Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms.
Journal
Nature reviews. Gastroenterology & hepatology
ISSN: 1759-5053
Titre abrégé: Nat Rev Gastroenterol Hepatol
Pays: England
ID NLM: 101500079
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
accepted:
05
05
2022
pubmed:
1
6
2022
medline:
30
9
2022
entrez:
31
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35641786
doi: 10.1038/s41575-022-00631-9
pii: 10.1038/s41575-022-00631-9
doi:
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
625-637Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. Springer Nature Limited.
Références
Cani, P. D. Gut microbiota-at the intersection of everything? Nat. Rev. Gastroenterol. Hepatol. 14, 321–322 (2017).
pubmed: 28442782
doi: 10.1038/nrgastro.2017.54
Paone, P. & Cani, P. D. Mucus barrier, mucins and gut microbiota: the expected slimy partners? Gut 69, 2232–2243 (2020).
pubmed: 32917747
doi: 10.1136/gutjnl-2020-322260
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).
pubmed: 15831389
doi: 10.1016/j.copbio.2005.01.007
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).
doi: 10.3389/fgene.2015.00081
pubmed: 25852737
pmcid: 4365749
Raimondi, S., Musmeci, E., Candeliere, F., Amaretti, A. & Rossi, M. Identification of mucin degraders of the human gut microbiota. Sci. Rep. 11, 11094 (2021).
pubmed: 34045537
pmcid: 8159939
doi: 10.1038/s41598-021-90553-4
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).
pubmed: 3920248
pmcid: 423632
doi: 10.1172/JCI111795
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).
doi: 10.1099/ijs.0.02873-0
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).
pubmed: 18083887
doi: 10.1128/AEM.01226-07
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).
doi: 10.3389/fmicb.2011.00166
pubmed: 21904534
pmcid: 3153965
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).
pubmed: 21390229
pmcid: 3048395
doi: 10.1371/journal.pone.0016876
Tramontano, M. et al. Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies. Nat. Microbiol. 3, 514–522 (2018).
pubmed: 29556107
doi: 10.1038/s41564-018-0123-9
Kostopoulos, I. et al. Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro. Sci. Rep. 10, 14330 (2020).
pubmed: 32868839
pmcid: 7459334
doi: 10.1038/s41598-020-71113-8
Luna, E. et al. Utilization efficiency of human milk oligosaccharides by human-associated Akkermansia is strain-dependent. Appl. Environ. Microbiol. 88, e0148721 (2021).
pubmed: 34669436
doi: 10.1128/AEM.01487-21
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).
pubmed: 17933936
pmcid: 2168041
doi: 10.1128/AEM.01477-07
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).
pubmed: 28530702
doi: 10.1038/nm.4345
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).
pubmed: 33790021
pmcid: 8823629
doi: 10.1126/scitranslmed.abb0322
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).
pubmed: 34361945
pmcid: 8305782
doi: 10.3390/microorganisms9071511
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).
doi: 10.1099/ijsem.0.001399
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).
pubmed: 34261503
pmcid: 8278651
doi: 10.1186/s13059-021-02427-7
Smits, S. A. et al. Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania. Science 357, 802–806 (2017).
pubmed: 28839072
pmcid: 5891123
doi: 10.1126/science.aan4834
Fragiadakis, G. K. et al. Links between environment, diet, and the hunter-gatherer microbiome. Gut Microbes 10, 216–227 (2019).
pubmed: 30118385
doi: 10.1080/19490976.2018.1494103
Geerlings, S. Y. et al. Genomic convergence between Akkermansia muciniphila in different mammalian hosts. BMC Microbiol. 21, 298 (2021).
pubmed: 34715771
pmcid: 8555344
doi: 10.1186/s12866-021-02360-6
Belzer, C. & de Vos, W. M. Microbes inside-from diversity to function: the case of Akkermansia. ISME J. 6, 1449–1458 (2012).
pubmed: 22437156
pmcid: 3401025
doi: 10.1038/ismej.2012.6
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).
pubmed: 31334133
pmcid: 6624636
doi: 10.3389/fcimb.2019.00239
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).
pubmed: 29047329
pmcid: 5648452
doi: 10.1186/s12864-017-4195-3
Becken, B. et al. Genotypic and phenotypic diversity among human isolates of Akkermansia muciniphila. mBio 12, e00478-21 (2021).
pubmed: 34006653
pmcid: 8262928
doi: 10.1128/mBio.00478-21
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).
