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.

Simple animal models for microbiome research

Abstract

The health and fitness of animals, including humans, are influenced by the presence and composition of resident microbial communities. The development of rational microbial therapies to alleviate chronic immunological, metabolic and neurobiological diseases requires an understanding of the processes underlying microbial community assembly and the mechanisms by which microorganisms influence host traits. For fundamental discovery, simple animal models (that is, lower vertebrate and invertebrate species with low diversity microbiomes) are more cost-effective and time-efficient than mammal models, especially for complex experimental designs and sophisticated genetic screens. Recent research on these simple models demonstrates how microbiome composition is shaped by the interplay between host controls, mediated largely via immune effectors, inter-microorganism competition, and neutral processes of passive dispersal and ecological drift. Parallel research on microbiome-dependent host traits has identified how specific metabolites and proteins released from microorganisms can shape host immune responsiveness, ameliorate metabolic dysfunction and influence behavioural traits. In this Review, the opportunity for microbiome research on the traditional biomedical models zebrafish, Drosophila melanogaster and Caenorhabditis elegans, which command superb research resources and tools, is discussed. Other systems, for example, hydra, squid and the honeybee, are valuable alternative models to address specific questions.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Simple animal models for microbiome research.
Fig. 2: Determinants of microbiota composition in animal hosts.
Fig. 3: The impact of the microbiome on host traits.

References

  1. 1.

    Knight, R. et al. The microbiome and human biology. Annu. Rev. Genomics Hum. Genet. 18, 65–86 (2017).

    CAS  PubMed  Google Scholar 

  2. 2.

    Franklin, C. L. & Ericsson, A. C. Microbiota and reproducibility of rodent models. Lab. Anim. (NY) 46, 114–122 (2017).

    Google Scholar 

  3. 3.

    Krams, I. A. et al. Microbiome symbionts and diet diversity incur costs on the immune system of insect larvae. J. Exp. Biol. 220, 4204–4212 (2017).

    PubMed  Google Scholar 

  4. 4.

    Mushegian, A. A., Arbore, R., Walser, J. C. & Ebert, D. Environmental sources of bacteria and genetic variation in behavior influence host-associated microbiota. Appl. Environ. Microbiol. 85, e01547-18 (2019).

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Marden, J. N., McClure, E. A., Beka, L. & Graf, J. Host matters: medicinal leech digestive-tract symbionts and their pathogenic potential. Front. Microbiol. 7, 1569 (2016).

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Fraune, S., Foret, S. & Reitzel, A. M. Using Nematostella vectensis to study the interactions between genome, epigenome, and bacteria in a changing environment. Front. Marine Sci. 3, 148 (2016).

    Google Scholar 

  7. 7.

    Koyle, M. L. et al. Rearing the fruit fly Drosophila melanogaster under axenic and gnotobiotic conditions. J. Vis. Exp. https://doi.org/10.3791/54219 (2016).

  8. 8.

    Szewczyk, N. J., Kozak, E. & Conley, C. A. Chemically defined medium and Caenorhabditis elegans. BMC Biotechnol. 3, 19 (2003).

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Melancon, E. et al. Best practices for germ-free derivation and gnotobiotic zebrafish husbandry. Methods Cell Biol. 138, 61–100 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Samuel, B. S., Rowedder, H., Braendle, C., Felix, M. A. & Ruvkun, G. Caenorhabditis elegans responses to bacteria from its natural habitats. Proc. Natl Acad. Sci. USA 113, E3941–E3949 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Flavel, M. R. et al. Growth of Caenorhabditis elegans in defined media is dependent on presence of particulate matter. G3 8, 567–575 (2018).

    CAS  PubMed  Google Scholar 

  12. 12.

    Pham, L. N., Kanther, M., Semova, I. & Rawls, J. F. Methods for generating and colonizing gnotobiotic zebrafish. Nat. Protoc. 3, 1862–1875 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Taormina, M. J. et al. Investigating bacterial-animal symbioses with light sheet microscopy. Biol. Bull. 223, 7–20 (2012).

