Microplastics in whole blood and gastric tissues of adults with obesity: associations with serum metabolomic and gut metagenomic profiles

Microplastics (MPs) are emerging environmental contaminants with potential impacts on metabolic and endocrine homeostasis. However, their molecular mechanisms and translational implications remain unclear. This study aimed to of MPs in whole blood and gastric tissues of adults with obesity and explore their associations with metabolic, microbial, and molecular profiles. Thirty obese adults undergoing bariatric surgery were enrolled. MPs in EDTA-anticoagulated whole blood, gastric mucosa (GM), and gastric serosa (GS) were quantified using Py-GCMS, with complementary characterization by LDIR and SEM. Untargeted serum metabolomics and fecal metagenomics were integrated to assess systemic metabolic and microbial alterations. Network pharmacology and protein-protein interaction analyses identified core molecular targets and signaling pathways related to MP-associated metabolic effects. MPs were detected in all three sample matrices, with the highest abundance in GS. Polyvinyl chloride (PVC) and polyethylene (PE) dominated. Whole-blood PA66 was positively associated with triglycerides ( r = 0.57), and whole-blood PET was inversely associated with BMI ( r =-0.51). In sensitivity analyses excluding estimates below the instrumental LOD, the PA66-triglyceride association remained significant, whereas the PET-BMI association was attenuated and no longer significant after FDR correction. Multi-omics analyses identified associations of microplastic burden with serum metabolites and gut microbial pathways related to phospholipid and bile acid metabolism. Exploratory network analysis identified AKT1, MTOR, CYP17A1, and SRC as central nodes in pathways related to steroid hormone biosynthesis and endocrine signaling. This study provides human evidence that MPs are present in whole blood and gastric tissues of adults with obesity and exhibit distinct distribution patterns across biological matrices. Their associations with serum metabolic and gut microbial profiles extend current understanding of the potential metabolic and microbial relevance of internal microplastic burden and provide a basis for future longitudinal and mechanistic investigations. This study was registered with ClinicalTrials.gov (NCT06826586) on February 10, 2025.