Current Infectious Disease Reports

, Volume 13, Issue 1, pp 28–34 | Cite as

Current Concepts of the Intestinal Microbiota and the Pathogenesis of Infection

  • Leslie H. Wardwell
  • Curtis Huttenhower
  • Wendy S. Garrett
Article

Abstract

The human gastrointestinal tract is populated by a vast and diverse community of microbes. This gut microbiota participates in host metabolism, protects from invading microbes, and facilitates immune system development and function. In this review, we consider the contributions of intestinal microbes to the pathogenesis of infectious diseases. Key concepts of colonization resistance, host-commensal microbe interaction in immunity, antibiotics and gut bacterial communities, viral-gut bacterial interactions, and evolving methods for studying commensal microbes are explored.

Keywords

Intestine Commensal Microbiota Infection Gut Bacteria Gastrointestinal Microbial community Infectious disease 

References

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

  1. 1.
    •• Frank DN, Pace NR: Gastrointestinal microbiology enters the metagenomics era. Curr Opin Gastroenterol 2008 24(1):4–10. An excellent review summarizing metagenomic techniques and their application to studies of human health and disease.CrossRefPubMedGoogle Scholar
  2. 2.
    Turnbaugh PJ, Hamady M, Yatsunenko T, et al.: A core gut microbiome in obese and lean twins. Nature 2009;457(7228):480–4.CrossRefPubMedGoogle Scholar
  3. 3.
    Qin J, Li R, Raes J, et al.: A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010;464:59–65.CrossRefPubMedGoogle Scholar
  4. 4.
    Wen L, Ley RE, Volchkov PY, et al.: Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008;455(7216):1109–13.CrossRefPubMedGoogle Scholar
  5. 5.
    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(5975):228–31.CrossRefPubMedGoogle Scholar
  6. 6.
    • Stecher B, Chaffron S, Käppeli R, et al.: Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria. PLoS Pathogens 2010;6:e1000711. An investigation of the mechanism underpinning colonization resistance using a mouse model of infection with Salmonella enterica.CrossRefPubMedGoogle Scholar
  7. 7.
    Macpherson AJ, Harris NL: Interactions between commensal intestinal bacteria and the immune system. Nature reviews Immunology 2004;4:478–85.CrossRefPubMedGoogle Scholar
  8. 8.
    •• Round JL, Mazmanian SK: The gut microbiota shapes intestinal immune responses during health and disease. Nature Reviews Immunology 2009;9:313–23. A thorough review of the role of gut commensal bacteria in immune system development and response.CrossRefPubMedGoogle Scholar
  9. 9.
    Mazmanian SK, Round JL, Kasper DL: A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 2008;453(7195):620–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Ochoa-Reparaz J, Mielcarz DW, Wang Y, et al.: A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol 2010;3(5):487–95.CrossRefPubMedGoogle Scholar
  11. 11.
    Korn T, Bettelli E, Oukka M, Kuchroo VK: IL-17 and Th17 Cells. Annual review of immunology 2009;27:485–517.CrossRefPubMedGoogle Scholar
  12. 12.
    Ivanov II, Atarashi K, Manel N, et al.: Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 2009;139:485–98.CrossRefPubMedGoogle Scholar
  13. 13.
    Hall JA, Bouladoux N, Sun CM, et al.: Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity 2008;29(4):637–49.CrossRefPubMedGoogle Scholar
  14. 14.
    Benson A, Pifer R, Behrendt CL, et al.: Gut commensal bacteria direct a protective immune response against Toxoplasma gondii. Cell host & microbe 2009;6:187–96.CrossRefGoogle Scholar
  15. 15.
    Kinnebrew MA, Ubeda C, Zenewicz LA, et al.: Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection. J Infect Dis Feb 15;201(4):534–43.Google Scholar
  16. 16.
    • Clarke TB, Davis KM, Lysenko ES, et al.: Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nature Medicine 2010;16:228–31. A recent paper demonstrating the role of commensal bacterial products for robust system immune function.CrossRefPubMedGoogle Scholar
