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. 2013 May 18;4(6):403–414. doi: 10.1007/s13238-013-3017-x

The role of gut microbiota in the gut-brain axis: current challenges and perspectives

Xiao Chen 1, Roshan D’Souza 2, Seong-Tshool Hong 1,✉
PMCID: PMC4875553  PMID: 23686721

Abstract

Brain and the gastrointestinal (GI) tract are intimately connected to form a bidirectional neurohumoral communication system. The communication between gut and brain, knows as the gut-brain axis, is so well established that the functional status of gut is always related to the condition of brain. The researches on the gut-brain axis were traditionally focused on the psychological status affecting the function of the GI tract. However, recent evidences showed that gut microbiota communicates with the brain via the gut-brain axis to modulate brain development and behavioral phenotypes. These recent findings on the new role of gut microbiota in the gut-brain axis implicate that gut microbiota could associate with brain functions as well as neurological diseases via the gut-brain axis. To elucidate the role of gut microbiota in the gut-brain axis, precise identification of the composition of microbes constituting gut microbiota is an essential step. However, identification of microbes constituting gut microbiota has been the main technological challenge currently due to massive amount of intestinal microbes and the difficulties in culture of gut microbes. Current methods for identification of microbes constituting gut microbiota are dependent on omics analysis methods by using advanced high tech equipment. Here, we review the association of gut microbiota with the gut-brain axis, including the pros and cons of the current high throughput methods for identification of microbes constituting gut microbiota to elucidate the role of gut microbiota in the gut-brain axis.

Keywords: gut microbiota, the gut-brain axis, central nervous system, high throughput methods, next-generation sequencings

Footnotes

These authors contributed equally to the work.

