Abstract
Ever since Akkermansia muciniphila was discovered and characterized two decades ago, numerous studies have shown that the lack or decreased abundance of this commensal bacterium was linked with multiple diseases (such as obesity, diabetes, liver steatosis, inflammation and response to cancer immunotherapies). Although primarily based on simple associations, there are nowadays an increasing number of studies moving from correlations to causality. The causal evidence derived from a variety of animal models performed in different laboratories and recently was also recapitulated in a human proof-of-concept trial. In this Review, we cover the history of the discovery of A. muciniphila and summarize the numerous findings and main mechanisms of action by which this intestinal symbiont improves health. A comparison of this microorganism with other next-generation beneficial microorganisms that are being developed is also made.
Key points
-
A lower abundance of Akkermansia muciniphila has been associated with multiple diseases in both mouse models and in humans.
-
A. muciniphila has proven efficacy to improve obesity, type 2 and type 1 diabetes mellitus, hepatic steatosis, intestinal inflammation and different cancers (colon cancer, response to immune checkpoints) in mice.
-
Numerous mechanisms linking A. muciniphila, specific metabolites or membrane proteins and host cell types or receptors have been identified.
-
Pasteurized A. muciniphila MucT is more efficient than the live bacterium and has proven safety and efficacy in numerous studies in mice and in a proof-of-concept study in humans.
-
A. muciniphila contributes to the maintenance of a healthy gut barrier, thereby regulating immunity, and also limits the onset of inflammation, which is the root cause of numerous diseases.
Change history
-
23 June 2022
A Correction to this paper has been published: https://doi.org/10.1038/s41575-022-00650-6
References
-
Cani, P. D. Gut microbiota-at the intersection of everything? Nat. Rev. Gastroenterol. Hepatol. 14, 321–322 (2017).
-
Paone, P. & Cani, P. D. Mucus barrier, mucins and gut microbiota: the expected slimy partners? Gut 69, 2232–2243 (2020).
-
Ouwehand, A. C., Derrien, M., de Vos, W., Tiihonen, K. & Rautonen, N. Prebiotics and other microbial substrates for gut functionality. Curr. Opin. Biotechnol. 16, 212–217 (2005).
-
Tailford, L., Crost, E., Kavanaugh, D. & Juge, N. Mucin glycan foraging in the human gut microbiome. Front. Genet. https://doi.org/10.3389/fgene.2015.00081 (2015).
-
Raimondi, S., Musmeci, E., Candeliere, F., Amaretti, A. & Rossi, M. Identification of mucin degraders of the human gut microbiota. Sci. Rep. 11, 11094 (2021).
-
Derrien, M. et al. The intestinal mucosa as a habitat of the gut microbiota and a rational target for probiotic functionality and safety. Microb. Ecol. Health Dis. 16, 137–144 (2004).
-
Hoskins, L. C. et al. Mucin degradation in human colon ecosystems. Isolation and properties of fecal strains that degrade ABH blood group antigens and oligosaccharides from mucin glycoproteins. J. Clin. Invest. 75, 944–953 (1985).
-
Derrien, M., Vaughan, E. E., Plugge, C. M. & de Vos, W. M. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int. J. Syst. Evolut. Microbiol. 54, 1469–1476 (2004).
-
Derrien, M., Collado, M. C., Ben-Amor, K., Salminen, S. & de Vos, W. M. The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl. Environ. Microbiol. 74, 1646–1648 (2008).
-
Derrien, M. et al. Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front. Microbiol. https://doi.org/10.3389/fmicb.2011.00166 (2011).
-
van Passel, M. W. J. et al. The Genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS ONE 6, e16876 (2011).
-
Tramontano, M. et al. Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies. Nat. Microbiol. 3, 514–522 (2018).
-
Kostopoulos, I. et al. Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro. Sci. Rep. 10, 14330 (2020).
-
Luna, E. et al. Utilization efficiency of human milk oligosaccharides by human-associated Akkermansia is strain-dependent. Appl. Environ. Microbiol. 88, e0148721 (2021).
-
Collado, M. C., Derrien, M., Isolauri, E., de Vos, W. M. & Salminen, S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl. Environ. Microbiol. 73, 7767–7770 (2007).
-
Wu, H. et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23, 850–858 (2017).
-
Ribo, S. et al. Increasing breast milk betaine modulates Akkermansia abundance in mammalian neonates and improves long-term metabolic health. Sci. Transl. Med. 13, eabb0322 (2021).
