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Genotype Is a Stronger Determinant than Sex of the Mouse Gut Microbiota

  • Environmental Microbiology
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Abstract

The mammalian gut microbiota is considered to be determined mostly by diet, while the effect of genotype is still controversial. Here, we examined the effect of genotype on the gut microbiota in normal populations, exhibiting only natural polymorphisms, and evaluated this effect in comparison to the effect of sex. DNA fingerprinting approaches were used to profile the gut microbiota of eight different recombinant inbred mouse lines of the collaborative cross consortium, whose level of genetic diversity mimics that of a natural human population. Analyses based on automated ribosomal internal transcribed spacer analysis demonstrated significant higher similarity of the gut microbiota composition within mouse lines than between them or within same-gender groups. Thus, genetic background significantly impacts the microbiota composition and is a stronger determinant than gender. These findings imply that genetic polymorphisms help shape the intestinal microbiota of mammals and consequently could affect host susceptibility to diseases.

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References

  1. Albert E, Sommerfeld K, Gophna S, Marshall J, Gophna U (2009) The gut microbiota of toll-like receptor 2-deficient mice exhibits lineage-specific modifications. Environ Microbiol Rep 1:65–70

    Article  CAS  Google Scholar 

  2. Baumgart M, Dogan B, Rishniw M, Weitzman G, Bosworth B, Yantiss R et al (2007) Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn’s disease involving the ileum. ISME J 1:403–418

    Article  CAS  PubMed  Google Scholar 

  3. Beery TA (2003) Sex differences in infection and sepsis. Crit Care Nurs Clin North Am 15:55–62

    Article  PubMed  Google Scholar 

  4. Bjerketorp J, Ng Tze Chiang A, Hjort K, Rosenquist M, Liu WT, Jansson JK (2008) Rapid lab-on-a-chip profiling of human gut bacteria. J Microbiol Methods 72:82–90

    Article  CAS  PubMed  Google Scholar 

  5. Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD, Beatty J et al (2004) The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet 36:1133–1137

    Article  CAS  PubMed  Google Scholar 

  6. Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL, Barnich N et al (2004) High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology 127:412–421

    Article  PubMed  Google Scholar 

  7. Dethlefsen L, Eckburg PB, Bik EM, Relman DA (2006) Assembly of the human intestinal microbiota. Trends Ecol Evol 21:517–523

    Article  PubMed  Google Scholar 

  8. Dicksved J, Floistrup H, Bergstrom A, Rosenquist M, Pershagen G, Scheynius A et al (2007) Molecular fingerprinting of the fecal microbiota of children raised according to different lifestyles. Appl Environ Microbiol 73:2284–2289

    Article  CAS  PubMed  Google Scholar 

  9. Dobrindt U, Hentschel U, Kaper JB, Hacker J (2002) Genome plasticity in pathogenic and nonpathogenic enterobacteria. Curr Top Microbiol Immunol 264:157–175

    CAS  PubMed  Google Scholar 

  10. Fisher MM, Triplett EW (1999) Automated approach for ribosomal intergenic spacer analysis of microbial diversity and its application to freshwater bacterial communities. Appl Environ Microbiol 65:4630–4636

    CAS  PubMed  Google Scholar 

  11. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104:13780–13785

    Article  CAS  PubMed  Google Scholar 

  12. Gophna U, Sommerfeld K, Gophna S, Doolittle WF, Veldhuyzen van Zanten SJ (2006) Differences between tissue-associated intestinal microfloras of patients with Crohn’s disease and ulcerative colitis. J Clin Microbiol 44:4136–4141

    Article  CAS  PubMed  Google Scholar 

  13. Hacker J, Kaper JB (2000) Pathogenicity islands and the evolution of microbes. Annu Rev Microbiol 54:641–679

    Article  CAS  PubMed  Google Scholar 

  14. Hammer Ø, Harper DAT, Ryan PD (2001) PAST: paleontological statistics software package for education and data analysis. Palaeontol Electr 4:1–9

    Google Scholar 

  15. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY et al (2009) High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137(1716–1724):e1711–e1712

    Google Scholar 

  16. Iraqi FA, Churchill G, Mott R (2008) The Collaborative Cross, developing a resource for mammalian systems genetics: a status report of the Wellcome Trust cohort. Mamm Genome 19:379–381

    Article  PubMed  Google Scholar 

  17. Kassinen A, Krogius-Kurikka L, Makivuokko H, Rinttila T, Paulin L, Corander J et al (2007) The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 133:24–33

    Article  CAS  PubMed  Google Scholar 

  18. Kovacs A, Yacoby K, Gophna U (2010) A systematic assessment of automated ribosomal intergenic spacer analysis (ARISA) as a tool for estimating bacterial richness. Res Microbiol 161:192–197

    Article  CAS  PubMed  Google Scholar 

  19. Lay C, Rigottier-Gois L, Holmstrom K, Rajilic M, Vaughan EE, de Vos WM et al (2005) Colonic microbiota signatures across five northern European countries. Appl Environ Microbiol 71:4153–4155

    Article  CAS  PubMed  Google Scholar 

  20. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102:11070–11075

    Article  CAS  PubMed  Google Scholar 

  21. Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444:1022–1023

    Article  CAS  PubMed  Google Scholar 

  22. Li M, Wang B, Zhang M, Rantalainen M, Wang S, Zhou H et al (2008) Symbiotic gut microbes modulate human metabolic phenotypes. Proc Natl Acad Sci USA 105:2117–2122

    Article  CAS  PubMed  Google Scholar 

  23. Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L et al (2006) Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55:205–211

