in

Slower-growing species promote interspecific cooperation and coexistence under acid stress through cross-feeding

Abstract

Acid stress is a central environmental factor shaping the structure and function of microbial communities worldwide. However, there is a lack of predictive understanding of how microbial communities respond physiologically and metabolically to acid stress. Here, we find that higher acid stress favors slower-growing species, promoting population growth and coexistence. Our experiments show that acid stress influences the spatial structure of communities, wherein coexistence is ordered over centimeter-length scales and determined by growth-tolerance trade-offs. We find that interspecific interactions are highly dynamic during acid stress changes, with shifts from competition to cooperation, enhancing resilience under high-stress intensities. Slower-growing species may bolster interspecific coexistence through stress-dependent excretion and cross-feeding of public goods. We construct a resource-consumer-based mathematical model to unravel the processes experienced by species in stress-induced coexistence and their distinct physiological states. Finally, our pairwise bacterial-fungal interaction experiments elucidate universalities in stress-induced coexistence between closely related and phylogenetically distant species with complementary phenotypic profiles. Overall, our work provides insights into how acid stress affects physiological and metabolic responses, as well as overall fitness, resilience, and coexistence.

Data availability

All data that support the findings of this study are provided in the Supplementary Information, Source Data file, and databases. Raw mass spectral data is deposited to MassIVE and accessible with the accession code MSV000099939. Source data are provided with this paper, and can also be found at https://doi.org/10.5281/zenodo.1732030972. Source data are provided as a Source Data file. Source data are provided with this paper.

Code availability

Based on the mathematical model provided in the Supplementary Notes, the code can be found at https://zenodo.org/records/17330958.

References

  1. The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

  2. Montoya, J. M., Pimm, S. L. & Solé, R. V. Ecological networks and their fragility. Nature 442, 259–264 (2006).

    Google Scholar 

  3. Liu, W., Cremer, J., Li, D., Hwa, T. & Liu, C. An evolutionarily stable strategy to colonize spatially extended habitats. Nature 575, 664–668 (2019).

    Google Scholar 

  4. Camenzind, T., Philipp Grenz, K., Lehmann, J. & Rillig, M. C. Soil fungal mycelia have unexpectedly flexible stoichiometric C:N and C:P ratios. Ecol. Lett. 24, 208–218 (2021).

    Google Scholar 

  5. Jiang, Y., Dong, W., Xin, F. & Jiang, M. Designing synthetic microbial consortia for biofuel production. Trends Biotechnol. 38, 828–831 (2020).

    Google Scholar 

  6. Cheng, M., Chen, D., Parales, R. E. & Jiang, J. Oxygenases as powerful weapons in the microbial degradation of pesticides. Annu. Rev. Microbiol. 76, 325–348 (2022).

    Google Scholar 

  7. Blasche, S. et al. Metabolic cooperation and spatiotemporal niche partitioning in a kefir microbial community. Nat. Microbiol. 6, 196–208 (2021).

    Google Scholar 

  8. Gopaulchan, D. et al. A defined microbial community reproduces attributes of fine flavour chocolate fermentation. Nat. Microbiol. 10, 2130–2152 (2025).

    Google Scholar 

  9. Ruan, Z. et al. Engineering natural microbiomes toward enhanced bioremediation by microbiome modeling. Nat. Commun. 15, 4694 (2024).

    Google Scholar 

  10. Hu, S. et al. A synergistic consortium involved in rac-dichlorprop degradation as revealed by DNA stable isotope probing and metagenomic analysis. Appl. Environ. Microbiol. 87, e0156221 (2021).

    Google Scholar 

  11. Widdig, M. et al. Effects of nitrogen and phosphorus addition on microbial community composition and element cycling in a grassland soil. Soil. Biol. Biochem. 151, 108041 (2020).

  12. Xun, W. et al. Diversity-triggered deterministic bacterial assembly constrains community functions. Nat. Commun. 10, 3833 (2019).

    Google Scholar 

  13. Hutchins, D. A. & Fu, F. Microorganisms and ocean global change. Nat. Microbiol. 2, 17058 (2017).

    Google Scholar 

  14. Hu, N., Bourdeau, P. E. & Hollander, J. Responses of marine trophic levels to the combined effects of ocean acidification and warming. Nat. Commun. 15, 3400 (2024).

    Google Scholar 

  15. Lampe, R. H. et al. Short-term acidification promotes diverse iron acquisition and conservation mechanisms in upwelling-associated phytoplankton. Nat. Commun. 14, 7215 (2023).