-
Yin, J. et al. Dose-dependent beneficial effects of tryptophan and its derived metabolites on Akkermansia in vitro: a preliminary prospective study. Microorganisms 9, 1511 (2021).
-
Ouwerkerk, J. P., Aalvink, S., Belzer, C. & de Vos, W. M. Akkermansia glycaniphila sp. nov., an anaerobic mucin-degrading bacterium isolated from reticulated python faeces. Int. J. Syst. Evolut. Microbiol. 66, 4614–4620 (2016).
-
Karcher, N. et al. Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly. Genome Biol. 22, 209 (2021).
-
Smits, S. A. et al. Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania. Science 357, 802–806 (2017).
-
Fragiadakis, G. K. et al. Links between environment, diet, and the hunter-gatherer microbiome. Gut Microbes 10, 216–227 (2019).
-
Geerlings, S. Y. et al. Genomic convergence between Akkermansia muciniphila in different mammalian hosts. BMC Microbiol. 21, 298 (2021).
-
Belzer, C. & de Vos, W. M. Microbes inside-from diversity to function: the case of Akkermansia. ISME J. 6, 1449–1458 (2012).
-
Zhai, R. et al. Strain-specific anti-inflammatory properties of two Akkermansia muciniphila strains on chronic colitis in mice. Front. Cell. Infect. Microbiol. 9, 239 (2019).
-
Guo, X. et al. 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, 800 (2017).
-
Becken, B. et al. Genotypic and phenotypic diversity among human isolates of Akkermansia muciniphila. mBio 12, e00478-21 (2021).
-
Yang, M. et al. Beneficial effects of newly isolated Akkermansia muciniphila strains from the human gut on obesity and metabolic dysregulation. Microorganisms 8, 1413 (2020).
-
Kirmiz, N. et al. Comparative genomics guides elucidation of vitamin B(12) biosynthesis in novel human-associated Akkermansia strains. Appl. Environ. Microbiol. 86, e02117-19 (2020).
-
Ottman, N. et al. Genome-scale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle. Appl. Environ. Microbiol. 83, e01014-17 (2017).
-
Belzer, C. et al. Microbial metabolic networks at the mucus layer lead to diet-independent butyrate and vitamin B(12) production by intestinal symbionts. mBio 8, e00770-17 (2017).
-
Vandeputte, D. et al. Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut 65, 57–62 (2016).
-
Asnicar, F. et al. Blue poo: impact of gut transit time on the gut microbiome using a novel marker. Gut 70, 1665–1674 (2021).
-
Manor, O. et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat. Commun. 11, 5206 (2020).
-
Mailing, L. J., Allen, J. M., Buford, T. W., Fields, C. J. & Woods, J. A. Exercise and the gut microbiome: a review of the evidence, potential mechanisms, and implications for human health. Exerc. Sport Sci. Rev. 47, 75–85 (2019).
-
Verhoog, S. et al. Dietary factors and modulation of bacteria strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: a systematic review. Nutrients 11, 1565 (2019).
-
von Schwartzenberg, R. J. et al. Caloric restriction disrupts the microbiota and colonization resistance. Nature 595, 272–277 (2021).
-
Leng, B. et al. Severe gut microbiota dysbiosis caused by malnourishment can be partly restored during 3 weeks of refeeding with fortified corn-soy-blend in a piglet model of childhood malnutrition. BMC Microbiol. 19, 277 (2019).
-
Remely, M. et al. Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii and Akkermansia after fasting: a pilot study. Wien. Klin. Wochenschr. 127, 394–398 (2015).
-
Everard, A. et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60, 2775–2786 (2011).
-
Jangi, S. et al. Alterations of the human gut microbiome in multiple sclerosis. Nat. Commun. 7, 12015 (2016).
-
Everard, A. et al. Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J. 8, 2116–2130 (2014).
-
Crovesy, L., Masterson, D. & Rosado, E. L. Profile of the gut microbiota of adults with obesity: a systematic review. Eur. J. Clin. Nutr. 74, 1251–1262 (2020).
-
Macchione, I. G. et al. Akkermansia muciniphila: key player in metabolic and gastrointestinal disorders. Eur. Rev. Med. Pharmacol. Sci. 23, 8075–8083 (2019).
-
Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl Acad. Sci. USA 110, 9066–9071 (2013).
