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.

  • Perspective
  • Published:

C. elegans: A biosensor for host–microbe interactions

Abstract

Microbes are an integral part of life on this planet. Microbes and their hosts influence each other in an endless dance that shapes how the meta-organism interacts with its environment. Although great advances have been made in microbiome research over the past 20 years, the mechanisms by which both hosts and their microbes interact with each other and the environment are still not well understood. The nematode Caenorhabditis elegans has been widely used as a model organism to study a remarkable number of human-like processes. Recent evidence shows that the worm is a powerful tool to investigate in fine detail the complexity that exists in microbe–host interactions. By combining the large array of genetic tools available for both organisms together with deep phenotyping approaches, it has been possible to uncover key effectors in the complex relationship between microbes and their hosts. In this perspective, we survey the literature for insightful discoveries in the microbiome field using the worm as a model. We discuss the latest conceptual and technological advances in the field and highlight the strengths that make C. elegans a valuable biosensor tool for the study of microbe–host interactions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Timeline of publications providing remarkable insights into C. elegans–microbe interactions.
Fig. 2: An experimental pipeline to explore host–microbe interactions.

Similar content being viewed by others

References

  1. Tashiro, T. et al. Early trace of life from 3.95 Ga sedimentary rocks in Labrador, Canada. Nature 549, 516–518 (2017).

    Article  PubMed  Google Scholar 

  2. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Groussin, M. et al. Unraveling the processes shaping mammalian gut microbiomes over evolutionary time. Nat. Commun. 8, 14319 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sharpton, T. J. Role of the gut microbiome in vertebrate evolution. mSystems 3, e00174-17 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Louca, S. et al. Function and functional redundancy in microbial systems. Nat. Ecol. Evol 2, 936–943 (2018).

    Article  PubMed  Google Scholar 

  6. Klassen, J. L. Defining microbiome function. Nat. Microbiol. 3, 864–869 (2018).

    Article  CAS  PubMed  Google Scholar 

  7. Skillings, D. Holobionts and the ecology of organisms: multi-species communities or integrated individuals? Biol. Philos. 31, 875–892 (2016).

    Article  Google Scholar 

  8. Hammer, T. J., Sanders, J. G. & Fierer, N. Not all animals need a microbiome. FEMS Microbiol. Lett. 366, 1–11 (2019).

    Article  CAS  Google Scholar 

  9. Lloyd-Price, J., Abu-Ali, G. & Huttenhower, C. The healthy human microbiome. Genome Med. 8, 1–11 (2016).

    Article  Google Scholar 

  10. Gonze, D., Lahti, L., Raes, J. & Faust, K. Multi-stability and the origin of microbial community types. ISME J. 11, 2159–2166 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Martí, J. M. et al. Health and disease imprinted in the time variability of the human microbiome. mSystems 2, e00144-16 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  12. D’hoe, K. et al. Integrated culturing, modeling and transcriptomics uncovers complex interactions and emergent behavior in a three-species synthetic gut community. Elife 7, 299644 (2018).

    Google Scholar 

  13. Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623–628 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Brochado, A. R. et al. Species-specific activity of antibacterial drug combinations. Nature 559, 259–263 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Douglas, A. E. Simple animal models for microbiome research. Nat. Rev. Microbiol. 17, 764–775 (2019).

    Article  CAS  PubMed  Google Scholar 

  16. Stagaman, K., Sharpton, T. J. & Guillemin, K. Zebrafish microbiome studies make waves. Lab Anim. (NY) 49, 201–207 (2020).

    Article  Google Scholar 

  17. Norvaisas, P. & Cabreiro, F. Pharmacology in the age of the holobiont. Curr. Opin. Syst. Biol. 10, 34–42 (2018).

    Article  Google Scholar 

  18. Frézal, L. & Félix, M.-A. C. elegans outside the Petri dish. Elife 4, 1–14 (2015).

    Article  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  20. Kim, W. et al. A new class of synthetic retinoid antibiotics effective against bacterial persisters. Nature 556, 103–107 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 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.e11 (2018).

    Article  CAS  PubMed  Google Scholar 

  22. Seth, P. et al. Regulation of microRNA machinery and development by interspecies S-nitrosylation. Cell 176, 1014–1025.e12 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dirksen, P. et al. The native microbiome of the nematode Caenorhabditis elegans: gateway to a new host-microbiome model. BMC Biol. 14, 1–16 (2016).