pmcid: 7564497
doi: 10.3390/microorganisms8091413
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).
pubmed: 31757822
pmcid: 6974653
doi: 10.1128/AEM.02117-19
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).
pubmed: 28687644
pmcid: 5583483
doi: 10.1128/AEM.01014-17
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).
pubmed: 28928206
pmcid: 5605934
doi: 10.1128/mBio.00770-17
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).
pubmed: 26069274
doi: 10.1136/gutjnl-2015-309618
Asnicar, F. et al. Blue poo: impact of gut transit time on the gut microbiome using a novel marker. Gut 70, 1665–1674 (2021).
pubmed: 33722860
doi: 10.1136/gutjnl-2020-323877
Manor, O. et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat. Commun. 11, 5206 (2020).
pubmed: 33060586
pmcid: 7562722
doi: 10.1038/s41467-020-18871-1
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).
pubmed: 30883471
doi: 10.1249/JES.0000000000000183
Verhoog, S. et al. Dietary factors and modulation of bacteria strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: a systematic review. Nutrients 11, 1565 (2019).
pmcid: 6683038
doi: 10.3390/nu11071565
von Schwartzenberg, R. J. et al. Caloric restriction disrupts the microbiota and colonization resistance. Nature 595, 272–277 (2021).
doi: 10.1038/s41586-021-03663-4
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).
pubmed: 31823731
pmcid: 6902335
doi: 10.1186/s12866-019-1658-5
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).
pubmed: 25763563
pmcid: 4452615
doi: 10.1007/s00508-015-0755-1
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).
pubmed: 21933985
pmcid: 3198091
doi: 10.2337/db11-0227
Jangi, S. et al. Alterations of the human gut microbiome in multiple sclerosis. Nat. Commun. 7, 12015 (2016).
pubmed: 27352007
pmcid: 4931233
doi: 10.1038/ncomms12015
Everard, A. et al. Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J. 8, 2116–2130 (2014).
pubmed: 24694712
pmcid: 4163056
doi: 10.1038/ismej.2014.45
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).
pubmed: 32231226
doi: 10.1038/s41430-020-0607-6
Macchione, I. G. et al. Akkermansia muciniphila: key player in metabolic and gastrointestinal disorders. Eur. Rev. Med. Pharmacol. Sci. 23, 8075–8083 (2019).
pubmed: 31599433
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).
pubmed: 23671105
pmcid: 3670398
doi: 10.1073/pnas.1219451110
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).
pubmed: 20205964
doi: 10.1017/S0007114510000176
Karlsson, C. L. et al. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity 20, 2257–2261 (2012).
pubmed: 22546742
doi: 10.1038/oby.2012.110
Zhang, X. et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS ONE 8, e71108 (2013).
pubmed: 24013136
pmcid: 3754967
doi: 10.1371/journal.pone.0071108
Li, J. et al. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome 5, 14 (2017).
pubmed: 28143587
pmcid: 5286796
doi: 10.1186/s40168-016-0222-x
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).
pubmed: 26100928
doi: 10.1136/gutjnl-2014-308778
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).
pubmed: 23804561
doi: 10.1136/gutjnl-2012-303839
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).
doi: 10.1080/13813455.2021.1871760
pubmed: 33449810
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).
pubmed: 34065217
pmcid: 8161007
doi: 10.3390/microorganisms9051098
Sheng, L. et al. Obesity treatment by epigallocatechin-3-gallate-regulated bile acid signaling and its enriched Akkermansia muciniphila. FASEB J. 32, fj201800370R (2018).
doi: 10.1096/fj.201800370R
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).
pubmed: 32167023
pmcid: 7524283
doi: 10.1080/19490976.2020.1737307
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).
pubmed: 27892954
doi: 10.1038/nm.4236
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).
pubmed: 34683361
pmcid: 8538271
doi: 10.3390/microorganisms9102039
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).
pubmed: 34549998
doi: 10.1128/Spectrum.00484-21
Ashrafian, F. et al. Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice. Sci. Rep. 11, 17898 (2021).
pubmed: 34504116
pmcid: 8429653
doi: 10.1038/s41598-021-95738-5
Hu, X. et al. Akkermansia muciniphila improves host defense against influenza virus infection. Front. Microbiol. 11, 586476 (2020).
pubmed: 33603716
doi: 10.3389/fmicb.2020.586476
Wang, L. et al. A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8
pubmed: 32169907
doi: 10.1136/gutjnl-2019-320105
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).
