Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Stress and stability: applying the Anna Karenina principle to animal microbiomes

Abstract

All animals studied to date are associated with symbiotic communities of microorganisms. These animal microbiotas often play important roles in normal physiological function and susceptibility to disease; predicting their responses to perturbation represents an essential challenge for microbiology. Most studies of microbiome dynamics test for patterns in which perturbation shifts animal microbiomes from a healthy to a dysbiotic stable state. Here, we consider a complementary alternative: that the microbiological changes induced by many perturbations are stochastic, and therefore lead to transitions from stable to unstable community states. The result is an ‘Anna Karenina principle’ for animal microbiomes, in which dysbiotic individuals vary more in microbial community composition than healthy individuals—paralleling Leo Tolstoy's dictum that “all happy families look alike; each unhappy family is unhappy in its own way”. We argue that Anna Karenina effects are a common and important response of animal microbiomes to stressors that reduce the ability of the host or its microbiome to regulate community composition. Patterns consistent with Anna Karenina effects have been found in systems ranging from the surface of threatened corals exposed to above-average temperatures, to the lungs of patients suffering from HIV/AIDs. However, despite their apparent ubiquity, these patterns are easily missed or discarded by some common workflows, and therefore probably underreported. Now that a substantial body of research has established the existence of these patterns in diverse systems, rigorous testing, intensive time-series datasets and improved stochastic modelling will help to explore their importance for topics ranging from personalized medicine to theories of the evolution of host–microorganism symbioses.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Anna Karenina principle of perturbations inducing microbiome destabilization.
Figure 2: Stochasticity produces contrasting effects of mild and severe perturbations under different models of microbiome dynamics.

References

  1. 1

    McFall-Ngai, M. et al. Animals in a bacterial world, a new imperative for the life sciences. Proc. Natl Acad. Sci. USA 110, 3229–3236 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  2. 2

    Pace, N. R. A molecular view of microbial diversity and the biosphere. Science 276, 734–740 (1997).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  3. 3

    Hug, L. A. et al. A new view of the tree of life. Nat. Microbiol. 1, 16048 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  4. 4

    Konstantinidis, K. T. & Tiedje, J. M. Towards a genome-based taxonomy for prokaryotes. J. Bacteriol. 187, 6258–6264 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. 5

    Chaffron, S., Rehrauer, H., Pernthaler, J. & von Mering, C. A global network of coexisting microorganisms from environmental and whole-genome sequence data. Genome Res. 20, 947–959 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. 6

    Zaneveld, J. R., Lozupone, C., Gordon, J. I. & Knight, R. Ribosomal RNA diversity predicts genome diversity in gut bacteria and their relatives. Nucleic Acids Res. 38, 3869–3879 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7

    Langille, M. G. I. et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat. Biotechnol. 31, 814–821 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. 8

    Rinke, C. et al. Insights into the phylogeny and coding potential of microbial dark matter. Nature 499, 431–437 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9

    Frost, L. S., Leplae, R., Summers, A. O. & Toussaint, A. Mobile genetic elements: the agents of open source evolution. Nat. Rev. Microbiol. 3, 722–732 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  10. 10

    Sachs, J. L., Skophammer, R. G. & Regus, J. U. Evolutionary transitions in bacterial symbiosis. Proc. Natl Acad. Sci. USA 108, 10800–10807 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  11. 11

    Sharon, G. et al. Commensal bacteria play a role in mating preference of Drosophila melanogaster. Proc. Natl Acad. Sci. USA 107, 20051–20056 (2010).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  12. 12

    Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. 13

    Nyholm, S. V. & McFall-Ngai, M. The winnowing: establishing the squid–vibrio symbiosis. Nat. Rev. Microbiol. 2, 632–642 (2004).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  14. 14

    Coppa, G. V., Bruni, S., Morelli, L., Soldi, S. & Gabrielli, O. The first prebiotics in humans: human milk oligosaccharides. J. Clin. Gastroenterol. 38, 80–83 (2004).

    Article  Google Scholar 

  15. 15

    Flórez, L. V., Biedermann, P. H. W., Engl, T. & Kaltenpoth, M. Defensive symbioses of animals with prokaryotic and eukaryotic microorganisms. Nat. Prod. Rep. 32, 904–936 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  16. 16

    Ellner, S. P., Schluter, J. & Foster, K. R. The evolution of mutualism in gut microbiota via host epithelial selection. PLoS Biol. 10, e1001424 (2012).