-
Santacruz, A. et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br. J. Nutr. 104, 83–92 (2010).
-
Karlsson, C. L. et al. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity 20, 2257–2261 (2012).
-
Zhang, X. et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS ONE 8, e71108 (2013).
-
Li, J. et al. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome 5, 14 (2017).
-
Dao, M. C. et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65, 426–436 (2016).
-
Shin, N. R. et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63, 727–735 (2014).
-
Roshanravan, N. et al. A comprehensive systematic review of the effectiveness of Akkermansia muciniphila, a member of the gut microbiome, for the management of obesity and associated metabolic disorders. Arch. Physiol. Biochem. https://doi.org/10.1080/13813455.2021.1871760 (2021).
-
Abuqwider, J. N., Mauriello, G. & Altamimi, M. Akkermansia muciniphila, a new generation of beneficial microbiota in modulating obesity: a systematic review. Microorganisms 9, 1098 (2021).
-
Sheng, L. et al. Obesity treatment by epigallocatechin-3-gallate-regulated bile acid signaling and its enriched Akkermansia muciniphila. FASEB J. 32, fj201800370R (2018).
-
Depommier, C. et al. Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice. Gut Microbes 11, 1231–1245 (2020).
-
Plovier, H. et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med. 23, 107–113 (2017).
-
Choi, Y. et al. Effects of live and pasteurized forms of Akkermansia from the human gut on obesity and metabolic dysregulation. Microorganisms 9, 2039 (2021).
-
Keshavarz Azizi Raftar, S. et al. The protective effects of live and pasteurized Akkermansia muciniphila and its extracellular vesicles against HFD/CCl4-induced liver injury. Microbiol. Spectr. 9, e0048421 (2021).
-
Ashrafian, F. et al. Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice. Sci. Rep. 11, 17898 (2021).
-
Hu, X. et al. Akkermansia muciniphila improves host defense against influenza virus infection. Front. Microbiol. 11, 586476 (2020).
-
Wang, L. et al. 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, 1988–1997 (2020).
-
Lawenius, L. et al. Pasteurized Akkermansia muciniphila protects from fat mass gain but not from bone loss. Am. J. Physiol. Endocrinol. Metab. 318, E480–E491 (2020).
-
Shen, J. et al. Low-density lipoprotein receptor signaling mediates the triglyceride-lowering action of Akkermansia muciniphila in genetic-induced hyperlipidemia. Arterioscler. Thromb. Vasc. Biol. 36, 1448–1456 (2016).
-
Kim, S. et al. Akkermansia muciniphila prevents fatty liver disease, decreases serum triglycerides, and maintains gut homeostasis. Appl. Environ. Microbiol. 86, e03004-19 (2020).
-
Everard, A. et al. Intestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis. Nat. Commun. 10, 457 (2019).
-
Grander, C. et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut 67, 891–901 (2018).
-
Li, J., Lin, S., Vanhoutte, P. M., Woo, C. W. & Xu, A. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe−/− mice. Circulation 133, 2434–2446 (2016).
-
Fassatoui, M. et al. Gut microbiota imbalances in Tunisian participants with type 1 and type 2 diabetes mellitus. Biosci. Rep. 39, BSR20182348 (2019).
-
Hansen, C. H. et al. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia 55, 2285–2294 (2012).
-
Hanninen, A. et al. Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice. Gut 67, 1445–1453 (2018).
-
Barcena, C. et al. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice. Nat. Med. 25, 1234–1242 (2019).
-
Bian, X. et al. Administration of Akkermansia muciniphila ameliorates dextran sulfate sodium-induced ulcerative colitis in mice. Front. Microbiol. 10, 2259 (2019).
-
Liu, Q. et al. Akkermansia muciniphila exerts strain-specific effects on DSS-induced ulcerative colitis in mice. Front. Cell Infect. Microbiol. 11, 698914 (2021).
-
Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60 (2012).
-
Cani, P. D. Human gut microbiome: hopes, threats and promises. Gut 67, 1716–1725 (2018).
-
Berer, K. et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc. Natl Acad. Sci. USA 114, 10719–10724 (2017).
-
Cekanaviciute, E. et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc. Natl Acad. Sci. USA 114, 10713–10718 (2017).
-
Tremlett, H. et al. Gut microbiota in early pediatric multiple sclerosis: a case-control study. Eur. J. Neurol. 23, 1308–1321 (2016).
