Skip to main content

Advertisement

Log in

The Colonic Microbiota and Colonic Disease

  • Large Intestine (B Cash, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

The colonic ecosystem differs from that in the proximal gut in several important respects. The colonic microbiota represents the largest population of microbes colonizing humans from birth. Constraints on bacterial numbers, composition, and interaction with the host involve not only the innate and acquired immune system, but also the colonic mucin structure. While the microbiota provides beneficial protective, trophic, nutritional, and metabolic signals for the host, it may become a risk factor for disease depending on context and host susceptibility. Technological advances including DNA-based high-throughput compositional analysis have linked changes in the indigenous microbiota with several human diseases. In some instances, these findings have the potential to serve as new biomarkers of risk of disease. In this overview, recent advances are focused upon in relation to irritable bowel syndrome, inflammatory bowel disease, and colon cancer. The possibility that the therapeutic solution to some of these disorders may reside within the microbiota will also be addressed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Sekhirov I, Gill N, Jagova M, et al. Gut microbiota in health and disease. Physiol Rev. 2010;90:859–904.

    Article  Google Scholar 

  2. Shanahan F. The gut microbiota in 2011. Translating the microbiota to medicine. Nat Rev Gastroenterol Hepatol. 2011;9:72–4.

    Article  PubMed  Google Scholar 

  3. Clemente JC, Ursell LK, Parfrey LW, et al. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148:1258–70.

    Article  PubMed  CAS  Google Scholar 

  4. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012;13:260–70.

    PubMed  CAS  Google Scholar 

  5. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18:363–74.

    Article  PubMed  CAS  Google Scholar 

  6. Garrett WS, Gordon JI, Glimcher LH. Homeostasis and inflammation in the intestine. Cell. 2010;140:859–70.

    Article  PubMed  CAS  Google Scholar 

  7. Hill DA, Artis D. Intestinal bacteria and the regulation of immune cell homeostasis. Annu Rev Immunol. 2010;28:623–67.

    Article  PubMed  CAS  Google Scholar 

  8. Macpherson AJ, Geuking MB, Slack E, et al. The habitat, double life, citizenship, and forgetfulness of IgA. Immunol Rev. 2012;245:132–46.

    Article  PubMed  CAS  Google Scholar 

  9. • Johansson ME, Larsson JM, Hansson GC. 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 1:4659–65. An excellent overview of the colonic mucus structure and function.

    Article  PubMed  CAS  Google Scholar 

  10. Maslowski KM, Vieira AT, Ng A, et al. Regulation of immunomodulatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282–6.

    Article  PubMed  CAS  Google Scholar 

  11. Fukuda S, Toh H, Hase K, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature. 2011;469:543–7.

    Article  PubMed  CAS  Google Scholar 

  12. Chow J, Lee SM, Shen Y, et al. Host-bacterial symbiosis in health and disease. Adv Immunol. 2010;107:243–74.

    Article  PubMed  CAS  Google Scholar 

  13. Marchesi JR. Human distal microbiome. Environ Microbiol. 2011;13:3088–102.

    Article  PubMed  Google Scholar 

  14. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174–80.

    Article  PubMed  CAS  Google Scholar 

  15. • Wu GU, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–8. An important illustration of the impact of diet on the microbiota.

    Article  PubMed  CAS  Google Scholar 

  16. Grenham S, Clarke G, Cryan JF, et al. Brain-gut-microbe communication in health and disease. Front Physiol. 2011;2:94. epub.

    Article  PubMed  Google Scholar 

  17. Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004;558(Pt 1):263–75.

    Article  PubMed  CAS  Google Scholar 

  18. Heijtz RD, Wang S, Anuar F, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA. 2011;108(7):3047–52.

    Article  CAS  Google Scholar 

  19. Bravo JA, Forsythe P, Chew MV, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA. 2011;108:16050–5.

    Article  PubMed  CAS  Google Scholar 

  20. Clarke G, Cryan JF, Dinan TG, et al. Review article: probiotics for the treatment of irritable bowel syndrome–focus on lactic acid bacteria. Aliment Pharmacol Ther. 2012;35:403–13.

    Article  PubMed  CAS  Google Scholar 

  21. Menees SB, Maneerattannaporn M, Kim HM, et al. The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis. Am J Gastroenterol. 2012;107:28–35.

    Article  PubMed  CAS  Google Scholar 

  22. Saulnier DM, Riehle K, Mistretta TA, et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology. 2011;141:1782–91.

    Article  PubMed  CAS  Google Scholar 

  23. Rajilić-Stojanović M, Biagi E, Heilig HG, et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011;141:1792–801.

    Article  PubMed  Google Scholar 

  24. Jeffery IB, O'Toole PW, Ohman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 2012;61(7):997–1006.

    Article  PubMed  Google Scholar 

  25. Langhorst J, Junge A, Rueffer A, et al. Elevated human beta-defensin-2 levels indicate an activation of the innate immune system in patients with irritable bowel syndrome. Am J Gastroenterol. 2009;104:404–10.