    Article  CAS  Google Scholar 

  17. 17

    Barr, J. J. et al. Bacteriophage adhering to mucus provide a non-host-derived immunity. Proc. Natl Acad. Sci. USA 110, 10771–10776 (2013).

    CAS  Article  PubMed  Google Scholar 

  18. 18

    Whittaker, R. H. Evolution and measurement of species diversity. Taxon 21, 213 (1972).

    Article  Google Scholar 

  19. 19

    Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2008).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  20. 20

    Jani, A. J. & Briggs, C. J. The pathogen Batrachochytrium dendrobatidis disturbs the frog skin microbiome during a natural epidemic and experimental infection. Proc. Natl Acad. Sci. USA 111, E5049–E5058 (2014).

    Article  CAS  Google Scholar 

  21. 21

    Thomas, T. et al. Diversity, structure and convergent evolution of the global sponge microbiome. Nat. Commun. 7, 11870 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22

    Yilmaz, Ö. et al. Microbiome profiles in periodontitis in relation to host and disease characteristics. PloS ONE 10, e0127077 (2015).

    Article  CAS  Google Scholar 

  23. 23

    Casey, J. M., Connolly, S. R. & Ainsworth, T. D. Coral transplantation triggers shift in microbiome and promotion of coral disease associated potential pathogens. Sci. Rep. 5, 11903 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  24. 24

    Kohl, K. D. et al. Gut microorganisms of mammalian herbivores facilitate intake of plant toxins. Ecol. Lett. 17, 1238–1246 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  25. 25

    Diamond, J. Guns, Germs, and Steel: The Fates of Human Societies (W. W. Norton, 1999).

    Google Scholar 

  26. 26

    Giongo, A. et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 5, 82–91 (2010).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  27. 27

    Gilbert, J. A., Holmes, I., Harris, K. & Quince, C. Dirichlet multinomial mixtures: generative models for microbial metagenomics. PLoS ONE 7, e30126 (2012).

    Article  Google Scholar 

  28. 28

    Dey, N., Soergel, D. A. W., Repo, S. & Brenner, S. E. Association of gut microbiota with post-operative clinical course in Crohn's disease. BMC Gastroenterol. 13, 131 (2013).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  29. 29

    Mutlu, E. A. et al. Colonic microbiome is altered in alcoholism. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G966–G978 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30

    Chen, Y. et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54, 562–572 (2011).

    PubMed  Article  PubMed Central  Google Scholar 

  31. 31

    Chen, Y. et al. Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality. J. Gastoenterol. Hepatol. 30, 1429–1437 (2015).

    CAS  Article  Google Scholar 

  32. 32

    Heimesaat, M. M. et al. Disordered microbial communities in the upper respiratory tract of cigarette smokers. PLoS ONE 5, e15216 (2010).

    Article  CAS  Google Scholar 

  33. 33

    Wu, J. et al. Cigarette smoking and the oral microbiome in a large study of American adults. ISME J. 10, 2435–2446 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34

    Zaneveld, J. R. et al. Overfishing and nutrient pollution interact with temperature to disrupt coral reefs down to microbial scales. Nat. Commun. 7, 11833 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35

    Voolstra, C. R. et al. Macroalgae decrease growth and alter microbial community structure of the reef-building coral, Porites astreoides. PLoS ONE 7, e44246 (2012).

    Article  CAS  Google Scholar 

  36. 36

    Lesser, M. P., Fiore, C., Slattery, M. & Zaneveld, J. Climate change stressors destabilize the microbiome of the Caribbean barrel sponge, Xestospongia muta. J. Exp. Mar. Biol. Ecol. 475, 11–18 (2016).

    Article  Google Scholar 

  37. 37

    Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 38

    Masur, H. et al. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: updated guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clin. Infect. Dis. 58, 1308–1311 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  39. 39

    Williams, B., Landay, A. & Presti, R. M. Microbiome alterations in HIV infection a review. Cell. Micobiol. 18, 645–651 (2016).

