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:

Oligomer nanoparticle release from polylactic acid plastics catalysed by gut enzymes triggers acute inflammation

Nature Nanotechnology volume 18, pages 403–411 (2023)Cite this article

Subjects

Abstract

The health risks of exposure to ‘eco-friendly’ biodegradable plastics of anthropogenic origin and their effects on the gastrointestinal tract are largely unknown. Here we demonstrate that the enzymatic hydrolysis of polylactic acid microplastics generated nanoplastic particles by competing for triglyceride-degrading lipase during gastrointestinal processes. Nanoparticle oligomers were formed by hydrophobically driven self-aggregation. In a mouse model, polylactic acid oligomers and their nanoparticles bioaccumulated in the liver, intestine and brain. Hydrolysed oligomers caused intestinal damage and acute inflammation. A large-scale pharmacophore model revealed that oligomers interacted with matrix metallopeptidase 12. Mechanistically, high binding affinity (Kd = 13.3 μmol l−1) of oligomers to the catalytic zinc-ion finger domain led to matrix metallopeptidase 12 inactivation, which might mediate the adverse bowel inflammatory effects after exposure to polylactic acid oligomers. Biodegradable plastics are considered to be a solution to address environmental plastic pollution. Thus, understanding the gastrointestinal fates and toxicities of bioplastics will provide insights into potential health risks.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Gastric lipases digests PLA MPs.
Fig. 2: Characterization of PLA nanoplastic formation.
Fig. 3: Biodistribution and histopathology of PLA nanoplastics/oligomers in vitro and in vivo.
Fig. 4: PLA oligomers inactivate MMP12.
Fig. 5: MMP12-inactivation-mediated intestinal inflammation induced by PLA oligomers.

Similar content being viewed by others

Data availability

All data supporting the findings of this study are available within this article and its Supplementary Information. Source data are provided with this paper.

References

  1. Hurley, R., Woodward, J. & Rothwell, J. J. Microplastic contamination of river beds significantly reduced by catchment-wide flooding. Nat. Geosci. 11, 251–257 (2018).

    Article  CAS  Google Scholar 

  2. Galloway, T. S., Cole, M. & Lewis, C. Interactions of microplastic debris throughout the marine ecosystem. Nat. Ecol. Evol. 1, 0116 (2017).

    Article  Google Scholar 

  3. Koelmans, A. A. et al. Risk assessment of microplastic particles. Nat. Rev. Mater. 7, 138–152 (2022).

    Article  Google Scholar 

  4. Li, D. et al. Microplastic release from the degradation of polypropylene feeding bottles during infant formula preparation. Nat. Food 1, 746–754 (2020).

    Article  CAS  Google Scholar 

  5. Senathirajah, K. et al. Estimation of the mass of microplastics ingested—a pivotal first step towards human health risk assessment. J. Hazard. Mater. 404, 124004 (2021).

    Article  CAS  Google Scholar 

  6. Schwabl, P. et al. Detection of various microplastics in human stool: a prospective case series. Ann. Intern. Med. 171, 453–457 (2019).

    Article  Google Scholar 

  7. Deng, Y. et al. Polystyrene microplastics affect the reproductive performance of male mice and lipid homeostasis in their offspring. Environ. Sci. Technol. Lett. 9, 752–757 (2022).

    Article  CAS  Google Scholar 

  8. Sussarellu, R. et al. Oyster reproduction is affected by exposure to polystyrene microplastics. Proc. Natl Acad. Sci. USA 113, 2430–2435 (2016).

    Article  CAS  Google Scholar 

  9. Choi, J. S., Kim, K., Hong, S. H., Park, K.-I. & Park, J.-W. Impact of polyethylene terephthalate microfiber length on cellular responses in the Mediterranean mussel Mytilus galloprovincialis. Mar. Environ. Res. 168, 105320 (2021).

    Article  CAS  Google Scholar 

  10. Jin, H. et al. Evaluation of neurotoxicity in BALB/c mice following chronic exposure to polystyrene microplastics. Environ. Health Perspect. 130, 107002 (2022).

    Article  CAS  Google Scholar 

  11. Geyer, R., Jambeck, J. R. & Law, K. L. Production, use, and fate of all plastics ever made. Sci. Adv. 3, e1700782 (2017).

    Article  Google Scholar 

  12. Aznar, M., Ubeda, S., Dreolin, N. & Nerin, C. Determination of non-volatile components of a biodegradable food packaging material based on polyester and polylactic acid (PLA) and its migration to food simulants. J. Chromatogr. A 1583, 1–8 (2019).

    Article  CAS  Google Scholar 

  13. Ncube, L. K., Ude, A. U., Ogunmuyiwa, E. N., Zulkifli, R. & Beas, I. N. Environmental impact of food packaging materials: a review of contemporary development from conventional plastics to polylactic acid based materials. Materials 13, 4994 (2020).

    Article  CAS  Google Scholar 

  14. Balla, E. et al. Poly (lactic acid): a versatile biobased polymer for the future with multifunctional properties—from monomer synthesis, polymerization techniques and molecular weight increase to PLA applications. Polymers 13, 1822 (2021).