References

  1. Albesharat R, Ehrmann MA, Korakli M, Yazaji S, Vogel RF. Phenotypic and genotypic analyses of lactic acid bacteria in local fermented food, breast milk and feces of mothers and their babies. Syst Appl Microbiol. 2011;34:148–155. doi: 10.1016/j.syapm.2010.12.001. [DOI] [PubMed] [Google Scholar]
  2. Andrew JW. The gut-brain axis in childhood developmental disorders. J Pediatr Gastroenterol Nutr. 2002;34:S14–17. doi: 10.1097/00005176-200205001-00004. [DOI] [PubMed] [Google Scholar]
  3. Angelakis E, Million M, Henry M, Raoult D. Rapid and accurate bacterial identification in probiotics and yoghurts by MALDI-TOF mass spectrometry. J Food Sci. 2011;76:M568–572. doi: 10.1111/j.1750-3841.2011.02369.x. [DOI] [PubMed] [Google Scholar]
  4. Anhalt JP, Fenselau C. Identification of bacteria using mass spectrometry. Anal Chem. 1975;47:219–225. doi: 10.1021/ac60352a007. [DOI] [Google Scholar]
  5. Barbara G, Brummer RJ, Delzenne N. Consensus Report. Warsaw. 2007. Investigating the crosstalk between the gut microbiota and the host: the gut-brain axis. [Google Scholar]
  6. Ben XM, Li J. Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli. World J Gastroenterol. 2008;14:6564–6568. doi: 10.3748/wjg.14.6564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Beraza N, Trautwein C. The Gut-Brain-Liver Axis: A New Option to Treat Obesity and Diabetes? Hepatology. 2008;48:1011–1013. doi: 10.1002/hep.22478. [DOI] [PubMed] [Google Scholar]
  8. Bercik P, Collins SM, Verdu EF. Microbes and the gutbrain axis. Neurogastroenterol Motil. 2012;224:405–413. doi: 10.1111/j.1365-2982.2012.01906.x. [DOI] [PubMed] [Google Scholar]
  9. Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, Deng Y, Blennerhassett P, Macri J, McCoy KD, et al. The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice. Gastroenterology. 2011;141:599–609. doi: 10.1053/j.gastro.2011.04.052. [DOI] [PubMed] [Google Scholar]
  10. Bishop R. Applications of fluorescence in situ hybridization (FISH) in detecting genetic aberrations of medical significance. Biosci Horizons. 2010;3:95–85. doi: 10.1093/biohorizons/hzq009. [DOI] [Google Scholar]
  11. Blaut M, Collins MD, Welling GW, Doré J, van L.J., de Vos W. Molecular methods for the analysis of gut microbiota. Microbial Ecology Health Disease. 2004;16:71–85. doi: 10.1080/08910600410032367. [DOI] [Google Scholar]
  12. Bocci V. The neglected organ: bacterial flora has a crucial immunostimulatory role. Perspect Biol Med. 1992;35:251–260. doi: 10.1353/pbm.1992.0004. [DOI] [PubMed] [Google Scholar]
  13. Brian W P, Elizabeth N, Elin O, Emrah K, Frode N, Simon TH, Calvin P, Mete C, Christoph DR, Brian JB, et al. Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice. Cell Metab. 2013;17:141–152. doi: 10.1016/j.cmet.2012.12.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Burcelin R, Serino M, Chabo C, Blasco-Baque V, Amar J. Gut microbiota and diabetes: from pathogenesis to therapeutic perspective. Acta Diabetol. 2011;4:257–273. doi: 10.1007/s00592-011-0333-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cattell M, Lai S, Cerny R, Medeiros DM. A new mechanistic scenario for the origin and evolution of vertebrate cartilage. PLoS ONE. 2011;6:e22474. doi: 10.1371/journal.pone.0022474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cecilia J, Sonja L. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology. 2010;156:113216–3223. doi: 10.1099/mic.0.040618-0. [DOI] [PubMed] [Google Scholar]
  17. Chong BE, Wall DB, Lubman DM, Flynn SJ. Rapid profiling of E. coli proteins up to 500 kDa from whole cell lysates using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom. 1997;11:1900–1908. doi: 10.1002/(SICI)1097-0231(199711)11:17<1900::AID-RCM95>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
  18. Claesson MJ, O’Sullivan O, Wang Q, Nikkilä J, Marchesi JR, Smidt H, De Vos WM, Ross RP, O’Toole PW. Comparative analysis of Pyrosequencing and a phylogenetic microarray for exploring microbial community structures in the human distal intestine. PLoS One. 2009;4:e6669. doi: 10.1371/journal.pone.0006669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Claesson MJ, Wang Q, O’Sullivan O, Greene-Diniz R, Cole JR, Ross RP, O’Toole PW. Comparison of two nextgeneration sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions. Nucleic Acids Res. 2010;38:e200. doi: 10.1093/nar/gkq873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Claydon MA, Davey SN, Edwards JV, Gordon DB. The rapid identification of intact microorganisms using mass spectrometry. Nat Biotechnol. 1996;14:1584–1586. doi: 10.1038/nbt1196-1584. [DOI] [PubMed] [Google Scholar]
