Akkermansia muciniphila in the human gastrointestinal tract: When, where, and how?

Microorganisms

Volumn 6, Issue 3, 2018, Pages

  Geerlings, Sharon Y ^a   Kostopoulos, Ioannis ^a   de Vos, Willem M ^a,b   Belzer, Clara ^a  

^a WAGENINGEN UNIVERSITY   (Netherlands)

^b UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Akkermansia muciniphila; Digestive tract; Ecological niches; Gut microbiota; Human breast milk; Mucin

Indexed keywords

EID: 85074020628     PISSN: None     EISSN: 20762607     Source Type: Journal    
DOI: 10.3390/microorganisms6030075     Document Type: Review

References (186)

1. Blaser, M.J. The microbiome revolution. J. Clin. Investig. 2014, 124, 4162–4165. [CrossRef] [PubMed]
2. Verdu, E.F.; Galipeau, H.J.; Jabri, B. Novel players in coeliac disease pathogenesis: Role of the gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 2015, 12, 497–506. [CrossRef] [PubMed]
3. Distrutti, E.; Monaldi, L.; Ricci, P.; Fiorucci, S. Gut microbiota role in irritable bowel syndrome: New therapeutic strategies. World J. Gastroenterol. 2016, 22, 2219–2241. [CrossRef] [PubMed]
4. Lopez-Siles, M.; Martinez-Medina, M.; Busquets, D.; Sabat-Mir, M.; Duncan, S.H.; Flint, H.J.; Aldeguer, X.; Garcia-Gil, L.J. Mucosa-associated Faecalibacterium prausnitzii and Escherichia coli co-abundance can distinguish Irritable Bowel Syndrome and Inflammatory Bowel Disease phenotypes. Int. J. Med. Microbiol. 2014, 304, 464–475. [CrossRef] [PubMed]
5. Sheehan, D.; Moran, C.; Shanahan, F. The microbiota in inflammatory bowel disease. J. Gastroenterol. 2015, 50, 495–507. [CrossRef] [PubMed]
6. Png, C.W.; Linden, S.K.; Gilshenan, K.S.; Zoetendal, E.G.; McSweeney, C.S.; Sly, L.I.; McGuckin, M.A.; Florin, T.H. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am. J. Gastroenterol. 2010, 105, 2420–2428. [CrossRef] [PubMed]
7. Rajilic-Stojanovic, M.; Shanahan, F.; Guarner, F.; de Vos, W.M. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm. Bowel. Dis. 2013, 19, 481–488. [CrossRef] [PubMed]
8. Zhang, X.; Shen, D.; Fang, Z.; Jie, Z.; Qiu, X.; Zhang, C.; Chen, Y.; Ji, L. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS ONE 2013, 8, e71108. [CrossRef] [PubMed]
9. Schneeberger, M.; Everard, A.; Gomez-Valades, A.G.; Matamoros, S.; Ramirez, S.; Delzenne, N.M.; Gomis, R.; Claret, M.; Cani, P.D. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci. Rep. 2015, 5, 16643. [CrossRef] [PubMed]
10. Everard, A.; Belzer, C.; Geurts, L.; Ouwerkerk, J.P.; Druart, C.; Bindels, L.B.; Guiot, Y.; Derrien, M.; Muccioli, G.G.; Delzenne, N.M.; et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA 2013, 110, 9066–9071. [CrossRef] [PubMed]
11. 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. 2004, 54, 1469–1476. [CrossRef] [PubMed]
12. Van Passel, M.W.; Kant, R.; Zoetendal, E.G.; Plugge, C.M.; Derrien, M.; Malfatti, S.A.; Chain, P.S.; Woyke, T.; Palva, A.; de Vos, W.M.; et al. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS ONE 2011, 6, e16876. [CrossRef] [PubMed]
13. De Vos, W.M. Microbe Profile: Akkermansia muciniphila: A conserved intestinal symbiont that acts as the gatekeeper of our mucosa. Microbiology 2017, 163, 646–648. [CrossRef] [PubMed]
14. Swidsinski, A.; Dorffel, Y.; Loening-Baucke, V.; Theissig, F.; Ruckert, J.C.; Ismail, M.; Rau, W.A.; Gaschler, D.; Weizenegger, M.; Kuhn, S.; et al. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum. Gut 2011, 60, 34–40. [CrossRef] [PubMed]
15. Karlsson, C.L.; Onnerfalt, J.; Xu, J.; Molin, G.; Ahrne, S.; Thorngren-Jerneck, K. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity 2012, 20, 2257–2261. [CrossRef] [PubMed]
16. Dao, M.C.; Everard, A.; Aron-Wisnewsky, J.; Sokolovska, N.; Prifti, E.; Verger, E.O.; Kayser, B.D.; Levenez, F.; Chilloux, J.; Hoyles, L.; et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: Relationship with gut microbiome richness and ecology. Gut 2015, 65, 426–436. [CrossRef] [PubMed]
17. Korpela, K.; Salonen, A.; Virta, L.J.; Kekkonen, R.A.; Forslund, K.; Bork, P.; de Vos, W.M. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat. Commun. 2016, 7, 10410. [CrossRef] [PubMed]
18. Clarke, S.F.; Murphy, E.F.; O’Sullivan, O.; Lucey, A.J.; Humphreys, M.; Hogan, A.; Hayes, P.; O’Reilly, M.; Jeffery, I.B.; Wood-Martin, R.; et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 2014, 63, 1913–1920. [CrossRef] [PubMed]
19. Barton, W.; Penney, N.C.; Cronin, O.; Garcia-Perez, I.; Molloy, M.G.; Holmes, E.; Shanahan, F.; Cotter, P.D.; O’Sullivan, O. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut 2018, 67, 625–633. [CrossRef] [PubMed]
20. Derrien, M.; Van Baarlen, P.; Hooiveld, G.; Norin, E.; Muller, M.; de Vos, W.M. Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila. Front. Microbiol. 2011, 2, 166. [CrossRef] [PubMed]
21. Lukovac, S.; Belzer, C.; Pellis, L.; Keijser, B.J.; de Vos, W.M.; Montijn, R.C.; Roeselers, G. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. mBio 2014, 5, e01438-14. [CrossRef] [PubMed]
22. Desai, M.S.; Seekatz, A.M.; Koropatkin, N.M.; Kamada, N.; Hickey, C.A.; Wolter, M.; Pudlo, N.A.; Kitamoto, S.; Terrapon, N.; Muller, A.; et al. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell 2016, 167, 1339–1353. [CrossRef] [PubMed]
23. Makki, K.; Deehan, E.C.; Walter, J.; Backhed, F. The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease. Cell Host Microbe 2018, 23, 705–715. [CrossRef] [PubMed]
24. Reunanen, J.; Kainulainen, V.; Huuskonen, L.; Ottman, N.; Belzer, C.; Huhtinen, H.; de Vos, W.M.; Satokari, R. Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer. Appl. Environ. Microbiol. 2015, 81, 3655–3662. [CrossRef] [PubMed]
25. Ottman, N.; Huuskonen, L.; Reunanen, J.; Boeren, S.; Klievink, J.; Smidt, H.; Belzer, C.; de Vos, W.M. Characterization of Outer Membrane Proteome of Akkermansia muciniphila Reveals Sets of Novel Proteins Exposed to the Human Intestine. Front. Microbiol. 2016, 7, 1157. [CrossRef] [PubMed]
26. Ottman, N.; Reunanen, J.; Meijerink, M.; Pietila, T.E.; Kainulainen, V.; Klievink, J.; Huuskonen, L.; Aalvink, S.; Skurnik, M.; Boeren, S.; et al. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS ONE 2017, 12, e0173004. [CrossRef] [PubMed]
27. 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. 2007, 73, 7767–7770. [CrossRef] [PubMed]
28. 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. 2008, 74, 1646–1648. [CrossRef] [PubMed]
29. Grzeskowiak, L.; Gronlund, M.M.; Beckmann, C.; Salminen, S.; von Berg, A.; Isolauri, E. The impact of perinatal probiotic intervention on gut microbiota: Double-blind placebo-controlled trials in Finland and Germany. Anaerobe 2012, 18, 7–13. [CrossRef] [PubMed]
30. Grzeskowiak, L.; Collado, M.C.; Mangani, C.; Maleta, K.; Laitinen, K.; Ashorn, P.; Isolauri, E.; Salminen, S. Distinct gut microbiota in southeastern African and northern European infants. J. Pediatr. Gastroenterol. Nutr. 2012, 54, 812–816. [CrossRef] [PubMed]
31. De Weerth, C.; Fuentes, S.; Puylaert, P.; de Vos, W.M. Intestinal microbiota of infants with colic: Development and specific signatures. Pediatrics 2013. Available online: http://pediatrics.aappublications.org/content/early/2013/01/08/peds.2012-1449.short (accessed on 18 May 2018).