    Article  CAS  Google Scholar 

  15. Ramot, Y., Haim-Zada, M., Domb, A. J. & Nyska, A. Biocompatibility and safety of PLA and its copolymers. Adv. Drug Deliv. Rev. 107, 153–162 (2016).

    Article  CAS  Google Scholar 

  16. Zhang, X. et al. Photolytic degradation elevated the toxicity of polylactic acid microplastics to developing zebrafish by triggering mitochondrial dysfunction and apoptosis. J. Hazard. Mater. 413, 125321 (2021).

    Article  CAS  Google Scholar 

  17. Duan, Z. et al. Diet preference of zebrafish (Danio rerio) for bio-based polylactic acid microplastics and induced intestinal damage and microbiota dysbiosis. J. Hazard. Mater. 429, 128332 (2022).

    Article  CAS  Google Scholar 

  18. Wang, L. et al. An in situ depolymerization and liquid chromatography–tandem mass spectrometry method for quantifying polylactic acid microplastics in environmental samples. Environ. Sci. Technol. 56, 13029–13035 (2022).

    Article  CAS  Google Scholar 

  19. Yan, M., Yang, J., Sun, H., Liu, C. & Wang, L. Occurrence and distribution of microplastics in sediments of a man-made lake receiving reclaimed water. Sci. Total Environ. 813, 152430 (2022).

    Article  CAS  Google Scholar 

  20. Wei, X. F. et al. Millions of microplastics released from a biodegradable polymer during biodegradation/enzymatic hydrolysis. Water Res. 211, 118068 (2022).

    Article  CAS  Google Scholar 

  21. González-Pleiter, M. et al. Secondary nanoplastics released from a biodegradable microplastic severely impact freshwater environments. Environ. Sci. Nano 6, 1382–1392 (2019).

    Article  Google Scholar 

  22. Lambert, S. & Wagner, M. Characterisation of nanoplastics during the degradation of polystyrene. Chemosphere 145, 265–268 (2016).

    Article  CAS  Google Scholar 

  23. Lambert, S. & Wagner, M. Formation of microscopic particles during the degradation of different polymers. Chemosphere 161, 510–517 (2016).

    Article  CAS  Google Scholar 

  24. Mattsson, K., Björkroth, F., Karlsson, T. & Hassellöv, M. Nanofragmentation of expanded polystyrene under simulated environmental weathering (thermooxidative degradation and hydrodynamic turbulence). Front. Mar. Sci. 7, 578178 (2021).

    Article  Google Scholar 

  25. Sorasan, C. et al. Generation of nanoplastics during the photoageing of low-density polyethylene. Environ. Pollut. 289, 117919 (2021).

    Article  CAS  Google Scholar 

  26. Su, Y. et al. Steam disinfection releases micro (nano) plastics from silicone-rubber baby teats as examined by optical photothermal infrared microspectroscopy. Nat. Nanotechnol. 17, 76–85 (2022).

    Article  CAS  Google Scholar 

  27. Wright, S. L. & Kelly, F. J. Plastic and human health: a micro issue? Environ. Sci. Technol. 51, 6634–6647 (2017).

    Article  CAS  Google Scholar 

  28. Gruber, M. M. et al. Plasma proteins facilitates placental transfer of polystyrene particles. J. Nanobiotechnol. 18, 128 (2020).

    Article  CAS  Google Scholar 

  29. Wang, H. F., Hu, Y., Sun, W. Q. & Xie, C. S. Polylactic acid nanoparticles across the brain-blood barrier observed with analytical electron microscopy. Chin. J. Biotechnol. 20, 790–794 (2004).

    CAS  Google Scholar 

  30. Dawson, A. L. et al. Turning microplastics into nanoplastics through digestive fragmentation by Antarctic krill. Nat. Commun. 9, 1001 (2018).

    Article  Google Scholar 

  31. Ubeda, S., Aznar, M., Alfaro, P. & Nerin, C. Migration of oligomers from a food-contact biopolymer based on polylactic acid (PLA) and polyester. Anal. Bioanal. Chem. 411, 3521–3532 (2019).

    Article  CAS  Google Scholar 

  32. Fan, P., Yu, H., Xi, B. & Tan, W. A review on the occurrence and influence of biodegradable microplastics in soil ecosystems: are biodegradable plastics substitute or threat? Environ. Int. 163, 107244 (2022).

    Article  Google Scholar 

  33. Manavitehrani, I., Fathi, A., Wang, Y., Maitz, P. K. & Dehghani, F. Reinforced poly(propylene carbonate) composite with enhanced and tunable characteristics, an alternative for poly(lactic acid). ACS Appl. Mater. Interfaces 7, 22421–22430 (2015).

    Article  CAS  Google Scholar 

  34. Navarro, S. M. et al. Biodistribution and toxicity of orally administered poly (lactic-co-glycolic) acid nanoparticles to F344 rats for 21 days. Nanomedicine 11, 1653–1669 (2016).