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Berg, M. et al. Assembly of the Caenorhabditis elegans gut microbiota from diverse soil microbial environments. ISME J 10, 1998–2009 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Berg, M., Zhou, X. Y. & Shapira, M. Host-specific functional significance of Caenorhabditis gut commensals. Front. Microbiol. 7, 1–9 (2016).

    Article  Google Scholar 

  27. Hoffman, C. L., Lalsiamthara, J. & Aballay, A. Host mucin is exploited by Pseudomonas aeruginosa to provide monosaccharides required for a successful infection. mBio 11, 1–15 (2020).

    Article  Google Scholar 

  28. Pryor, R. et al. Host-microbe-drug-nutrient screen identifies bacterial effectors of metformin therapy. Cell 178, 1299–1312.e29 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Scott, T. A. et al. Host-microbe co-metabolism dictates cancer drug efficacy in C. elegans. Cell 169, 442–456.e18 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Han, B. et al. Microbial genetic composition tunes host longevity. Cell 169, 1249–1262.e13 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Govindan, J. A., Jayamani, E. & Ruvkun, G. ROS-based lethality of Caenorhabditis elegans mitochondrial electron transport mutants grown on Escherichia coli siderophore iron release mutants. Proc. Natl Acad. Sci. U. S. A. 116, 21651–21658 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Maynard, C., Cummings, I., Green, J. & Weinkove, D. A bacterial route for folic acid supplementation. BMC Biol. 16, 67 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Van Opijnen, T. & Camilli, A. Transposon insertion sequencing: a new tool for systems-level analysis of microorganisms. Nat. Rev. Microbiol. 11, 435–442 (2013).

    Article  PubMed  CAS  Google Scholar 

  35. Lodish, H. et al. Constructing DNA libraries with λ phage and other cloning vectors. Molecular Cell Biology. Edn. 4 (W.H. Freeman, New York, NY, USA, 2000).

    Google Scholar 

  36. Warnhoff, K. & Ruvkun, G. Molybdenum cofactor transfer from bacteria to nematode mediates sulfite detoxification. Nat. Chem. Biol. 15, 480–488 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kitagawa, M. et al. Complete set of ORF clones of Escherichia coli ASKA library (a complete set of E. coli K-12 ORF archive): unique resources for biological research. DNA Res 12, 291–299 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R. & Goodman, A. L. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 570, 462–467 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sifri, C. D., Begun, J., Ausubel, F. M. & Calderwood, S. B. Caenorhabditis elegans as a model host for Staphylococcus aureus pathogenesis. Infect. Immun. 71, 2208–2217 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Irazoqui, J. E. et al. Distinct pathogenesis and host responses during infection of C. elegans by P. aeruginosa and S. aureus. PLoS Pathog. 6, e1000982 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Kaletsky, R. et al. C. elegans interprets bacterial non-coding RNAs to learn pathogenic avoidance. Nature 566, 445–451 (2020).

    Article  CAS  Google Scholar 

  42. Kirienko, N. V., Cezairliyan, B. O., Ausubel, F. M. & Powell, J. R. Pseudomonas aeruginosa PA14 pathogenesis in Caenorhabditis elegans. In (eds. Filloux, A. & Ramos, J.-L.) 653–669 (Springer, New York, NY, USA, 2014).

  43. Dirksen, P. et al. CeMbio—The Caenorhabditis elegans microbiome resource. G3 10, 3025–3039 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zhernakova, A. et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565–569 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fisher, C. K. & Mehta, P. Identifying keystone species in the human gut microbiome from metagenomic timeseries using sparse linear regression. PLoS One 9, e102451 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Heintz-Buschart, A. & Wilmes, P. Human gut microbiome: function matters. Trends Microbiol 26, 563–574 (2018).

    Article  CAS  PubMed  Google Scholar 

  47. Costea, P. I. et al. Enterotypes in the landscape of gut microbial community composition. Nat. Microbiol. 3, 8–16 (2018).

    Article  CAS  PubMed  Google Scholar 

  48. 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, 1–19 (2017).

    Article  Google Scholar 

  49. Virk, B. et al. Folate acts in E. coli to accelerate C. elegans aging independently of bacterial biosynthesis. Cell Rep 14, 1611–1620 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Watson, E. et al. Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans. Elife 5, 1–21 (2016).

    Article  Google Scholar 

  51. Watson, E. et al. Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits. Cell 156, 759–770 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang, J. et al. A delicate balance between bacterial iron and reactive oxygen species supports optimal C. elegans development. Cell Host Microbe 26, 400–411.e3 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Schiffer, J. A. et al. Caenorhabditis elegans processes sensory information to choose between freeloading and self-defense strategies. Elife 9, 1–29 (2020).