32. Biagi, E.; Nylund, L.; Candela, M.; Ostan, R.; Bucci, L.; Pini, E.; Nikkila, J.; Monti, D.; Satokari, R.; Franceschi, C.; et al. Through ageing, and beyond: Gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE 2010, 5, e10667. [CrossRef]
33. Biagi, E.; Franceschi, C.; Rampelli, S.; Severgnini, M.; Ostan, R.; Turroni, S.; Consolandi, C.; Quercia, S.; Scurti, M.; Monti, D.; et al. Gut Microbiota and Extreme Longevity. Curr. Biol. 2016, 26, 1480–1485. [CrossRef] [PubMed]
34. Momozawa, Y.; Deffontaine, V.; Louis, E.; Medrano, J.F. Characterization of bacteria in biopsies of colon and stools by high throughput sequencing of the V2 region of bacterial 16S rRNA gene in human. PLoS ONE 2011, 6, e16952. [CrossRef] [PubMed]
35. Li, J.; Jia, H.; Cai, X.; Zhong, H.; Feng, Q.; Sunagawa, S.; Arumugam, M.; Kultima, J.R.; Prifti, E.; Nielsen, T.; et al. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 2014, 32, 834–841. [CrossRef] [PubMed]
36. Smits, S.A.; Leach, J.; Sonnenburg, E.D.; Gonzalez, C.G.; Lichtman, J.S.; Reid, G.; Knight, R.; Manjurano, A.; Changalucha, J.; Elias, J.E.; et al. Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania. Science 2017, 357, 802–806. [CrossRef] [PubMed]
37. Costea, P.I.; Zeller, G.; Sunagawa, S.; Pelletier, E.; Alberti, A.; Levenez, F.; Tramontano, M.; Driessen, M.; Hercog, R.; Jung, F.E.; et al. Towards standards for human fecal sample processing in metagenomic studies. Nat. Biotechnol. 2017, 35, 1069–1076. [CrossRef] [PubMed]
38. Guo, X.; Zhang, J.; Wu, F.; Zhang, M.; Yi, M.; Peng, Y. Different subtype strains of Akkermansia muciniphila abundantly colonize in southern China. J. Appl. Microbiol. 2016, 120, 452–459. [CrossRef] [PubMed]
39. Guo, X.; Li, S.; Zhang, J.; Wu, F.; Li, X.; Wu, D.; Zhang, M.; Ou, Z.; Jie, Z.; Yan, Q.; 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 Genom. 2017, 18, 800. [CrossRef] [PubMed]
40. 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. 2016, 66, 4614–4620. [CrossRef] [PubMed]
41. Ouwerkerk, J.P.; Koehorst, J.J.; Schaap, P.J.; Ritari, J.; Paulin, L.; Belzer, C.; de Vos, W.M. Complete Genome Sequence of Akkermansia glycaniphila Strain PytT, a Mucin-Degrading Specialist of the Reticulated Python Gut. Genome Announc. 2017, 5, e01098-16. [CrossRef] [PubMed]
42. Ludwig, W.; Strunk, O.; Westram, R.; Richter, L.; Meier, H.; Yadhukumar, Y.; Buchner, A.; Lai, T.; Steppi, S.; Jobb, G.; et al. ARB: A software environment for sequence data. Nucleic Acids Res. 2004, 32, 1363–1371.
43. Ottman, N.; Davids, M.; Suarez-Diez, M.; Boeren, S.; Schaap, P.J.; Martins Dos Santos, V.A.P.; Smidt, H.; Belzer, C.; de Vos, W.M. Genome-Scale Model and Omics Analysis of Metabolic Capacities of Akkermansia muciniphila Reveal a Preferential Mucin-Degrading Lifestyle. Appl. Environ. Microbiol. 2017, 83, e01014-17. [CrossRef] [PubMed]
44. Ouwerkerk, J.P.; van der Ark, K.C.; Davids, M.; Claassens, N.J.; Robert Finestra, T.; de Vos, W.M.; Belzer, C. Adaptation of Akkermansia muciniphila to the oxic-anoxic interface of the mucus layer. Appl. Environ. Microbiol. 2016, 82, 6983–6993. [CrossRef] [PubMed]
45. Van der Ark, K.C.H.; Aalvink, S.; Suarez-Diez, M.; Schaap, P.J.; de Vos, W.M.; Belzer, C. Model-driven design of a minimal medium for Akkermansia muciniphila confirms mucus adaptation. Microb. Biotechnol. 2018, 11, 476–485. [CrossRef] [PubMed]
46. Van der Ark, K.C.H.; Nugroho, A.D.W.; Berton-Carabin, C.; Wang, C.; Belzer, C.; de Vos, W.M.; Schroen, K. Encapsulation of the therapeutic microbe Akkermansia muciniphila in a double emulsion enhances survival in simulated gastric conditions. Food Res. Int. 2017, 102, 372–379. [CrossRef] [PubMed]
47. Pierre, J.F.; Martinez, K.B.; Ye, H.; Nadimpalli, A.; Morton, T.C.; Yang, J.; Wang, Q.; Patno, N.; Chang, E.B.; Yin, D.P. Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2016, 311, G286–G304. [CrossRef] [PubMed]
48. Van der Ark, K. Metabolic Characterization and Viable Delivery of Akkermansia muciniphila for Its Future Application. Ph.D. Thesis, Wageningen University, Wageningen, The Netherlands, 2018.
