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.

  • Review Article
  • Published:

Intrahost evolution of the gut microbiota

Abstract

A massive number of microorganisms, belonging to different species, continuously divide inside the guts of animals and humans. The large size of these communities and their rapid division times imply that we should be able to watch microbial evolution in the gut in real time, in a similar manner to what has been done in vitro. Here, we review recent findings on how natural selection shapes intrahost evolution (also known as within-host evolution), with a focus on the intestines of mice and humans. The microbiota of a healthy host is not as static as initially thought from the information measured at only one genomic marker. Rather, the genomes of each gut-colonizing species can be highly dynamic, and such dynamism seems to be related to the microbiota species diversity. Genetic and bioinformatic tools, and analysis of time series data, allow quantification of the selection strength on emerging mutations and horizontal transfer events in gut ecosystems. The drivers and functional consequences of gut evolution can now begin to be grasped. The rules of this intrahost microbiota evolution, and how they depend on the biology of each species, need to be understood for more effective development of microbiota therapies to help maintain or restore host health.

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: Ecological interactions, microbiota composition and intrahost evolution in the gut.
Fig. 2: Mechanisms of evolution.
Fig. 3: Strain-specific evolution.
Fig. 4: Evolution of communities.

Similar content being viewed by others

References

  1. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Manor, O. et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat. Commun. 11, 5206 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Stein, R. R. et al. Ecological modeling from time-series inference: insight into dynamics and stability of intestinal microbiota. PLoS Comput. Biol. 9, e1003388 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Buffie, C. G. et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517, 205–208 (2015).

    Article  CAS  PubMed  Google Scholar 

  6. Mainali, K., Bewick, S., Vecchio-Pagan, B., Karig, D. & Fagan, W. F. Detecting interaction networks in the human microbiome with conditional Granger causality. PLoS Comput. Biol. 15, e1007037 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Palmer, J. D. & Foster, K. R. Bacterial species rarely work together. Science 376, 581–582 (2022).

    Article  CAS  PubMed  Google Scholar 

  9. Rakoff-Nahoum, S., Foster, K. R. & Comstock, L. E. The evolution of cooperation within the gut microbiota. Nature 533, 255–259 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Huus, K. E. et al. Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition. Nat. Commun. 12, 6860 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Caballero-Flores, G., Pickard, J. M., Fukuda, S., Inohara, N. & Núñez, G. An enteric pathogen subverts colonization resistance by evading competition for amino acids in the gut. Cell Host Microbe 28, 526–533.e5 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Seedorf, H. et al. Bacteria from diverse habitats colonize and compete in the mouse gut. Cell 159, 253–266 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lee, S. M. et al. Bacterial colonization factors control specificity and stability of the gut microbiota. Nature 501, 426–429 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Caballero-Flores, G., Pickard, J. M. & Núñez, G. Microbiota-mediated colonization resistance: mechanisms and regulation. Nat. Rev. Microbiol. https://doi.org/10.1038/s41579-022-00833-7 (2022).

    Article  PubMed  Google Scholar 

  15. Trevelline, B. K. & Kohl, K. D. The gut microbiome influences host diet selection behavior. Proc. Natl Acad. Sci. USA 119, e2117537119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gomez de Agüero, M. et al. The maternal microbiota drives early postnatal innate immune development. Science 351, 1296–1302 (2016).

    Article  PubMed  Google Scholar 

  17. Ansaldo, E., Farley, T. K. & Belkaid, Y. Control of immunity by the microbiota. Annu. Rev. Immunol. 39, 449–479 (2021).

    Article  CAS  PubMed  Google Scholar 

  18. Guzman-Bautista, E. R., Suzuki, K., Asami, S. & Fagarasan, S. Bacteria-immune cells dialog and the homeostasis of the systems. Curr. Opin. Immunol. 66, 82–89 (2020).

    Article  CAS  PubMed  Google Scholar 

  19. Zhang, H., Sparks, J. B., Karyala, S. V., Settlage, R. & Luo, X. M. Host adaptive immunity alters gut microbiota. ISME J. 9, 770–781 (2015).