    Article  Google Scholar 

  54. Donato, V. et al. Bacillus subtilis biofilm extends Caenorhabditis elegans longevity through downregulation of the insulin-like signalling pathway. Nat. Commun. 8, 14332 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gusarov, I. et al. Bacterial nitric oxide extends the lifespan of C. elegans. Cell 152, 818–830 (2013).

    Article  CAS  PubMed  Google Scholar 

  56. Gruber, J. & Kennedy, B. K. Microbiome and longevity: gut microbes send signals to host mitochondria. Cell 169, 1168–1169 (2017).

    Article  CAS  PubMed  Google Scholar 

  57. Hartsough, L. A. et al. Optogenetic control of gut bacterial metabolism to promote longevity. Elife 9, e56849 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Shin, M.-G. et al. Bacteria-derived metabolite, methylglyoxal, modulates the longevity of C. elegans through TORC2/SGK-1/DAF-16 signaling. Proc. Natl Acad. Sci. U. S. A. 117, 17142–17150 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Virk, B. et al. Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model. BMC Biol. 10, 67 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Saiki, R. et al. Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q. Aging Cell 7, 291–304 (2008).

    Article  CAS  PubMed  Google Scholar 

  61. Larsen, P. L. Extension of life-span in Caenorhabditis elegans by a diet lacking coenzyme Q. Science 295, 120–123 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. Lin, C.-C. C. J. & Wang, M. C. Microbial metabolites regulate host lipid metabolism through NR5A-Hedgehog signalling. Nat. Cell Biol. 19, 550–557 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kumar, A. et al. Caenorhabditis elegans: a model to understand host–microbe interactions. Cell. Mol. Life Sci. 77, 1229–1249 (2020).

    Article  CAS  PubMed  Google Scholar 

  64. Goya, M. E. et al. Probiotic Bacillus subtilis protects against α-synuclein aggregation in C. elegans. Cell Rep. 30, 367–380.e7 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Urrutia, A. et al. Bacterially produced metabolites protect C. elegans neurons from degeneration. PLoS Biol. 18, e3000638 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sampson, T. R. et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167, 1469–1480.e12 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. O’Donnell, M. P., Fox, B. W., Chao, P.-H., Schroeder, F. C. & Sengupta, P. A neurotransmitter produced by gut bacteria modulates host sensory behaviour. Nature 583, 415–420 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Kissoyan, K. A. B. B. et al. Natural C. elegans microbiota protects against infection via production of a cyclic lipopeptide of the viscosin group. Curr. Biol. 29, 1030–1037.e5 (2019).

    Article  CAS  PubMed  Google Scholar 

  69. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Smolentseva, O. et al. Mechanism of biofilm-mediated stress resistance and lifespan extension in C. elegans. Sci. Rep. 7, 7137 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Liu, Y., Samuel, B. S., Breen, P. C. & Ruvkun, G. Caenorhabditis elegans pathways that surveil and defend mitochondria. Nature 508, 406–410 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Bana, B. & Cabreiro, F. The microbiome and aging. Annu. Rev. Genet. 53, 239–261 (2019).

    Article  CAS  PubMed  Google Scholar 

  74. Watson, E., MacNeil, L. T., Arda, H. E., Zhu, L. J. & Walhout, A. J. M. Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response. Cell 153, 253–266 (2013).

    Article  CAS  PubMed  Google Scholar 

  75. Essmann, C. L. et al. Mechanical properties measured by atomic force microscopy define health biomarkers in ageing C. elegans. Nat. Commun. 11, 1043 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Patel, D. S., Xu, N. & Lu, H. Digging deeper: methodologies for high-content phenotyping in Caenorhabditis elegans. Lab Anim. (NY) 48, 207–216 (2019).

    Article  Google Scholar 

  77. Kaletta, T. & Hengartner, M. O. Finding function in novel targets: C. elegans as a model organism. Nat. Rev. Drug Discov. 5, 387–399 (2006).

    Article  CAS  PubMed  Google Scholar 

  78. Nance, J. & Frøkjær-Jensen, C. The Caenorhabditis elegans transgenic toolbox. Genetics 212, 959–990 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Dickinson, D. J. & Goldstein, B. CRISPR-based methods for Caenorhabditis elegans genome engineering. Genetics 202, 885–901 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Evans, T. Transformation and microinjection. (April 6, 2006) WormBook (ed. The C. elegans Research Community) http://www.wormbook.org/chapters/www_transformationmicroinjection/transformationmicroinjection.html (2006).