49. Dubourg, G.; Lagier, J.C.; Armougom, F.; Robert, C.; Audoly, G.; Papazian, L.; Raoult, D. High-level colonisation of the human gut by Verrucomicrobia following broad-spectrum antibiotic treatment. Int. J. Antimicrob. Agents 2013, 41, 149–155. [CrossRef] [PubMed]
50. Dubourg, G.; Cornu, F.; Edouard, S.; Battaini, A.; Tsimaratos, M.; Raoult, D. First isolation of Akkermansia muciniphila in a blood-culture sample. Clin. Microbiol. Infect. 2017, 23, 682–683. [CrossRef] [PubMed]
51. Caputo, A.; Dubourg, G.; Croce, O.; Gupta, S.; Robert, C.; Papazian, L.; Rolain, J.M.; Raoult, D. Whole-genome assembly of Akkermansia muciniphila sequenced directly from human stool. Biol. Direct 2015, 10, 5. [CrossRef] [PubMed]
52. Espey, M.G. Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota. Free Radic. Biol. Med. 2013, 55, 130–140. [CrossRef] [PubMed]
53. Johansson, M.E.; Ambort, D.; Pelaseyed, T.; Schutte, A.; Gustafsson, J.K.; Ermund, A.; Subramani, D.B.; Holmen-Larsson, J.M.; Thomsson, K.A.; Bergstrom, J.H.; et al. Composition and functional role of the mucus layers in the intestine. Cell. Mol. Life Sci. 2011, 68, 3635–3641. [CrossRef] [PubMed]
54. Santiago, A.; Pozuelo, M.; Poca, M.; Gely, C.; Nieto, J.C.; Torras, X.; Roman, E.; Campos, D.; Sarrabayrouse, G.; Vidal, S.; et al. Alteration of the serum microbiome composition in cirrhotic patients with ascites. Sci. Rep. 2016, 6, 25001. [CrossRef] [PubMed]
55. Traykova, D.; Schneider, B.; Chojkier, M.; Buck, M. Blood Microbiome Quantity and the Hyperdynamic Circulation in Decompensated Cirrhotic Patients. PLoS ONE 2017, 12, e0169310. [CrossRef] [PubMed]
56. Gomez-Gallego, C.; Collado, M.C.; Perez, G.; Ilo, T.; Jaakkola, U.M.; Bernal, M.J.; Periago, M.J.; Frias, R.; Ros, G.; Salminen, S. Resembling breast milk: Influence of polyamine-supplemented formula on neonatal BALB/cOlaHsd mouse microbiota. Br. J. Nutr. 2014, 111, 1050–1058. [CrossRef] [PubMed]
57. Marcotte, H.; Lavoie, M.C. Oral microbial ecology and the role of salivary immunoglobulin A. Microbiol. Mol. Biol. Rev. 1998, 62, 71–109. [PubMed]
58. Aframian, D.J.; Davidowitz, T.; Benoliel, R. The distribution of oral mucosal pH values in healthy saliva secretors. Oral Dis. 2006, 12, 420–423. [CrossRef] [PubMed]
59. Aas, J.A.; Paster, B.J.; Stokes, L.N.; Olsen, I.; Dewhirst, F.E. Defining the normal bacterial flora of the oral cavity. J. Clin. Microbiol. 2005, 43, 5721–5732. [CrossRef] [PubMed]
60. Shaw, L.; Ribeiro, A.L.R.; Levine, A.P.; Pontikos, N.; Balloux, F.; Segal, A.W.; Roberts, A.P.; Smith, A.M. The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals. mBio 2017, 8, e01237-17. [CrossRef] [PubMed]
61. Bik, E.M.; Long, C.D.; Armitage, G.C.; Loomer, P.; Emerson, J.; Mongodin, E.F.; Nelson, K.E.; Gill, S.R.; Fraser-Liggett, C.M.; Relman, D.A. Bacterial diversity in the oral cavity of 10 healthy individuals. ISME J. 2010, 4, 962–974. [CrossRef] [PubMed]
62. Nasidze, I.; Quinque, D.; Li, J.; Li, M.; Tang, K.; Stoneking, M. Comparative analysis of human saliva microbiome diversity by barcoded pyrosequencing and cloning approaches. Anal. Biochem. 2009, 391, 64–68. [CrossRef] [PubMed]
63. Sarkar, A.; Stoneking, M.; Nandineni, M.R. Unraveling the human salivary microbiome diversity in Indian populations. PLoS ONE 2017, 12, e0184515. [CrossRef] [PubMed]
64. Leake, S.L.; Pagni, M.; Falquet, L.; Taroni, F.; Greub, G. The salivary microbiome for differentiating individuals: Proof of principle. Microbes Infect. 2016, 18, 399–405. [CrossRef] [PubMed]
65. Ye, F.; Shen, H.; Li, Z.; Meng, F.; Li, L.; Yang, J.; Chen, Y.; Bo, X.; Zhang, X.; Ni, M. Influence of the Biliary System on Biliary Bacteria Revealed by Bacterial Communities of the Human Biliary and Upper Digestive Tracts. PLoS ONE 2016, 11, e0150519. [CrossRef] [PubMed]
66. Marsh, P.D.; Head, D.A.; Devine, D.A. Ecological approaches to oral biofilms: Control without killing. Caries Res. 2015, 49 (Suppl. 1), 46–54. [CrossRef] [PubMed]
67. Linden, S.K.; Sutton, P.; Karlsson, N.G.; Korolik, V.; McGuckin, M.A. Mucins in the mucosal barrier to infection. Mucosal Immunol. 2008, 1, 183–197. [CrossRef] [PubMed]
68. Nielsen, P.A.; Bennett, E.P.; Wandall, H.H.; Therkildsen, M.H.; Hannibal, J.; Clausen, H. Identification of a major human high molecular weight salivary mucin (MG1) as tracheobronchial mucin MUC5B. Glycobiology 1997, 7, 413–419. [CrossRef] [PubMed]
69. Thornton, D.J.; Khan, N.; Mehrotra, R.; Howard, M.; Veerman, E.; Packer, N.H.; Sheehan, J.K. Salivary mucin MG1 is comprised almost entirely of different glycosylated forms of the MUC5B gene product. Glycobiology 1999, 9, 293–302. [CrossRef] [PubMed]
70. Van der Hoeven, J.S.; van den Kieboom, C.W.; Camp, P.J. Utilization of mucin by oral Streptococcus species. Antonie Leeuwenhoek 1990, 57, 165–172. [CrossRef] [PubMed]