    Article  CAS  PubMed  Google Scholar 

  20. Khan, A. A. et al. Polymorphic immune mechanisms regulate commensal repertoire. Cell Rep. 29, 541–550.e4 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Van Averbeke, V. et al. Host immunity influences the composition of murine gut microbiota. Front. Immunol. 13, 828016 (2022).

    Article  PubMed  Google Scholar 

  22. Fadlallah, J. et al. Microbial ecology perturbation in human IgA deficiency. Sci. Transl Med. 10, eaan1217 (2018).

    Article  PubMed  Google Scholar 

  23. Gopalakrishna, K. P. et al. Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants. Nat. Med. 25, 1110–1115 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rao, C. et al. Multi-kingdom ecological drivers of microbiota assembly in preterm infants. Nature 591, 633–638 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Garud, N. R. & Pollard, K. S. Population genetics in the human microbiome. Trends Genet. 36, 53–67 (2020).

    Article  CAS  PubMed  Google Scholar 

  26. Zhang, J. & Knight, R. Genomic mutations within the host microbiome: adaptive evolution or purifying selection. Engineering 20, 96–102 (2022).

    Article  Google Scholar 

  27. Ho, P.-Y., Good, B. H. & Huang, K. C. Competition for fluctuating resources reproduces statistics of species abundance over time across wide-ranging microbiotas. eLife 11, e75168 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sansonetti, P. J. & Medzhitov, R. Learning tolerance while fighting ignorance. Cell 138, 416–420 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Korem, T. et al. Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples. Science 349, 1101–1106 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Drake, J. W., Charlesworth, B., Charlesworth, D. & Crow, J. F. Rates of spontaneous mutation. Genetics 148, 1667–1686 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gillespie, J. H. Population Genetics: A Concise Guide (The Johns Hopkins Univ. Press, 1998).

  32. Rocha, E. P. C. Neutral theory, microbial practice: challenges in bacterial population genetics. Mol. Biol. Evol. 35, 1338–1347 (2018).

    Article  CAS  PubMed  Google Scholar 

  33. Schloissnig, S. et al. Genomic variation landscape of the human gut microbiome. Nature 493, 45–50 (2013).

    Article  PubMed  Google Scholar 

  34. Gordo, I. & Charlesworth, B. Genetic linkage and molecular evolution. Curr. Biol. 11, R684–R686 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Felsenstein, J. The evolutionary advantage of recombination. Genetics 78, 737–756 (1974).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gerrish, P. J. & Lenski, R. E. The fate of competing beneficial mutations in an asexual population. Genetica 102–103, 127–144 (1998).

    Article  PubMed  Google Scholar 

  37. Amicone, M. & Gordo, I. Molecular signatures of resource competition: clonal interference favors ecological diversification and can lead to incipient speciation. Evolution 75, 2641–2657 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Peck, J. R. A ruby in the rubbish: beneficial mutations, deleterious mutations and the evolution of sex. Genetics 137, 597–606 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ochman, H., Lawrence, J. G. & Groisman, E. A. Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299–304 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Liu, L. et al. The human microbiome: a hot spot of microbial horizontal gene transfer. Genomics 100, 265–270 (2012).

    Article  CAS  PubMed  Google Scholar 

  41. Smillie, C. S. et al. Ecology drives a global network of gene exchange connecting the human microbiome. Nature 480, 241–244 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Groussin, M. et al. Elevated rates of horizontal gene transfer in the industrialized human microbiome. Cell 184, 2053–2067.e18 (2021).

