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.

  • Article
  • Published:

Mesospace domain orchestrates microbial consortia by β-barrel porin modulation and local molecule enrichment for wastewater treatment

Nature Water volume 4, pages 294–306 (2026)Cite this article

Subjects

Abstract

Microbial consortia hold immense promise for wastewater treatment by harnessing metabolite exchange-based interspecies interactions to drive energy and matter flow. Yet, challenges in the coordinated modulation of transmembrane transport proteins and extracellular metabolite distribution limit cross-species interactions within consortia. Here we propose a mesospace-domain regulation strategy that leverages hydrogel-assembled mesoscale habitats to precisely modulate β-barrel membrane porins and locally enrich cross-fed molecules, thus remodelling interspecific cooperative metabolism for efficient wastewater treatment. Confining a carefully designed microbiota within mesospace enhances organic wastewater treatment for hexanoate production, achieving a 307.2% higher yield than unconfined systems. This improvement is attributed to mesospace-governed porin regulation and exometabolite enrichment, which reprogram interbacterial interactions from unidirectional electron transfer to bidirectional multimetabolite cross-feeding. This regulatory strategy is also applicable to other wastewater treatment systems, markedly enhancing succinic acid production, denitrification of low carbon-to-nitrogen ratio wastewater and removal of emerging contaminants. These findings illuminate how the mesospace domain orchestrates microbiota metabolism to boost bioconversion efficiency and selectivity for sustainable wastewater management.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

Fig. 1: Schematic illustration of the mesospace domain for orchestrating interspecies metabolic cross-feeding within microbial consortia for wastewater treatment.
Fig. 2: Biotreatment performance and structural characterization of the microbial platforms.
Fig. 3: Microbial physicochemical characterization and biosynthesis metabolic pathway.
Fig. 4: Metabolic cross-feeding interactions across consortium species.
Fig. 5: Modulation of β-barrel membrane porin and transmembrane molecular transport.

Similar content being viewed by others

Data availability

All data generated in this study are included in the Article and its Supplementary Information. Proteomic raw data have been deposited to the ProteomeXchange Consortium through the iProX partner repository with the dataset identifier PXD057916. The 16S rRNA sequencing data have been deposited to the National Center for Biotechnology Information short-read archive under accession no. PRJNA1377884. Source data are provided with this paper.

References

  1. Flemming, H.-C. & Wuertz, S. Bacteria and archaea on Earth and their abundance in biofilms. Nat. Rev. Microbiol. 17, 247–260 (2019).

    Article  CAS  PubMed  Google Scholar 

  2. Kost, C., Patil, K. R., Friedman, J., Garcia, S. L. & Ralser, M. Metabolic exchanges are ubiquitous in natural microbial communities. Nat. Microbiol. 8, 2244–2252 (2023).

    Article  CAS  PubMed  Google Scholar 

  3. Wang, M. et al. Enhanced anaerobic wastewater treatment by a binary electroactive material: pseudocapacitance/conductance-mediated microbial interspecies electron transfer. Environ. Sci. Technol. 57, 12072–12082 (2023).

    Article  CAS  PubMed  Google Scholar 

  4. Raghoebarsing, A. A. et al. A microbial consortium couples anaerobic methane oxidation to denitrification. Nature 440, 918–921 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Zhao, C. et al. Metabolite cross-feeding promoting NADH production and electron transfer during efficient SMX biodegradation by a denitrifier and S. oneidensis MR-1 in the presence of nitrate. Environ. Sci. Technol. 57, 18306–18316 (2023).

    Article  CAS  PubMed  Google Scholar 

  6. D’Souza, G. et al. Ecology and evolution of metabolic cross-feeding interactions in bacteria. Nat. Prod. Rep. 35, 455–488 (2018).

    Article  PubMed  Google Scholar 

  7. Liu, X. et al. Syntrophic interspecies electron transfer drives carbon fixation and growth by Rhodopseudomonas palustris under dark, anoxic conditions. Sci. Adv. 7, eabh1852 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tsoi, R. et al. Metabolic division of labor in microbial systems. Proc. Natl Acad. Sci. USA 115, 2526–2531 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ren, S. et al. Hydrochar-facilitated anaerobic digestion: Evidence for direct interspecies electron transfer mediated through surface oxygen-containing functional groups. Environ. Sci. Technol. 54, 5755–5766 (2020).