71. Derrien, M.; van Passel, M.W.; van de Bovenkamp, J.H.; Schipper, R.G.; de Vos, W.M.; Dekker, J. Mucin-bacterial interactions in the human oral cavity and digestive tract. Gut Microbes 2010, 1, 254–268. [CrossRef] [PubMed]
72. Tan, G.D. The pancreas. Anaesth. Intensive Care Med. 2014, 15, 485–488. [CrossRef]
73. Leal-Lopes, C.; Velloso, F.J.; Campopiano, J.C.; Sogayar, M.C.; Correa, R.G. Roles of Commensal Microbiota in Pancreas Homeostasis and Pancreatic Pathologies. J. Diabetes Res. 2015, 2015, 284680. [CrossRef] [PubMed]
74. Jouvet, N.; Estall, J.L. The pancreas: Bandmaster of glucose homeostasis. Exp. Cell Res. 2017, 360, 19–23. [CrossRef] [PubMed]
75. Patel, A.G.; Toyama, M.T.; Alvarez, C.; Nguyen, T.N.; Reber, P.U.; Ashley, S.W.; Reber, H.A. Pancreatic interstitial pH in human and feline chronic pancreatitis. Gastroenterology 1995, 109, 1639–1645. [CrossRef]
76. Memba, R.; Duggan, S.N.; Ni Chonchubhair, H.M.; Griffin, O.M.; Bashir, Y.; O’Connor, D.B.; Murphy, A.; McMahon, J.; Volcov, Y.; Ryan, B.M.; et al. The potential role of gut microbiota in pancreatic disease: A systematic review. Pancreatology 2017, 17, 867–874. [CrossRef] [PubMed]
77. Rogers, M.B.; Aveson, V.; Firek, B.; Yeh, A.; Brooks, B.; Brower-Sinning, R.; Steve, J.; Banfield, J.F.; Zureikat, A.; Hogg, M.; et al. Disturbances of the Perioperative Microbiome Across Multiple Body Sites in Patients Undergoing Pancreaticoduodenectomy. Pancreas 2017, 46, 260–267. [CrossRef] [PubMed]
78. Nishiyama, H.; Nagai, T.; Kudo, M.; Okazaki, Y.; Azuma, Y.; Watanabe, T.; Goto, S.; Ogata, H.; Sakurai, T. Supplementation of pancreatic digestive enzymes alters the composition of intestinal microbiota in mice. Biochem. Biophys. Res. Commun. 2018, 495, 273–279. [CrossRef] [PubMed]
79. Boyer, J.L. Mechanisms of bile secretion and hepatic transport. In Physiology of Membrane Disorders; Andreoli, T.E., Hoffman, J.F., Fanestil, D.D., Schultz, S.G., Eds.; Springer: Boston, MA, USA, 1986; pp. 609–636.
80. Sutor, D.J.; Wilkie, L.I. Diurnal variations in the pH of pathological gallbladder bile. Gut 1976, 17, 971–974. [CrossRef] [PubMed]
81. Boyer, J.L. Bile formation and secretion. Compr. Physiol. 2013, 3, 1035–1078. [PubMed]
82. Islam, K.B.; Fukiya, S.; Hagio, M.; Fujii, N.; Ishizuka, S.; Ooka, T.; Ogura, Y.; Hayashi, T.; Yokota, A. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 2011, 141, 1773–1781. [CrossRef] [PubMed]
83. Inagaki, T.; Moschetta, A.; Lee, Y.K.; Peng, L.; Zhao, G.; Downes, M.; Yu, R.T.; Shelton, J.M.; Richardson, J.A.; Repa, J.J.; et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc. Natl. Acad. Sci. USA 2006, 103, 3920–3925. [CrossRef] [PubMed]
84. Gass, J.; Vora, H.; Hofmann, A.F.; Gray, G.M.; Khosla, C. Enhancement of dietary protein digestion by conjugated bile acids. Gastroenterology 2007, 133, 16–23. [CrossRef] [PubMed]
85. Hofmann, A.F. The enterohepatic circulation of bile acids in man. Adv. Intern. Med. 1976, 21, 501–534. [PubMed]
86. Csendes, A.; Fernandez, M.; Uribe, P. Bacteriology of the gallbladder bile in normal subjects. Am. J. Surg. 1975, 129, 629–631. [CrossRef]
87. Shen, H.; Ye, F.; Xie, L.; Yang, J.; Li, Z.; Xu, P.; Meng, F.; Li, L.; Chen, Y.; Bo, X.; et al. Metagenomic sequencing of bile from gallstone patients to identify different microbial community patterns and novel biliary bacteria. Sci. Rep. 2015, 5, 17450. [CrossRef] [PubMed]
88. Wu, T.; Zhang, Z.; Liu, B.; Hou, D.; Liang, Y.; Zhang, J.; Shi, P. Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study. BMC Genom. 2013, 14, 669. [CrossRef] [PubMed]
89. Pereira, P.; Aho, V.; Arola, J.; Boyd, S.; Jokelainen, K.; Paulin, L.; Auvinen, P.; Farkkila, M. Bile microbiota in primary sclerosing cholangitis: Impact on disease progression and development of biliary dysplasia. PLoS ONE 2017, 12, e0182924. [CrossRef] [PubMed]
90. Scheithauer, B.K.; Wos-Oxley, M.L.; Ferslev, B.; Jablonowski, H.; Pieper, D.H. Characterization of the complex bacterial communities colonizing biliary stents reveals a host-dependent diversity. ISME J. 2009, 3, 797–807. [CrossRef] [PubMed]
91. Stearns, J.C.; Lynch, M.D.; Senadheera, D.B.; Tenenbaum, H.C.; Goldberg, M.B.; Cvitkovitch, D.G.; Croitoru, K.; Moreno-Hagelsieb, G.; Neufeld, J.D. Bacterial biogeography of the human digestive tract. Sci. Rep. 2011, 1, 170. [CrossRef] [PubMed]
92. Belzer, C.; Kusters, J.G.; Kuipers, E.J.; van Vliet, A.H. Urease induced calcium precipitation by Helicobacter species may initiate gallstone formation. Gut 2006, 55, 1678–1679. [CrossRef] [PubMed]
93. Saltykova, I.V.; Petrov, V.A.; Logacheva, M.D.; Ivanova, P.G.; Merzlikin, N.V.; Sazonov, A.E.; Ogorodova, L.M.; Brindley, P.J. Biliary Microbiota, Gallstone Disease and Infection with Opisthorchis felineus. PLoS Negl. Trop. Dis. 2016, 10, e0004809. [CrossRef] [PubMed]
94. Fedorova, O.S.; Fedotova, M.M.; Sokolova, T.S.; Golovach, E.A.; Kovshirina, Y.V.; Ageeva, T.S.; Kovshirina, A.E.; Kobyakova, O.S.; Ogorodova, L.M.; Odermatt, P. Opisthorchis felineus infection prevalence in Western Siberia: A review of Russian literature. Acta Trop. 2018, 178, 196–204. [CrossRef] [PubMed]