    Article  CAS  PubMed  Google Scholar 

  43. Coyne, M. J., Zitomersky, N. L., McGuire, A. M., Earl, A. M. & Comstock, L. E. Evidence of extensive DNA transfer between bacteroidales species within the human gut. mBio 5, e01305–e01314 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  44. García-Bayona, L., Coyne, M. J. & Comstock, L. E. Mobile type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species spread and geographical clustering. PLoS Genet. 17, e1009541 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Frazão, N. et al. Two modes of evolution shape bacterial strain diversity in the mammalian gut for thousands of generations. Nat. Commun. 13, 5604 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Frazão, N., Sousa, A., Lässig, M. & Gordo, I. Horizontal gene transfer overrides mutation in Escherichia coli colonizing the mammalian gut. Proc. Natl Acad. Sci. USA 116, 17906–17915 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Roodgar, M. et al. Longitudinal linked-read sequencing reveals ecological and evolutionary responses of a human gut microbiome during antibiotic treatment. Genome Res. 31, 1433–1446 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Toprak, E. et al. Evolutionary paths to antibiotic resistance under dynamically sustained drug selection. Nat. Genet. 44, 101–105 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Baym, M. et al. Spatiotemporal microbial evolution on antibiotic landscapes. Science 353, 1147–1151 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Miskinyte, M. et al. The genetic basis of Escherichia coli pathoadaptation to macrophages. PLoS Pathog. 9, e1003802 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Maharjan, R., Seeto, S., Notley-McRobb, L. & Ferenci, T. Clonal adaptive radiation in a constant environment. Science 313, 514–517 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. San Roman, M. & Wagner, A. An enormous potential for niche construction through bacterial cross-feeding in a homogeneous environment. PLoS Comput. Biol. 14, e1006340 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Yi, X. & Dean, A. M. Bounded population sizes, fluctuating selection and the tempo and mode of coexistence. Proc. Natl Acad. Sci. USA 110, 16945–16950 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Pennisi, E. The man who bottled evolution. Science 342, 790–793 (2013).

    Article  CAS  PubMed  Google Scholar 

  55. Tenaillon, O. et al. The molecular diversity of adaptive convergence. Science 335, 457–461 (2012).

    Article  CAS  PubMed  Google Scholar 

  56. Schenk, M. F. et al. Population size mediates the contribution of high-rate and large-benefit mutations to parallel evolution. Nat. Ecol. Evol. 6, 439–447 (2022).

    Article  PubMed  Google Scholar 

  57. Gatt, Y. E. & Margalit, H. Common adaptive strategies underlie within-host evolution of bacterial pathogens. Mol. Biol. Evol. 38, 1101–1121 (2021).

    Article  CAS  PubMed  Google Scholar 

  58. Poeschla, M. & Valenzano, D. R. The turquoise killifish: a genetically tractable model for the study of aging. J. Exp. Biol. 223, jeb209296 (2020).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Kešnerová, L. et al. Gut microbiota structure differs between honeybees in winter and summer. ISME J. 14, 801–814 (2020).

    Article  PubMed  Google Scholar 

  62. Barlow, J. T., Bogatyrev, S. R. & Ismagilov, R. F. A quantitative sequencing framework for absolute abundance measurements of mucosal and lumenal microbial communities. Nat. Commun. 11, 2590 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Giraud, A. et al. Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut. Science 291, 2606–2608 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. Oliver, A., Cantón, R., Campo, P., Baquero, F. & Blázquez, J. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288, 1251–1254 (2000).

    Article  CAS  PubMed  Google Scholar 

  65. Oliver, A. Mutators in cystic fibrosis chronic lung infection: prevalence, mechanisms, and consequences for antimicrobial therapy. Int. J. Med. Microbiol. 300, 563–572 (2010).

    Article  CAS  PubMed  Google Scholar 

  66. Ramiro, R. S., Durão, P., Bank, C. & Gordo, I. Low mutational load and high mutation rate variation in gut commensal bacteria. PLoS Biol. 18, e3000617 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. De Paepe, M. et al. Trade-off between bile resistance and nutritional competence drives Escherichia coli diversification in the mouse gut. PLoS Genet. 7, e1002107 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Barroso-Batista, J. et al. Specific eco-evolutionary contexts in the mouse gut reveal Escherichia coli metabolic versatility. Curr. Biol. 30, 1049–1062.e7 (2020).

    Article  CAS  PubMed  Google Scholar 

  69. Vasquez, K. S. et al. Quantifying rapid bacterial evolution and transmission within the mouse intestine. Cell Host Microbe 29, 1454–1468.e4 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Freter, R., Brickner, H., Fekete, J., Vickerman, M. M. & Carey, K. E. Survival and implantation of Escherichia coli in the intestinal tract. Infect. Immun. 39, 686–703 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Conway, T., Krogfelt, K. A. & Cohen, P. S. The life of commensal Escherichia coli in the mammalian intestine. EcoSal https://doi.org/10.1128/ecosalplus.8.3.1.2 (2004).