    Article  CAS  PubMed  Google Scholar 

  10. Zhang, P., Zhang, J., Zhang, T., Zhang, L. & He, Y. Zero-valent iron enhanced methane production of anaerobic digestion by reinforcing microbial electron bifurcation coupled with direct inter-species electron transfer. Water Res. 255, 121428 (2024).

    Article  CAS  PubMed  Google Scholar 

  11. Sokolovskaya, O. M., Shelton, A. N. & Taga, M. E. Sharing vitamins: cobamides unveil microbial interactions. Science 369, eaba0165 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nikaido, H. & Saier, M. H. Jr Transport proteins in bacteria: common themes in their design. Science 258, 936–942 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev. 67, 593–656 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cowan, S. et al. The structure of OmpF porin in a tetragonal crystal form. Structure 3, 1041–1050 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. Fritts, R. K., McCully, A. L. & McKinlay, J. B. Extracellular metabolism sets the table for microbial cross-feeding. Microbiol. Mol. Bio. Rev. 85, e00135–20 (2021).

    Article  CAS  Google Scholar 

  16. Kong, L. et al. Cross-feeding between filamentous cyanobacteria and symbiotic bacteria favors rapid photogranulation. Environ. Sci. Technol. 57, 16953–16963 (2023).

    Article  CAS  PubMed  Google Scholar 

  17. Pronk, M. et al. Full scale performance of the aerobic granular sludge process for sewage treatment. Water Res. 84, 207–217 (2015).

    Article  CAS  PubMed  Google Scholar 

  18. Zhou, Y. et al. Mass flow and metabolic pathway of nonaeration greywater treatment in an oxygenic microalgal–bacterial biofilm. Environ. Sci. Technol. 58, 534–544 (2023).

    Article  PubMed  Google Scholar 

  19. Wang, Y., Gao, H. & Wells, G. F. Integrated omics analyses reveal differential gene expression and potential for cooperation between denitrifying polyphosphate and glycogen accumulating organisms. Environ. Microbiol. 23, 3274–3293 (2021).

    Article  CAS  PubMed  Google Scholar 

  20. Cheng, C. et al. Electricity-enhanced anaerobic, non-photosynthetic mixotrophy by Clostridium carboxidivorans with increased carbon efficiency and alcohol production. Energy Convers. Manage. 252, 115118 (2022).

    Article  CAS  Google Scholar 

  21. Li, F. et al. Modular engineering to increase intracellular NAD(H/+) promotes rate of extracellular electron transfer of Shewanella oneidensis. Nat. Commun. 9, 3637 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Wirth, S. & Dürre, P. Investigation of putative genes for the production of medium-chained acids and alcohols in autotrophic acetogenic bacteria. Metab. Eng. 66, 296–307 (2021).

    Article  CAS  PubMed  Google Scholar 

  23. Shen, S. et al. Effect of temperature and surfactant on biomass growth and higher-alcohol production during syngas fermentation by Clostridium carboxidivorans P7. Bioresour. Bioprocess. 7, 1–13 (2020).

    Article  CAS  Google Scholar 

  24. Marsili, E. et al. Shewanella secretes flavins that mediate extracellular electron transfer. Proc. Natl Acad. Sci. USA 105, 3968–3973 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Waldrop, G. L., Holden, H. M. & Maurice, M. S. The enzymes of biotin dependent CO2 metabolism: what structures reveal about their reaction mechanisms. Protein Sci. 21, 1597–1619 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Appel, A. M. et al. Frontiers, opportunities, and challenges in biochemical and chemical catalysis of CO2 fixation. Chem. Rev. 113, 6621–6658 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liu, Z., Wang, K., Chen, Y., Tan, T. & Nielsen, J. Third-generation biorefineries as the means to produce fuels and chemicals from CO2. Nat. Catal. 3, 274–288 (2020).