    Article  CAS  Google Scholar 

  35. Bellac, C. L., Dufour, A., Krisinger, M. J., Loonchanta, A. & Starr, A. E. Macrophage matrix metalloproteinase-12 dampens inflammation and neutrophil influx in arthritis. Cell Rep. 9, 618–632 (2014).

    Article  CAS  Google Scholar 

  36. Zangmeister, C. D., Radney, J. G., Benkstein, K. D. & Kalanyan, B. Common single-use consumer plastic products release trillions of sub-100 nm nanoparticles per liter into water during normal use. Environ. Sci. Technol. 56, 5448–5455 (2022).

    Article  CAS  Google Scholar 

  37. Hernandez, L. M. et al. Plastic teabags release billions of microparticles and nanoparticles into tea. Environ. Sci. Technol. 53, 12300–12310 (2019).

    Article  CAS  Google Scholar 

  38. Tilston, E. L., Gibson, G. R. & Collins, C. D. Colon extended physiologically based extraction test (CE-PBET) increases bioaccessibility of soil-bound PAH. Environ. Sci. Technol. 45, 5301–5308 (2011).

    Article  CAS  Google Scholar 

  39. Macfarlane, G. T., Macfarlane, S. & Gibson, G. Validation of a three-stage compound continuous culture system for investigating the effect of retention time on the ecology and metabolism of bacteria in the human colon. Microb. Ecol. 35, 180–187 (1998).

    Article  CAS  Google Scholar 

  40. Capolino, P. et al. In vitro gastrointestinal lipolysis: replacement of human digestive lipases by a combination of rabbit gastric and porcine pancreatic extracts. Food Dig. 2, 43–51 (2011).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was primarily supported by the National Key R&D Program (nos. 2022YFC3702600 and 2022YFC3702601), the Singapore Ministry of Education Academic Research Fund Tier 1 (04MNP000567C120), the Ministry of Science and Technology of China (2022YF3701101), Startup Grant of Fudan University (no. JIH 1829010Y), Education Department of Anhui Province for Excellent Young Scientist (2022AH030076) and Second Tibetan Plateau Scientific Expedition and Research program (2019QZKK0682). We also acknowledge Y. Deng from Jinan University and Y. Zhan from Nanjing University for professional discussion and H. Yang, Y. Hua and S. Li from Research Center for Eco-Environmental Sciences for help with the NTA experiment.

Author information

Authors and Affiliations

  1. Department of Environmental Science and Engineering, Fudan University, Shanghai, China

    Mengjing Wang, Changzhi Shi, Jianmin Chen & Mingliang Fang

  2. School of Civil and Environmental Engineering, Nanyang Technological University, Singapore, Singapore

    Mengjing Wang, Junjie Yang, Linran Jia & Mingliang Fang

  3. Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China

    Qianqian Li

  4. Department of Toxicology, School of Public Health; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China

    Jia Lv & Yichao Huang

  5. State Key Laboratory of Proteomics, National Center for Protein Sciences–Beijing, Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, China

    Youdong Xu

  6. School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore

    Shae Linn Chua

  7. Sunlipo Biotech Research Center for Nanomedicine, Shanghai, China

    Huaiwen Chen

  8. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China

    Qian Liu

  9. School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, Singapore

    Changjin Huang

  10. Institute of Eco-Chongming, Shanghai, China

    Mingliang Fang

Authors
  1. Mengjing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qianqian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Changzhi Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jia Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Youdong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junjie Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shae Linn Chua
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Linran Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Huaiwen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Qian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Changjin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yichao Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jianmin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Mingliang Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.W. and M.F. conceived and designed the study. Y.H., J.C. and M.F. supervised the study. M.W., Q.L. and J.L. performed the in vivo experiments and data analysis. C.S. and J.Y. conducted the mass spectrometry experiments. M.W. and Y.X. performed the MD simulations. M.W., Q.L., L.J. and Q.L. contributed to the biochemistry and characterization experiments. H.C. contributed to the synthesis experiments. S.L.C. and C.H. performed HepG2 cellular uptake experiments. M.W., Y.H., J.C. and M.F. wrote the manuscript with input from all the authors. All the authors discussed the results.

Corresponding authors

Correspondence to Yichao Huang, Jianmin Chen or Mingliang Fang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Nanotechnology thanks Mathilde Body-Malapel 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

Supplementary Figs. 1–28, Tables 1 and 2, and Methods.

Reporting Summary

Supplementary Data 1

Source data for supplementary figures.

Source data

Source Data Fig. 1

Data underlying Fig. 1.

Source Data Fig. 2

Data underlying Fig. 2.

Source Data Fig. 3

Data underlying Fig. 3.

Source Data Fig. 4

Data underlying Fig. 4.

Source Data Fig. 5

Data underlying Fig. 5.

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

Wang, M., Li, Q., Shi, C. et al. Oligomer nanoparticle release from polylactic acid plastics catalysed by gut enzymes triggers acute inflammation. Nat. Nanotechnol. 18, 403–411 (2023). https://doi.org/10.1038/s41565-023-01329-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41565-023-01329-y

This article is cited by

Search

Advanced 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