    Article  Google Scholar 

  72. Barroso-Batista, J. et al. The first steps of adaptation of Escherichia coli to the gut are dominated by soft sweeps. PLoS Genet. 10, e1004182 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Lescat, M. et al. Using long-term experimental evolution to uncover the patterns and determinants of molecular evolution of an Escherichia coli natural isolate in the streptomycin-treated mouse gut. Mol. Ecol. 26, 1802–1817 (2017).

    Article  CAS  PubMed  Google Scholar 

  74. Ghalayini, M. et al. Long-term evolution of the natural isolate of Escherichia coli 536 in the mouse gut colonized after maternal transmission reveals convergence in the constitutive expression of the lactose operon. Mol. Ecol. 28, 4470–4485 (2019).

    Article  CAS  PubMed  Google Scholar 

  75. Barreto, H. C., Sousa, A. & Gordo, I. The landscape of adaptive evolution of a gut commensal bacteria in aging mice. Curr. Biol. 30, 1102–1109.e5 (2020).

    Article  CAS  PubMed  Google Scholar 

  76. Barreto, H. C., Frazão, N., Sousa, A., Konrad, A. & Gordo, I. Mutation accumulation and horizontal gene transfer in Escherichia coli colonizing the gut of old mice. Commun. Integr. Biol. 13, 89–96 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Barreto, H. C., Abreu, B. & Gordo, I. Fluctuating selection on bacterial iron regulation in the mammalian gut. Curr. Biol. 32, 3261–3275.e4 (2022).

    Article  CAS  PubMed  Google Scholar 

  78. Dapa, T., Ramiro, R. S., Pedro, M. F., Gordo, I. & Xavier, K. B. Diet leaves a genetic signature in a keystone member of the gut microbiota. Cell Host Microbe 30, 183–199.e10 (2022).

    Article  CAS  PubMed  Google Scholar 

  79. Ghalayini, M. et al. Evolution of a dominant natural isolate of Escherichia coli in the human gut over the course of a year suggests a neutral evolution with reduced effective population size. Appl. Env. Microbiol. 84, e02377-17 (2018).

    Article  Google Scholar 

  80. Zhao, S. et al. Adaptive evolution within gut microbiomes of healthy people. Cell Host Microbe 25, 656–667.e8 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Garud, N. R., Good, B. H., Hallatschek, O. & Pollard, K. S. Evolutionary dynamics of bacteria in the gut microbiome within and across hosts. PLoS Biol. 17, e3000102 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Sousa, A. et al. Recurrent reverse evolution maintains polymorphism after strong bottlenecks in commensal gut bacteria. Mol. Biol. Evol. 34, 2879–2892 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Minot, S. et al. Rapid evolution of the human gut virome. Proc. Natl Acad. Sci. USA 110, 12450–12455 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Poyet, M. et al. A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research. Nat. Med. 25, 1442–1452 (2019).

    Article  CAS  PubMed  Google Scholar 

  85. Zlitni, S. et al. Strain-resolved microbiome sequencing reveals mobile elements that drive bacterial competition on a clinical timescale. Genome Med. 12, 50 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Scheuerl, T. et al. Bacterial adaptation is constrained in complex communities. Nat. Commun. 11, 754 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Emerson, B. C. & Kolm, N. Species diversity can drive speciation. Nature 434, 1015–1017 (2005).

    Article  CAS  PubMed  Google Scholar 

  88. Lawrence, D. et al. Species interactions alter evolutionary responses to a novel environment. PLoS Biol. 10, e1001330 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Stevens, E. J., Bates, K. A. & King, K. C. Host microbiota can facilitate pathogen infection. PLoS Pathog. 17, e1009514 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zhang, F. et al. Natural genetic variation drives microbiome selection in the Caenorhabditis elegans gut. Curr. Biol. 31, 2603–2618.e9 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Yilmaz, B. et al. Long-term evolution and short-term adaptation of microbiota strains and sub-strains in mice. Cell Host Microbe 29, 650–663.e9 (2021).

