Evaluation of microbial-derived metabolites in patients with acute pulmonary embolism: findings from the MICTEP study.

Introduction: Functional analysis of microbiome with microbial-derived metabolites (MDMs) has emerged as key for several inflammatory and cardiovascular diseases. However, the data on the relationship of pulmonary embolism (PE) to microbiome are scarce. This study aimed to compare MDM levels between acute PE patients and healthy controls, and to investigate their associations with predisposing factors (i.e. unprovoked, provoked and cancer-associated thrombosis). Methods: We collected serum samples from a multicentric cohort, including 96 patients with acute PE at hospital admission and 30 healthy controls. Serum concentrations of MDMs and inflammation/coagulation-related markers were quantified by liquid chromatography-mass spectrometry and flow cytometry, respectively. Results: Compared with healthy controls, patients with acute PE showed significantly higher serum levels of trimethylamine N-oxide (TMAO) (11.5 μM versus 6.7 μM; p=0.02) and acetate (48.3 μM versus 33.0 μM; p=0.04); and lower levels of propionate (3.8 μM versus 5.3 μM; p=0.007), butyrate (4.03 µM versus 7.68 µM; p=0.009), isobutyrate (5.0 μM versus 7.32 μM; p=0.002) and valerate (0.4 μM versus 0.63 μM; p<0.001). Valerate showed the best discrimination between PE and controls (area under the receiver operating characteristic curve 0.758, 95% CI 0.66-0.86). In the multinomial analysis, higher values of TMAO and acetate were associated with a higher probability of unprovoked PE. MDM levels exhibited different correlation with inflammation-related markers highlighting TGF-β1, CCL2 and CXCL10. Conclusion: These findings reveal imbalances in the serological concentrations of MDMs in patients with acute PE and highlight the potential role of the microbiome and its functional metabolites as novel predisposing risk factors for PE.