    Article  PubMed  CAS  Google Scholar 

  26. Brint EK, MacSharry J, Fanning A, et al. Differential expression of toll-like receptors in patients with irritable bowel syndrome. Am J Gastroenterol. 2011;106:329–36.

    Article  PubMed  CAS  Google Scholar 

  27. Bernstein CN, Shanahan F. Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut. 2008;57:1185–91.

    Article  PubMed  Google Scholar 

  28. Hviid A, Svanström H, Frisch M. Antibiotic use in inflammatory bowel diseases in childhood. Gut. 2011;60:49–54.

    Article  PubMed  Google Scholar 

  29. Shaw SY, Blanchard JF, Bernstein CN. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. Am J Gastroenterol. 2010;105:2687–92.

    Article  PubMed  Google Scholar 

  30. Murphy EF, Cotter PD, Healy S, et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut. 2010;59:1635–42.

    Article  PubMed  CAS  Google Scholar 

  31. De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 2010;107:14691–6.

    Article  PubMed  Google Scholar 

  32. Shanahan F, Murphy E. The hybrid science of diet, microbes and metabolic health. Am J Clin Nutr. 2011;94(1):1–2.

    Article  PubMed  CAS  Google Scholar 

  33. Shoda R, Matsueda K, Yamato S, et al. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr. 1996;63:741–5.

    PubMed  CAS  Google Scholar 

  34. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009;137:1716–24.

    Article  PubMed  CAS  Google Scholar 

  35. Muegge BD, Kuczynski J, Knights D, et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science. 2011;332:970–4.

    Article  PubMed  CAS  Google Scholar 

  36. Faith JJ, McNulty NP, Rey FE, Gordon JI. Predicting a Human Gut Microbiota's Response to Diet in Gnotobiotic Mice. Science. 2011;333(6038):101–4.

    Article  PubMed  CAS  Google Scholar 

  37. Benjamin JL, Hedin CR, Koutsoumpas A, et al. Smokers with active Crohn's disease have a clinically relevant dysbiosis of the gastrointestinal microbiota. Inflamm Bowel Dis. 2012;18(6):1092–100.

    Article  PubMed  Google Scholar 

  38. Vijay-Kumar M, Aitken JD, Carvalho FA, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328:228–31.

    Article  PubMed  CAS  Google Scholar 

  39. Garrett WS, Lord GM, Punit S, et al. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. 2007;131:33–45.

    Article  PubMed  CAS  Google Scholar 

  40. Garrett WS, Gallini CA, Yatsunenko T, et al. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe. 2010;8:292–300.

    Article  PubMed  CAS  Google Scholar 

  41. • Bloom SM, Bijanki VN, Nava GM, et al. Commensal bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe. 2011;9:390–403. An important demonstration of the colitogenic potential of the microbiota depending on the host genotype.

    Article  PubMed  CAS  Google Scholar 

  42. • Cadwell K, Patel KK, Maloney NS, et al. Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell. 2010;141:1135–45. An important series of observations indicating the interplay of multiple factors in determining who gets sick with colitis.

    Article  PubMed  CAS  Google Scholar 

  43. • Elinav E, Strowig T, Kau AL, et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell. 2011;145:1–13. A new finding of the role of the epithelium in discriminating dangerous microbes from harmless commensals.

    Article  Google Scholar 

  44. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.

    Article  PubMed  CAS  Google Scholar 

  45. Sartor RB. Genetics and environmental interactions shape the intestinal microbiome to promote inflammatory bowel disease versus mucosal homeostasis. Gastroenterology. 2010;139:1816–33.

    Article  PubMed  Google Scholar 

  46. Swidsinski A, Ladhoff A, Pernthaler A, et al. Mucosal flora in inflammatory bowel disease. Gastroenterology. 2002;122:44.

    Article  PubMed  Google Scholar 

  47. Abubakar I, Myhill D, Aliyu SH, et al. Detection of Mycobacterium avium subspecies paratuberculosis from patients with Crohn's disease using nucleic acid-based techniques: a systematic review and meta-analysis. Inflamm Bowel Dis. 2008;14:401–10.

    Article  PubMed  CAS  Google Scholar 

  48. Darfeuille-Michaud A, Boudeau J, Bulois P, et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology. 2004;127:412–21.

    Article  PubMed  Google Scholar 

  49. Clayton EM, Rea MC, Shanahan F, et al. The vexed relationship between Clostridium difficile and inflammatory bowel disease: an assessment of carriage in an outpatient setting among patients in remission. Am J Gastroenterol. 2009;104:1162–9.

    Article  PubMed  Google Scholar 

  50. Peterson DA, Frank DN, Pace NR, et al. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe. 2008;3:417–27.

    Article  PubMed  CAS  Google Scholar 

  51. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA. 2008;105:16731–6.