    Article  CAS  PubMed  Google Scholar 

  92. Brugiroux, S. et al. Genome-guided design of a defined mouse microbiota that confers colonization resistance against Salmonella enterica serovar Typhimurium. Nat. Microbiol. 2, 16215 (2016).

    Article  CAS  PubMed  Google Scholar 

  93. Faith, J. J., McNulty, N. P., Rey, F. E. & Gordon, J. I. Predicting a human gut microbiota’s response to diet in gnotobiotic mice. Science 333, 101–104 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Reyes, A., Wu, M., McNulty, N. P., Rohwer, F. L. & Gordon, J. I. Gnotobiotic mouse model of phage-bacterial host dynamics in the human gut. Proc. Natl Acad. Sci. USA 110, 20236–20241 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Cheng, A. G. et al. Design, construction, and in vivo augmentation of a complex gut microbiome. Cell https://doi.org/10.1016/j.cell.2022.08.003 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Chen, D. W. & Garud, N. R. Rapid evolution and strain turnover in the infant gut microbiome. Genome Res. 32, 1124–1136 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Yaffe, E. & Relman, D. A. Tracking microbial evolution in the human gut using Hi-C reveals extensive horizontal gene transfer, persistence and adaptation. Nat. Microbiol. 5, 343–353 (2020).

    Article  CAS  PubMed  Google Scholar 

  98. Chen, L. et al. The long-term genetic stability and individual specificity of the human gut microbiome. Cell 184, 2302–2315.e12 (2021).

    Article  CAS  PubMed  Google Scholar 

  99. Levin, B. R. & Bull, J. J. Short-sighted evolution and the virulence of pathogenic microorganisms. Trends Microbiol. 2, 76–81 (1994).

    Article  CAS  PubMed  Google Scholar 

  100. Sokurenko, E. V., Hasty, D. L. & Dykhuizen, D. E. Pathoadaptive mutations: gene loss and variation in bacterial pathogens. Trends Microbiol. 7, 191–195 (1999).

    Article  CAS  PubMed  Google Scholar 

  101. Smith, H. W. Transfer of antibiotic resistance from animal and human strains of Escherichia coli to resident E. coli in the alimentary tract of man. Lancet 1, 1174–1176 (1969).

    Article  CAS  PubMed  Google Scholar 

  102. Chaguza, C. et al. Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation. Nat. Commun. 11, 3442 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yang, Y. et al. Within-host evolution of a gut pathobiont facilitates liver translocation. Nature 607, 563–570 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Antia, R., Regoes, R. R., Koella, J. C. & Bergstrom, C. T. The role of evolution in the emergence of infectious diseases. Nature 426, 658–661 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Caugant, D. A., Levin, B. R. & Selander, R. K. Genetic diversity and temporal variation in the E. coli population of a human host. Genetics 98, 467–490 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Eberl, C. et al. E. coli enhance colonization resistance against Salmonella Typhimurium by competing for galactitol, a context-dependent limiting carbon source. Cell Host Microbe 29, 1680–1692.e7 (2021).

    Article  CAS  PubMed  Google Scholar 

  107. Kisiela, D. I. et al. Inactivation of transcriptional regulators during within-household evolution of Escherichia coli. J. Bacteriol. 199, e00036-17 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Thänert, R. et al. Persisting uropathogenic Escherichia coli lineages show signatures of niche-specific within-host adaptation mediated by mobile genetic elements. Cell Host Microbe 30, 1034–1047.e6 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Andersson, D. I. & Levin, B. R. The biological cost of antibiotic resistance. Curr. Opin. Microbiol. 2, 489–493 (1999).

    Article  CAS  PubMed  Google Scholar 

  110. San Millan, A. Evolution of plasmid-mediated antibiotic resistance in the clinical context. Trends Microbiol. 26, 978–985 (2018).

    Article  CAS  PubMed  Google Scholar 

  111. Leónidas Cardoso, L., Durão, P., Amicone, M. & Gordo, I. Dysbiosis individualizes the fitness effect of antibiotic resistance in the mammalian gut. Nat. Ecol. Evol. 4, 1268–1278 (2020).