  17. 17.
    Dethlefsen L, Huse S, Sogin ML, Relman DA: The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 2008;6(11):e280.CrossRefPubMedGoogle Scholar
  18. 18.
    Sekirov I, Tam NM, Jogova M, et al.: Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection. Infection and immunity 2008;76:4726–36.CrossRefPubMedGoogle Scholar
  19. 19.
    Hill DA, Hoffmann C, Abt MC, et al.: Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal immunology 2010;3:148–58.CrossRefPubMedGoogle Scholar
  20. 20.
    Giongo A, Gano KA, Crabb DB, et al.: Toward defining the autoimmune microbiome for type 1 diabetes. ISME J Jul 8.Google Scholar
  21. 21.
    Onderdonk AB, Garrett WS: Gas Gangrene and Other Clostridium-Associated Diseases. In: Mandell GL, Bennett, J.E., and Dolin R., ed. Mandell, Douglas, and Bennett’s Principles adn Practice of Infectious Disease, 7th Edition. 7th ed Vol. 2. Philadelphia: Churchill, Livingstone, Elsevier, 2010:3103–9.Google Scholar
  22. 22.
    • Walk ST, Young VB: Emerging insights into antibiotic-associated diarrhea and Clostridium difficile infection through the lens of microbial ecology. Interdisciplinary perspectives on infectious diseases 2008;2008:125081. An interesting review of Antibiotic-associated diarrhea and Clostridium difficile. CrossRefPubMedGoogle Scholar
  23. 23.
    • Giel JL, Sorg JA, Sonenshein AL, Zhu J: Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PloS one 2010;5:e8740. A recent paper providing insight into the contribution of commensal microbes to Clostridium difficile sporulation.CrossRefPubMedGoogle Scholar
  24. 24.
    Sekirov I, Finlay BB: The role of the intestinal microbiota in enteric infection. The Journal of physiology 2009;587:4159–67.CrossRefPubMedGoogle Scholar
  25. 25.
    Marshall BM, Ochieng DJ, Levy SB: Commensals: Underappreciated Reservoir of Antibiotic Resistance. Microbe 2009;4:231–8.Google Scholar
  26. 26.
    • Allen HK, Donato J, Wang HH, et al.: Call of the wild: antibiotic resistance genes in natural environments. Nature Reviews Microbiology 2010;8:251–9. A comprehensive review of the types and functions of antibiotic resistance genes found in environmental microbes.CrossRefPubMedGoogle Scholar
  27. 27.
    Sjolund MS, Andersson DI, Blaser MJ, Engstrand A: Brief Communication Long-Term Persistence of Resistant Enterococcus Species after Antibiotics To Eradicate Helicobacter pylori. Annals of Internal Medicine 2003:483–8.Google Scholar
  28. 28.
    •• Sommer MO, Dantas G, Church GM: Functional characterization of the antibiotic resistance reservoir in the human microflora. Science (New York, NY) 2009;325:1128–31. This article demonstrates that the gut microbiome represents a key reservoir for antibiotic resistance genes.CrossRefGoogle Scholar
  29. 29.
    Bobak DA, Guerrant RL: Nausea, Vomiting, and Noninflammatory Diarrhea. In: Mandell GL, Bennett, J.E., and Dolin R., ed. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Disease, 7th Edition Vol. 1. Philadelphia: Churchill, Livingstone, Elsevier, 2010:1359–73.Google Scholar
  30. 30.
    Fankhauser RL, Monroe SS, Noel JS, et al.: Epidemiologic and molecular trends of “Norwalk-like viruses” associated with outbreaks of gastroenteritis in the United States. The Journal of infectious diseases 2002;186:1–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Lyman WH, Walsh JF, Kotch JB, et al.: Prospective study of etiologic agents of acute gastroenteritis outbreaks in child care centers. The Journal of pediatrics 2009;154:253–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Moser LA, Carter M, Schultz-Cherry S: Astrovirus increases epithelial barrier permeability independently of viral replication. Journal of virology 2007;81:11937–45.CrossRefPubMedGoogle Scholar
  33. 33.
    Fang S-B, Lee H-C, Hu J-J, et al.: Dose-dependent effect of Lactobacillus rhamnosus on quantitative reduction of faecal rotavirus shedding in children. Journal of tropical pediatrics 2009;55:297–301.CrossRefPubMedGoogle Scholar
  34. 34.