95. Fanning, S.; Hall, L.J.; Cronin, M.; Zomer, A.; MacSharry, J.; Goulding, D.; Motherway, M.O.; Shanahan, F.; Nally, K.; Dougan, G.; et al. Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection. Proc. Natl. Acad. Sci. USA 2012, 109, 2108–2113. [CrossRef] [PubMed]
96. Ruas-Madiedo, P.; Gueimonde, M.; Arigoni, F.; de los Reyes-Gavilan, C.G.; Margolles, A. Bile affects the synthesis of exopolysaccharides by Bifidobacterium animalis. Appl. Environ. Microbiol. 2009, 75, 1204–1207. [CrossRef] [PubMed]
97. Gum, J.R., Jr.; Ho, J.J.; Pratt, W.S.; Hicks, J.W.; Hill, A.S.; Vinall, L.E.; Roberton, A.M.; Swallow, D.M.; Kim, Y.S. MUC3 human intestinal mucin. Analysis of gene structure, the carboxyl terminus, and a novel upstream repetitive region. J. Biol. Chem. 1997, 272, 26678–26686. [CrossRef] [PubMed]
98. Pigny, P.; Guyonnet-Duperat, V.; Hill, A.S.; Pratt, W.S.; Galiegue-Zouitina, S.; d’Hooge, M.C.; Laine, A.; Van-Seuningen, I.; Degand, P.; Gum, J.R.; et al. Human mucin genes assigned to 11p15.5: Identification and organization of a cluster of genes. Genomics 1996, 38, 340–352. [CrossRef] [PubMed]
99. Keates, A.C.; Nunes, D.P.; Afdhal, N.H.; Troxler, R.F.; Offner, G.D. Molecular cloning of a major human gall bladder mucin: Complete C-terminal sequence and genomic organization of MUC5B. Biochem. J. 1997, 324, 295–303. [CrossRef] [PubMed]
100. Yoo, K.S.; Choi, H.S.; Jun, D.W.; Lee, H.L.; Lee, O.Y.; Yoon, B.C.; Lee, K.G.; Paik, S.S.; Kim, Y.S.; Lee, J. MUC Expression in Gallbladder Epithelial Tissues in Cholesterol-Associated Gallbladder Disease. Gut Liver 2016, 10, 851–858. [CrossRef] [PubMed]
101. Zoetendal, E.G.; Raes, J.; van den Bogert, B.; Arumugam, M.; Booijink, C.C.; Troost, F.J.; Bork, P.; Wels, M.; de Vos, W.M.; Kleerebezem, M. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J. 2012, 6, 1415–1426. [CrossRef] [PubMed]
102. Savage, D.C. Microbial ecology of the gastrointestinal tract. Annu. Rev. Microbiol. 1977, 31, 107–133. [CrossRef] [PubMed]
103. Hung, G.U.; Tsai, C.C.; Lin, W.Y. Development of a new method for small bowel transit study. Ann. Nucl. Med. 2006, 20, 387–392. [CrossRef] [PubMed]
104. Ovesen, L.; Bendtsen, F.; Tage-Jensen, U.; Pedersen, N.T.; Gram, B.R.; Rune, S.J. Intraluminal pH in the stomach, duodenum, and proximal jejunum in normal subjects and patients with exocrine pancreatic insufficiency. Gastroenterology 1986, 90, 958–962. [CrossRef]
105. Koziolek, M.; Grimm, M.; Becker, D.; Iordanov, V.; Zou, H.; Shimizu, J.; Wanke, C.; Garbacz, G.; Weitschies, W. Investigation of pH and Temperature Profiles in the GI Tract of Fasted Human Subjects Using the Intellicap((R)) System. J. Pharm. Sci. 2015, 104, 2855–2863. [CrossRef] [PubMed]
106. Atuma, C.; Strugala, V.; Allen, A.; Holm, L. The adherent gastrointestinal mucus gel layer: Thickness and physical state in vivo. Am. J. Physiol. Gastrointest. Liver Physiol. 2001, 280, G922–G929. [CrossRef] [PubMed]
107. Johansson, M.E.; Phillipson, M.; Petersson, J.; Velcich, A.; Holm, L.; Hansson, G.C. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl. Acad. Sci. USA 2008, 105, 15064–15069. [CrossRef] [PubMed]
108. Sender, R.; Fuchs, S.; Milo, R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016, 14, e1002533. [CrossRef] [PubMed]
109. Donaldson, G.P.; Lee, S.M.; Mazmanian, S.K. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 2016, 14, 20–32. [CrossRef] [PubMed]
110. Morikawa, M.; Tsujibe, S.; Kiyoshima-Shibata, J.; Watanabe, Y.; Kato-Nagaoka, N.; Shida, K.; Matsumoto, S. Microbiota of the Small Intestine Is Selectively Engulfed by Phagocytes of the Lamina Propria and Peyer’s Patches. PLoS ONE 2016, 11, e0163607. [CrossRef] [PubMed]
111. Sundin, O.H.; Mendoza-Ladd, A.; Zeng, M.; Diaz-Arevalo, D.; Morales, E.; Fagan, B.M.; Ordonez, J.; Velez, P.; Antony, N.; McCallum, R.W. The human jejunum has an endogenous microbiota that differs from those in the oral cavity and colon. BMC Microbiol. 2017, 17, 160. [CrossRef] [PubMed]
112. Angelakis, E.; Armougom, F.; Carriere, F.; Bachar, D.; Laugier, R.; Lagier, J.C.; Robert, C.; Michelle, C.; Henrissat, B.; Raoult, D. A Metagenomic Investigation of the Duodenal Microbiota Reveals Links with Obesity. PLoS ONE 2015, 10, e0137784. [CrossRef] [PubMed]
113. Shanahan, E.R.; Zhong, L.; Talley, N.J.; Morrison, M.; Holtmann, G. Characterisation of the gastrointestinal mucosa-associated microbiota: A novel technique to prevent cross-contamination during endoscopic procedures. Aliment. Pharmacol. Ther. 2016, 43, 1186–1196. [CrossRef] [PubMed]
114. Li, E.; Hamm, C.M.; Gulati, A.S.; Sartor, R.B.; Chen, H.; Wu, X.; Zhang, T.; Rohlf, F.J.; Zhu, W.; Gu, C.; et al. Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition. PLoS ONE 2012, 7, e26284. [CrossRef] [PubMed]