    Article  PubMed  Google Scholar 

  112. Hertz, F. B., Marvig, R. L., Frimodt-Møller, N. & Nielsen, K. L. In vitro relative fitness, in vivo intestinal colonization and genomic differences of Escherichia coli of ST131 carrying bla CTX-M-15. Front. Microbiol. 12, 798473 (2021).

    Article  PubMed  Google Scholar 

  113. Baumgartner, M., Bayer, F., Pfrunder-Cardozo, K. R., Buckling, A. & Hall, A. R. Resident microbial communities inhibit growth and antibiotic-resistance evolution of Escherichia coli in human gut microbiome samples. PLoS Biol. 18, e3000465 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Gumpert, H. et al. Transfer and persistence of a multi-drug resistance plasmid in situ of the infant gut microbiota in the absence of antibiotic treatment. Front. Microbiol. 8, 1852 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  115. Forster, S. C. et al. Strain-level characterization of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome. Nat. Commun. 13, 1445 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Alonso-Del Valle, A. et al. Variability of plasmid fitness effects contributes to plasmid persistence in bacterial communities. Nat. Commun. 12, 2653 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kent, A. G., Vill, A. C., Shi, Q., Satlin, M. J. & Brito, I. L. Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C. Nat. Commun. 11, 4379 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Silva, R. F. et al. Pervasive sign epistasis between conjugative plasmids and drug-resistance chromosomal mutations. PLoS Genet. 7, e1002181 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. De La Cochetière, M. F. et al. Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. J. Clin. Microbiol. 43, 5588–5592 (2005).

    Article  PubMed  Google Scholar 

  120. 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 (2011).

    Article  CAS  PubMed  Google Scholar 

  121. Ng, K. M. et al. Recovery of the gut microbiota after antibiotics depends on host diet, community context, and environmental reservoirs. Cell Host Microbe 26, 650–665.e4 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Anthony, W. E. et al. Acute and persistent effects of commonly used antibiotics on the gut microbiome and resistome in healthy adults. Cell Rep. 39, 110649 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Long, H. et al. Antibiotic treatment enhances the genome-wide mutation rate of target cells. Proc. Natl Acad. Sci. USA 113, E2498–E2505 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Barreto, H. C., Cordeiro, T. N., Henriques, A. O. & Gordo, I. Rampant loss of social traits during domestication of a Bacillus subtilis natural isolate. Sci. Rep. 10, 18886 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Huang, S. et al. Candidate probiotic Lactiplantibacillus plantarum HNU082 rapidly and convergently evolves within human, mice, and zebrafish gut but differentially influences the resident microbiome. Microbiome 9, 151 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Song, Y. et al. Genomic variations in probiotic Lactobacillus plantarum P-8 in the human and rat gut. Front. Microbiol. 9, 893 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Li, W. et al. Comparative genomics of in vitro and in vivo evolution of probiotics reveals energy restriction not the main evolution driving force in short term. Genomics 113, 3373–3380 (2021).

    Article  CAS  PubMed  Google Scholar 

  128. Crook, N. et al. Adaptive strategies of the candidate probiotic E. coli Nissle in the mammalian gut. Cell Host Microbe 25, 499–512.e8 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Yelin, I. et al. Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients. Nat. Med. 25, 1728–1732 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ma, C. et al. Probiotic consumption influences universal adaptive mutations in indigenous human and mouse gut microbiota. Commun. Biol. 4, 1198 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Bakken, J. S. et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin. Gastroenterol. Hepatol. 9, 1044–1049 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  132. Ratner, M. Microbial cocktails join fecal transplants in IBD treatment trials. Nat. Biotechnol. 33, 787–788 (2015).

    Article  CAS  PubMed  Google Scholar 

  133. Danne, C., Rolhion, N. & Sokol, H. Recipient factors in faecal microbiota transplantation: one stool does not fit all. Nat. Rev. Gastroenterol. Hepatol. 18, 503–513 (2021).

    Article  PubMed  Google Scholar 

  134. Ianiro, G. et al. Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases. Nat. Med. 28, 1913–1923 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Schmidt, T. S. B. et al. Drivers and determinants of strain dynamics following fecal microbiota transplantation. Nat. Med. 28, 1902–1912 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Gibson, B. & Eyre-Walker, A. Investigating evolutionary rate variation in bacteria. J. Mol. Evol. 87, 317–326 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Eyre-Walker, A. & Keightley, P. D. The distribution of fitness effects of new mutations. Nat. Rev. Genet. 8, 610–618 (2007).