    CAS  Article  Google Scholar 

  40. 40

    Beck, J. M. et al. Multicenter comparison of lung and oral microbiomes of HIV-infected and HIV-uninfected individuals. Am. J. Respir. Crit. Care Med. 192, 1335–1344 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  41. 41

    Twigg, H. L. et al. Effect of advanced HIV infection on the respiratory microbiome. Am. J. Respir. Crit. Care Med. 194, 226–235 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42

    Dinh, D. M. et al. Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV Infection. J. Infect. Dis. 211, 19–27 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  43. 43

    Sun, Y. et al. Fecal bacterial microbiome diversity in chronic HIV-infected patients in China. Emerg. Microbes Infect. 5, e31 (2016).

    PubMed  PubMed Central  Google Scholar 

  44. 44

    Moeller, A. H. et al. SIV-induced instability of the chimpanzee gut microbiome. Cell Host Microbe 14, 340–345 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45

    Barbian, H. J. et al. Destabilization of the gut microbiome marks the end-stage of simian immunodeficiency virus infection in wild chimpanzees. Am. J. Primatol. http://dx.doi.org/10.1002/ajp.22515 (2015).

  46. 46

    Moeller, A. H. et al. Stability of the gorilla microbiome despite simian immunodeficiency virus infection. Mol. Ecol. 24, 690–697 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47

    Weese, S. J., Nichols, J., Jalali, M. & Litster, A. The oral and conjunctival microbiotas in cats with and without feline immunodeficiency virus infection. Vet. Res. 46, 21 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  48. 48

    Charlson, E. S. et al. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. Am. J. Respir. Crit. Care Med. 186, 536–545 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  49. 49

    Lu, H. et al. Assessment of microbiome variation during the perioperative period in liver transplant patients: a retrospective analysis. Microb. Ecol. 65, 781–791 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  50. 50

    Raju, R. et al. burn injury alters the intestinal microbiome and increases gut permeability and bacterial translocation. PloS ONE 10, e0129996 (2015).

    Article  CAS  Google Scholar 

  51. 51

    Zhang, H., Sparks, J. B., Karyala, S. V., Settlage, R. & Luo, X. M. Host adaptive immunity alters gut microbiota. ISME J. 9, 770–781 (2014).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  52. 52

    Palm, Noah W. et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158, 1000–1010 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. 53

    Pérez-Brocal, V. et al. Study of the viral and microbial communities associated with Crohn's disease: a metagenomic approach. Clin. Transl. Gastroenterol. 4, e36 (2013).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  54. 54

    Martinez, C. et al. Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am. J. Gastroenterol. 103, 643–648 (2008).

    PubMed  Article  PubMed Central  Google Scholar 

  55. 55

    Berry, D. et al. Intestinal microbiota signatures associated with inflammation history in mice experiencing recurring colitis. Front. Microbiol. 6, 1408 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  56. 56

    Halfvarson, J. et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat. Microbiol. 2, 17004 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. 57

    Tsolis, R. M. et al. Expression of the blood-group-related gene B4galnt2 alters susceptibility to Salmonella infection. PLoS Pathog. 11, e1005008 (2015).

    Article  CAS  Google Scholar 

  58. 58

    Allen, I. C. et al. Chronic Trichuris muris infection decreases diversity of the intestinal microbiota and concomitantly increases the abundance of Lactobacilli. PLoS ONE 10, e0125495 (2015).

    Article  CAS  Google Scholar 

  59. 59

    Kim, C. H. et al. Chronic Trichuris muris infection in C57BL/6 mice causes significant changes in host microbiota and metabolome: effects reversed by pathogen clearance. PLoS ONE 10, e0125945 (2015).

    Article  CAS  Google Scholar 

  60. 60

    McMahon, T. A. et al. Chytrid fungus Batrachochytrium dendrobatidis has nonamphibian hosts and releases chemicals that cause pathology in the absence of infection. Proc. Natl Acad. Sci. USA 110, 210–215 (2012).

    PubMed  Article  PubMed Central  Google Scholar 

  61. 61

    Fisher, M. C. et al. Community structure and function of amphibian skin microbes: an experiment with bullfrogs exposed to a chytrid fungus. PloS ONE 10, e0139848 (2015).

    Article  CAS  Google Scholar 

  62. 62

    Clarke, K. R. Non-parametric multivariate analyses of changes in community structure. Austral. Ecol. 18, 117–143 (1993).

    Article  Google Scholar 

  63. 63

    Anderson, M. J. A new method for non-parametric multivariate analysis of variance. Austral. Ecol. 26, 32–46 (2001).