115. Hartman, A.L.; Lough, D.M.; Barupal, D.K.; Fiehn, O.; Fishbein, T.; Zasloff, M.; Eisen, J.A. Human gut microbiome adopts an alternative state following small bowel transplantation. Proc. Natl. Acad. Sci. USA 2009, 106, 17187–17192. [CrossRef] [PubMed]
116. Haberman, Y.; Tickle, T.L.; Dexheimer, P.J.; Kim, M.O.; Tang, D.; Karns, R.; Baldassano, R.N.; Noe, J.D.; Rosh, J.; Markowitz, J.; et al. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. J. Clin. Investig. 2014, 124, 3617–3633. [CrossRef] [PubMed]
117. Dlugosz, A.; Winckler, B.; Lundin, E.; Zakikhany, K.; Sandstrom, G.; Ye, W.; Engstrand, L.; Lindberg, G. No difference in small bowel microbiota between patients with irritable bowel syndrome and healthy controls. Sci. Rep. 2015, 5, 8508. [CrossRef] [PubMed]
118. Chen, Y.; Ji, F.; Guo, J.; Shi, D.; Fang, D.; Li, L. Dysbiosis of small intestinal microbiota in liver cirrhosis and its association with etiology. Sci. Rep. 2016, 6, 34055. [CrossRef] [PubMed]
119. Assa, A.; Butcher, J.; Li, J.; Elkadri, A.; Sherman, P.M.; Muise, A.M.; Stintzi, A.; Mack, D. Mucosa-Associated Ileal Microbiota in New-Onset Pediatric Crohn’s Disease. Inflamm. Bowel. Dis. 2016, 22, 1533–1539. [CrossRef] [PubMed]
120. Li, G.; Yang, M.; Zhou, K.; Zhang, L.; Tian, L.; Lv, S.; Jin, Y.; Qian, W.; Xiong, H.; Lin, R.; et al. Diversity of Duodenal and Rectal Microbiota in Biopsy Tissues and Luminal Contents in Healthy Volunteers. J. Microbiol. Biotechnol. 2015, 25, 1136–1145. [CrossRef] [PubMed]
121. Wang, M.; Ahrne, S.; Jeppsson, B.; Molin, G. Comparison of bacterial diversity along the human intestinal tract by direct cloning and sequencing of 16S rRNA genes. FEMS Microbiol. Ecol. 2005, 54, 219–231. [CrossRef] [PubMed]
122. Rossen, N.G.; Fuentes, S.; Boonstra, K.; D’Haens, G.R.; Heilig, H.G.; Zoetendal, E.G.; de Vos, W.M.; Ponsioen, C.Y. The mucosa-associated microbiota of PSC patients is characterized by low diversity and low abundance of uncultured Clostridiales II. J. Crohns Colitis 2015, 9, 342–348. [CrossRef] [PubMed]
123. Patrascu, O.; Beguet-Crespel, F.; Marinelli, L.; Le Chatelier, E.; Abraham, A.L.; Leclerc, M.; Klopp, C.; Terrapon, N.; Henrissat, B.; Blottiere, H.M.; et al. A fibrolytic potential in the human ileum mucosal microbiota revealed by functional metagenomic. Sci. Rep. 2017, 7, 40248. [CrossRef] [PubMed]
124. Plovier, H.; Everard, A.; Druart, C.; Depommier, C.; Van Hul, M.; Geurts, L.; Chilloux, J.; Ottman, N.; Duparc, T.; Lichtenstein, L.; et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med. 2017, 23, 107–113. [CrossRef] [PubMed]
125. Macfarlane, G.T.; Macfarlane, S. Models for intestinal fermentation: Association between food components, delivery systems, bioavailability and functional interactions in the gut. Curr. Opin. Biotechnol. 2007, 18, 156–162. [CrossRef] [PubMed]
126. Madsen, J.L. Effects of gender, age, and body mass index on gastrointestinal transit times. Dig. Dis. Sci. 1992, 37, 1548–1553. [CrossRef] [PubMed]
127. Nugent, S.G.; Kumar, D.; Rampton, D.S.; Evans, D.F. Intestinal luminal pH in inflammatory bowel disease: Possible determinants and implications for therapy with aminosalicylates and other drugs. Gut 2001, 48, 571–577. [CrossRef] [PubMed]
128. McDougall, C.J.; Wong, R.; Scudera, P.; Lesser, M.; DeCosse, J.J. Colonic mucosal pH in humans. Dig. Dis. Sci. 1993, 38, 542–545. [CrossRef] [PubMed]
129. Johansson, M.E.; Larsson, J.M.; Hansson, G.C. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc. Natl. Acad. Sci. USA 2011, 108 (Suppl. 1), 4659–4665. [CrossRef] [PubMed]
130. Ambort, D.; Johansson, M.E.; Gustafsson, J.K.; Nilsson, H.E.; Ermund, A.; Johansson, B.R.; Koeck, P.J.; Hebert, H.; Hansson, G.C. Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin. Proc. Natl. Acad. Sci. USA 2012, 109, 5645–5650. [CrossRef] [PubMed]
131. Johansson, M.E.; Hansson, G.C. Immunological aspects of intestinal mucus and mucins. Nat. Rev. Immunol. 2016, 16, 639–649. [CrossRef] [PubMed]
132. Zhang, Z.; Geng, J.; Tang, X.; Fan, H.; Xu, J.; Wen, X.; Ma, Z.S.; Shi, P. Spatial heterogeneity and co-occurrence patterns of human mucosal-associated intestinal microbiota. ISME J. 2014, 8, 881–893. [CrossRef] [PubMed]
133. Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D.R.; Fernandes, G.R.; Tap, J.; Bruls, T.; Batto, J.M.; et al. Enterotypes of the human gut microbiome. Nature 2011, 473, 174–180. [CrossRef] [PubMed]
134. Costea, P.I.; Hildebrand, F.; Arumugam, M.; Backhed, F.; Blaser, M.J.; Bushman, F.D.; de Vos, W.M.; Ehrlich, S.D.; Fraser, C.M.; Hattori, M.; et al. Enterotypes in the landscape of gut microbial community composition. Nat. Microbiol. 2018, 3, 8–16. [CrossRef] [PubMed]
135. Walker, A.W.; Sanderson, J.D.; Churcher, C.; Parkes, G.C.; Hudspith, B.N.; Rayment, N.; Brostoff, J.; Parkhill, J.; Dougan, G.; Petrovska, L. High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol. 2011, 11, 7. [CrossRef] [PubMed]