pubmed: 31961709
pmcid: 7191407
doi: 10.1152/ajpendo.00425.2019
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).
pubmed: 27230129
doi: 10.1161/ATVBAHA.116.307597
Kim, S. et al. Akkermansia muciniphila prevents fatty liver disease, decreases serum triglycerides, and maintains gut homeostasis. Appl. Environ. Microbiol. 86, e03004-19 (2020).
pubmed: 31953338
pmcid: 7082569
doi: 10.1128/AEM.03004-19
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).
pubmed: 30692526
pmcid: 6349942
doi: 10.1038/s41467-018-08051-7
Grander, C. et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut 67, 891–901 (2018).
pubmed: 28550049
doi: 10.1136/gutjnl-2016-313432
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
pubmed: 27143680
doi: 10.1161/CIRCULATIONAHA.115.019645
Fassatoui, M. et al. Gut microbiota imbalances in Tunisian participants with type 1 and type 2 diabetes mellitus. Biosci. Rep. 39, BSR20182348 (2019).
pubmed: 31147456
pmcid: 6579978
doi: 10.1042/BSR20182348
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).
pubmed: 22572803
doi: 10.1007/s00125-012-2564-7
Hanninen, A. et al. Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice. Gut 67, 1445–1453 (2018).
pubmed: 29269438
doi: 10.1136/gutjnl-2017-314508
Barcena, C. et al. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice. Nat. Med. 25, 1234–1242 (2019).
pubmed: 31332389
doi: 10.1038/s41591-019-0504-5
Bian, X. et al. Administration of Akkermansia muciniphila ameliorates dextran sulfate sodium-induced ulcerative colitis in mice. Front. Microbiol. 10, 2259 (2019).
pubmed: 31632373
pmcid: 6779789
doi: 10.3389/fmicb.2019.02259
Liu, Q. et al. Akkermansia muciniphila exerts strain-specific effects on DSS-induced ulcerative colitis in mice. Front. Cell Infect. Microbiol. 11, 698914 (2021).
pubmed: 34422681
pmcid: 8371549
doi: 10.3389/fcimb.2021.698914
Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60 (2012).
pubmed: 23023125
doi: 10.1038/nature11450
Cani, P. D. Human gut microbiome: hopes, threats and promises. Gut 67, 1716–1725 (2018).
pubmed: 29934437
doi: 10.1136/gutjnl-2018-316723
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).
pubmed: 28893994
pmcid: 5635914
doi: 10.1073/pnas.1711233114
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).
pubmed: 28893978
pmcid: 5635915
doi: 10.1073/pnas.1711235114
Tremlett, H. et al. Gut microbiota in early pediatric multiple sclerosis: a case-control study. Eur. J. Neurol. 23, 1308–1321 (2016).
pubmed: 27176462
pmcid: 4955679
doi: 10.1111/ene.13026
Lin, C. H. et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease. J. Neuroinflamm. 16, 129 (2019).
doi: 10.1186/s12974-019-1528-y
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).
pubmed: 33099131
doi: 10.1016/j.parkreldis.2020.10.034
Vallino, A. et al. Gut bacteria Akkermansia elicit a specific IgG response in CSF of patients with MS. Neurol. Neuroimmunol. Neuroinflamm. 7, e688 (2020).
pubmed: 32123045
pmcid: 7136044
doi: 10.1212/NXI.0000000000000688
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).
pubmed: 34100959
doi: 10.1007/s00109-021-02085-z
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).
pubmed: 31784260
pmcid: 6948921
doi: 10.1016/j.chom.2019.10.008
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).
pubmed: 19494326
doi: 10.4049/jimmunol.0803563
Wang, J. et al. HLA-DR15 molecules jointly shape an autoreactive T cell repertoire in multiple sclerosis. Cell 183, 1264–1281.e20 (2020).
pubmed: 33091337
pmcid: 7707104
doi: 10.1016/j.cell.2020.09.054
Qian, Y. et al. Gut metagenomics-derived genes as potential biomarkers of Parkinson’s disease. Brain 143, 2474–2489 (2020).
pubmed: 32844199
doi: 10.1093/brain/awaa201
Weis, S. et al. Association between Parkinson’s disease and the faecal eukaryotic microbiota. NPJ Parkinsons Dis. 7, 101 (2021).
pubmed: 34795317
pmcid: 8602383
doi: 10.1038/s41531-021-00244-0
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).