    Google Scholar 

  16. Bitter, M. C., Kapsenberg, L., Gattuso, J. P. & Pfister, C. A. Standing genetic variation fuels rapid adaptation to ocean acidification. Nat. Commun. 10, 5821 (2019).

    Google Scholar 

  17. Bokulich, N. A., Thorngate, J. H., Richardson, P. M. & Mills, D. A. Microbial biogeography of wine grapes is conditioned by cultivar, vintage, and climate. Proc. Natl. Acad. Sci. USA 111, E139–E148 (2014).

    Google Scholar 

  18. Rath, K. M., Fierer, N., Murphy, D. V. & Rousk, J. Linking bacterial community composition to soil salinity along environmental gradients. Isme J. 13, 836–846 (2019).

    Google Scholar 

  19. De Vos, W. M. et al. Phytate metabolism is mediated by microbial cross-feeding in the gut microbiota. Nat. Microbiol. 9, 1812–1827 (2024).

    Google Scholar 

  20. Ross, F. C. et al. The interplay between diet and the gut microbiome: implications for health and disease. Nat. Rev. Microbiol. 22, 671–686 (2024).

  21. Ghoul, M. & Mitri, S. The ecology and evolution of microbial competition. Trends Microbiol. 24, 833–845 (2016).

    Google Scholar 

  22. Tecon, R. et al. Bridging the holistic-reductionist divide in microbial ecology. mSystems 4, 10–1128 (2019).

  23. Zhao, Y. et al. Inter-bacterial mutualism promoted by public goods in a system characterized by deterministic temperature variation. Nat. Commun. 14, 5394 (2023).

    Google Scholar 

  24. Michielsen, S., Vercelli, G. T., Cordero, O. X. & Bachmann, H. Spatially structured microbial consortia and their role in food fermentations. Curr. Opin. Biotechnol. 87, 103102 (2024).

    Google Scholar 

  25. Luo, N. et al. The collapse of cooperation during range expansion of Pseudomonas aeruginosa. Nat. Microbiol. 9, 1220–1230 (2024).

    Google Scholar 

  26. Grandel, N. E., Reyes Gamas, K. & Bennett, M. R. Control of synthetic microbial consortia in time, space, and composition. Trends Microbiol. 29, 1095–1105 (2021).

    Google Scholar 

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

    Google Scholar 

  28. Piccardi, P., Vessman, B. & Mitri, S. Toxicity drives facilitation between 4 bacterial species. Proc. Natl. Acad. Sci. USA 116, 15979–15984 (2019).

    Google Scholar 

  29. García, F. C. et al. The temperature dependence of microbial community respiration is amplified by changes in species interactions. Nat. Microbiol. 8, 272–283 (2023).

    Google Scholar 

  30. Li, S. et al. Regulation of species metabolism in synthetic community systems by environmental pH oscillations. Nat. Commun. 14, 7507 (2023).

    Google Scholar 

  31. Gänzle, M. G. Lactic metabolism revisited: metabolism of lactic acid bacteria in food fermentations and food spoilage. Curr. Opin. Food Sci. 2, 106–117 (2015).

    Google Scholar 

  32. Wang, Y., Zhang, C., Liu, F., Jin, Z. & Xia, X. Ecological succession and functional characteristics of lactic acid bacteria in traditional fermented foods. Crit. Rev. Food Sci. Nutr. 63, 5841–5855 (2022).

  33. Yanni, D., Márquez-Zacarías, P., Yunker, P. J. & Ratcliff, W. C. Drivers of spatial structure in social microbial communities. Curr. Biol. 29, R545–r550 (2019).

    Google Scholar 

  34. Chacón, J. M., Möbius, W. & Harcombe, W. R. The spatial and metabolic basis of colony size variation. Isme J. 12, 669–680 (2018).

    Google Scholar 

  35. Gude, S. et al. Bacterial coexistence driven by motility and spatial competition. Nature 578, 588–592 (2020).

    Google Scholar 

  36. Liao, H., Luo, Y., Huang, X. & Xia, X. Dynamics of quality attributes, flavor compounds, and microbial communities during multi-driven-levels chili fermentation: interactions between the metabolome and microbiome. Food Chem. 405, 134936 (2023).