  21. Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr. 2008;88:894–899. doi: 10.1093/ajcn/88.4.894. [DOI] [PubMed] [Google Scholar]
  22. Collins SM, Surette M, Bercik P. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol. 2012;10:735–742. doi: 10.1038/nrmicro2876. [DOI] [PubMed] [Google Scholar]
  23. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behavior. Nat Rev Neurosci. 2012;13:701–712. doi: 10.1038/nrn3346. [DOI] [PubMed] [Google Scholar]
  24. Cryan JF, O’Mahony SM. The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterol Motil. 2011;23:187–192. doi: 10.1111/j.1365-2982.2010.01664.x. [DOI] [PubMed] [Google Scholar]
  25. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43:164–174. doi: 10.1016/j.jpsychires.2008.03.009. [DOI] [PubMed] [Google Scholar]
  26. Dethlefsen L, Sue H, Mitchell LS, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6:e280. doi: 10.1371/journal.pbio.0060280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Dumont MG, Neufeld JD, Murrell JC. Isotopes as tools for microbial ecologists. Curr Opin Biotech. 2006;17:57–58. doi: 10.1016/j.copbio.2006.01.004. [DOI] [Google Scholar]
  28. Eckburg PB, Elisabeth MB, Charles NB, Elizabeth P, Dethlefsen L, Sargent M, Gill RS, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–1638. doi: 10.1126/science.1110591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zhang S M, Tian F, Huang Q F, Zhao Y F, Guo X K, Zhang F Q. Bacterial diversity of subgingival plaque in 6 healthy Chinese individuals. Exp Ther Med. 2011;2:1023–1029. doi: 10.3892/etm.2011.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, McTeague M, Sandler R, Wexler H, Marlowe EM, et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002;35:S6–16. doi: 10.1086/341914. [DOI] [PubMed] [Google Scholar]
  31. Fredrik B, Ruth EL, Justin LS, Daniel AP, Jeffrey IG. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915–1920. doi: 10.1126/science.1104816. [DOI] [PubMed] [Google Scholar]
  32. Gill SR, Pop M, DeBoy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman DA, Fraser-Liggett CM, Karen E. Nelson metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355–1359. doi: 10.1126/science.1124234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Greenblum S, Turnbaugh PJ, Borenstein E. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease. Proc Natl Acad Sci U S A. 2012;109:594–599. doi: 10.1073/pnas.1116053109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Greiner T, Bäckhed F. Effects of the gut microbiota on obesity and glucose homeostasis. Trends Endocrinol Metab. 2011;22:117–123. doi: 10.1016/j.tem.2011.01.002. [DOI] [PubMed] [Google Scholar]
  35. Hamady M, Walker JJ, Harris JK, Gold NJ, Knight R. Error correcting barcoded primers for pyrosequencing hundreds of samples in multiplex. Nat Methods. 2008;5:235–237. doi: 10.1038/nmeth.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. He Z, Gentry TJ, Schadt CW, Wu L, Liebich J, Chong SC, Huang Z, Wu W, Gu B, Jardine P, et al. GeoChip: a comprehensive microarray for investigating biogeochemical, ecological and environmental processes. ISME J. 2007;1:67–77. doi: 10.1038/ismej.2007.2. [DOI] [PubMed] [Google Scholar]
  37. Heijtz RD, Wang S, Anuar F, Qian Y, Björkholm B, Samuelsson A, Hibberd ML, Forssberg H, Pettersson S. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A. 2011;108:3047–3052. doi: 10.1073/pnas.1010529108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Hernandez-Sanabria E, Guan LL, Laksiri A, Li M, Mujibi DF, Stothard P, Moore SS, Leon-Quintero MC. Correlation of particular bacterial PCR-denaturing gradient gel electrophoresis patterns with bovine ruminal fermentation parameters and feed efficiency traits. App Envior Biol. 2010;76:6338–6350. doi: 10.1128/AEM.01052-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Holland RD, Wilkes JG, Rafii F, Sutherland JB, Persons CC, Voorhees KJ, Lay JO., Jr. Rapid identification of intact whole bacteria based on spectral patterns using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry. Rapid Commun Mass Spectrom. 1996;10:1227–1232. doi: 10.1002/(SICI)1097-0231(19960731)10:10<1227::AID-RCM659>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  40. Hopkins MJ, Sharp R. Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles. Gut. 2001;48:198–205. doi: 10.1136/gut.48.2.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Huang WE, Stoecker K, Griffiths R, Newbold L, Daims H, Whiteley AS, Wagner M. Raman-fish: Combining stableisotope Raman spectroscopy and fluorescence in situ hybridization for the single cell analysis of identity and function. Environ Microbiol. 2007;9:1878–1889. doi: 10.1111/j.1462-2920.2007.01352.x. [DOI] [PubMed] [Google Scholar]