136. Codling, C.; O’Mahony, L.; Shanahan, F.; Quigley, E.M.; Marchesi, J.R. A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome. Dig. Dis. Sci. 2010, 55, 392–397. [CrossRef] [PubMed]
137. Carroll, I.M.; Ringel-Kulka, T.; Siddle, J.P.; Ringel, Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol. Motil. 2012, 24, 521–530. [CrossRef] [PubMed]
138. Tap, J.; Derrien, M.; Tornblom, H.; Brazeilles, R.; Cools-Portier, S.; Dore, J.; Storsrud, S.; Le Neve, B.; Ohman, L.; Simren, M. Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome. Gastroenterology 2017, 152, 111–123. [CrossRef] [PubMed]
139. Ley, R.E.; Backhed, F.; Turnbaugh, P.; Lozupone, C.A.; Knight, R.D.; Gordon, J.I. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 2005, 102, 11070–11075. [CrossRef] [PubMed]
140. Schwiertz, A.; Taras, D.; Schafer, K.; Beijer, S.; Bos, N.A.; Donus, C.; Hardt, P.D. Microbiota and SCFA in lean and overweight healthy subjects. Obesity 2010, 18, 190–195. [CrossRef] [PubMed]
141. Qin, J.; Li, Y.; Cai, Z.; Li, S.; Zhu, J.; Zhang, F.; Liang, S.; Zhang, W.; Guan, Y.; Shen, D.; et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012, 490, 55–60. [CrossRef] [PubMed]
142. Cummings, J.H.; Macfarlane, G.T. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 1991, 70, 443–459. [CrossRef] [PubMed]
143. Clausen, M.R.; Mortensen, P.B. Kinetic studies on colonocyte metabolism of short chain fatty acids and glucose in ulcerative colitis. Gut 1995, 37, 684–689. [CrossRef] [PubMed]
144. Le Poul, E.; Loison, C.; Struyf, S.; Springael, J.Y.; Lannoy, V.; Decobecq, M.E.; Brezillon, S.; Dupriez, V.; Vassart, G.; Van Damme, J.; et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 2003, 278, 25481–25489. [CrossRef] [PubMed]
145. Brown, A.J.; Goldsworthy, S.M.; Barnes, A.A.; Eilert, M.M.; Tcheang, L.; Daniels, D.; Muir, A.I.; Wigglesworth, M.J.; Kinghorn, I.; Fraser, N.J.; et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 2003, 278, 11312–11319. [CrossRef] [PubMed]
146. Nilsson, N.E.; Kotarsky, K.; Owman, C.; Olde, B. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem. Biophys. Res. Commun. 2003, 303, 1047–1052. [CrossRef]
147. Flint, H.J.; Scott, K.P.; Louis, P.; Duncan, S.H. The role of the gut microbiota in nutrition and health. Nat. Rev. Gastroenterol. Hepatol. 2012, 9, 577–589. [CrossRef] [PubMed]
148. Possemiers, S.; Bolca, S.; Verstraete, W.; Heyerick, A. The intestinal microbiome: A separate organ inside the body with the metabolic potential to influence the bioactivity of botanicals. Fitoterapia 2011, 82, 53–66. [CrossRef] [PubMed]
149. Kamada, N.; Chen, G.Y.; Inohara, N.; Nunez, G. Control of pathogens and pathobionts by the gut microbiota. Nat. Immunol. 2013, 14, 685–690. [CrossRef] [PubMed]
150. McHardy, I.H.; Goudarzi, M.; Tong, M.; Ruegger, P.M.; Schwager, E.; Weger, J.R.; Graeber, T.G.; Sonnenburg, J.L.; Horvath, S.; Huttenhower, C.; et al. Integrative analysis of the microbiome and metabolome of the human intestinal mucosal surface reveals exquisite inter-relationships. Microbiome 2013, 1, 17. [CrossRef] [PubMed]
151. Lyra, A.; Forssten, S.; Rolny, P.; Wettergren, Y.; Lahtinen, S.J.; Salli, K.; Cedgard, L.; Odin, E.; Gustavsson, B.; Ouwehand, A.C. Comparison of bacterial quantities in left and right colon biopsies and faeces. World J. Gastroenterol. 2012, 18, 4404–4411. [CrossRef] [PubMed]
152. Hong, P.Y.; Croix, J.A.; Greenberg, E.; Gaskins, H.R.; Mackie, R.I. Pyrosequencing-based analysis of the mucosal microbiota in healthy individuals reveals ubiquitous bacterial groups and micro-heterogeneity. PLoS ONE 2011, 6, e25042. [CrossRef] [PubMed]
153. Sanapareddy, N.; Legge, R.M.; Jovov, B.; McCoy, A.; Burcal, L.; Araujo-Perez, F.; Randall, T.A.; Galanko, J.; Benson, A.; Sandler, R.S.; et al. Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans. ISME J. 2012, 6, 1858–1868. [CrossRef] [PubMed]
154. Belzer, C.; Chia, L.W.; Aalvink, S.; Chamlagain, B.; Piironen, V.; Knol, J.; de Vos, W.M. Microbial Metabolic Networks at the Mucus Layer Lead to Diet-Independent Butyrate and Vitamin B12 Production by Intestinal Symbionts. mBio 2017, 8, e00770-17. [CrossRef] [PubMed]
155. Derrien, M. Mucin Utilisation and Host Interactions of the Novel Intestinal Microbe Akkermansia muciniphila. Ph.D. Thesis, Wageningen University, Wageningen, The Netherlands, 2007.
156. Willis, C.L.; Cummings, J.H.; Neale, G.; Gibson, G.R. In VitroEffects of Mucin Fermentation on the Growth of Human Colonic Sulphate-Reducing Bacteria: Ecology. Anaerobe 1996, 2, 117–122. [CrossRef]
157. Ottman, N.; Geerlings, S.Y.; Aalvink, S.; de Vos, W.M.; Belzer, C. Action and function of Akkermansia muciniphila in microbiome ecology, health and disease. Best Pract. Res. Clin. Gastroenterol. 2017, 31, 637–642. [CrossRef] [PubMed]
158. Randal Bollinger, R.; Barbas, A.S.; Bush, E.L.; Lin, S.S.; Parker, W. Biofilms in the large bowel suggest an apparent function of the human vermiform appendix. J. Theor. Biol. 2007, 249, 826–831. [CrossRef] [PubMed]