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Markow, T. A. The secret lives of Drosophila flies. eLife https://doi.org/10.7554/eLife.06793 (2015).

  15. 15.

    Frezal, L. & Felix, M. A. C. elegans outside the Petri dish. eLife https://doi.org/10.7554/eLife.05849 (2015).

  16. 16.

    Parichy, D. M. Advancing biology through a deeper understanding of zebrafish ecology and evolution. eLife 4 https://doi.org/10.7554/eLife.05635 (2015).

  17. 17.

    Cabreiro, F. & Gems, D. Worms need microbes too: microbiota, health and aging in Caenorhabditis elegans. EMBO Mol. Med. 5, 1300–1310 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Zheng, H., Powell, J. E., Steele, M. I., Dietrich, C. & Moran, N. A. Honeybee gut microbiota promotes host weight gain via bacterial metabolism and hormonal signaling. Proc. Natl Acad. Sci. USA 114, 4775–4780 (2017).

    CAS  PubMed  Google Scholar 

  19. 19.

    Blum, J. E., Fischer, C. N., Miles, J. & Handelsman, J. Frequent replenishment sustains the beneficial microbiome of Drosophila melanogaster. mBio 4, e00860-13 (2013).

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Pais, I. S., Valente, R. S., Sporniak, M. & Teixeira, L. Drosophila melanogaster establishes a species-specific mutualistic interaction with stable gut-colonizing bacteria. PLOS Biol. 16, e2005710 (2018).

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Inamine, H. et al. Spatiotemporally heterogeneous population dynamics of gut bacteria inferred from fecal time series data. mBio 9, e01453-17 (2018).

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Obadia, B. et al. Probabilistic invasion underlies natural gut microbiome stability. Curr. Biol. 27, 1999–2006.e8 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    McFall-Ngai, M. Divining the essence of symbiosis: insights from the squid-vibrio model. PLOS Biol. 12, e1001783 (2014).

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Augustin, R. & Bosch, T. C. Revisiting the cutaneous epithelium: insights from a nontraditional model system. Akt. Dermatol. 42, 414–420 (2016).

    Google Scholar 

  25. 25.

    Suryanarayanan, S. et al. Collaboration matters: honey bee health as a transdisciplinary model for understanding real-world complexity. Bioscience 68, 990–995 (2018).

    PubMed  Google Scholar 

  26. 26.

    Zheng, H., Steele, M. I., Leonard, S. P., Motta, E. V. S. & Moran, N. A. Honey bees as models for gut microbiota research. Lab. Anim. (NY) 47, 317–325 (2018).

    PubMed  PubMed Central  Google Scholar 

  27. 27.

    Douglas, A. E. Fundamentals of Microbiome Science (Princeton University Press, 2018).

  28. 28.

    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  Google Scholar 

  29. 29.

    Fraune, S. & Bosch, T. C. Long-term maintenance of species-specific bacterial microbiota in the basal metazoan Hydra. Proc. Natl Acad. Sci. USA 104, 13146–13151 (2007).

    CAS  PubMed  Google Scholar 

  30. 30.

    Franzenburg, S. et al. Distinct antimicrobial peptide expression determines host species-specific bacterial associations. Proc. Natl Acad. Sci. USA 110, E3730–E3738 (2013).

    CAS  PubMed  Google Scholar 

  31. 31.

    Nyholm, S. V., Stabb, E. V., Ruby, E. G. & McFall-Ngai, M. J. Establishment of an animal-bacterial association: recruiting symbiotic vibrios from the environment. Proc. Natl Acad. Sci. USA 97, 10231–10235 (2000).

    CAS  PubMed  Google Scholar 

  32. 32.

    Hanlon, R. T., Claes, M. F., Ashcraft, S. E. & Dunlap, P. V. Laboratory culture of the sepiolid squid Euprymna scolopes: a model system for bacteria-animal symbiosis. Biol. Bull. 192, 364–374 (1997).

