We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Exploring the genetic diversity of the 16S rRNA gene of Akkermansia muciniphila in IBD and IBS

    Alessandra Lo Presti

    *Author for correspondence:

    E-mail Address: alessandra.lopresti@iss.it

    Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy

    ,
    Federica Del Chierico

    Human Microbiome Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

    ,
    Annamaria Altomare

    Unit of Digestive Disease, Campus Bio-Medico University, Rome, Italy

    ,
    Francesca Zorzi

    Gastrointestinal Unit, Department of Systems Medicine, University Tor Vergata, Rome, Italy

    ,
    Eleonora Cella

    Unit of Medical Statistics & Molecular Epidemiology, University Campus Bio-Medico, Rome, Italy

    ,
    Lorenza Putignani

    Unit of Parasitology and Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy

    ,
    Michele Pier Luca Guarino

    Unit of Digestive Disease, Campus Bio-Medico University, Rome, Italy

    ,
    Giovanni Monteleone

    Gastrointestinal Unit, Department of Systems Medicine, University Tor Vergata, Rome, Italy

    ,
    Michele Cicala

    Unit of Digestive Disease, Campus Bio-Medico University, Rome, Italy

    ,
    Silvia Angeletti

    Unit of Clinical Laboratory Science, University Campus Bio-Medico, Rome, Italy

    &
    Massimo Ciccozzi

    Unit of Medical Statistics & Molecular Epidemiology, University Campus Bio-Medico, Rome, Italy