159. Darwin, C. The Descent of Man and Selection in Relation to Sex Darwin; John Murray: London, UK, 1871.
160. Smith, H.F.; Parker, W.; Kotzé, S.H.; Laurin, M. Multiple independent appearances of the cecal appendix in mammalian evolution and an investigation of related ecological and anatomical factors. C. R. Palevol. 2013, 12, 339–354. [CrossRef]
161. Berry, R.J. The True Caecal Apex, or the Vermiform Appendix: Its Minute and Comparative Anatomy. J. Anat. Physiol. 1900, 35, 83–100. [PubMed]
162. Merchant, H.A.; McConnell, E.L.; Liu, F.; Ramaswamy, C.; Kulkarni, R.P.; Basit, A.W.; Murdan, S. Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development. Eur. J. Pharm. Sci. 2011, 42, 3–10. [CrossRef] [PubMed]
163. Zhong, D.; Brower-Sinning, R.; Firek, B.; Morowitz, M.J. Acute appendicitis in children is associated with an abundance of bacteria from the phylum Fusobacteria. J. Pediatr. Surg. 2014, 49, 441–446. [CrossRef] [PubMed]
164. Jackson, H.T.; Mongodin, E.F.; Davenport, K.P.; Fraser, C.M.; Sandler, A.D.; Zeichner, S.L. Culture-independent evaluation of the appendix and rectum microbiomes in children with and without appendicitis. PLoS ONE 2014, 9, e95414. [CrossRef] [PubMed]
165. Salo, M.; Marungruang, N.; Roth, B.; Sundberg, T.; Stenstrom, P.; Arnbjornsson, E.; Fak, F.; Ohlsson, B. Evaluation of the microbiome in children’s appendicitis. Int. J. Colorectal. Dis. 2017, 32, 19–28. [CrossRef] [PubMed]
166. Guinane, C.M.; Tadrous, A.; Fouhy, F.; Ryan, C.A.; Dempsey, E.M.; Murphy, B.; Andrews, E.; Cotter, P.D.; Stanton, C.; Ross, R.P. Microbial composition of human appendices from patients following appendectomy. mBio 2013, 4, e00366-12. [CrossRef] [PubMed]
167. Bode, L. Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology 2012, 22, 1147–1162. [CrossRef] [PubMed]
168. Zivkovic, A.M.; German, J.B.; Lebrilla, C.B.; Mills, D.A. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc. Natl. Acad. Sci. USA 2011, 108 (Suppl. 1), 4653–4658. [CrossRef] [PubMed]
169. Bidart, G.N.; Rodriguez-Diaz, J.; Monedero, V.; Yebra, M.J. A unique gene cluster for the utilization of the mucosal and human milk-associated glycans galacto-N-biose and lacto-N-biose in Lactobacillus casei. Mol. Microbiol. 2014, 93, 521–538. [CrossRef] [PubMed]
170. Jost, T.; Lacroix, C.; Braegger, C.; Chassard, C. Impact of human milk bacteria and oligosaccharides on neonatal gut microbiota establishment and gut health. Nutr. Rev. 2015, 73, 426–437. [CrossRef] [PubMed]
171. Newburg, D.S. Oligosaccharides in human milk and bacterial colonization. J. Pediatr. Gastroenterol. Nutr. 2000, 30 (Suppl. 2), S8–S17. [CrossRef] [PubMed]
172. Collado, M.C.; Laitinen, K.; Salminen, S.; Isolauri, E. Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk. Pediatr. Res. 2012, 72, 77–85. [CrossRef] [PubMed]
173. Aakko, J.; Kumar, H.; Rautava, S.; Wise, A.; Autran, C.; Bode, L.; Isolauri, E.; Salminen, S. Human milk oligosaccharide categories define the microbiota composition in human colostrum. Benef. Microbes 2017, 8, 563–567. [CrossRef] [PubMed]
174. Urbaniak, C.; Cummins, J.; Brackstone, M.; Macklaim, J.M.; Gloor, G.B.; Baban, C.K.; Scott, L.; O’Hanlon, D.M.; Burton, J.P.; Francis, K.P.; et al. Microbiota of human breast tissue. Appl. Environ. Microbiol. 2014, 80, 3007–3014. [CrossRef] [PubMed]
175. Koropatkin, N.M.; Cameron, E.A.; Martens, E.C. How glycan metabolism shapes the human gut microbiota. Nat. Rev. Microbiol. 2012, 10, 323–335. [CrossRef] [PubMed]
176. Tailford, L.E.; Crost, E.H.; Kavanaugh, D.; Juge, N. Mucin glycan foraging in the human gut microbiome. Front. Genet. 2015, 6, 81. [CrossRef] [PubMed]
177. Ottman, N. Host Immunostimulation and Substrate Utilization of the Gut Symbiont Akkermansia muciniphila. Ph.D. Thesis, Wageningen University, Wageningen, The Netherlands, 2015.
178. Mateo Anson, N.; van den Berg, R.; Havenaar, R.; Bast, A.; Haenen, G.R.M.M. Bioavailability of ferulic acid is determined by its bioaccessibility. J. Cereal Sci. 2009, 49, 296–300. [CrossRef]
179. Rajilic-Stojanovic, M.; Maathuis, A.; Heilig, H.G.; Venema, K.; de Vos, W.M.; Smidt, H. Evaluating the microbial diversity of an in vitro model of the human large intestine by phylogenetic microarray analysis. Microbiology 2010, 156, 3270–3281. [CrossRef] [PubMed]
180. Molly, K.; Vande Woestyne, M.; Verstraete, W. Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem. Appl. Microbiol. Biotechnol. 1993, 39, 254–258. [CrossRef] [PubMed]
181. Van den Abbeele, P.; Roos, S.; Eeckhaut, V.; MacKenzie, D.A.; Derde, M.; Verstraete, W.; Marzorati, M.; Possemiers, S.; Vanhoecke, B.; Van Immerseel, F.; et al. Incorporating a mucosal environment in a dynamic gut model results in a more representative colonization by lactobacilli. Microb. Biotechnol. 2012, 5, 106–115. [CrossRef] [PubMed]
182. Van den Abbeele, P.; Grootaert, C.; Marzorati, M.; Possemiers, S.; Verstraete, W.; Gérard, P.; Rabot, S.; Bruneau, A.; El Aidy, S.; Derrien, M.; et al. Microbial Community Development in a Dynamic Gut Model Is Reproducible, Colon Region Specific, and Selective for Bacteroidetes and Clostridium Cluster IX. Appl. Environ. Microbiol. 2010, 76, 5237–5246. [CrossRef] [PubMed]
183. Van Herreweghen, F.; Van den Abbeele, P.; De Mulder, T.; De Weirdt, R.; Geirnaert, A.; Hernandez-Sanabria, E.; Vilchez-Vargas, R.; Jauregui, R.; Pieper, D.H.; Belzer, C.; et al. In vitro colonisation of the distal colon by Akkermansia muciniphila is largely mucin and pH dependent. Benef. Microbes 2017, 8, 81–96. [CrossRef] [PubMed]
184. Kemperman, R.A.; Gross, G.; Mondot, S.; Possemiers, S.; Marzorati, M.; Van de Wiele, T.; Doré, J.; Vaughan, E.E. Impact of polyphenols from black tea and red wine/grape juice on a gut model microbiome. Food Res. Int. 2013, 53, 659–669. [CrossRef]
185. Garcia-Villalba, R.; Vissenaekens, H.; Pitart, J.; Romo-Vaquero, M.; Espin, J.C.; Grootaert, C.; Selma, M.V.; Raes, K.; Smagghe, G.; Possemiers, S.; et al. Gastrointestinal Simulation Model TWIN-SHIME Shows Differences between Human Urolithin-Metabotypes in Gut Microbiota Composition, Pomegranate Polyphenol Metabolism, and Transport along the Intestinal Tract. J. Agric. Food Chem. 2017, 65, 5480–5493. [CrossRef] [PubMed]
186. Van den Abbeele, P.; Belzer, C.; Goossens, M.; Kleerebezem, M.; De Vos, W.M.; Thas, O.; De Weirdt, R.; Kerckhof, F.M.; Van de Wiele, T. Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model. ISME J. 2013, 7, 949–961. [CrossRef] [PubMed]