  81. Merritt, C. et al. Transgenic solutions for the germline. (February 8, 2010) WormBook (ed. The C. elegans Research Community) 1–21 http://www.wormbook.org/chapters/www_transgenic/transgenic.html (2010).

  82. Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71–94 (1974).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kutscher, L. M., Shaham, S. Forward and reverse mutagenesis in C. elegans. (January 17, 2014) WormBook (ed. The C. elegans Research Community) 1–26 http://www.wormbook.org/chapters/www_frmutagenesis/frmutagenesis.html (2014).

  84. Lehrbach, N. J., Ji, F. & Sadreyev, R. Next-generation sequencing for identification of EMS-induced mutations in Caenorhabditis elegans. Curr. Protoc. Mol. Biol. 117, 7.29.1–7.29.12 (2017).

    Article  CAS  Google Scholar 

  85. Thompson, O. et al. The million mutation project: a new approach to genetics in Caenorhabditis elegans. Genome Res 23, 1749–1762 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kamath, R. S. et al. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421, 231–237 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. Melo, J. A. & Ruvkun, G. Inactivation of conserved C. elegans genes engages pathogen- and xenobiotic-associated defenses. Cell 149, 452–466 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hunt-Newbury, R. et al. High-throughput in vivo analysis of gene expression in Caenorhabditis elegans. PLoS Biol. 5, e237 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Burton, N. O. et al. Cysteine synthases CYSL-1 and CYSL-2 mediate C. elegans heritable adaptation to P. vranovensis infection. Nat. Commun. 11, 1741 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kirienko, K., Revtovich, A. & Kirienko, N. A high-content, phenotypic screen identifies fluorouridine as an inhibitor of pyoverdine biosynthesis and Pseudomonas aeruginosa virulence. mSphere 1, e00217-16 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Mylonakis, E., Ausubel, F. M., Perfect, J. R., Heitman, J. & Calderwood, S. B. Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis. Proc. Natl Acad. Sci. U. S. A. 99, 15675–15680 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Tan, M.-W. W., Mahajan-Miklos, S. & Ausubel, F. M. Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc. Natl Acad. Sci. U. S. A. 96, 715–720 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Benedetto, A. et al. New label‐free automated survival assays reveal unexpected stress resistance patterns during C. elegans aging. Aging Cell 18, 1–10 (2019).

    Article  CAS  Google Scholar 

  94. Chi, C. et al. Nucleotide levels regulate germline proliferation through modulating GLP-1/Notch signaling in C. elegans. Genes Dev 30, 307–320 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Rendueles, O. & Ghigo, J.-M. Mechanisms of competition in biofilm communities. Microbiol. Spectr. 3, 1–18 (2015).

    Article  Google Scholar 

  96. Ding, S. S., Schumacher, L. J., Javer, A. E., Endres, R. G. & Brown, A. E. X. Shared behavioral mechanisms underlie C. elegans aggregation and swarming. Elife 8, 1–32 (2019).

    Article  CAS  Google Scholar 

  97. Le, K. N. et al. An automated platform to monitor long-term behavior and healthspan in Caenorhabditis elegans under precise environmental control. Commun. Biol 3, 297 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Pulak, R. Techniques for analysis, sorting, and dispensing of C. elegans on the COPASTM flow-sorting system. In C. elegans: Methods and Applications Vol. 351 (ed. Strange, K.) 275–286 (Humana Press, Totowa, NJ, USA, 2006).

  99. Churgin, M. A. & Fang-Yen, C. An imaging system for C. elegans behavior. In C. elegans: Methods and Applications Edn. 2 Vol. 1327 (eds. Biron, D. & Haspel, G.) 199–207 (Humana Press, Totowa, NJ, USA, 2015).

  100. Stroustrup, N. et al. The Caenorhabditis elegans lifespan machine. Nat. Methods 10, 665–670 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Yemini, E. I. & Brown, A. E. X. Tracking single C. elegans using a USB microscope on a motorized stage. In C. elegans: Methods and Applications Edn. 2 Vol. 1327 (eds. Biron, D. & Haspel, G.) 181–197 (Humana Press, Totowa, NJ, USA, 2015).

  102. Koopman, M. et al. Assessing motor-related phenotypes of Caenorhabditis elegans with the wide field-of-view nematode tracking platform. Nat. Protoc. 15, 2071–2106 (2020).