    Published Online:https://doi.org/10.2217/fmb-2019-0175

    Aim: The human gastrointestinal tract harbors diverse, abundant microbiota and Akkermansia muciniphila is involved in this community. The aim of this study is to characterize 16 new A. muciniphila 16S ribosomal RNA sequences selected from a metagenomic database from stools of patients with irritable bowel syndrome (IBS), inflammatory bowel diseases and control (CTRLs) subjects by a phylogenetic approach. Materials & methods: A phylogenetic approach was used to study the genetic diversity and SNPs in 16 A. muciniphila 16S ribosomal RNA sequences from stools of 107 individuals, 36 of which were patients affected by IBS, 30 by inflammatory bowel disease and 41 were CTRLs. Results: Phylogenetic analysis confirmed the subdivision into different supported clusters. An increase of variability in IBS has been identified. Conclusion: The genetic variation combined to the relative abundance, contribute to the protective role of A. muciniphila. Phylogenesis represent an additional approach to investigate genetic variability.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science 292(5519), 1115–1118 (2001). • Contains a detailed description of the interactions between bacteria and their hosts, in terms of a continuum between symbiosis, commensalism and pathogenicity. Describes the intestine as an arena for studying mutualistic relationships and the contributions of the commensal flora to pathologic states.
    • 2. Gómez-Gallego C, Pohl S, Salminen S, De Vos WM, Kneifel W. Akkermansia muciniphila: a novel functional microbe with probiotic properties. Benef. Microbes 7(4), 571–584 (2016).
    • 3. Derrien M, Collado MC, Ben-Amor K, Salminen S, de Vos WM. The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl. Environ. Microbiol. 74(5), 1646–1648 (2008).
    • 4. Le Chatelier E, Nielsen T, Qin J et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500(7464), 541–546 (2013).
    • 5. Falony G, Joossens M, Vieira-Silva S et al. Population-level analysis of gut microbiome variation. Science 352(6285), 560–564 (2016).
    • 6. Swidsinski A, Weber J, Loening-Baucke V, Hale LP, Lochs H. Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J. Clin. Microbiol. 43(7), 3380–3389 (2005).
    • 7. Rajilić-Stojanović M, Shanahan F, Guarner F, de Vos WM. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm. Bowel Dis. 19(3), 481–488 (2013).
    • 8. Png CW, Lindén SK, Gilshenan KS et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am. J. Gastroenterol. 105(11), 2420–2428 (2010). •• Provides a description of the increased prevalence of mucolytic bacteria in inflammatory bowel disease mucosa. Reported that among the most abundantly detected mucolytic bacterium, in controls, Akkermansia muciniphila, was found reduced many fold in Crohn’s disease and in ulcerative colitis. Relevant reference supporting our findings.
    • 9. Dao MC, Everard A, Aron-Wisnewsky J et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65(3), 426–436 (2016).
    • 10. Karlsson CLJ, Onnerfält J, Xu J, Molin G, Ahrné S, Thorngren-Jerneck K. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity (Silver Spring) 20(11), 2257–2261 (2012).
    • 11. Swidsinski A, Dörffel Y, Loening-Baucke V et al. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum. Gut 60(1), 34–40 (2011).
    • 12. Tan L, Zhao S, Zhu W et al. The Akkermansia muciniphila is a gut microbiota signature in psoriasis. Exp. Dermatol. 27(2), 144–149 (2018).
    • 13. Gobert AP, Sagrestani G, Delmas E et al. The human intestinal microbiota of constipated-predominant irritable bowel syndrome patients exhibits anti-inflammatory properties. Sci. Rep. 6(1), 39399 (2016). •• Contains experiments and description on the dysbiosis of intestinal microbiota of C-irritable bowel syndrome (IBS) patients. Relevant for this article mainly for the findings related to the increase of A. muciniphila in C-IBS patients compared with healthy individuals.
    • 14. Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS ONE 8(8), e70807083 (2013).
    • 15. Byrd JC, Bresalier RS. Mucins and mucin binding proteins in colorectal cancer. Cancer Metastasis Rev. 23(1–2), 77–99 (2004).
    • 16. Ottman N, Reunanen J, Meijerink M et al. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS ONE 12(3), e017300017304 (2017).
    • 17. Plovier H, Everard A, Druart C et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med. 23(1), 107–113 (2017).
    • 18. Derrien M, Belzer C, de Vos WM. Akkermansia muciniphila and its role in regulating host functions. Microb. Pathog. 106, 171–181 (2017).
    • 19. Everard A, Belzer C, Geurts L et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl Acad. Sci. USA 110(22), 9066–9071 (2013).
    • 20. Geerlings S, Kostopoulos I, de Vos W, Belzer C. Akkermansia muciniphila in the Human Gastrointestinal Tract: When, Where, and How? Microorganisms 6(3), 75 (2018).
    • 21. Neef A, Sanz Y. Future for probiotic science in functional food and dietary supplement development. Curr. Opin. Clin. Nutr. Metab. Care 16(6), 679–687 (2013).
    • 22. O’Toole PW, Marchesi JR, Hill C. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat. Microbiol. 2, 17051707 (2017).
    • 23. Zhang T, Li Q, Cheng L, Buch H, Zhang F. Akkermansia muciniphila is a promising probiotic. Microb. Biotechnol. 12(6), 1109–1125 (2019).
    • 24. Cani PD, de Vos WM. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front. Microbiol. 1765, 8 (2017).
    • 25. Depommier C, Everard A, Druart C et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat. Med. 25(7), 1096–1103 (2019).
    • 26. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448(7152), 427–434 (2007).
    • 27. Molodecky NA, Soon IS, Rabi DM et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142(1), 46.e42–54.e42; quiz e30 (2012).
    • 28. Zuo T, Ng SC. The gut microbiota in the pathogenesis and therapeutics of inflammatory bowel disease. Front. Microbiol. 2247, 9 (2018).
    • 29. Ng SC, Shi HY, Hamidi N et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 390(10114), 2769–2778 (2017).
    • 30. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 130(5), 1480–1491 (2006).
    • 31. Lacy BE, Patel NK. Rome criteria and a diagnostic approach to irritable bowel syndrome. J. Clin. Med. 6(11), 99 (2017). • Relevant for Rome criteria diagnostic approach in IBS.
