Abstract
Microplastics (MPs) are widespread, making it urgent to elucidate their toxicity and identify intervention strategies. Here, we designed a two-phase population trial, comprising a baseline pilot population (n = 151) and a 28-day randomized, double-blind, placebo-controlled trial (n = 98). Primary outcomes include fecal MP concentration and blood parameters (complete blood count, glycemic and lipid, and cytokines), with exploratory outcomes comprising fecal metagenomics and plasma metabolomics. The median MP concentration in 151 participants’ fecal samples is 158.28 μg/g dry weight, correlating with levels of 7 inflammatory indexes, 4 cytokines, and 2 lipid indicators. Composite polyphenols (CP) significantly reduced plasma levels of IL-1β (P = 0.045, effect sizes = −0.463), IL-6 (P = 0.023, effect sizes = −0.576) and IL-8 (P = 0.022, effect sizes = −0.529). 507 differentially expressed microbiotas (DEMs; P < 0.05) and 144 significantly different metabolites (SDMs; P-FDR < 0.25, VIP ≥ 1) are observed between the high and low MP exposure groups; 108 DEMs and 85 SDMs are identified following CP intervention. Notably, CP could mitigate the pro-inflammatory effects of high MP exposure by modulating gut microbiota and up-regulating glycerophospholipid metabolism and arginine biosynthesis. The gut bacteria Staphylococcus and the plasma metabolite PC (22:5/0:0) are identified as potential mediators in this protective effect. Trial registration: ClinicalTrials.gov: NCT06437119.
Data availability
The MP detection data generated in this study have been deposited in the Mendeley Data database under accession code: doi 10.17632/zjrkjzzg66.2. [https://data.mendeley.com/drafts/zjrkjzzg66]. The metagenomic sequencing data generated in this study have been deposited in the National Center for Biotechnology Information (NCBI) database under accession code: bioproject_accession number PRJNA1274175 and SRA number SRP590969 [https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1274175]. The metabolomics data generated in this study have been deposited in the MetaboLights database under accession code: MTBLS12863. Source Data are provided in this paper. The study protocol is publicly available in the Supplementary. After signing the Data Use Agreement (DUA), de-identified individual clinical data can be shared with other researchers solely for non-commercial research purposes, and the sharing period extends from the publication of the article until the term stipulated in the DUA (at least one year). Data can be shared after publication by contacting the corresponding author, ruihua_dong@fudan.edu.cn. Source data are provided with this paper.
Code availability
The software used in the article has been described in the Qualification and statistical analysis section. No custom code was employed.
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Acknowledgements
This study was supported by the General Program of the National Natural Science Foundation of China (82574038) (R.D.), and the Key disciplines in the three-year Plan of Shanghai municipal public health system (2023–2025) (GWVI-11.1-42) (R.D.). We would like to thank all the staff and study participants who took part in the trial. Participants’ sample collection was completed at the School of Public Health, Fudan University. Fecal metagenome and plasma metabolome analysis were performed using the online platform of Majorbio Cloud Platform (www.majorbio.com). We are grateful to Amway (China) Co., Ltd. for providing the composite polyphenols intervention agent and placebo.
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L.Z.: Conceptualization, Visualization, Writing—Original Draft. Y.S.: Conceptualization, Methodology, Writing—Original Draft. J.Z.: Conceptualization, Investigation, Supervision. X.X.: Data Curation. X.L.: Investigation. J.Y.: Formal analysis. J.L.: Data Curation. B.Y.: Resources. L.C.: Investigation. F.W.: Investigation. S.L.: Writing—Review & Editing. X.P.: Writing—Review & Editing. J.D.: Writing—Review & Editing. R.D.: Conceptualization, Methodology, Writing—Review & Editing. All authors made substantial contributions and approved the final version of the manuscript.
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Zhao, L., Zheng, J., Shen, Y. et al. Composite polyphenols mitigate microplastic exposure-related immune disturbances: a two-phase population trial. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71167-8
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DOI: https://doi.org/10.1038/s41467-026-71167-8