    Article  CAS  PubMed  Google Scholar 

  103. Swierczek, N. A., Giles, A. C., Rankin, C. H. & Kerr, R. A. High-throughput behavioral analysis in C. elegans. Nat. Methods 8, 592–598 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Restif, C. et al. CeleST: computer vision software for quantitative analysis of C. elegans swim behavior reveals novel features of locomotion. PLoS Comput. Biol. 10, e1003702 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Ramot, D., Johnson, B. E., Berry, T. L., Carnell, L. & Goodman, M. B. The parallel Worm Tracker: a platform for measuring average speed and drug-induced paralysis in nematodes. PLoS One 3, e2208 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Zhang, W. B. et al. Extended twilight among isogenic C. elegans causes a disproportionate scaling between lifespan and health. Cell Syst 3, 333–345.e4 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Banse, S. A., Blue, B. W., Robinson, K. J., Jarrett, C. M. & Phillips, P. C. The Stress-Chip: a microfluidic platform for stress analysis in Caenorhabditis elegans. PLoS One 14, e0216283 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Baris Atakan, H., Alkanat, T., Cornaglia, M., Trouillon, R. & Gijs, M. A. M. Automated phenotyping of Caenorhabditis elegans embryos with a high-throughput-screening microfluidic platform. Microsystems Nanoeng 6, 24 (2020).

    Article  CAS  Google Scholar 

  109. Chung, K., Crane, M. M. & Lu, H. Automated on-chip rapid microscopy, phenotyping and sorting of C. elegans. Nat. Methods 5, 637–643 (2008).

    Article  CAS  PubMed  Google Scholar 

  110. Mondal, S. et al. Large-scale microfluidics providing high-resolution and high-throughput screening of Caenorhabditis elegans poly-glutamine aggregation model. Nat. Commun. 7, 13023 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Cermak, N. et al. Whole-organism behavioral profiling reveals a role for dopamine in state-dependent motor program coupling in C. elegans. Elife 9, 1–34 (2020).

    Article  Google Scholar 

  112. Hernando-Rodríguez, B. et al. Combined flow cytometry and high-throughput image analysis for the study of essential genes in Caenorhabditis elegans. BMC Biol. 16, 36 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Li, X. et al. Systems properties and spatiotemporal regulation of cell position variability during embryogenesis. Cell Rep 26, 313–321.e7 (2019).

    Article  CAS  PubMed  Google Scholar 

  114. Wang, Q. et al. Host and microbiome multi-omics integration: applications and methodologies. Biophys. Rev. 11, 55–65 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Yang, J. H. et al. A white-box machine learning approach for revealing antibiotic mechanisms of action. Cell 177, 1649–1661.e9 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Bochner, B. R. Phenotype microArrays for high-throughput phenotypic testing and assay of gene function. Genome Res 11, 1246–1255 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Zimmermann, J. et al. The functional repertoire contained within the native microbiota of the model nematode Caenorhabditis elegans. ISME J 14, 26–38 (2020).

    Article  CAS  PubMed  Google Scholar 

  118. Freed, N. E. Creation of a dense transposon insertion library using bacterial conjugation in enterobacterial strains such as Escherichia coli or Shigella flexneri. J. Vis. Exp. (127), 56216 (2017).

  119. van Opijnen, T., Bodi, K. L. & Camilli, A. Tn-seq: high-throughput parallel sequencing for fitness and genetic interaction studies in microorganisms. Nat. Methods 6, 767–772 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Kwon, Y. M., Ricke, S. C. & Mandal, R. K. Transposon sequencing: methods and expanding applications. Appl. Microbiol. Biotechnol. 100, 31–43 (2016).

    Article  CAS  PubMed  Google Scholar 

  121. Price, M. N. et al. Mutant phenotypes for thousands of bacterial genes of unknown function. Nature 557, 503–509 (2018).

    Article  CAS  PubMed  Google Scholar 

  122. Baba, T. et al. Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol. Syst. Biol. 2, 2006.0008 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Govindan, J. A., Jayamani, E., Zhang, X., Mylonakis, E. & Ruvkun, G. Dialogue between E. coli free radical pathways and the mitochondria of C. elegans. Proc. Natl Acad. Sci. U. S. A. 112, 12456–12461 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Brooks, J. F. et al. Global discovery of colonization determinants in the squid symbiont Vibrio fischeri. Proc. Natl Acad. Sci. U. S. A. 111, 17284–17289 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Goodman, A. L. et al. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe 6, 279–289 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R. & Goodman, A. L. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science 363, eaat993 (2019).