    CAS  PubMed  Google Scholar 

  33. 33.

    Belcaid, M. et al. Symbiotic organs shaped by distinct modes of genome evolution in cephalopods. Proc. Natl Acad. Sci. USA 116, 3030–3035 (2019).

    CAS  PubMed  Google Scholar 

  34. 34.

    Vanengelsdorp, D. et al. Colony collapse disorder: a descriptive study. PLOS ONE 4, e6481 (2009).

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Raymann, K. & Moran, N. A. The role of the gut microbiome in health and disease of adult honey bee workers. Curr. Opin. Insect Sci. 26, 97–104 (2018).

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Cho, I. & Blaser, M. J. The human microbiome: at the interface of health and disease. Nat. Rev. Genet. 13, 260–270 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Kwong, W. K. & Moran, N. A. Gut microbial communities of social bees. Nat. Rev. Microbiol. 14, 374–384 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Douglas, A. E. The Symbiotic Habit (Princeton University Press, 2010).

  39. 39.

    Wang, Y. et al. Vibrio fischeri flavohaemoglobin protects against nitric oxide during initiation of the squid-Vibrio symbiosis. Mol. Microbiol. 78, 903–915 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Foster, K. R., Schluter, J., Coyte, K. Z. & Rakoff-Nahoum, S. The evolution of the host microbiome as an ecosystem on a leash. Nature 548, 43–51 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Coyte, K. Z., Schluter, J. & Foster, K. R. The ecology of the microbiome: networks, competition, and stability. Science 350, 663–666 (2015).

    CAS  PubMed  Google Scholar 

  42. 42.

    Rolig, A. S. et al. A bacterial immunomodulatory protein with lipocalin-like domains facilitates host-bacteria mutualism in larval zebrafish. eLife 7, e37172 (2018). This study identifies a specific protein of an Aeromonas gut bacterium that functions to suppress gut inflammation, essential for the sustained health and survival of the zebrafish host.

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    Berg, M. et al. TGFβ/BMP immune signaling affects abundance and function of C. elegans gut commensals. Nat. Commun. 10, 604 (2019).

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Ryu, J. H. et al. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 319, 777–782 (2008).

    CAS  PubMed  Google Scholar 

  45. 45.

    Adair, K. L. & Douglas, A. E. Making a microbiome: the many determinants of host-associated microbial community composition. Curr. Opin. Microbiol. 35, 23–29 (2017).

    PubMed  Google Scholar 

  46. 46.

    Miller, E. T., Svanback, R. & Bohannan, B. J. M. Microbiomes as metacommunties: understanding host-associated microbes through metacommunity ecology. Trends Ecol. Evol. 33, 926–935 (2018). This opinion article provides a balanced overview of the diverse processes that shape the composition of microbiomes, and includes a succinct introduction to metacommunity theory and evolutionary feedback as applied to microbial communities in animals.

  47. 47.

    Newell, P. D. & Douglas, A. E. Interspecies interactions determine the impact of the gut microbiota on nutrient allocation in Drosophila melanogaster. Appl. Environ. Microbiol. 80, 788–796 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Sommer, A. J. & Newell, P. D. Metabolic basis for mutualism between gut bacteria and its impact on their host Drosophila melanogaster. Appl. Environ. Microbiol. 85, e01882-18 (2019).

    PubMed  PubMed Central  Google Scholar 

  49. 49.

    Gould, A. L. et al. Microbiome interactions shape host fitness. Proc. Natl Acad. Sci. USA 115, E11951–E11960 (2018). This analysis of Drosophila associations with different combinations of gut bacteria demonstrates how among-microorganism interactions, as well as the traits of individual bacterial taxa, are important in shaping bacterial abundance in the host and host fitness.

    CAS  PubMed  Google Scholar 

  50. 50.

    Wong, A. C., Chaston, J. M. & Douglas, A. E. The inconstant gut microbiota of Drosophila species revealed by 16S rRNA gene analysis. ISME J. 7, 1922–1932 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Adair, K. L., Wilson, M., Bost, A. & Douglas, A. E. Microbial community assembly in wild populations of the fruit fly Drosophila melanogaster. ISME J. 12, 959–972 (2018).