-
Lin, C. H. et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease. J. Neuroinflamm. 16, 129 (2019).
-
Zhang, F. et al. Altered gut microbiota in Parkinson’s disease patients/healthy spouses and its association with clinical features. Parkinsonism Relat. Disord. 81, 84–88 (2020).
-
Vallino, A. et al. Gut bacteria Akkermansia elicit a specific IgG response in CSF of patients with MS. Neurol. Neuroimmunol. Neuroinflamm. 7, e688 (2020).
-
Eckman, E. et al. Spinal fluid IgG antibodies from patients with demyelinating diseases bind multiple sclerosis-associated bacteria. J. Mol. Med. 99, 1399–1411 (2021).
-
Liu, S. et al. Oral administration of miR-30d from feces of MS patients suppresses MS-like symptoms in mice by expanding Akkermansia muciniphila. Cell Host Microbe 26, 779–794.e8 (2019).
-
Nath, N. et al. Metformin attenuated the autoimmune disease of the central nervous system in animal models of multiple sclerosis. J. Immunol. 182, 8005–8014 (2009).
-
Wang, J. et al. HLA-DR15 molecules jointly shape an autoreactive T cell repertoire in multiple sclerosis. Cell 183, 1264–1281.e20 (2020).
-
Qian, Y. et al. Gut metagenomics-derived genes as potential biomarkers of Parkinson’s disease. Brain 143, 2474–2489 (2020).
-
Weis, S. et al. Association between Parkinson’s disease and the faecal eukaryotic microbiota. NPJ Parkinsons Dis. 7, 101 (2021).
-
Murros, K. E., Huynh, V. A., Takala, T. M. & Saris, P. E. J. Desulfovibrio bacteria are associated with Parkinson’s disease. Front. Cell Infect. Microbiol. 11, 652617 (2021).
-
Vogt, N. M. et al. Gut microbiome alterations in Alzheimer’s disease. Sci. Rep. 7, 13537 (2017).
-
Ling, Z. et al. Structural and functional dysbiosis of fecal microbiota in chinese patients with Alzheimer’s disease. Front. Cell Dev. Biol. 8, 634069 (2020).
-
Ou, Z. et al. Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer’s disease. Nutr. Diabetes 10, 12 (2020).
-
Yang, Y. et al. Early-life high-fat diet-induced obesity programs hippocampal development and cognitive functions via regulation of gut commensal Akkermansia muciniphila. Neuropsychopharmacology 44, 2054–2064 (2019).
-
Olson, C. A. et al. The gut microbiota mediates the anti-seizure effects of the Ketogenic diet. Cell 173, 1728–1741.e13 (2018).
-
Blacher, E. et al. Potential roles of gut microbiome and metabolites in modulating ALS in mice. Nature 572, 474–480 (2019).
-
Kennedy, L. B. & Salama, A. K. S. A review of cancer immunotherapy toxicity. CA Cancer J. Clin. 70, 86–104 (2020).
-
Routy, B. et al. The gut microbiota influences anticancer immunosurveillance and general health. Nat. Rev. Clin. Oncol. 15, 382–396 (2018).
-
Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018).
-
Derosa, L. et al. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. Nat. Med. 28, 315–324 (2022).
-
Matson, V. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359, 104–108 (2018).
-
Mager, L. F. et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science 369, 1481–1489 (2020).
-
Chelakkot, C. et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp. Mol. Med. 50, e450 (2018).
-
Png, C. W. et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am. J. Gastroenterol. 105, 2420–2428 (2010).
-
Rajilic-Stojanovic, M., Shanahan, F., Guarner, F. & de Vos, W. M. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm. Bowel Dis. 19, 481–488 (2013).
-
Kang, C. S. et al. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis. PLoS ONE 8, e76520 (2013).
-
Ferrucci, L. & Fabbri, E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat. Rev. Cardiol. 15, 505–522 (2018).
-
Biagi, E. et al. Gut microbiota and extreme longevity. Curr. Biol. 26, 1480–1485 (2016).
-
Kong, F. et al. Gut microbiota signatures of longevity. Curr. Biol. 26, R832–R833 (2016).
-
van der Lugt, B. et al. Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1-/Δ7 mice. Immun. Ageing 16, 6 (2019).