    Article  CAS  PubMed  Google Scholar 

  138. Arnold, B. J., Huang, I.-T. & Hanage, W. P. Horizontal gene transfer and adaptive evolution in bacteria. Nat. Rev. Microbiol. 20, 206–218 (2022).

    Article  CAS  PubMed  Google Scholar 

  139. Zinder, N. D. & Lederberg, J. Genetic exchange in Salmonella. J. Bacteriol. 64, 679–699 (1952).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Morse, M. L., Lederberg, E. M. & Lederberg, J. Transduction in Escherichia coli K-12. Genetics 41, 142–156 (1956).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Chen, J. et al. Genome hypermobility by lateral transduction. Science 362, 207–212 (2018).

    Article  CAS  PubMed  Google Scholar 

  142. Lederberg, J. & Tatum, E. L. Gene recombination in Escherichia coli. Nature 158, 558 (1946).

    Article  CAS  PubMed  Google Scholar 

  143. Bakkeren, E. et al. Impact of horizontal gene transfer on emergence and stability of cooperative virulence in Salmonella Typhimurium. Nat. Commun. 13, 1939 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Domingues, S. & Nielsen, K. M. Membrane vesicles and horizontal gene transfer in prokaryotes. Curr. Opin. Microbiol. 38, 16–21 (2017).

    Article  CAS  PubMed  Google Scholar 

  145. Dubey, G. P. & Ben-Yehuda, S. Intercellular nanotubes mediate bacterial communication. Cell 144, 590–600 (2011).

    Article  CAS  PubMed  Google Scholar 

  146. Bárdy, P. et al. Structure and mechanism of DNA delivery of a gene transfer agent. Nat. Commun. 11, 3034 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Tenaillon, O. The utility of Fisher’s geometric model in evolutionary genetics. Annu. Rev. Ecol. Evol. Syst. 45, 179–201 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Orr, H. A. Theories of adaptation: what they do and don’t say. Genetica 123, 3–13 (2005).

    Article  PubMed  Google Scholar 

  149. Good, B. H., McDonald, M. J., Barrick, J. E., Lenski, R. E. & Desai, M. M. The dynamics of molecular evolution over 60,000 generations. Nature 551, 45–50 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  150. Reddy, G. & Desai, M. M. Global epistasis emerges from a generic model of a complex trait. eLife 10, e64740 (2021).

    CAS  Google Scholar 

  151. Rozen, D. E. & Lenski, R. E. Long-term experimental evolution in Escherichia coli. VIII. Dynamics of a balanced polymorphism. Am. Nat. 155, 24–35 (2000).

    Article  PubMed  Google Scholar 

  152. Lebov, J. F., Schlomann, B. H., Robinson, C. D. & Bohannan, B. J. M. Phenotypic parallelism during experimental adaptation of a free-living bacterium to the zebrafish gut. mBio 11, e01519–e01520 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Martino, M. E. et al. Bacterial adaptation to the host’s diet is a key evolutionary force shaping DrosophilaLactobacillus symbiosis. Cell Host Microbe 24, 109–119.e6 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Ekroth, A. K. E., Gerth, M., Stevens, E. J., Ford, S. A. & King, K. C. Host genotype and genetic diversity shape the evolution of a novel bacterial infection. ISME J. 15, 2146–2157 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Gordo’s laboratory members for critically reading this manuscript. This work was supported by PTDC/BIA-EVL/7546/2020, from the FCT (“Fundação para a Ciência e a Tecnologia”) to I.G. H.C.B. was the recipient of a doctoral fellowship (PD/BD/128429/2017) from the FCT.

Author information

Authors and Affiliations

Authors

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Isabel Gordo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Microbiology thanks Benjamin Good, Mathieu Groussin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barreto, H.C., Gordo, I. Intrahost evolution of the gut microbiota. Nat Rev Microbiol 21, 590–603 (2023). https://doi.org/10.1038/s41579-023-00890-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41579-023-00890-6

This article is cited by

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