  42. Jock S, Geider K. Molecular differentiation of Erwinia amylovora strains from North America and of two Asian pear pathogens by analyses of PFGE patterns and hrpN genes. Environ Microbiol. 2004;6:480–490. doi: 10.1111/j.1462-2920.2004.00583.x. [DOI] [PubMed] [Google Scholar]
  43. Kim PI, Erickson BD, Cerniglia CE. A membranearray method to detect specific human intestinal bacteria in fecal samples using reverse transcriptase-PCR and chemiluminescence. J Microbiol Biotechnol. 2005;15:310–320. [Google Scholar]
  44. Krishnamurthy T, Ross PL. Rapid identification of bacteria by direct matrix-assisted laser desorption/ionization mass spectrometric analysis of whole cells. Rapid Commun Mass Spectrom. 1996;10:1992–1996. doi: 10.1002/(SICI)1097-0231(199612)10:15<1992::AID-RCM789>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
  45. Kurz CM, Moosdijk SV, Thielecke H, Velten T. Conf Proc IEEE Eng Med Biol Soc. 2011. Towards a cellular multi-parameter analysis platform: fluorescence in situ hybridization (FISH) on microhole-array chips; pp. 8408–8411. [DOI] [PubMed] [Google Scholar]
  46. Kuypers MMM, Jørgensen BB. The future of single-cell environmental microbiology. Environ Microbiol. 2007;9:6–7. doi: 10.1111/j.1462-2920.2006.01222_5.x. [DOI] [PubMed] [Google Scholar]
  47. Lagier JC, Million M, Hugon P, Armougom F, Raoult D. Human Gut Microbiota: Repertoire and Variations. Front Cell Infect Microbiol. 2012;2:136. doi: 10.3389/fcimb.2012.00136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Lewis S, Cochrane S. Alteration of sulfate and hydrogen metabolism in the human colon by changing intestinal transit rate. Am J Gastroenterol. 2007;102:624–633. doi: 10.1111/j.1572-0241.2006.01020.x. [DOI] [PubMed] [Google Scholar]
  49. Lotta N, Reetta S, Janne N. Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease. BMC Microbiology. 2013;13:12. doi: 10.1186/1471-2180-13-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Loy A, Lehner A, Lee N. Oligonucleotide microarray for 16S rRNA gene-based detection of all recognized lineages of sulfate-reducing prokaryotes in the environment. Appl Environ Microbiol. 2002;68:5064–5081. doi: 10.1128/AEM.68.10.5064-5081.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Manco M. Gut microbiota and developmental programming of the brain: from evidence in behavioral endophenotypes to novel perspective in obesity. Front Cell Inf Microbio. 2012;2:109. doi: 10.3389/fcimb.2012.00109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Migrenne S, Marsollier N, Cruciani-Guglielmacci C, Magnan C. Importance of the gut-brain axis in the control of glucose Homeostasis. Curr Opin Pharmacol. 2006;6:592–597. doi: 10.1016/j.coph.2006.08.004. [DOI] [PubMed] [Google Scholar]
  53. Musso G, Gambino M, Cassader M. Obesity, diabetes, and gut microbiota. Diabetes Care. 2010;33:2277–2284. doi: 10.2337/dc10-0556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Neufeld KM, Kang N, Bienenstock J, Foster JA. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil. 2011;23:255–264. doi: 10.1111/j.1365-2982.2010.01620.x. [DOI] [PubMed] [Google Scholar]
  55. Nordlie RC, Foster JD. Regulation of glucose production by the liver. Annu Rev Nutr. 1999;19:379–406. doi: 10.1146/annurev.nutr.19.1.379. [DOI] [PubMed] [Google Scholar]
  56. Paliy O, Kenche H, Abernathy F, Michail S. Highthroughput quantitative analysis of the human intestinal microbiota with a phylogenetic microarray. Appl Environ Microbiol. 2009;75:3572–3579. doi: 10.1128/AEM.02764-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Palmer C, Bik EM, DiGiulio DB. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5:e177. doi: 10.1371/journal.pbio.0050177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Palmer C, Bik EM, Eisen MB. Rapid quantitative profiling of complex microbial populations. Nucleic Acids Res. 2006;34:e5. doi: 10.1093/nar/gnj007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Peterson DA, Frank DN, Pace NR, Gordon JI. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe. 2008;3:417–427. doi: 10.1016/j.chom.2008.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Rakoff NS, Paglino J, Eslami VF, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229–241. doi: 10.1016/j.cell.2004.07.002. [DOI] [PubMed] [Google Scholar]