    Article  CAS  Google Scholar 

  28. Waters, C. M. & Bassler, B. L. Quorum sensing: cell-to-cell communication in bacteria. Annu. Rev. Cell Dev. Biol. 21, 319–346 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Mukherjee, S. & Bassler, B. L. Bacterial quorum sensing in complex and dynamically changing environments. Nat. Rev. Microbiol. 17, 371–382 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Abraham, M. J. et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2, 19–25 (2015).

    Article  Google Scholar 

  31. Tombola, R., Buttiglieri, G., Auset, M. & Gonzalez-Olmos, R. Recycled corrugated wire hose cover as biological carriers for greywater treatment in a sequential batch biofilm reactor. J. Environ. Manage. 240, 475–484 (2019).

    Article  CAS  PubMed  Google Scholar 

  32. Yang, X., Zhou, Y., Zhang, L., Benally, C. & Liu, Y. Enhanced biofilm formation and municipal wastewater treatment efficiency using granular activated carbon modified bio-ball carriers in moving bed biofilm reactor. Bioresour. Technol. 435, 132947 (2025).

    Article  CAS  PubMed  Google Scholar 

  33. Li, Y. et al. Microbial engineering for the production of C2–C6 organic acids. Nat. Prod. Rep. 38, 1518–1546 (2021).

    Article  CAS  PubMed  Google Scholar 

  34. Hoff, B. et al. Unlocking nature’s biosynthetic power—metabolic engineering for the fermentative production of chemicals. Angew. Chem. Int. Ed. 60, 2258–2278 (2020).

    Article  Google Scholar 

  35. Dueholm, M. K. D. et al. MiDAS 4: A global catalogue of full-length 16S rRNA gene sequences and taxonomy for studies of bacterial communities in wastewater treatment plants. Nat. Commun. 13, 1908 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ye, J. et al. Wastewater denitrification driven by mechanical energy through cellular piezo-sensitization. Nat. Water 2, 531–540 (2024).

    Article  CAS  Google Scholar 

  37. Ravishankara, A., Daniel, J. S. & Portmann, R. W. Nitrous oxide (N2O): the dominant ozone-depleting substance emitted in the 21st century. Science 326, 123–125 (2009).

    Article  CAS  PubMed  Google Scholar 

  38. Canfield, D. E., Glazer, A. N. & Falkowski, P. G. The evolution and future of Earth’s nitrogen cycle. Science 330, 192–196 (2010).

    Article  CAS  PubMed  Google Scholar 

  39. Zhang, W., Guan, A., Peng, Q., Qi, W. & Qu, J. Microbe-mediated simultaneous nitrogen reduction and sulfamethoxazole/N-acetylsulfamethoxazole removal in lab-scale constructed wetlands. Water Res. 242, 120233 (2023).

    Article  CAS  PubMed  Google Scholar 

  40. Choe, D. et al. Adaptive laboratory evolution of a genome-reduced Escherichia coli. Nat. Commun. 10, 935 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Moon, E. C. et al. Physiological cost of antibiotic resistance: insights from a ribosome variant in bacteria. Sci. Adv. 10, eadq5249 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hu, G. et al. Light-driven CO2 sequestration in Escherichia coli to achieve theoretical yield of chemicals. Nat. Catal. 4, 395–406 (2021).

    Article  CAS  Google Scholar 

  43. Cui, W. et al. Gut microbial metabolite facilitates colorectal cancer development via ferroptosis inhibition. Nat. Cell Biol. 26, 124–137 (2024).

    Article  CAS  PubMed  Google Scholar 

  44. Cooper, R. E. et al. Iron is not everything: Unexpected complex metabolic responses between iron–cycling microorganisms. ISME J 14, 2675–2690 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lindorff-Larsen, K. et al. Improved side-chain torsion potentials for the Amber ff99SB protein force field. J. Comput. Chem. 78, 1950–1958 (2010).

    CAS  Google Scholar 

  46. Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A. & Case, D. A. Development and testing of a General Amber Force Field. J. Comput. Chem. 25, 1157–1174 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Eberhardt, J., Santos-Martins, D., Tillack, A. F. & Forli, S. AutoDock Vina 1.2. 0: new docking methods, expanded force field, and Python bindings. J. Comput. Chem. 61, 3891–3898 (2021).

