Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 suppress polystyrene nanoplastic transcellular permeability and internalization by intestinal epithelial cells

1. Geyer, R., Jambeck, J. R. & Law, K. L. Production, use, and fate of all plastics ever made. Sci. Adv. 3, e1700782. https://doi.org/10.1126/sciadv.1700782 (2017).

   Google Scholar 

2. Shruti, V. C., Perez-Guevara, F., Elizalde-Martinez, I. & Kutralam-Muniasamy, G. Toward a unified framework for investigating micro(nano)plastics in packaged beverages intended for human consumption. Environ. Pollut. 268, 115811. https://doi.org/10.1016/j.envpol.2020.115811 (2021).

   Google Scholar 

3. Chain, E. P. o. C. i. t. F. Presence of microplastics and nanoplastics in food, with particular focus on seafood. EFSA J. 14, e04501. https://doi.org/10.2903/j.efsa.2016.4501 (2016).

   Google Scholar 

4. Smith, M., Love, D. C., Rochman, C. M. & Neff, R. A. Microplastics in seafood and the implications for human health. Curr. Environ. Health Rep. 5, 375–386. https://doi.org/10.1007/s40572-018-0206-z (2018).

   Google Scholar 

5. Cox, K. D. et al. Human consumption of microplastics. Environ. Sci. Technol. 53, 7068–7074. https://doi.org/10.1021/acs.est.9b01517 (2019).

   Google Scholar 

6. Schymanski, D., Goldbeck, C., Humpf, H. U. & Furst, P. Analysis of microplastics in water by micro-Raman spectroscopy: release of plastic particles from different packaging into mineral water. Water Res. 129, 154–162. https://doi.org/10.1016/j.watres.2017.11.011 (2018).

   Google Scholar 

7. 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. https://doi.org/10.1016/j.jhazmat.2020.124004 (2021).

   Google Scholar 

8. Huang, S. et al. Detection and analysis of microplastics in human sputum. Environ. Sci. Technol. 56, 2476–2486. https://doi.org/10.1021/acs.est.1c03859 (2022).

   Google Scholar 

9. Abbasi, S. & Turner, A. Human exposure to microplastics: A study in Iran. J. Hazard. Mater. 403, 123799. https://doi.org/10.1016/j.jhazmat.2020.123799 (2021).

   Google Scholar 

10. Schwabl, P. et al. Detection of various microplastics in human stool: A prospective case series. Ann. Intern. Med. 171, 453–457. https://doi.org/10.7326/M19-0618 (2019).

    Google Scholar 

11. Khan, A. & Jia, Z. Recent insights into uptake, toxicity, and molecular targets of microplastics and nanoplastics relevant to human health impacts. iScience 26, 106061. https://doi.org/10.1016/j.isci.2023.106061 (2023).

    Google Scholar 

12. dos Santos, T., Varela, J., Lynch, I., Salvati, A. & Dawson, K. A. Effects of transport inhibitors on the cellular uptake of carboxylated polystyrene nanoparticles in different cell lines. PLoS One. 6, e24438. https://doi.org/10.1371/journal.pone.0024438 (2011).

    Google Scholar 

13. Domenech, J. et al. Long-term effects of polystyrene nanoplastics in human intestinal Caco-2 cells. Biomolecules 11 https://doi.org/10.3390/biom11101442 (2021).

14. Bannunah, A., Cavanagh, R., Shubber, S., Vllasaliu, D. & Stolnik, S. Difference in endocytosis pathways used by differentiated versus nondifferentiated epithelial Caco-2 cells to internalize nanosized particles. Mol. Pharm. 21, 3603–3612. https://doi.org/10.1021/acs.molpharmaceut.4c00333 (2024).

    Google Scholar 

15. Xu, D., Ma, Y., Han, X. & Chen, Y. Systematic toxicity evaluation of polystyrene nanoplastics on mice and molecular mechanism investigation about their internalization into Caco-2 cells. J. Hazard. Mater. 417, 126092. https://doi.org/10.1016/j.jhazmat.2021.126092 (2021).