  61. Sam AH, Troke RC, Tan TM, Bewick GA. The role of the gut/brain axis in modulating food intake. Neuropharmacology. 2012;63:46–56. doi: 10.1016/j.neuropharm.2011.10.008. [DOI] [PubMed] [Google Scholar]
  62. Savage DC. Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol. 1977;31:107–133. doi: 10.1146/annurev.mi.31.100177.000543. [DOI] [PubMed] [Google Scholar]
  63. Shanahan F. The host-microbe interface within the gut. Best Pract Res Clin Gastroenterol. 2002;16:915–931. doi: 10.1053/bega.2002.0342. [DOI] [PubMed] [Google Scholar]
  64. Sintchenko V, Iredell JR, Gilbert GL. Pathogen profiling for disease management and surveillance. Nat Rev Microbiol. 2007;5:464–470. doi: 10.1038/nrmicro1656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Sogin LM, Morrison HG, Huber JA, Welch DM, Huse SM, Neal PR, Arrieta JM, Herndl JG. Microbial diversity in the deep sea and the underexplored “rare biosphere”. Proc Natl Acad Sci U S A. 2006;103:12115–12120. doi: 10.1073/pnas.0605127103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Stappenbeck TS, Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science. 2001;292:1115–1118. doi: 10.1126/science.1058709. [DOI] [PubMed] [Google Scholar]
  67. Stappenbeck TS, Hooper LV, Gordon JI. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A. 2002;99:15451–15455. doi: 10.1073/pnas.202604299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, Kubo C, Koga Y. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004;558:263–275. doi: 10.1113/jphysiol.2004.063388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, et al. A core gut microbiome in obese and lean twins. Nature. 2008;457:480–484. doi: 10.1038/nature07540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Turnbull AV, Rivier CL. Regulation of the hypothalamicpituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol rev. 1999;79:1–71. doi: 10.1152/physrev.1999.79.1.1. [DOI] [PubMed] [Google Scholar]
  71. Walker JR, Ediger JP, Graff LA, Greenfeld JM, Clara I, Lix L, Rawsthorne P, Miller N, Rogala L, McPhail CM, Bernstein CN. The Manitoba IBD cohort study: a populationbased study of the prevalence of lifetime and 12-month anxiety and mood disorders. Am J Gastroenterol. 2008;103:1989–1997. doi: 10.1111/j.1572-0241.2008.01980.x. [DOI] [PubMed] [Google Scholar]
  72. Wang PY, Caspi L, Lam CK, Chari M, Li X, Light PE, Gutierrez-Juarez R, Ang M, Schwartz GJ, Lam TK. Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production. Nature. 2008;452:1012–1016. doi: 10.1038/nature06852. [DOI] [PubMed] [Google Scholar]
  73. Welker M. MALDI-TOF MS for identification of microorganisms: a new era in clinical microbiological research and diagnosis. In: Hays JP, van Leeuwen WB, editors. The Role of New Technologies in Medical Microbiological Research and Diagnosis. Bussum: Bentham Science Publishers; 2012. [Google Scholar]
  74. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications. Gastroenterology. 2002;122:1140–1156. doi: 10.1053/gast.2002.32392. [DOI] [PubMed] [Google Scholar]
  75. Wook HS, Kim IS, Lee JS, Chung KS. Culture-Based and Denaturing Gradient Gel Electrophoresis Analysis of the Bacterial Community Structure from the Intestinal Tracts of Earthworms (Eisenia fetida) J Microbiol Biotechnol. 2011;21:885–892. doi: 10.4014/jmb.1009.09041. [DOI] [PubMed] [Google Scholar]
  76. Wu L, Thompson DK, Liu X, Fields MW, Bagwell CE, Tiedje JM, Zhou J. Development and evaluation of microarray-based whole genome hybridization for detection of microorganisms within the context of environmental applications. Environ Sci Technol. 2004;38:6775–6782. doi: 10.1021/es049508i. [DOI] [PubMed] [Google Scholar]
  77. Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A. 2009;106:2365–2370. doi: 10.1073/pnas.0812600106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Zimmer C. How microbes defend and define us. 2010. [Google Scholar]
  79. Simrén M, Barbara G, Flint HJ, Spiegel B M, Spiller R C, Vanner S, Verdu E F, Whorwell P J, Zoetendal E G. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013;62:159–176. doi: 10.1136/gutjnl-2012-302167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Sekirov I, Russell S L, Antunes L C M, Brett Finlay B. Gut Microbiota in Health and Disease. Physiol Rev. 2010;90:859–904. doi: 10.1152/physrev.00045.2009. [DOI] [PubMed] [Google Scholar]

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