    CAS  Google Scholar 

  48. Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Kumar, S., Rosenberg, J. M., Bouzida, D., Swendsen, R. H. & Kollman, P. A. The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method. J. Comput. Chem. 13, 1011–1021 (1992).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant nos. 52300172 to C.L. and 52470053 to Y.C.), the National Key R&D Program of China (grant no. 2025YFE0208000 to Y.C.), the Shanghai Rising-Star Program (grant no. 23YF1448900 to C.L.) and the China Postdoctoral Science Foundation Program (grant nos. 2024T170665 and 2022M722396 to C.L.).

Author information

Authors and Affiliations

  1. State Key Laboratory of Water Pollution Control and Green Resource Recycling, Shanghai Institute of Pollution Control and Ecological Security, College of Environmental Science and Engineering, Tongji University, Shanghai, China

    Chao Liu, Xuemeng Zhang, Qingran Zhang, Mengru Zhu & Yinguang Chen

  2. Department of Civil and Environmental Engineering, Imperial College London, London, UK

    Yue Yin

  3. Department of Civil and Environmental Engineering, William and Cloy Codiga Resource Recovery Center, Stanford University, Stanford, CA, USA

    Wei-Min Wu

  4. School of Environment, Nanjing University, Nanjing, China

    Bingcai Pan, Hongqiang Ren & Jinfeng Wang

  5. CAS Key Laboratory of Urban Pollutant Conversion, Department of Environmental Science and Engineering, University of Science and Technology of China, Hefei, China

    Han-Qing Yu

Authors
  1. Chao Liu
    View author publications

    Search author on:PubMed Google Scholar

  2. Yue Yin
    View author publications

    Search author on:PubMed Google Scholar

  3. Xuemeng Zhang
    View author publications

    Search author on:PubMed Google Scholar

  4. Wei-Min Wu
    View author publications

    Search author on:PubMed Google Scholar

  5. Bingcai Pan
    View author publications

    Search author on:PubMed Google Scholar

  6. Hongqiang Ren
    View author publications

    Search author on:PubMed Google Scholar

  7. Qingran Zhang
    View author publications

    Search author on:PubMed Google Scholar

  8. Han-Qing Yu
    View author publications

    Search author on:PubMed Google Scholar

  9. Jinfeng Wang
    View author publications

    Search author on:PubMed Google Scholar

  10. Mengru Zhu
    View author publications

    Search author on:PubMed Google Scholar

  11. Yinguang Chen
    View author publications

    Search author on:PubMed Google Scholar

Contributions

C.L. and Y.C. developed the research concept, designed experiments, discussed the results and wrote the manuscript; C.L., Y.Y., X.Z. and M.Z. performed the experiments and data analyses; B.P., Q.Z. and J.W. provided constructive advice on experiments and result interpretation; W.-M.W., H.R. and H.-Q.Y. assisted in research design and manuscript editing. All authors discussed, commented on and approved the final manuscript.

Corresponding author

Correspondence to Yinguang Chen.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Water thanks Liangyan Rong, Qidong Yin 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.

Supplementary information

Supplementary Information (download PDF )

Supplementary Texts 1–28, Figs. 1–30, Tables 1–15 and References.

Reporting Summary (download PDF )

Supplementary Video 1 (download MP4 )

The SMD simulation of a serine molecule being pulled through the OmpF.

Supplementary Video 2 (download MP4 )

The SMD simulation of a serine molecule being pulled through the AI-2-docked OmpF.

Supplementary Data 1 (download XLSX )

Source data for Supplementary Figs. 1, 2, 4–9, 11–19, 21–23 and 25–30.

Source data

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

Liu, C., Yin, Y., Zhang, X. et al. Mesospace domain orchestrates microbial consortia by β-barrel porin modulation and local molecule enrichment for wastewater treatment. Nat Water 4, 294–306 (2026). https://doi.org/10.1038/s44221-025-00579-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s44221-025-00579-5

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research