    Google Scholar 

  37. Goldford, J. E. et al. Emergent simplicity in microbial community assembly. Science 361, 469–474 (2018).

    Google Scholar 

  38. Dal Bello, M., Lee, H., Goyal, A. & Gore, J. Resource-diversity relationships in bacterial communities reflect the network structure of microbial metabolism. Nat. Ecol. Evol. 5, 1424–1434 (2021).

    Google Scholar 

  39. Burkart, T., Willeke, J. & Frey, E. Periodic temporal environmental variations induce coexistence in resource competition models. Phys. Rev. E 108, 034404 (2023).

    Google Scholar 

  40. Ratzke, C. & Gore, J. Modifying and reacting to the environmental pH can drive bacterial interactions. PLoS Biol. 16, e2004248 (2018).

    Google Scholar 

  41. Herschend, J. et al. In vitro community synergy between bacterial soil isolates can be facilitated by pH Stabilization of the Environment. Appl. Environ. Microbiol. 84, e01450–18 (2018).

  42. Souza, A. L. & Patti, G. J. A protocol for untargeted metabolomic analysis: from sample preparation to data processing. Methods Mol. Biol. 2276, 357–382 (2021).

    Google Scholar 

  43. Bauermeister, A., Mannochio-Russo, H., Costa-Lotufo, L. V., Jarmusch, A. K. & Dorrestein, P. C. Mass spectrometry-based metabolomics in microbiome investigations. Nat. Rev. Microbiol. 20, 143–160 (2022).

    Google Scholar 

  44. Liu, Y., Tang, H., Lin, Z. & Xu, P. Mechanisms of acid tolerance in bacteria and prospects in biotechnology and bioremediation. Biotechnol. Adv. 33, 1484–1492 (2015).

    Google Scholar 

  45. Bennett, B. D. et al. Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli. Nat. Chem. Biol. 5, 593–599 (2009).

    Google Scholar 

  46. Widder, S. et al. Challenges in microbial ecology: building predictive understanding of community function and dynamics. Isme J. 10, 2557–2568 (2016).

    Google Scholar 

  47. Faust, K. & Raes, J. Microbial interactions: from networks to models. Nat. Rev. Microbiol. 10, 538–550 (2012).

    Google Scholar 

  48. Martin-Gallausiaux, C., Marinelli, L., Blottière, H. M., Larraufie, P. & Lapaque, N. SCFA: mechanisms and functional importance in the gut. Proc. Nutr. Soc. 80, 37–49 (2021).

    Google Scholar 

  49. Ponomarova, O. et al. Yeast creates a niche for symbiotic lactic acid bacteria through nitrogen overflow. Cell Syst. 5, e346 (2017).

    Google Scholar 

  50. Daudé, D., Remaud-Siméon, M. & André, I. Sucrose analogs: an attractive (bio)source for glycodiversification. Nat. Prod. Rep. 29, 945–960 (2012).

    Google Scholar 

  51. Hernandez, D. J., David, A. S., Menges, E. S., Searcy, C. A. & Afkhami, M. E. Environmental stress destabilizes microbial networks. Isme J. 15, 1722–1734 (2021).

    Google Scholar 

  52. Gao, C. et al. Co-occurrence networks reveal more complexity than community composition in resistance and resilience of microbial communities. Nat. Commun. 13, 3867 (2022).

    Google Scholar 

  53. Hofmann, G. E. et al. High-frequency dynamics of ocean pH: a multi-ecosystem comparison. PLoS One 6, e28983 (2011).

    Google Scholar 

  54. Hallatschek, O., Hersen, P., Ramanathan, S. & Nelson, D. R. Genetic drift at expanding frontiers promotes gene segregation. Proc. Natl. Acad. Sci. USA 104, 19926–19930 (2007).

    Google Scholar 

  55. Datta, M. S., Korolev, K. S., Cvijovic, I., Dudley, C. & Gore, J. Range expansion promotes cooperation in an experimental microbial metapopulation. Proc. Natl. Acad. Sci. USA 110, 7354–7359 (2013).

    Google Scholar 

  56. Dal Co, A., van Vliet, S., Kiviet, D. J., Schlegel, S. & Ackermann, M. Short-range interactions govern the dynamics and functions of microbial communities. Nat. Ecol. Evol. 4, 366–375 (2020).

    Google Scholar 

  57. Abreu, C. I., Dal Bello, M., Bunse, C., Pinhassi, J. & Gore, J. Warmer temperatures favor slower-growing bacteria in natural marine communities. Sci. Adv. 9, eade8352 (2023).