pubmed: 34012926
pmcid: 8126658
doi: 10.3389/fcimb.2021.652617
Vogt, N. M. et al. Gut microbiome alterations in Alzheimer’s disease. Sci. Rep. 7, 13537 (2017).
pubmed: 29051531
pmcid: 5648830
doi: 10.1038/s41598-017-13601-y
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).
pubmed: 33614635
doi: 10.3389/fcell.2020.634069
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).
pubmed: 32321934
pmcid: 7176648
doi: 10.1038/s41387-020-0115-8
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).
pubmed: 31207607
pmcid: 6897910
doi: 10.1038/s41386-019-0437-1
Olson, C. A. et al. The gut microbiota mediates the anti-seizure effects of the Ketogenic diet. Cell 173, 1728–1741.e13 (2018).
pubmed: 29804833
pmcid: 6003870
doi: 10.1016/j.cell.2018.04.027
Blacher, E. et al. Potential roles of gut microbiome and metabolites in modulating ALS in mice. Nature 572, 474–480 (2019).
pubmed: 31330533
doi: 10.1038/s41586-019-1443-5
Kennedy, L. B. & Salama, A. K. S. A review of cancer immunotherapy toxicity. CA Cancer J. Clin. 70, 86–104 (2020).
pubmed: 31944278
doi: 10.3322/caac.21596
Routy, B. et al. The gut microbiota influences anticancer immunosurveillance and general health. Nat. Rev. Clin. Oncol. 15, 382–396 (2018).
pubmed: 29636538
doi: 10.1038/s41571-018-0006-2
Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018).
pubmed: 29097494
doi: 10.1126/science.aan3706
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).
pubmed: 35115705
pmcid: 9330544
doi: 10.1038/s41591-021-01655-5
Matson, V. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359, 104–108 (2018).
pubmed: 29302014
pmcid: 6707353
doi: 10.1126/science.aao3290
Mager, L. F. et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science 369, 1481–1489 (2020).
pubmed: 32792462
doi: 10.1126/science.abc3421
Chelakkot, C. et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp. Mol. Med. 50, e450 (2018).
pubmed: 29472701
pmcid: 5903829
doi: 10.1038/emm.2017.282
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).
pubmed: 20648002
doi: 10.1038/ajg.2010.281
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).
pubmed: 23385241
doi: 10.1097/MIB.0b013e31827fec6d
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).
pubmed: 24204633
pmcid: 3811976
doi: 10.1371/journal.pone.0076520
Ferrucci, L. & Fabbri, E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat. Rev. Cardiol. 15, 505–522 (2018).
pubmed: 30065258
pmcid: 6146930
doi: 10.1038/s41569-018-0064-2
Biagi, E. et al. Gut microbiota and extreme longevity. Curr. Biol. 26, 1480–1485 (2016).
pubmed: 27185560
doi: 10.1016/j.cub.2016.04.016
Kong, F. et al. Gut microbiota signatures of longevity. Curr. Biol. 26, R832–R833 (2016).
pubmed: 27676296
doi: 10.1016/j.cub.2016.08.015
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
pubmed: 30899315
pmcid: 6408808
doi: 10.1186/s12979-019-0145-z
Bodogai, M. et al. Commensal bacteria contribute to insulin resistance in aging by activating innate B1a cells. Sci. Transl. Med. 10, eaat4271 (2018).
pubmed: 30429354
pmcid: 6445267
doi: 10.1126/scitranslmed.aat4271
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).
pubmed: 34729669
doi: 10.1007/s10522-021-09943-w
Hagi, T. & Belzer, C. The interaction of Akkermansia muciniphila with host-derived substances, bacteria and diets. Appl. Microbiol. Biotechnol. 105, 4833–4841 (2021).
pubmed: 34125276
pmcid: 8236039
doi: 10.1007/s00253-021-11362-3
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).
pubmed: 23727645
doi: 10.3177/jnsv.59.144
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).
pubmed: 16101937
doi: 10.1111/j.1399-3038.2005.00284.x
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).
pubmed: 31263284
pmcid: 6699990
doi: 10.1038/s41591-019-0495-2
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).
pubmed: 32675291
pmcid: 7368581
doi: 10.1136/bmjdrc-2020-001319
Druart, C. et al. Toxicological safety evaluation of pasteurized Akkermansia muciniphila. J. Appl. Toxicol. 41, 276–290 (2021).