-
Bodogai, M. et al. Commensal bacteria contribute to insulin resistance in aging by activating innate B1a cells. Sci. Transl. Med. 10, eaat4271 (2018).
-
Cerro, E. D. et al. Daily ingestion of Akkermansia mucciniphila for one month promotes healthy aging and increases lifespan in old female mice. Biogerontology 23, 35–52 (2021).
-
Hagi, T. & Belzer, C. The interaction of Akkermansia muciniphila with host-derived substances, bacteria and diets. Appl. Microbiol. Biotechnol. 105, 4833–4841 (2021).
-
Sakai, T. et al. Lactobacillus plantarum OLL2712 regulates glucose metabolism in C57BL/6 mice fed a high-fat diet. J. Nutr. Sci. Vitaminol. 59, 144–147 (2013).
-
Peng, G. C. & Hsu, C. H. The efficacy and safety of heat-killed Lactobacillus paracasei for treatment of perennial allergic rhinitis induced by house-dust mite. Pediatr. Allergy Immunol. 16, 433–438 (2005).
-
Depommier, C. et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat. Med. 25, 1096–1103 (2019).
-
Perraudeau, F. et al. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res. Care 8, e001319 (2020).
-
Druart, C. et al. Toxicological safety evaluation of pasteurized Akkermansia muciniphila. J. Appl. Toxicol. 41, 276–290 (2021).
-
EFSA Panel on Nutrition, Novel Foodds and Food Allergens (NDA)et al. Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 19, e06780 (2021).
-
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04797442 (2021).
-
Pinto, F. C. S., Silva, A. A. M. & Souza, S. L. Repercussions of intermittent fasting on the intestinal microbiota community and body composition: a systematic review. Nutr. Rev. 80, 613–628 (2022).
-
Lukovac, S. et al. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. MBio 5, e01438-14 (2014).
-
Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).
-
Wang, J. et al. The outer membrane protein Amuc_1100 of Akkermansia muciniphila promotes intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling. Food Funct. 12, 3597–3610 (2021).
-
Yoon, H. S. et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat. Microbiol. 6, 563–573 (2021).
-
Meng, X., Zhang, J., Wu, H., Yu, D. & Fang, X. Akkermansia muciniphila aspartic protease Amuc_1434* inhibits human colorectal cancer LS174T cell viability via TRAIL-mediated apoptosis pathway. Int. J. Mol. Sci. 21, 3385 (2020).
-
Qian, K. et al. A β-N-acetylhexosaminidase Amuc_2109 from Akkermansia muciniphila protects against dextran sulfate sodium-induced colitis in mice by enhancing intestinal barrier and modulating gut microbiota. Food Funct. 13, 2216–2227 (2022).
-
Ottman, N. et al. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS ONE 12, e0173004 (2017).
-
Depommier, C. et al. Beneficial Effects of Akkermansia muciniphila are not associated with major changes in the circulating endocannabinoidome but linked to higher mono-palmitoyl-glycerol levels as new PPARalpha agonists. Cells 10, 185 (2021).
-
Depommier, C. et al. Serum metabolite profiling yields insights into health promoting effect of A. muciniphila in human volunteers with a metabolic syndrome. Gut Microbes 13, 1994270 (2021).
-
Grajeda-Iglesias, C. et al. Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites. Aging 13, 6375–6405 (2021).
-
de Vos, W. M., Tilg, H., Van Hul, M. & Cani, P. D. Gut microbiome and health: mechanistic insights. Gut 71, 1020–1032 (2022).
-
Viola, M. F. & Boeckxstaens, G. Niche-specific functional heterogeneity of intestinal resident macrophages. Gut 70, 1383–1395 (2021).
-
Tranah, T. H., Edwards, L. A., Schnabl, B. & Shawcross, D. L. Targeting the gut-liver-immune axis to treat cirrhosis. Gut 70, 982–994 (2021).
-
Kuczma, M. P. et al. Self and microbiota-derived epitopes induce CD4+ T cell anergy and conversion into CD4+Foxp3+ regulatory cells. Mucosal Immunol. 14, 443–454 (2021).
-
O’Toole, P. W., Marchesi, J. R. & Hill, C. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat. Microbiol. 2, 17057 (2017).
-
Bui, T. P. N. & de Vos, W. M. Next-generation therapeutic bacteria for treatment of obesity, diabetes, and other endocrine diseases. Best. Pract. Res. Clin. Endocrinol. Metab. 35, 101504 (2021).
