Composite polyphenols mitigate microplastic exposure-related immune disturbances: a two-phase population trial

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.