    PubMed  PubMed Central  Google Scholar 

  52. 52.

    Vega, N. M. & Gore, J. Stochastic assembly produces heterogeneous communities in the Caenorhabditis elegans intestine. PLOS Biol. 15, e2000633 (2017). This study of C. elegans colonized with functionally equivalent bacteria identifies the importance of stochastic processes in shaping community composition.

    PubMed  PubMed Central  Google Scholar 

  53. 53.

    Burns, A. R. et al. Contribution of neutral processes to the assembly of gut microbial communities in the zebrafish over host development. ISME J. 10, 655–664 (2016).

    CAS  PubMed  Google Scholar 

  54. 54.

    Sieber, M. et al. Neutrality in the metaorganism. PLOS Biol. 17, e3000298 (2019).

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Burns, A. R. et al. Interhost dispersal alters microbiome assembly and can overwhelm host innate immunity in an experimental zebrafish model. Proc. Natl Acad. Sci. USA 114, 11181–11186 (2017).

    CAS  PubMed  Google Scholar 

  56. 56.

    Tung, J. et al. Social networks predict gut microbiome composition in wild baboons. eLife 4, e05224 (2015).

    PubMed Central  Google Scholar 

  57. 57.

    Dill-McFarland, D. A. et al. Close social relationships correlate with human gut microbiota composition. Sci. Rep. 9, 703 (2019).

    PubMed  PubMed Central  Google Scholar 

  58. 58.

    Moeller, A. H. et al. Social behavior shapes the chimpanzee pan-microbiome. Sci. Adv. 2, e1500997 (2016).

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Louis, M. & de Polavieja, G. Collective behavior: social digging in Drosophila larvae. Curr. Biol. 27, R1010–R1012 (2017).

    CAS  PubMed  Google Scholar 

  60. 60.

    Hoang, K. L., Morran, L. T. & Gerardo, N. M. Experimental evolution as an underutilized tool for studying beneficial animal-microbe interactions. Front. Microbiol. 7, 1444 (2016).

    PubMed  PubMed Central  Google Scholar 

  61. 61.

    Robinson, C. D. et al. Experimental bacterial adaptation to the zebrafish gut reveals a primary role for immigration. PLOS Biol. 16, e2006893 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Martino, M. E. et al. Bacterial adaptation to the host’s diet is a key evolutionary force shaping Drosophila-Lactobacillus symbiosis. Cell Host Microbe 24, 109–119 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Lyell, N. L. et al. An expanded transposon mutant library reveals that Vibrio fischeri delta-aminolevulinate auxotrophs can colonize Euprymna scolopes. Appl. Environ. Microb. 83, e02470-16 (2017).

    Google Scholar 

  64. 64.

    Powell, J. E., Leonard, S. P., Kwong, W. K., Engel, P. & Moran, N. A. Genome-wide screen identifies host colonization determinants in a bacterial gut symbiont. Proc. Natl Acad. Sci. USA 113, 13887–13892 (2016).

    CAS  PubMed  Google Scholar 

  65. 65.

    Matos, R. C. et al. D-Alanylation of teichoic acids contributes to Lactobacillus plantarum-mediated Drosophila growth during chronic undernutrition. Nat. Microbiol. 2, 1635–1647 (2017).

    CAS  Google Scholar 

  66. 66.

    Shin, S. C. et al. Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science 334, 670–674 (2011).

    CAS  PubMed  Google Scholar 

  67. 67.

    Qi, B. & Han, M. Microbial siderophore enterobactin promotes mitochondrial iron uptake and development of the host via interaction with ATP synthase. Cell 175, 571–582 (2018).

    CAS  PubMed  Google Scholar 

  68. 68.

    Light, S. H. et al. A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria. Nature 562, 140–144 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Wong, A. C., Dobson, A. J. & Douglas, A. E. Gut microbiota dictates the metabolic response of Drosophila to diet. J. Exp. Biol. 217, 1894–1901 (2014).