    Article  PubMed  CAS  Google Scholar 

  52. Schwiertz A, Jacobi M, Frick J-S, et al. Microbiota in pediatric inflammatory bowel disease. J Pediatr. 2010;157:240–4.e1.

    Article  PubMed  Google Scholar 

  53. Frank DN. St. Amand AL, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA. 2007;104:13780–5.

    Article  PubMed  CAS  Google Scholar 

  54. 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. 2010;105:2420–8.

    Article  PubMed  CAS  Google Scholar 

  55. Pruteanu M, Hyland NP, Clarke DJ, et al. Degradation of the extracellular matrix components by bacterial-derived metalloproteases: implications for inflammatory bowel diseases. Inflamm Bowel Dis. 2011;17:1189–200.

    Article  PubMed  Google Scholar 

  56. • Steck N, Hoffmann M, Sava IG, et al. Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology. 2011;141:959–71. A demonstration that the luminal bacteria elaborate mucolytic and proteolytic enzymes, which may cause tissue damage in susceptible hosts.

    Article  PubMed  CAS  Google Scholar 

  57. Sibartie S, Scully P, Keohane J, et al. Mycobacterium avium subsp. Paratuberculosis (MAP) as a modifying factor in Crohn's disease. Inflamm Bowel Dis. 2010;16:296–304.

    PubMed  Google Scholar 

  58. Sewell GW, Marks DJB. SegalAW. The immunopathogenesis of Crohn's disease: a three-stage model. Curr Opin Immunol. 2009;21:506–13.

    Article  PubMed  CAS  Google Scholar 

  59. Marchesi JR, Dutilh BE, Hall N, et al. Towards the human colorectal cancer microbiome. PLoS One. 2011;6(5):e20447. doi:10.1371/journal.pone.0020447.

    Article  PubMed  CAS  Google Scholar 

  60. Sears CL, Pardoll DM. Perspective: Alpha-bugs, their microbial partners and the link to colon cancer. JID. 2011;203:306–11.

    Article  PubMed  Google Scholar 

  61. • Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22(2):292–8. This and the following paper raise the possibility of a new microbial biomarker of colon cancer but cause and effect relationships have not been established.

    Article  PubMed  CAS  Google Scholar 

  62. Castellarin M, Warren RL, Freeman JD, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22:299–306.

    Article  PubMed  CAS  Google Scholar 

  63. Ohkusa T, Okayasu I, Ogihara T, et al. Induction of experimental ulcerative colitis by Fusobacterium varium isolated from colonic mucosa of patients with ulcerative colitis. Gut. 2003;52:79–83.

    Article  PubMed  CAS  Google Scholar 

  64. Swidsinski A, Dörffel Y, Loening-Baucke V, et al. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum. Gut. 2011;60:34–40.

    Article  PubMed  Google Scholar 

  65. Strauss J, Kaplan GG, Beck PL, et al. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis. 2011;17(9):1971–8.

    Article  PubMed  Google Scholar 

  66. Allen-Vercoe E, Strauss J, Chadee K. Fusobacterium nucleatum: An emerging gut pathogen? Gut Microbes. 2011 Sep 1;2(5). [Epub ahead of print].

  67. • Wallace BD, Wang H, Lane KT, et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010;330:831–5. An intriguing example of the microbiome as a drug target.

    Article  PubMed  CAS  Google Scholar 

  68. Shanahan F. Gut microbes: from bugs to drugs. Am J Gastroenterol. 2010;105:275–9.

    Article  PubMed  Google Scholar 

  69. Im GY, Modayil RJ, Lin CT, et al. The appendix may protect against Clostridium difficile recurrence. Clin Gastroenterol Hepatol. 2011;9:1072–7.

    Article  PubMed  Google Scholar 

  70. Na X, Kelly C. The vermiform appendix and recurrent Clostridium difficile infection: a curious connection. Clin Gastroenterol Hepatol. 2011;9:1017–9.

    Article  PubMed  Google Scholar 

  71. Guo B, Harstall C, Louie T, et al. Systematic review: faecal transplantation for the treatment of Clostridium difficile-associated disease. Aliment Pharmacol Ther. 2012;35:865–75.

    Article  PubMed  CAS  Google Scholar 

  72. Hamilton MJ, Weingarden AR, Sadowsky MJ, et al. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(5):761–7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

The author is supported, in part, by Science Foundation Ireland, and by grants from Alimentary Health Ltd and GlaxoSmithKline Ltd. The content of this article was neither influenced nor constrained by these facts.

Disclosure

Dr. F. Shanahan has received grant support for his institution from the Science Foundation Ireland.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fergus Shanahan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shanahan, F. The Colonic Microbiota and Colonic Disease. Curr Gastroenterol Rep 14, 446–452 (2012). https://doi.org/10.1007/s11894-012-0281-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-012-0281-5

Keywords

Navigation