    Vandenplas Y, Salvatore S, Vieira M, et al.: Probiotics in infectious diarrhoea in children: are they indicated? European journal of pediatrics 2007;166:1211–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Frank DN, St. Amand AL, Feldman RA, et al.: Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences of the United States of America 2007;104:13780–5CrossRefPubMedGoogle Scholar
  36. 36.
    Barrett JC, Hansoul S, Nicolae DL, et al.: Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 2008;40(8):955–62.CrossRefPubMedGoogle Scholar
  37. 37.
    •• 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(7):1135–45. This article provides insight into the contribution of genes and environment to the pathophysiology of Crohn’s disease by revealing links between the host Atg16L1 gene, specific norovirus infection, and bacterial gut communities.CrossRefPubMedGoogle Scholar
  38. 38.
    Letarov A, Kulikov E: The bacteriophages in human- and animal body-associated microbial communities. Journal of applied microbiology 2009;107:1–13.CrossRefPubMedGoogle Scholar
  39. 39.
    •• Reyes A, Haynes M, Hanson N, et al.: Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 2010;466(7304):334–8. This study of monozygotic twins and their mothers describes the diversity and variation of fecal phage viromes in healthy individuals.CrossRefPubMedGoogle Scholar
  40. 40.
    Brenchley JM, Schacker TW, Ruff LE, et al.: CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. The Journal of experimental medicine 2004;200:749–59.CrossRefPubMedGoogle Scholar
  41. 41.
    Douek D: HIV disease progression: immune activation, microbes, and a leaky gut. Topics in HIV medicine : a publication of the International AIDS Society, USA 2007;15:114–7.Google Scholar
  42. 42.
    Brenchley JM, Price DA, Schacker TW, et al.: Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nature medicine 2006;12:1365–71.CrossRefPubMedGoogle Scholar
  43. 43.
    Hofer U, Schlaepfer E, Baenziger S, et al.: Inadequate clearance of translocated bacterial products in HIV-infected humanized mice. PLoS pathogens 2010;6:e1000867.CrossRefPubMedGoogle Scholar
  44. 44.
    Nazli A, Chan O, Dobson-Belaire WN, et al.: Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS pathogens 2010;6:e1000852.CrossRefPubMedGoogle Scholar
  45. 45.
    •• Hamady M, Knight R: Microbial community profiling for human microbiome projects: tools, techniques, and challenges. Genome Res 2009;19(7):1141–52. A thorough review of sequencing techniques, analytic methods, and experimental design for studies directed at the human microbiome.CrossRefPubMedGoogle Scholar
  46. 46.
    Tringe SG, Hugenholtz P: A renaissance for the pioneering 16S rRNA gene. Curr Opin Microbiol 2008;11(5):442–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Peterson DA, Frank DN, Pace NR, Gordon JI: Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe 2008;3(6):417–27.CrossRefPubMedGoogle Scholar
  48. 48.
    Caporaso JG, Kuczynski J, Stombaugh J, et al.: QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010;7(5):335–6.CrossRefPubMedGoogle Scholar
  49. 49.
    Meyer F, Paarmann D, D’Souza M, et al.: The metagenomics RAST server—a public resource for the automatic phylogenetic and functional analysis of metagenomes. BMC Bioinformatics 2008;9:386.CrossRefPubMedGoogle Scholar
  50. 50.
    Mitra S, Klar B, Huson DH: Visual and statistical comparison of metagenomes. Bioinformatics 2009;25(15):1849–55.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Leslie H. Wardwell
    • 1
    • 4
  • Curtis Huttenhower
    • 3
  • Wendy S. Garrett
    • 1
    • 2
    • 4
    • 5
  1. 1.Department of Immunology and Infectious DiseasesHarvard School of Public HealthBostonUSA
  2. 2.Department of Genetics and Complex DiseasesHarvard School of Public HealthBostonUSA
  3. 3.Department of BiostatisticsHarvard School of Public HealthBostonUSA
  4. 4.Harvard Medical SchoolBostonUSA
  5. 5.Dana Farber Cancer InstituteBostonUSA

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