    PubMed  PubMed Central  Google Scholar 

  70. 70.

    Sannino, D. R., Dobson, A. J., Edwards, K., Angert, E. R. & Buchon, N. The Drosophila melanogaster gut microbiota provisions thiamine to its host. mBio 9, e00155-18 (2018).

    PubMed  PubMed Central  Google Scholar 

  71. 71.

    Qi, B., Kniazeva, M. & Han, M. A vitamin-B2-sensing mechanism that regulates gut protease activity to impact animal’s food behavior and growth. eLife 6, e26243 (2017).

    PubMed  PubMed Central  Google Scholar 

  72. 72.

    Kesnerova, L. et al. Disentangling metabolic functions of bacteria in the honey bee gut. PLOS Biol. 15, e2003467 (2017). This study on the hindgut microbiota of honeybees identifies the contribution of individual bacterial taxa to host nutrition and, despite instances of among-taxon cross-feeding of metabolites, reveals little metabolic inter-dependence among the microbial taxa.

    PubMed  PubMed Central  Google Scholar 

  73. 73.

    Hill, J. H., Franzosa, E. A., Huttenhower, C. & Guillemin, K. A conserved bacterial protein induces pancreatic beta cell expansion during zebrafish development. eLife 5, e20145 (2016).

    PubMed  PubMed Central  Google Scholar 

  74. 74.

    Koropatnick, T. A. et al. Microbial factor-mediated development in a host-bacterial mutualism. Science 306, 1186–1188 (2004).

    CAS  PubMed  Google Scholar 

  75. 75.

    Murillo-Rincon, A. P. et al. Spontaneous body contractions are modulated by the microbiome of Hydra. Sci. Rep. 7, 15937 (2017). This study finds that the microbial community promotes regular contractions of the body column of hydra, elegantly demonstrating the value of a simple system for behavioural studies, with potential relevance to microbial impacts on gut peristalsis in other animals.

    PubMed  PubMed Central  Google Scholar 

  76. 76.

    Fraune, S. et al. Bacteria-bacteria interactions within the microbiota of the ancestral metazoan Hydra contribute to fungal resistance. ISME J. 9, 1543–1556 (2015).

    CAS  PubMed  Google Scholar 

  77. 77.

    Fischer, C. N. et al. Metabolite exchange between microbiome members produces compounds that influence Drosophila behavior. eLife 6, e18855 (2017).

    PubMed  PubMed Central  Google Scholar 

  78. 78.

    Farine, J. P., Habbachi, W., Cortot, J., Roche, S. & Ferveur, J. F. Maternally-transmitted microbiota affects odor emission and preference in Drosophila larva. Sci. Rep. 7, 6062 (2017).

    PubMed  PubMed Central  Google Scholar 

  79. 79.

    Clark, L. C. & Hodgkin, J. Commensals, probiotics and pathogens in the Caenorhabditis elegans model. Cell Microbiol. 16, 27–38 (2014).

    CAS  PubMed  Google Scholar 

  80. 80.

    Erkosar, B., Storelli, G., Defaye, A. & Leulier, F. Host-intestinal microbiota mutualism: “Learning on the Fly”. Cell Host Microbe 13, 8–14 (2013).

    CAS  PubMed  Google Scholar 

  81. 81.

    Li, H., Qi, Y. & Jasper, H. Preventing age-related decline of gut compartmentalization limits microbiota dysbiosis and extends lifespan. Cell Host Microbe 19, 240–253 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Rooks, M. G. & Garrett, W. S. Gut microbiota, metabolites and host immunity. Nat. Rev. Immunol. 16, 341–352 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Belkaid, Y. & Harrison, O. J. Homeostatic immunity and the microbiota. Immunity 46, 562–576 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Montalvo-Katz, S., Huang, H., Appel, M. D., Berg, M. & Shapira, M. Association with soil bacteria enhances p38-dependent infection resistance in Caenorhabditis elegans. Infect. Immun. 81, 514–520 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Berg, M., Zhou, X. Y. & Shapira, M. Host-specific functional significance of Caenorhabditis gut commensals. Front. Microbiol. 7, 1622 (2016). This study on C. elegans and the related nematode C. briggsiae reveals host specificity of the protective function of gut microorganisms against pathogens, suggestive of possible co-evolutionary interactions between the host and members of its microbiome.