    • 32. Lacy BE, Mearin F, Chang L et al. Bowel disorders. Gastroenterology 150(6), 1393.e5–1407.e5 (2016). • Relevant for Rome criteria diagnostic approach in IBS.
    • 33. Satsangi J, Silverberg MS, Vermeire S, Colombel J-F. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 55(6), 749–753 (2006). • Provides Montreal classification criteria for inflammatory bowel disease.
    • 34. Lo Presti A, Zorzi F, Del Chierico F et al. Fecal and mucosal microbiota profiling in irritable bowel syndrome and inflammatory bowel disease. Front. Microbiol. 1655, 10 (2019).
    • 35. Del Chierico F, Nobili V, Vernocchi P et al. Gut microbiota profiling of pediatric NAFLD and obese patients unveiled by an integrated meta-omics based approach. Hepatology 65(2), 451–464 (2016).
    • 36. Caporaso JG, Kuczynski J, Stombaugh J et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7(5), 335–336 (2010).
    • 37. Reeder J, Knight R. Rapidly denoising pyrosequencing amplicon reads by exploiting rank-abundance distributions. Nat. Methods 7(9), 668–669 (2010).
    • 38. Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26(19), 2460–2461 (2010).
    • 39. Navas-Molina JA, Peralta-Sánchez JM, González A et al. Advancing our understanding of the human microbiome using QIIME. Meth. Enzymol. 531, 371–444 (2013).
    • 40. Guo X, Li S, Zhang J 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(1), 800 (2017). •• Contains genome description and phylogeny of 39 A. muciniphila isolates in mammalian gut microbiotas.
    • 41. Derrien M, Belzer C, de Vos WM. Akkermansia muciniphila and its role in regulating host functions. Microb. Pathog. 106, 171–181 (2017).
    • 42. Hall T. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp. Ser. 41, 95–98 (1999).
    • 43. Posada D. jModelTest: phylogenetic model averaging. Mol. Biol. Evol. 25(7), 1253–1256 (2008).
    • 44. Strimmer K, von Haeseler A. Likelihood-mapping: a simple method to visualize phylogenetic content of a sequence alignment. Proc. Natl Acad. Sci. USA 94(13), 6815–6819 (1997).
    • 45. Lo Presti A, Ciccozzi M, Cella E et al. Origin, evolution, and phylogeography of recent epidemic CHIKV strains. Infect. Genet. Evol. 12(2), 392–398 (2012).
    • 46. Schmidt HA, Strimmer K, Vingron M, von Haeseler A. TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics 18(3), 502–504 (2002).
    • 47. Guindon S, Dufayard J-F, Lefort V, Anisimova M, Hordijk W, Gascuel O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 59(3), 307–321 (2010).
    • 48. Huelsenbeck JP, Ronquist F. MRBAYES: bayesian inference of phylogenetic trees. Bioinformatics 17(8), 754–755 (2001).
    • 49. Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 33(7), 1870–1874 (2016).
    • 50. Kearse M, Moir R, Wilson A et al. Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28(12), 1647–1649 (2012).
    • 51. Han XY. Bacterial identification based on 16S ribosomal RNA gene sequence analysis. In: Advanced Techniques in Diagnostic Microbiology. Tang Y-WStratton CW (Eds). Springer US, MA, USA, 323–332 (2006).
    • 52. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int. J. Syst. Evol. Microbiol. 54(Pt 5), 1469–1476 (2004).
    • 53. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell 148(6), 1258–1270 (2012).
    • 54. Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel diseases: current status and the future ahead. Gastroenterology 146(6), 1489–1499 (2014).
    • 55. Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J. Gastroenterol. 22(7), 2219–2241 (2016).
    • 56. Hayashi H, Sakamoto M, Benno Y. Phylogenetic analysis of the human gut microbiota using 16S rDNA clone libraries and strictly anaerobic culture-based methods. Microbiol. Immunol. 46(8), 535–548 (2002). •• Provides a description and phylogeny of human gut microbiota from healthy subjects compared by the use of sequence analysis of 16S.
    • 57. Kassinen A, Krogius-Kurikka L, Mäkivuokko H et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 133(1), 24–33 (2007). •• Relevant for the differences found between IBS patients and healthy subjects.
    • 58. Dunn KA, Moore-Connors J, MacIntyre B et al. Early changes in microbial community structure are associated with sustained remission after nutritional treatment of pediatric Crohn’s disease. Inflamm. Bowel Dis. 22(12), 2853–2862 (2016).
    • 59. de Meij TGJ, de Groot EFJ, Peeters CFW et al. Variability of core microbiota in newly diagnosed treatment-naïve paediatric inflammatory bowel disease patients. PLoS ONE 13(8), e019764019769 (2018).
    • 60. Lopez-Siles M, Enrich-Capó N, Aldeguer X et al. Alterations in the abundance and co-occurrence of Akkermansia muciniphila and Faecalibacterium prausnitzii in the colonic mucosa of inflammatory bowel disease subjects. Front. Cell. Infect. Microbiol. 281, 8 (2018).
    • 61. Ottman N, Geerlings SY, Aalvink S, de Vos WM, Belzer C. Action and function of Akkermansia muciniphila in microbiome ecology, health and disease. Best Pract. Res. Clin. Gastroenterol. 31(6), 637–642 (2017).
    • 62. Png CW, Lindén SK, Gilshenan KS et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am. J. Gastroenterol. 105(11), 2420–2428 (2010).
    • 63. Cao H, Liu X, An Y et al. Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine. Sci. Rep. 7, 10322 (2017).
    • 64. Awad M, Ouda O, El-Refy A, El-Feky FA, Mosa KA, Helmy M. FN-Identify: novel restriction enzymes-based method for bacterial identification in absence of genome sequencing. Adv. Bioinformatics 2015, 303605 (2015).
    • 65. Rossen NG, Fuentes S, van der Spek MJ et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149(1), 110.e4–118.e4 (2015).
    • 66. Moayyedi P, Surette MG, Kim PT et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149(1), 102.e6–109.e6 (2015). •• Relevant for the study of the new therapeutic approach in other words, fecal microbiota transplantation.
    • 67. Paramsothy S, Kamm MA, Kaakoush NO et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 389(10075), 1218–1228 (2017). •• Relevant for the study of the new therapeutic approach in other words, fecal microbiota transplantation.
    • 68. Kump P, Wurm P, Gröchenig HP et al. The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis. Aliment. Pharmacol. Ther. 47(1), 67–77 (2018).