    Google Scholar 

16. Wang, F. et al. Time resolved study of cell death mechanisms induced by amine-modified polystyrene nanoparticles. Nanoscale 5, 10868–10876. https://doi.org/10.1039/c3nr03249c (2013).

    Google Scholar 

17. Han, S. W., Choi, J. & Ryu, K. Y. Stress response of mouse embryonic fibroblasts exposed to polystyrene nanoplastics. Int. J. Mol. Sci. 22 https://doi.org/10.3390/ijms22042094 (2021).

18. Martinez, B., Rodriguez, A., Kulakauskas, S. & Chapot-Chartier, M. P. Cell wall homeostasis in lactic acid bacteria: threats and defences. FEMS Microbiol. Rev. 44, 538–564. https://doi.org/10.1093/femsre/fuaa021 (2020).

    Google Scholar 

19. Araujo, M. M. & Botelho, P. B. Probiotics, prebiotics, and synbiotics in chronic constipation: outstanding aspects to be considered for the current evidence. Front. Nutr. 9, 935830. https://doi.org/10.3389/fnut.2022.935830 (2022).

    Google Scholar 

20. Madsen, K. L., Doyle, J. S., Jewell, L. D., Tavernini, M. M. & Fedorak, R. N. Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology 116, 1107–1114. https://doi.org/10.1016/s0016-5085(99)70013-2 (1999).

    Google Scholar 

21. Usui, Y. et al. Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice. Int. Immunol. 30, 319–331. https://doi.org/10.1093/intimm/dxy035 (2018).

    Google Scholar 

22. Kobayashi, K., Honme, Y. & Sashihara, T. Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 induce the expression of the REG3 family in the small intestine of mice via the stimulation of dendritic cells and type 3 innate lymphoid cells. Nutrients 11 https://doi.org/10.3390/nu11122998 (2019).

23. Kobayashi, K., Mochizuki, J., Yamazaki, F. & Sashihara, T. Yogurt starter strains ameliorate intestinal barrier dysfunction via activating AMPK in Caco-2 cells. Tissue Barriers 2184157 https://doi.org/10.1080/21688370.2023.2184157 (2023).

24. Kobayashi, K. et al. Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 ameliorate barrier dysfunction in human induced pluripotent stem cell-derived crypt-villus structural small intestine. Front. Immunol. 16 (1585007). https://doi.org/10.3389/fimmu.2025.1585007 (2025).

25. Wang, Y. et al. Intestinal nanoparticle delivery and cellular response: a review of the bidirectional nanoparticle-cell interplay in mucosa based on physiochemical properties. J. Nanobiotechnol. 22, 669. https://doi.org/10.1186/s12951-024-02930-6 (2024).

    Google Scholar 

26. Mahler, G. J. et al. Oral exposure to polystyrene nanoparticles affects iron absorption. Nat. Nanotechnol. 7, 264–271. https://doi.org/10.1038/nnano.2012.3 (2012).

    Google Scholar 

27. Choi, H. et al. Size-dependent internalization of microplastics and nanoplastics using in vitro model of the human intestine-contribution of each cell in the tri-culture models. Nanomaterials (Basel) 14. https://doi.org/10.3390/nano14171435 (2024).

28. Wu, L. L. et al. Commensal bacterial endocytosis in epithelial cells is dependent on myosin light chain kinase-activated brush border fanning by interferon-gamma. Am. J. Pathol. 184, 2260–2274. https://doi.org/10.1016/j.ajpath.2014.05.003 (2014).

    Google Scholar 

29. Wang, Y., Liu, Y., Zhou, W., Lin, J. & Wen, L. Myosin light-chain kinase inhibitors attenuate nanoparticles-induced autophagy and cytotoxicity by suppression endocytosis. J. Nanosci. Nanotechnol. 19, 3792–3797. https://doi.org/10.1166/jnn.2019.16324 (2019).