    PubMed  PubMed Central  Google Scholar 

  86. 86.

    Zhang, F. et al. Caenorhabditis elegans as a model for microbiome research. Front. Microbiol. 8, 485 (2017).

    PubMed  PubMed Central  Google Scholar 

  87. 87.

    Nyholm, S. V., Stewart, J. J., Ruby, E. G. & Mcfall-Ngai, M. J. Recognition between symbiotic Vibrio fischeri and the hemocytes of Euprymna scolopes. Environ. Microbiol. 11, 483–493 (2009). This elegant analysis of the functional response of squid haemocytes to bacteria reveals that haemocytes from squid containing the native symbiont V. fischeri are specifically inactive against V. fischeri, thereby protecting the association from deleterious immunological attack.

    PubMed  PubMed Central  Google Scholar 

  88. 88.

    Collins, A. J., Schleicher, T. R., Rader, B. A. & Nyholm, S. V. Understanding the role of host hemocytes in a squid/vibrio symbiosis using transcriptomics and proteomics. Front. Immunol. 3, 91 (2012).

    PubMed  PubMed Central  Google Scholar 

  89. 89.

    Schleicher, T. R., VerBerkmoes, N. C., Shah, M. & Nyholm, S. V. Colonization state influences the hemocyte proteome in a beneficial squid-Vibrio symbiosis. Mol. Cell Proteomics 13, 2673–2686 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Huang, J. H. & Douglas, A. E. Consumption of dietary sugar by gut bacteria determines Drosophila lipid content. Biol. Lett. 11, 20150469 (2015).

    PubMed  PubMed Central  Google Scholar 

  91. 91.

    Kamareddine, L., Robins, W. P., Berkey, C. D., Mekalanos, J. J. & Watnick, P. I. The Drosophila immune deficiency pathway modulates enteroendocrine function and host metabolism. Cell Metab. 28, 449–462 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Musselman, L. P. & Kuhnlein, R. P. Drosophila as a model to study obesity and metabolic disease. J. Exp. Biol. 221, 163881 (2018).

    Google Scholar 

  93. 93.

    Kleinert, M. et al. Animal models of obesity and diabetes mellitus. Nat. Rev. Endocrinol. 14, 140–162 (2018).

    PubMed  Google Scholar 

  94. 94.

    Koh, A., De Vadder, F., Kovatcheva-Datchary, P. & Backhed, F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165, 1332–1345 (2016).

    CAS  PubMed  Google Scholar 

  95. 95.

    Smith, K., McCoy, K. D. & Macpherson, A. J. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin. Immunol. 19, 59–69 (2007).

    CAS  Google Scholar 

  96. 96.

    Martinez-Guryn, K. et al. Small intestine microbiota regulate host digestive and absorptive adaptive responses to dietary lipids. Cell Host Microbe 23, 458–469.e5 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Semova, I. et al. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish. Cell Host Microbe 12, 277–288 (2012).

    CAS  PubMed  Google Scholar 

  98. 98.

    Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

    PubMed  PubMed Central  Google Scholar 

  99. 99.

    Wong, S. et al. Ontogenetic differences in dietary fat influence microbiota assembly in the zebrafish gut. mBio 6, e00687-15 (2015).

    PubMed  PubMed Central  Google Scholar 

  100. 100.

    Whon, T. W. et al. Conditionally pathogenic gut microbes promote larval growth by increasing redox-dependent fat storage in high-sugar diet-fed Drosophila. Antioxid. Redox Signal. 27, 1361–1380 (2017).

    CAS  PubMed  Google Scholar 

  101. 101.