    Article  CAS  Google Scholar 

  128. García-González, A. P. et al. Bacterial metabolism affects the C. elegans response to cancer chemotherapeutics. Cell 169, 431–441.e8 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Koo, B. M. et al. Construction and analysis of two genome-scale deletion libraries for Bacillus subtilis. Cell Syst. 4, 291–305.e7 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Chan, J. P. et al. Using bacterial transcriptomics to investigate targets of host-bacterial interactions in Caenorhabditis elegans. Sci. Rep. 9, 5545 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Johnson, E. L. et al. Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels. Nat. Commun. 11, 2471 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Rutter, J. W. et al. Detecting changes in the Caenorhabditis elegans intestinal environment using an engineered bacterial biosensor. ACS Synth. Biol. 8, 2620–2628 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Ding, S. S., Romenskyy, M., Sarkisyan, K. S. & Brown, A. E. X. Measuring Caenorhabditis elegans spatial foraging and food intake using bioluminescent bacteria. Genetics 214, 577–587 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016).

    Article  CAS  PubMed  Google Scholar 

  135. Rothschild, D. et al. Environment dominates over host genetics in shaping human gut microbiota. Nature 555, 210–215 (2018).

    Article  CAS  PubMed  Google Scholar 

  136. Westman, E. L. et al. Bacterial inactivation of the anticancer drug doxorubicin. Chem. Biol. 19, 1255–1264 (2012).

    Article  CAS  PubMed  Google Scholar 

  137. Yan, A. et al. Transformation of the anticancer drug doxorubicin in the human gut microbiome. ACS Infect. Dis 4, 68–76 (2018).

    Article  CAS  PubMed  Google Scholar 

  138. Javdan, B. et al. Personalized mapping of drug metabolism by the human gut microbiome. Cell 7, 1661–1679.e22 (2020).

    Article  CAS  Google Scholar 

  139. Willing, B. P., Russell, S. L. & Finlay, B. B. Shifting the balance: antibiotic effects on host-microbiota mutualism. Nat. Rev. Microbiol. 9, 233–243 (2011).

    Article  CAS  PubMed  Google Scholar 

  140. van Kessel, S. P. et al. Gut bacterial tyrosine decarboxylases restrict the bioavailability of levodopa, the primary treatment in Parkinson’s disease. Nat. Commun. 31, 1–31 (2018).

    Google Scholar 

  141. Fijlstra, M. et al. Substantial decreases in the number and diversity of microbiota during chemotherapy-induced gastrointestinal mucositis in a rat model. Support. Care Cancer 23, 1513–1522 (2015).

    Article  PubMed  Google Scholar 

  142. Wallace, B. D. et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330, 831–835 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Pryor, R., Martinez-Martinez, D., Quintaneiro, L. & Cabreiro, F. The role of the microbiome in drug response. Annu. Rev. Pharmacol. Toxicol. 60, 417–435 (2020).

    Article  CAS  PubMed  Google Scholar 

  144. Leffler, D. A. & Lamont, J. T. Clostridium difficile infection. N. Engl. J. Med. 372, 1539–1548 (2015).

    Article  CAS  PubMed  Google Scholar 

  145. Ke, W. et al. Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion. Nat. Commun. 11, 2587 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Barabási, A.-L., Menichetti, G. & Loscalzo, J. The unmapped chemical complexity of our diet. Nat. Food 1, 33–37 (2020).

    Article  Google Scholar 

  147. Cabreiro, F. et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153, 228–239 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Cabreiro, F. Metformin joins forces with microbes. Cell Host Microbe 19, 1–3 (2016).

    Article  CAS  PubMed  Google Scholar 

  149. Forslund, K. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528, 262–266 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Wu, H. et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23, 850–858 (2017).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Helena Cochemé (MRC London Institute of Medical Sciences) for feedback on the manuscript and to Jennifer van der Laan (Institute of Clinical Sciences, Imperial College London) for assistance with the draft of the figures. F.C. acknowledges funding from the Wellcome Trust/Royal Society (102532/Z/12/Z and 102531/Z/13/A) and Medical Research Council (MC-A654-5QC80).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Filipe Cabreiro.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Lab Animal thanks Katja Dierking, Marina Ezcurra and François Leulier for their contribution to the peer review of this work.

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Backes, C., Martinez-Martinez, D. & Cabreiro, F. C. elegans: A biosensor for host–microbe interactions. Lab Anim 50, 127–135 (2021). https://doi.org/10.1038/s41684-021-00724-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41684-021-00724-z

This article is cited by

Search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

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