    Google Scholar 

30. Haque, M. et al. Lactobacillus acidophilus inhibits the TNF-α-induced increase in intestinal epithelial tight junction permeability via a TLR-2 and PI3K-dependent inhibition of NF-κB activation. Front. Immunol. 15, 1348010. https://doi.org/10.3389/fimmu.2024.1348010 (2024).

    Google Scholar 

31. Schwandner, R., Dziarski, R., Wesche, H., Rothe, M. & Kirschning, C. J. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J. Biol. Chem. 274, 17406–17409. https://doi.org/10.1074/jbc.274.25.17406 (1999).

    Google Scholar 

32. Yoshimura, A. et al. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J. Immunol. 163, 1–5. https://doi.org/10.4049/jimmunol.163.1.1 (1999).

    Google Scholar 

33. Yang, G. et al. Glucuronidation: driving factors and their impact on glucuronide disposition. Drug Metab. Rev. 49, 105–138. https://doi.org/10.1080/03602532.2017.1293682 (2017).

    Google Scholar 

34. Spencer, J. P. et al. The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett. 458, 224–230. https://doi.org/10.1016/s0014-5793(99)01160-6 (1999).

    Google Scholar 

35. Tian, C., Hao, L., Yi, W., Ding, S. & Xu, F. Polyphenols, oxidative stress, and metabolic syndrome. Oxid. Med. Cell. Longev. 2020 (7398453). https://doi.org/10.1155/2020/7398453 (2020).

36. Yahfoufi, N., Alsadi, N., Jambi, M. & Matar, C. The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients 10 https://doi.org/10.3390/nu10111618 (2018).

37. Mizuma, T., Momota, R., Haga, M. & Hayashi, M. Factors affecting glucuronidation activity in Caco-2 cells. Drug Metab. Pharmacokinet. 19, 130–134. https://doi.org/10.2133/dmpk.19.130 (2004).

    Google Scholar 

38. Chen, J. et al. Surface functionalization-dependent inflammatory potential of polystyrene nanoplastics through the activation of MAPK/ NF-κB signaling pathways in macrophage Raw 264.7. Ecotoxicol. Environ. Saf. 251, 114520. https://doi.org/10.1016/j.ecoenv.2023.114520 (2023).

    Google Scholar 

39. Leslie, H. A. et al. Discovery and quantification of plastic particle pollution in human blood. Environ. Int. 163, 107199. https://doi.org/10.1016/j.envint.2022.107199 (2022).

    Google Scholar 

40. Marfella, R. et al. Microplastics and nanoplastics in atheromas and cardiovascular events. N Engl. J. Med. 390, 900–910. https://doi.org/10.1056/NEJMoa2309822 (2024).

    Google Scholar 

41. Vollmer, W., Blanot, D. & de Pedro, M. A. Peptidoglycan structure and architecture. FEMS Microbiol. Rev. 32, 149–167. https://doi.org/10.1111/j.1574-6976.2007.00094.x (2008).

    Google Scholar 

42. Shiraishi, T., Yokota, S., Fukiya, S. & Yokota, A. Structural diversity and biological significance of lipoteichoic acid in Gram-positive bacteria: focusing on beneficial probiotic lactic acid bacteria. Biosci. Microbiota Food Health. 35, 147–161. https://doi.org/10.12938/bmfh.2016-006 (2016).

    Google Scholar 

43. Walczak, A. P. et al. Translocation of differently sized and charged polystyrene nanoparticles in in vitro intestinal cell models of increasing complexity. Nanotoxicology 9, 453–461. https://doi.org/10.3109/17435390.2014.944599 (2015).

    Google Scholar 

44. Stock, V. et al. Uptake and cellular effects of PE, PP, PET and PVC microplastic particles. Toxicol. Vitro. 70, 105021. https://doi.org/10.1016/j.tiv.2020.105021 (2021).

    Google Scholar 

45. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U S A. 102, 15545–15550. https://doi.org/10.1073/pnas.0506580102 (2005).

    Google Scholar 

46. Mootha, V. K. et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273. https://doi.org/10.1038/ng1180 (2003).

    Google Scholar 

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