    Article  CAS  PubMed  Google Scholar 

  24. Manter DK, Weir TL, Vivanco JM (2010) Negative effects of sample pooling on PCR-based estimates of soil microbial richness and community structure. Appl Environ Microbiol 76:2086–2090

    Article  CAS  PubMed  Google Scholar 

  25. Matto J, Maunuksela L, Kajander K, Palva A, Korpela R, Kassinen A, Saarela M (2005) Composition and temporal stability of gastrointestinal microbiota in irritable bowel syndrome—a longitudinal study in IBS and control subjects. FEMS Immunol Med Microbiol 43:213–222

    Article  PubMed  Google Scholar 

  26. Morell V (1995) Zeroing in on how hormones affect the immune system. Science 269:773–775

    Article  CAS  PubMed  Google Scholar 

  27. Mueller S, Saunier K, Hanisch C, Norin E, Alm L, Midtvedt T et al (2006) Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol 72:1027–1033

    Article  CAS  PubMed  Google Scholar 

  28. Ott SJ, Musfeldt M, Wenderoth DF, Hampe J, Brant O, Folsch UR et al (2004) Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 53:685–693

    Article  CAS  PubMed  Google Scholar 

  29. Pasche B, Kalaydjiev S, Franz TJ, Kremmer E, Gailus-Durner V, Fuchs H et al (2005) Sex-dependent susceptibility to Listeria monocytogenes infection is mediated by differential interleukin-10 production. Infect Immun 73:5952–5960

    Article  CAS  PubMed  Google Scholar 

  30. Roberts A, Pardo-Manuel de Villena F, Wang W, McMillan L, Threadgill DW (2007) The polymorphism architecture of mouse genetic resources elucidated using genome-wide resequencing data: implications for QTL discovery and systems genetics. Mamm Genome 18:473–481

    Article  CAS  PubMed  Google Scholar 

  31. Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9:313–323

    Article  CAS  PubMed  Google Scholar 

  32. Salem ML (2004) Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production. Curr Drug Targets Inflamm Allergy 3:97–104

    Article  CAS  PubMed  Google Scholar 

  33. Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjoberg J, Amir E et al (2010) Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 11:76–83

    Article  CAS  PubMed  Google Scholar 

  34. Stewart JA, Chadwick VS, Murray A (2005) Investigations into the influence of host genetics on the predominant eubacteria in the faecal microflora of children. J Med Microbiol 54:1239–1242

    Article  CAS  PubMed  Google Scholar 

  35. Suzuki M, Rappe MS, Giovannoni SJ (1998) Kinetic bias in estimates of coastal picoplankton community structure obtained by measurements of small-subunit rRNA gene PCR amplicon length heterogeneity. Appl Environ Microbiol 64:4522–4529

    CAS  PubMed  Google Scholar 

  36. Swidsinski A, Khilkin M, Kerjaschki D, Schreiber S, Ortner M, Weber J, Lochs H (1998) Association between intraepithelial Escherichia coli and colorectal cancer. Gastroenterology 115:281–286

    Article  CAS  PubMed  Google Scholar 

  37. Terres G, Morrison SL, Habicht GS (1968) A quantitative difference in the immune response between male and female mice. Proc Soc Exp Biol Med 127:664–667

    CAS  PubMed  Google Scholar 

  38. Toivanen P, Vaahtovuo J, Eerola E (2001) Influence of major histocompatibility complex on bacterial composition of fecal flora. Infect Immun 69:2372–2377

    Article  CAS  PubMed  Google Scholar 

  39. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031

    Article  PubMed  Google Scholar 

  40. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE et al (2009) A core gut microbiome in obese and lean twins. Nature 457:480–484

    Article  CAS  PubMed  Google Scholar 

  41. Yeretssian G, Doiron K, Shao W, Leavitt BR, Hayden MR, Nicholson DW, Saleh M (2009) Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection. Proc Natl Acad Sci USA 106:9016–9020

    Article  CAS  PubMed  Google Scholar 

  42. Zhang C, Zhang M, Wang S, Han R, Cao Y, Hua W et al (2010) Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. Isme J 4:232–241

    Article  CAS  PubMed  Google Scholar 

  43. Zoetendal EG, Akkermans ADL, Akkermans-van Vliet WM, de Visser JAGM, de Vos WM (2001) The host genotype affects the bacterial community in the human gastronintestinal tract. Microb Ecol Health Dis 13:129–134

    Article  Google Scholar 

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Acknowledgements

E.H. was supported by the Israeli Science Foundation, the National Science Foundation, and is a faculty fellow of the Edmond J. Safra Bioinformatics program at Tel-Aviv University. F.A.I. was supported by the Wellcome trust. U.G was supported by grants from the McDonnell Foundation, the Kurt Lion Foundation, and the Israeli Ministry of Health.

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Authors and Affiliations

  1. Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv, 69978, Israel

    Amir Kovacs, Noa Ben-Jacob, Eran Halperin & Uri Gophna

  2. Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, 69978, Israel

    Hanna Tayem & Fuad A. Iraqi

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  1. Amir Kovacs
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  2. Noa Ben-Jacob
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  3. Hanna Tayem
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  5. Fuad A. Iraqi
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  6. Uri Gophna
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Correspondence to Uri Gophna.

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Kovacs, A., Ben-Jacob, N., Tayem, H. et al. Genotype Is a Stronger Determinant than Sex of the Mouse Gut Microbiota. Microb Ecol 61, 423–428 (2011). https://doi.org/10.1007/s00248-010-9787-2

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  • DOI: https://doi.org/10.1007/s00248-010-9787-2

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