Exposure to Size-Fractioned Ambient Particles Associated with Alterations in Gut Microbiome and Pro-Atherosclerotic Biomarkers in Young Adults

Abstract Background: Ambient fine and ultrafine particles are linked to the progression of atherosclerotic cardiovascular diseases, wherein gut microbiome may play a critical role. However, the underlying mechanisms and relevant metabolic pathways are not yet fully understood. Objectives: To identify the features and metabolic pathways of gut microbiome, and to explore their potential roles in the pro-inflammatory and pro-atherosclerotic effects of particles in size ranges of 5–560 nm (measured as number concentration, PNC5–560). Methods: We conducted a longitudinal panel study of 152 young adults in Beijing, China, with four monthly clinical examinations between September 2019 and January 2020. Gut microbiome, fecal metabolome, and circulating pro-inflammatory and pro-atherosclerotic biomarkers were measured. Linear mixed-effects models were used to examine the associations linking short-term PNC5–560 exposure to health indicators. We further evaluated whether gut microbiota could mediate changes in these biomarkers and identified the underlying metabolic pathways. Results: Major sources of PNC5–560 in the study area were identified as diesel vehicle emissions (37.9%), gasoline vehicle emissions (39.4%), nucleation (9.2%), and secondary aerosols (11.9%). Per interquartile range increment in PNC5–560 over the preceding 7 days was associated with significant elevations in circulating pro-inflammatory and pro-atherosclerotic biomarkers, with effect estimates ranging from 2.1% (95% CI: 0.4%, 3.8%) to 198.6% (95% CI: 29.3%, 365.8%). PNC5–560 exposure was also associated with decreased gut microbial α-diversity (e.g., Shannon, Simpson, and Chao1) and altered taxonomic composition. Several microbial species (e.g., Solibaculum mannosilyticum, Bacteroides stercoris, and Bifidobacterium longum) were identified as potential mediators of the effects of PNC5–560 on pro-inflammatory and pro-atherosclerotic responses, with mediation proportions up to 9.8% (95% CI: 0.8, 38.3) and 4.8% (95% CI: 0.09, 22.5), respectively. Functional analyses further revealed that these mediating effects involved perturbations in nucleotide and amino acid metabolism pathways. Conclusions: This study provides evidence suggesting that gut microbiome may regulate nucleotide and amino acid metabolism, thereby partially mediating the detrimental cardiovascular effects of size-fractioned ambient particles.