    Chaston, J. M., Newell, P. D. & Douglas, A. E. Metagenome-wide association of microbial determinants of host phenotype in Drosophila melanogaster. mBio 5, e01631-14 (2014).

    PubMed  PubMed Central  Google Scholar 

  102. 102.

    Brooks, K. K., Liang, B. & Watts, J. L. The influence of bacterial diet on fat storage in C. elegans. PLOS ONE 4, e7545 (2009).

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Falcinelli, S. et al. Lactobacillus rhamnosus lowers zebrafish lipid content by changing gut microbiota and host transcription of genes involved in lipid metabolism. Sci. Rep. 5, 9336 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Falcinelli, S. et al. Probiotic treatment reduces appetite and glucose level in the zebrafish model. Sci. Rep. 6, 18061 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Valles-Colomer, M. et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat. Microbiol. 4, 623–632 (2019).

    CAS  PubMed  Google Scholar 

  106. 106.

    Vuong, H. E., Yano, J. M., Fung, T. C. & Hsiao, E. Y. The microbiome and host behavior. Annu. Rev. Neurosci. 40, 21–49 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Luczynski, P. et al. Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior. Int. J. Neuropsychopharmacol. 19, pyw020 (2016).

    PubMed  PubMed Central  Google Scholar 

  108. 108.

    Davis, D. J., Bryda, E. C., Gillespie, C. H. & Ericsson, A. C. Microbial modulation of behavior and stress responses in zebrafish larvae. Behav. Brain Res. 311, 219–227 (2016).

    PubMed  PubMed Central  Google Scholar 

  109. 109.

    Phelps, D. et al. Microbial colonization is required for normal neurobehavioral development in zebrafish. Sci. Rep. 7, 11244 (2017).

    PubMed  PubMed Central  Google Scholar 

  110. 110.

    Schretter, C. E. et al. A gut microbial factor modulates locomotor behaviour in Drosophila. Nature 563, 402–406 (2018). This study of Drosophila behaviour identified an enzyme, xylose isomerase, produced by a gut bacterium as the determinant of microbial-mediated reduction of host locomotory activity, mediated by changes in the activity of octopaminergic neurons in the brain.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. 111.

    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  Google Scholar 

  112. 112.

    Najarro, M. A., Sumethasorn, M., Lamoureux, A. & Turner, T. L. Choosing mates based on the diet of your ancestors: replication of non-genetic assortative mating in Drosophila melanogaster. PeerJ 3, e1173 (2015).

    PubMed  PubMed Central  Google Scholar 

  113. 113.

    Leftwich, P. T., Clarke, N. V. E., Hutchings, M. I. & Chapman, T. Gut microbiomes and reproductive isolation in Drosophila. Proc. Natl Acad. Sci. USA 114, 12767–12772 (2017).

    CAS  PubMed  Google Scholar 

  114. 114.

    Rajpurohit, S. et al. Adaptive dynamics of cuticular hydrocarbons in Drosophila. J. Evol. Biol. 30, 66–80 (2017).

    CAS  PubMed  Google Scholar 

  115. 115.

    Kuo, T. H. et al. Insulin signaling mediates sexual attractiveness in Drosophila. PLOS Genet. 8, e1002684 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. 116.

    Nelson, C. M., Ihle, K. E., Fondrk, M. K., Page, R. E. & Amdam, G. V. The gene vitellogenin has multiple coordinating effects on social organization. PLOS Biol. 5, e62 (2007).

    PubMed  PubMed Central  Google Scholar 

  117. 117.

    Schwarz, R. S., Moran, N. A. & Evans, J. D. Early gut colonizers shape parasite susceptibility and microbiota composition in honey bee workers. Proc. Natl Acad. Sci. USA 113, 9345–9350 (2016).

    CAS  PubMed  Google Scholar 

  118. 118.

    Jones, J. C. et al. The gut microbiome is associated with behavioural task in honey bees. Insectes Soc. 65, 419–429 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. 119.

