahar Sabahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mahdi Asghari Ozma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masoud Lahouty
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ramin Aslani
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Amir M. Mortazavian
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception of idea: A.A. and A.M.M. Design of review outline: A.A., A.M.M., A.G.D.C., and S.S. Sourcing literature: N.Kh., S.B., Y.R.S., M.A.O., M.L., and R.A. Drafting the article: A.A., Y.R.S., N.Kh., E.Kh., and S.S. Designing the figures: A.A. Reviewing and revising the manuscript: A.A., A.M.M., E.Kh., and Y.R.S. Editing the manuscript: A.A. and A.M.M.

Corresponding author

Correspondence to Amir M. Mortazavian.

Ethics declarations

Ethics Approval

This study was approved by the ethics committee of the research and technology deputy of Shahid Beheshti University of Medical Sciences (IR.SBMU.RETECH.REC.1400.845). All methods were carried out in accordance with relevant guidelines and regulations.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Highlights

• Akkermansia muciniphila is a significant bacterium that promotes host physiology.

• Due to the high inherent tendency of A. muciniphila to adapt and colonize in the intestinal environment as well as its numerous health effects, it can be considered a next-generation probiotic.

• The abundance of A. muciniphila in the gut milieu is regulated by many genetic and dietary variables.

• Pasteurized form or/and postbiotic metabolites of A. muciniphila possess high potential to be utilized in various functional food formulations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abbasi, A., Bazzaz, S., Da Cruz, A.G. et al. A Critical Review on Akkermansia muciniphila: Functional Mechanisms, Technological Challenges, and Safety Issues. Probiotics & Antimicro. Prot. (2023). https://doi.org/10.1007/s12602-023-10118-x

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12602-023-10118-x

Keywords

Search

Navigation