    Google Scholar 

  58. Frey, E. Evolutionary game theory: theoretical concepts and applications to microbial communities. Phys. A 389, 4265–4298 (2010).

    Google Scholar 

  59. West, S. A., Griffin, A. S. & Gardner, A. Social semantics: altruism, cooperation, mutualism, strong reciprocity and group selection. J. Evol. Biol. 20, 415–432 (2007).

    Google Scholar 

  60. Tripathi, B. M. et al. Soil pH mediates the balance between stochastic and deterministic assembly of bacteria. Isme J. 12, 1072–1083 (2018).

    Google Scholar 

  61. Di Martino, R., Picot, A. & Mitri, S. Oxidative stress changes interactions between 2 bacterial species from competitive to facilitative. PLoS Biol. 22, e3002482 (2024).

    Google Scholar 

  62. Maestre, F. T., Callaway, R. M., Valladares, F. & Lortie, C. J. Refining the stress-gradient hypothesis for competition and facilitation in plant communities. J. Ecol. 97, 199–205 (2009).

    Google Scholar 

  63. Basan, M. et al. Overflow metabolism in Escherichia coli results from efficient proteome allocation. Nature 528, 99–104 (2015).

    Google Scholar 

  64. Schink, S. J. et al. Glycolysis/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing. Mol. Syst. Biol. 18, e10704 (2022).

    Google Scholar 

  65. Kaleta, C., Schäuble, S., Rinas, U. & Schuster, S. Metabolic costs of amino acid and protein production in Escherichia coli. Biotechnol. J. 8, 1105–1114 (2013).

    Google Scholar 

  66. Guan, N. et al. Microbial response to environmental stresses: from fundamental mechanisms to practical applications. Appl. Microbiol. Biotechnol. 101, 3991–4008 (2017).

    Google Scholar 

  67. Russell, J. B. & Diez-Gonzalez, F. The effects of fermentation acids on bacterial growth. Adv. Micro. Physiol. 39, 205–234 (1998).

    Google Scholar 

  68. Iffland-Stettner, A. et al. A genome-scale metabolic model of marine heterotroph Vibrio splendidus strain 1A01. mSystems 8, e0037722 (2023).

    Google Scholar 

  69. Young, J. W. et al. Measuring single-cell gene expression dynamics in bacteria using fluorescence time-lapse microscopy. Nat. Protoc. 7, 80–88 (2011).

    Google Scholar 

  70. Skinner, S. O., Sepúlveda, L. A., Xu, H. & Golding, I. Measuring mRNA copy number in individual Escherichia coli cells using single-molecule fluorescent in situ hybridization. Nat. Protoc. 8, 1100–1113 (2013).

    Google Scholar 

  71. Ikeda, T. P., Shauger, A. E. & Kustu, S. Salmonella typhimurium apparently perceives external nitrogen limitation as internal glutamine limitation. J. Mol. Biol. 259, 589–607 (1996).

    Google Scholar 

  72. Liao, H. et al. Slower-growing species promote interspecific cooperation and coexistence under acid stress through cross-feeding. Zenodo https://doi.org/10.5281/zenodo.17320309 (2025).

Download references

Acknowledgements

This work was funded by a grant from the National Natural Science Foundation of China (31972064 (X.X.)), the Basic Research Program of Jiangsu (BK20252085 (X.X.), BK20251603 (H.L.)), and Jiangsu Funding Program for Excellent Postdoctoral Talent (2025ZB880 (H.L.)).

Author information

Authors and Affiliations

Authors

Contributions

H.L., L.W., Y.L., and X.H. performed the experiments. H.L. analyzed the experimental data. A.H. and X.X. carried out manuscript revisions. X.X. directed the study. H.L. and L.W. wrote the manuscript, and all authors read and approved the final manuscript.

Corresponding author

Correspondence to
Xiaole Xia.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Communications thanks Wenping Cui, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

Additional information

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

Supplementary information

Supplementary Information

Reporting Summary

Transparent Peer Review file

Source data

Source Data

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Cite this article

Liao, H., Wu, L., Luo, Y. et al. Slower-growing species promote interspecific cooperation and coexistence under acid stress through cross-feeding.
Nat Commun (2025). https://doi.org/10.1038/s41467-025-67395-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41467-025-67395-z


Source: Ecology - nature.com

New SAR11 isolate genomes and global marine metagenomes resolve ecologically relevant units within the Pelagibacterales

Defensive responses of titan triggerfish to tiger sharks at a provisioned reef

Back to Top