pubmed: 32725676
doi: 10.1002/jat.4044
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).
pubmed: 35020929
doi: 10.1093/nutrit/nuab108
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).
pubmed: 25118238
pmcid: 4145684
doi: 10.1128/mBio.01438-14
Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).
pubmed: 24226773
pmcid: 3869884
doi: 10.1038/nature12726
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).
pubmed: 33900345
doi: 10.1039/D1FO00115A
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).
pubmed: 33820962
doi: 10.1038/s41564-021-00880-5
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).
pmcid: 7246985
doi: 10.3390/ijms21093385
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).
pubmed: 35133390
doi: 10.1039/D1FO04094D
Ottman, N. et al. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS ONE 12, e0173004 (2017).
pubmed: 28249045
pmcid: 5332112
doi: 10.1371/journal.pone.0173004
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).
pubmed: 33477821
pmcid: 7832901
doi: 10.3390/cells10010185
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).
pubmed: 34812127
pmcid: 8632301
doi: 10.1080/19490976.2021.1994270
Grajeda-Iglesias, C. et al. Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites. Aging 13, 6375–6405 (2021).
pubmed: 33653967
pmcid: 7993698
doi: 10.18632/aging.202739
de Vos, W. M., Tilg, H., Van Hul, M. & Cani, P. D. Gut microbiome and health: mechanistic insights. Gut 71, 1020–1032 (2022).
pubmed: 35105664
doi: 10.1136/gutjnl-2021-326789
Viola, M. F. & Boeckxstaens, G. Niche-specific functional heterogeneity of intestinal resident macrophages. Gut 70, 1383–1395 (2021).
pubmed: 33384336
doi: 10.1136/gutjnl-2020-323121
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).
pubmed: 33060124
doi: 10.1136/gutjnl-2020-320786
Kuczma, M. P. et al. Self and microbiota-derived epitopes induce CD4
pubmed: 33139845
doi: 10.1038/s41385-020-00349-4
O’Toole, P. W., Marchesi, J. R. & Hill, C. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat. Microbiol. 2, 17057 (2017).
pubmed: 28440276
doi: 10.1038/nmicrobiol.2017.57
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).
pubmed: 33785319
doi: 10.1016/j.beem.2021.101504
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).
pubmed: 29033923
pmcid: 5626839
doi: 10.3389/fmicb.2017.01889
Udayappan, S. et al. Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice. NPJ Biofilms Microbiomes 2, 16009 (2016).
pubmed: 28721246
pmcid: 5515273
doi: 10.1038/npjbiofilms.2016.9
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).
doi: 10.1136/gutjnl-2020-323297
pubmed: 34697034
Seegers, J. et al. Toxicological safety evaluation of live Anaerobutyricum soehngenii strain CH106. J. Appl. Toxicol. 42, 244–257 (2021).
pubmed: 34184753
pmcid: 9292162
doi: 10.1002/jat.4207
Cordaillat-Simmons, M., Rouanet, A. & Pot, B. Live biotherapeutic products: the importance of a defined regulatory framework. Exp. Mol. Med. 52, 1397–1406 (2020).
pubmed: 32908212
pmcid: 8080583
doi: 10.1038/s12276-020-0437-6
Barcenilla, A. et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Environ. Microbiol. 66, 1654–1661 (2000).
pubmed: 10742256
pmcid: 92037
doi: 10.1128/AEM.66.4.1654-1661.2000
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).
pubmed: 18936492
pmcid: 2575488
doi: 10.1073/pnas.0804812105
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).
pubmed: 24418903
doi: 10.1097/01.MIB.0000440815.76627.64
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).
pubmed: 26045134
doi: 10.1136/gutjnl-2014-307649
Lenoir, M. et al. Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3. Gut Microbes 12, 1–16 (2020).
pubmed: 33054518
doi: 10.1080/19490976.2020.1826748
Mazier, W. et al. A new strain of Christensenella minuta as a potential biotherapy for obesity and associated metabolic diseases. Cells 10, 823 (2021).
pubmed: 33917566
pmcid: 8067450
doi: 10.3390/cells10040823
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).
pubmed: 32221294
pmcid: 7101376
doi: 10.1038/s41522-020-0127-0
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).
pubmed: 3994481
doi: 10.1007/BF00446731
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).
pubmed: 28718073
doi: 10.1007/s00240-017-0998-6
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).
pubmed: 27924398
doi: 10.1007/s00467-016-3553-8