-
El Hage, R., Hernandez-Sanabria, E. & Van de Wiele, T. Emerging trends in “smart probiotics”: functional consideration for the development of novel health and industrial applications. Front. Microbiol. 8, 1889 (2017).
-
Udayappan, S. et al. Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice. NPJ Biofilms Microbiomes 2, 16009 (2016).
-
Koopen, A. et al. Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study. Gut https://doi.org/10.1136/gutjnl-2020-323297 (2021).
-
Seegers, J. et al. Toxicological safety evaluation of live Anaerobutyricum soehngenii strain CH106. J. Appl. Toxicol. 42, 244–257 (2021).
-
Cordaillat-Simmons, M., Rouanet, A. & Pot, B. Live biotherapeutic products: the importance of a defined regulatory framework. Exp. Mol. Med. 52, 1397–1406 (2020).
-
Barcenilla, A. et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Environ. Microbiol. 66, 1654–1661 (2000).
-
Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 16731–16736 (2008).
-
Martin, R. et al. The commensal bacterium Faecalibacterium prausnitzii is protective in DNBS-induced chronic moderate and severe colitis models. Inflamm. Bowel Dis. 20, 417–430 (2014).
-
Quevrain, E. et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut 65, 415–425 (2016).
-
Lenoir, M. et al. Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3. Gut Microbes 12, 1–16 (2020).
-
Mazier, W. et al. A new strain of Christensenella minuta as a potential biotherapy for obesity and associated metabolic diseases. Cells 10, 823 (2021).
-
Gilijamse, P. W. et al. Treatment with Anaerobutyricum soehngenii: a pilot study of safety and dose–response effects on glucose metabolism in human subjects with metabolic syndrome. NPJ Biofilms Microbiomes 6, 16 (2020).
-
Allison, M. J., Dawson, K. A., Mayberry, W. R. & Foss, J. G. Oxalobacter formigenes gen. nov., sp. nov.: oxalate-degrading anaerobes that inhabit the gastrointestinal tract. Arch. Microbiol. 141, 1–7 (1985).
-
Milliner, D., Hoppe, B. & Groothoff, J. A randomised phase II/III study to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria. Urolithiasis 46, 313–323 (2018).
-
Hoppe, B. et al. A randomised phase I/II trial to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria. Pediatr. Nephrol. 32, 781–790 (2017).
Acknowledgements
P.D.C. is research director and A.E. is research associate at FRS-FNRS (Fonds de la Recherche Scientifique) and are recipients of grants from FNRS (Projet de Recherche PDR-convention: FNRS T.0030.21, CDR-convention: J.0027.22, FRFS-WELBIO: WELBIO-CR-2022A-02, WELBIO-CR-2019C-02R, WELBIO-CR-2019S-03, WELBIO-CR-2019S-03R, EOS: program no. 30770923 and program no. 40007505). W.M.dV. was supported by the SIAM Gravitation Grant [024.002.002] of the Netherlands Organization for Scientific Research.
Author information
Authors and Affiliations
Contributions
The authors contributed equally to all aspects of the article.
Corresponding author
Ethics declarations
Competing interests
P.D.C., A.E. and W.M.dV. are inventors on patent applications dealing with the use of Akkermansia muciniphila and its components in the treatment of metabolic disorders. P.D.C. and W.M.dV. are co-founders of A-Mansia biotech. M.D. is an employee at Danone Nutricia Research. P.D.C. is co-founder of Enterosys. W.M.dV. is co-founder of Caelus Health and named inventor on patents on the use of Eubacterium hallii. C.D. declares no competing interests.
Peer review
Peer review information
Nature Reviews Gastroenterology & Hepatology thanks Glenn Gibson, Dennish Sandris Nielsen and Jonathan Schertzer for their contribution to the peer review of this work.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Cani, P.D., Depommier, C., Derrien, M. et al. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nat Rev Gastroenterol Hepatol 19, 625–637 (2022). https://doi.org/10.1038/s41575-022-00631-9
-
Accepted
-
Published
-
Issue Date
-
DOIhttps://doi.org/10.1038/s41575-022-00631-9
Plaats een reactie ...
Reageer op "Akkermansia muciniphila, een probiotica bacterie, blijkt de effectiviteit van immuuntherapie bij kankerpatienten sterk te verbeteren, blijkt uit meerdere studies"