    Motta, E. V. S., Raymann, K. & Moran, N. A. Glyphosate perturbs the gut microbiota of honey bees. Proc. Natl Acad. Sci. USA 115, 10305–10310 (2018).

    CAS  PubMed  Google Scholar 

  120. 120.

    Balbuena, M. S. et al. Effects of sublethal doses of glyphosate on honeybee navigation. J. Exp. Biol. 218, 2799–2805 (2015).

    PubMed  Google Scholar 

  121. 121.

    Arora, A. K. & Douglas, A. E. Hype or opportunity? Using microbial symbionts in novel strategies for insect pest control. J. Insect. Physiol. 103, 10–17 (2017).

    CAS  PubMed  Google Scholar 

  122. 122.

    Damjanovic, K., Blackall, L. L., Webster, N. S. & van Oppen, M. J. H. The contribution of microbial biotechnology to mitigating coral reef degradation. Microb. Biotechnol. 10, 1236–1243 (2017).

    PubMed  PubMed Central  Google Scholar 

  123. 123.

    Matthews, C. et al. The rumen microbiome: a crucial consideration when optimising milk and meat production and nitrogen utilisation efficiency. Gut Microbes 10, 115–132 (2019).

    PubMed  PubMed Central  Google Scholar 

  124. 124.

    Nguyen, T. L., Vieira-Silva, S., Liston, A. & Raes, J. How informative is the mouse for human gut microbiota research? Dis. Model Mech. 8, 1–16 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. 125.

    Collins, J. et al. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature 553, 291–294 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. 126.

    Bein, A. et al. Microfluidic organ-on-a-chip models of human intestine. Cell Mol. Gastroenterol. Hepatol. 5, 659–668 (2018).

    PubMed  PubMed Central  Google Scholar 

  127. 127.

    Gierer, A. The hydra model — a model for what? Int. J. Dev. Biol. 56, 437–445 (2012).

    PubMed  Google Scholar 

  128. 128.

    Kim, Y. & Mylonakis, E. Caenorhabditis elegans immune conditioning with the probiotic bacterium Lactobacillus acidophilus strain NCFM enhances gram-positive immune responses. Infect. Immun. 80, 2500–2508 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. 129.

    Bilder, D. & Irvine, K. D. Taking stock of the Drosophila research ecosystem. Genetics 206, 1227–1236 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. 130.

    Meyers, J. R. Zebrafish: development of a vertebrate model organism. Curr. Protocols Essent. Lab. Techn. e19 (2018).

  131. 131.

    Stephens, W. Z. et al. The composition of the zebrafish intestinal microbial community varies across development. ISME J. 10, 644–654 (2016).

    PubMed  Google Scholar 

  132. 132.

    Engel, P. et al. The bee microbiome: impact on bee health and model for evolution and ecology of host-microbe interactions. mBio 7, e02164-15 (2016).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This Review was written with the financial support from NIH grant R01GM095372.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Angela E. Douglas.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Blind-ended gut

The gut has a single opening to the exterior, through which the food is ingested and, following digestion and absorption, waste is egested.

Nerve net

Two-dimensional lattice of neurons connected by synapses that includes sensory, motor and integrative elements, and transmits impulses in all directions.

Glycocalyx

Extracellular matrix of glycoprotein and glycolipid bounding the external surface of many cells.

Shoaling

Staying together as a group while swimming, for example, in fish.

Aggregative feeding

Feeding in a group.

Octopaminergic neurons

Neurons that release the neurotransmitter octopamine.

Vitellogenin

The major yolk protein in animal eggs, also present in the haemolymph (blood) of the non-reproductive worker caste of the honeybee.

Glyphosate

An organophosphorus compound that inhibits the plant enzyme 5-enolpyruvylshikimate-3-phosphate synthase, and widely used as a herbicide under the trade name Roundup.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Douglas, A.E. Simple animal models for microbiome research. Nat Rev Microbiol 17, 764–775 (2019). https://doi.org/10.1038/s41579-019-0242-1

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