PM2.5 and Serum Metabolome and Insulin Resistance, Potential Mediation by the Gut Microbiome: A Population-Based Panel Study of Older Adults in China

Abstract

Background: Insulin resistance (IR) affects the development of type 2 diabetes mellitus (T2DM), which is also influenced by accumulated fine particle air pollution [particulate matter (PM) with aerodynamic diameter of $<2.5\mu m$ (${\mathrm{PM}}_{2.5}$)] exposure. Previous experimental and epidemiological studies have proposed several potential mechanisms by which ${\mathrm{PM}}_{2.5}$ contributes to IR/T2DM, including inflammation imbalance, oxidative stress, and endothelial dysfunction. Recent evidence suggests that the imbalance of the gut microbiota affects the metabolic process and may precede IR. However, the underlying mechanisms of ${\mathrm{PM}}_{2.5}$, gut microbiota, and metabolic diseases are unclear.

Objectives: We investigated the associations between personal exposure to ${\mathrm{PM}}_{2.5}$ and fasting blood glucose and insulin levels, the IR index, and other related biomarkers. We also explored the potential underlying mechanisms (systemic inflammation and sphingolipid metabolism) between ${\mathrm{PM}}_{2.5}$ and insulin resistance and the mediating effects between ${\mathrm{PM}}_{2.5}$ and sphingolipid metabolism.

Methods: We recruited 76 healthy seniors to participate in a repeated-measures panel study and conducted clinical examinations every month from September 2018 to January 2019. Linear mixed-effects (LME) models were used to analyze the associations between ${\mathrm{PM}}_{2.5}$ and health data (e.g., functional factors, the IR index, inflammation and other IR-related biomarkers, metabolites, and gut microbiota). We also performed mediation analyses to evaluate the effects of mediators (gut microbiota) on the associations between exposures (${\mathrm{PM}}_{2.5}$) and featured metabolism outcomes.

Results: Our prospective panel study illustrated that exposure to ${\mathrm{PM}}_{2.5}$ was associated with an increased risk of higher IR index and functional biomarkers, and our study provided mechanistic evidence suggesting that ${\mathrm{PM}}_{2.5}$ exposure may contribute to systemic inflammation and altered sphingolipid metabolism.

Discussion: Our findings demonstrated that ${\mathrm{PM}}_{2.5}$ was associated with the genera of the gut microbiota, which partially mediated the association between ${\mathrm{PM}}_{2.5}$ and sphingolipid metabolism. These findings may extend our current understanding of the pathways of ${\mathrm{PM}}_{2.5}$ and IR. https://doi.org/10.1289/EHP9688.