    Google Scholar 

  64. 64

    Haiser, H. J. et al. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 341, 295–298 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. 65

    Lehouritis, P. et al. Local bacteria affect the efficacy of chemotherapeutic drugs. Sci. Rep. 5, 14554 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. 66

    Lee, Y. K. & Mazmanian, S. K. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330, 1768–1773 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67

    Brüssow, H. How stable is the human gut microbiota? And why this question matters. Environ. Microbiol. 18, 2779–2783 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  68. 68

    David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2013).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  69. 69

    Sonnenburg, E. D. et al. Diet-induced extinctions in the gut microbiota compound over generations. Nature 529, 212–215 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. 70

    Rebollar, E. A. et al. Skin bacterial diversity of Panamanian frogs is associated with host susceptibility and presence of Batrachochytrium dendrobatidis. ISME J. 10, 1682–1695 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. 71

    Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7, 335–336 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. 72

    Faust, K., Lahti, L., Gonze, D., de Vos, W. M. & Raes, J. Metagenomics meets time series analysis: unraveling microbial community dynamics. Curr. Opin. Microbiol. 25, 56–66 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  73. 73

    Weiss, S. et al. Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome 5, 27 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  74. 74

    Dethlefsen, L. & Relman, D. A. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl Acad. Sci. USA 108, 4554–4561 (2010).

    PubMed  Article  PubMed Central  Google Scholar 

  75. 75

    Meadow, J. F., Bateman, A. C., Herkert, K. M., O'Connor, T. K. & Green, J. L. Significant changes in the skin microbiome mediated by the sport of roller derby. PeerJ 1, e53 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  76. 76

    McDonald, D. et al. Extreme dysbiosis of the microbiome in critical illness. mSphere 1, e00199-16 (2016).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  77. 77

    Prescott, H. C., Dickson, R. P., Rogers, M. A. M., Langa, K. M. & Iwashyna, T. J. Hospitalization type and subsequent severe sepsis. Am. J. Respir. Crit. Care Med 192, 581–588 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  78. 78

    Scheuring, I., Yu, D. W. & van Baalen, M. How to assemble a beneficial microbiome in three easy steps. Ecol. Lett. 15, 1300–1307 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  79. 79

    Gonze, D., Lahti, L., Raes, J. & Faust, K. Multi-stability and the origin of microbial community types. ISME J. http://dx.doi.org/10.1038/ismej.2017.60 (2017).

  80. 80

    Kirst, M. E. et al. Dysbiosis and alterations in predicted functions of the subgingival microbiome in chronic periodontitis. Appl. Environ. Microbiol. 81, 783–793 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  81. 81

    Kong, H. H. et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 22, 850–859 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. 82

    Pereira, D. I. A. et al. Dietary iron depletion at weaning imprints low microbiome diversity and this is not recovered with oral nano Fe(III). MicrobiologyOpen 4, 12–27 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  83. 83

    Clayton, T. A., Baker, D., Lindon, J. C., Everett, J. R. & Nicholson, J. K. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc. Natl Acad. Sci. USA 106, 14728–14733 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  84. 84

    Holmes, E. et al. Therapeutic modulation of microbiota-host metabolic interactions. Sci. Transl. Med. 4, 137rv6 (2012).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  85. 85

    Gurwitz, D. The gut microbiome: insights for personalized medicine. Drug Dev. Res. 74, 341–343 (2013).

    CAS  Article  Google Scholar 

  86. 86

    Gibbons, S. M. et al. Disturbance regimes predictably alter diversity in an ecologically complex bacterial system. mBio 7, e01372-16 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank D. Burkepile, J. Gilbert, D. McDonald, T. Sharpton, C. Armour, J. Jensen, C. Chang and many other colleagues for useful discussions. This work was supported by a National Science Foundation Dimensions of Biodiversity grant (no. 1442306).

Author information

Affiliations

Authors

Contributions

J.R.Z. wrote the manuscript. All authors conducted research, contributed intellectually, and edited the manuscript.

Corresponding authors

Correspondence to Jesse R. Zaneveld or Rebecca Vega Thurber.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zaneveld, J., McMinds, R. & Vega Thurber, R. Stress and stability: applying the Anna Karenina principle to animal microbiomes. Nat Microbiol 2, 17121 (2017). https://doi.org/10.1038/nmicrobiol.2017.121

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing