Home LiteratureArticle Details
PMID: 19307217 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation.

Infection and immunity ·Vol. 77 ·No. 6 ·2009-06-00 ·Pages 2367-75

Antonopoulos DA, Huse SM, Morrison HG, Schmidt TM, Sogin ML, Young VB

Abstract

Shifts in microbial communities are implicated in the pathogenesis of a number of gastrointestinal diseases, but we have limited understanding of the mechanisms that lead to altered community structures. One difficulty with studying these mechanisms in human subjects is the inherent baseline variability of the microbiota in different individuals. In an effort to overcome this baseline variability, we employed a mouse model to control the host genotype, diet, and other possible influences on the microbiota. This allowed us to determine whether the indigenous microbiota in such mice had a stable baseline community structure and whether this community exhibited a consistent response following antibiotic administration. We employed a tag-sequencing strategy targeting the V6 hypervariable region of the bacterial small-subunit (16S) rRNA combined with massively parallel sequencing to determine the community structure of the gut microbiota. Inbred mice in a controlled environment harbored a reproducible baseline community that was significantly impacted by antibiotic administration. The ability of the gut microbial community to recover to baseline following the cessation of antibiotic administration differed according to the antibiotic regimen administered. Severe antibiotic pressure resulted in reproducible, long-lasting alterations in the gut microbial community, including a decrease in overall diversity. The finding of stereotypic responses of the indigenous microbiota to ecologic stress suggests that a better understanding of the factors that govern community structure could lead to strategies for the intentional manipulation of this ecosystem so as to preserve or restore a healthy microbiota.

MeSH Terms
Animals Anti-Bacterial Agents/pharmacology Bacteria/classification,drug effects,genetics Biodiversity DNA, Bacterial/chemistry,genetics DNA, Ribosomal/chemistry,genetics Gastrointestinal Tract/microbiology Mice Mice, Inbred C57BL Mice, Knockout RNA, Ribosomal, 16S/genetics Sequence Analysis, DNA
Chemicals
Anti-Bacterial Agents DNA, Bacterial DNA, Ribosomal RNA, Ribosomal, 16S
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Antonopoulos Dionysios A
Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI 48109-5623, USA.
Huse Susan M
Morrison Hilary G
Schmidt Thomas M
Sogin Mitchell L
Young Vincent B
References (59)
59 references, click to expand
  1. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine.
    Cell Host Microbe. 2008 Oct 16;4(4):337-49 PMID: 18854238
  2. Clindamycin-induced enrichment and long-term persistence of resistant Bacteroides spp. and resistance genes.
    J Antimicrob Chemother. 2006 Dec;58(6):1160-7 PMID: 17046967
  3. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.
    PLoS Biol. 2008 Nov 18;6(11):e280 PMID: 19018661
  4. Human fecal flora: variation in bacterial composition within individuals and a possible effect of emotional stress.
    Appl Environ Microbiol. 1976 Mar;31(3):359-75 PMID: 938032
  5. Analyzing real-time PCR data by the comparative C(T) method.
    Nat Protoc. 2008;3(6):1101-8 PMID: 18546601
  6. Microbial ecology of the gastrointestinal tract.
    Annu Rev Microbiol. 1977;31:107-33 PMID: 334036
  7. Molecular monitoring of the fecal microbiota of healthy human subjects during administration of lactulose and Saccharomyces boulardii.
    Appl Environ Microbiol. 2006 Sep;72(9):5990-7 PMID: 16957220
  8. An antibiotic-responsive mouse model of fulminant ulcerative colitis.
    PLoS Med. 2008 Mar 4;5(3):e41 PMID: 18318596
  9. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits.
    Nature. 2008 Oct 9;455(7214):804-7 PMID: 18724361
  10. Exploring microbial diversity and taxonomy using SSU rRNA hypervariable tag sequencing.
    PLoS Genet. 2008 Nov;4(11):e1000255 PMID: 19023400
  11. Quantification of human cells in NOD/SCID mice by duplex real-time polymerase-chain reaction.
    Haematologica. 2001 Jul;86(7):693-9 PMID: 11454523
  12. Gastrointestinal microbiology enters the metagenomics era.
    Curr Opin Gastroenterol. 2008 Jan;24(1):4-10 PMID: 18043225
  13. Introducing DOTUR, a computer program for defining operational taxonomic units and estimating species richness.
    Appl Environ Microbiol. 2005 Mar;71(3):1501-6 PMID: 15746353
  14. An obesity-associated gut microbiome with increased capacity for energy harvest.
    Nature. 2006 Dec 21;444(7122):1027-31 PMID: 17183312
  15. Assembly of the human intestinal microbiota.
    Trends Ecol Evol. 2006 Sep;21(9):517-23 PMID: 16820245
  16. A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism.
    Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):10011-6 PMID: 16782812
  17. Evolution of mammals and their gut microbes.
    Science. 2008 Jun 20;320(5883):1647-51 PMID: 18497261
  18. Colloquium paper: resistance, resilience, and redundancy in microbial communities.
    Proc Natl Acad Sci U S A. 2008 Aug 12;105 Suppl 1:11512-9 PMID: 18695234
  19. Prevalence and temporal stability of selected clostridial groups in irritable bowel syndrome in relation to predominant faecal bacteria.
    J Med Microbiol. 2006 May;55(Pt 5):625-633 PMID: 16585652
  20. In vivo and in vitro antagonism of intestinal bacteria against Shigellaflexneri. II. The inhibitory mechanism.
    J Infect Dis. 1962 Jan-Feb;110:38-46 PMID: 13895061
  21. Microbial ecology: human gut microbes associated with obesity.
    Nature. 2006 Dec 21;444(7122):1022-3 PMID: 17183309
  22. Mechanisms of action of probiotics.
    Clin Infect Dis. 2008 Feb 1;46 Suppl 2:S87-91; discussion S144-51 PMID: 18181730
  23. Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set.
    Microbiology (Reading). 2002 Jan;148(Pt 1):257-266 PMID: 11782518
  24. The "Microflora Hypothesis" of allergic disease.
    Adv Exp Med Biol. 2008;635:113-34 PMID: 18841708
  25. A mouse model of Clostridium difficile-associated disease.
    Gastroenterology. 2008 Dec;135(6):1984-92 PMID: 18848941
  26. Microbial diversity in the deep sea and the underexplored "rare biosphere".
    Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):12115-20 PMID: 16880384
  27. Colonization resistance.
    Antimicrob Agents Chemother. 1994 Mar;38(3):409-14 PMID: 8203832
  28. Host-bacterial mutualism in the human intestine.
    Science. 2005 Mar 25;307(5717):1915-20 PMID: 15790844
  29. Rules of engagement: interspecies interactions that regulate microbial communities.
    Annu Rev Microbiol. 2008;62:375-401 PMID: 18544040
  30. A molecular view of microbial diversity and the biosphere.
    Science. 1997 May 2;276(5313):734-40 PMID: 9115194
  31. Debugging how bacteria manipulate the immune response.
    Immunity. 2007 Feb;26(2):149-61 PMID: 17307704
  32. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases.
    Cell Host Microbe. 2008 Jun 12;3(6):417-27 PMID: 18541218
  33. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients.
    Lancet. 1989 May 27;1(8648):1156-60 PMID: 2566734
  34. Effect of antibiotic therapy on human fecal microbiota and the relation to the development of Clostridium difficile.
    Microb Ecol. 2008 Oct;56(3):395-402 PMID: 18209965
  35. Bacterial modulation of mucosal innate immunity.
    Mol Immunol. 2005 May;42(8):895-901 PMID: 15829279
  36. Accuracy and quality of massively parallel DNA pyrosequencing.
    Genome Biol. 2007;8(7):R143 PMID: 17659080
  37. Antibiotic therapy attenuates colitis in interleukin 10 gene-deficient mice.
    Gastroenterology. 2000 Jun;118(6):1094-105 PMID: 10833484
  38. Microbial population structures in the deep marine biosphere.
    Science. 2007 Oct 5;318(5847):97-100 PMID: 17916733
  39. Probiotics: definition, sources, selection, and uses.
    Clin Infect Dis. 2008 Feb 1;46 Suppl 2:S58-61; discussion S144-51 PMID: 18181724
  40. Microbial influences in inflammatory bowel diseases.
    Gastroenterology. 2008 Feb;134(2):577-94 PMID: 18242222
  41. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.
    Cell. 2004 Jul 23;118(2):229-41 PMID: 15260992
  42. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota.
    ISME J. 2007 May;1(1):56-66 PMID: 18043614
  43. Clostridium difficile--Associated diarrhea: A review.
    Arch Intern Med. 2001 Feb 26;161(4):525-33 PMID: 11252111
  44. Ecological and evolutionary forces shaping microbial diversity in the human intestine.
    Cell. 2006 Feb 24;124(4):837-48 PMID: 16497592
  45. Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal samples reveals stable and host-specific communities of active bacteria.
    Appl Environ Microbiol. 1998 Oct;64(10):3854-9 PMID: 9758810
  46. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea.
    J Infect Dis. 2008 Feb 1;197(3):435-8 PMID: 18199029
  47. A molecular sensor that allows a gut commensal to control its nutrient foundation in a competitive ecosystem.
    Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9833-8 PMID: 10449780
  48. Probiotics and chronic disease.
    J Clin Gastroenterol. 2006 Mar;40(3):270-4 PMID: 16633135
  49. Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn's disease.
    J Clin Microbiol. 2006 Nov;44(11):3980-8 PMID: 16988018
  50. Human colonic biota studied by ribosomal DNA sequence analysis.
    Appl Environ Microbiol. 1996 Jul;62(7):2273-8 PMID: 8779565
  51. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice.
    FASEB J. 2008 Jul;22(7):2416-26 PMID: 18326786
  52. Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection.
    Infect Immun. 2008 Oct;76(10):4726-36 PMID: 18678663
  53. In vivo and in vitro antagonism of intestinal bacteria against Shigella flexneri. I. Correlation between various tests.
    J Infect Dis. 1962 Jan-Feb;110:30-7 PMID: 13906576
  54. Recurrent clostridium difficile.
    Gastroenterology. 2006 Apr;130(4):1311-6 PMID: 16618421
  55. Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube.
    Clin Infect Dis. 2003 Mar 1;36(5):580-5 PMID: 12594638
  56. Diversity of the human intestinal microbial flora.
    Science. 2005 Jun 10;308(5728):1635-8 PMID: 15831718
  57. Historical perspectives on studies of Clostridium difficile and C. difficile infection.
    Clin Infect Dis. 2008 Jan 15;46 Suppl 1:S4-11 PMID: 18177220
  58. MUSCLE: multiple sequence alignment with high accuracy and high throughput.
    Nucleic Acids Res. 2004 Mar 19;32(5):1792-7 PMID: 15034147
  59. The microecology of Clostridium difficile.
    Clin Infect Dis. 1993 Jun;16 Suppl 4:S214-8 PMID: 8324122
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
1098-5522
Published
2009-06-00
Epub
2009-00-23
Pages
2367-75
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC2687343
Subset
IM
Grants
NHLBI NIH HHS · T32 HL007749 · United States
NIAID NIH HHS · N01-AI-30058 · United States
NIAID NIH HHS · N01AI30058 · United States
NIDDK NIH HHS · R01 DK070875 · United States
NIEHS NIH HHS · 1 P50 ES012742-01 · United States
NIDDK NIH HHS · R01 DK070875-02 · United States
NIEHS NIH HHS · P50 ES012742 · United States
NHLBI NIH HHS · T32 HL07749 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com