PM_2.5 exposure associated with microbiota gut-brain axis: Multi-omics mechanistic implications from the BAPE study

Recent studies have shown that PM_2.5 may activate the hypothalamus-pituitary-adrenal (HPA) axis by inducing hormonal changes, potentially explaining the increase in neurological and cardiovascular risks. In addition, an association between PM_2.5 and gut microbiota and metabolites was established. The above evidence represents crucial parts of the gut-brain axis (GBA). In view of this evidence, we proposed a hypothesis that PM_2.5 exposure may affect the HPA axis through the gastrointestinal tract microbiota pathway (GBA mechanism), leading to an increased risk of neurological and cardiovascular diseases. We conducted a real-world prospective repeated panel study in Jinan, China. At each visit, we measured real-time personal PM_2.5 and collected fecal and blood samples. A linear mixed-effects model was used to analyze the association between PM_2.5 and serum biomarkers, gut microbiota, and metabolites. We found that PM_2.5 was associated with increased serum levels of hormones, especially the adrenocorticotropic hormone (ACTH) and cortisol, which are reliable hormones of the HPA axis. Gut microbiota and tryptophan metabolites and inflammation, which are important components of the GBA, were significantly associated with PM_2.5. We also found links between PM_2.5 and changes in the nervous and cardiovascular outcomes, e.g., increases of 19.77% (95% CI: -36.44, 125.69) in anxiety, 1.19% (95% CI: 0.65, 1.74) in fasting blood glucose (FBG), 2.09% (95% CI: 1.48, 2.70) in total cholesterol (TCHOL), and 0.93% (95% CI: 0.14, 1.72) in triglycerides (TG), were associated with 10 μg/m³ increase in PM_2.5 at the lag 0-72 h, which represent the main effects of GBA. This study indicated the link between PM_2.5 and the microbiota GBA for the first time, providing evidence of the potential mechanism for PM_2.5 with neurological and cardiovascular system dysfunction.