Role of microbial-derived metabolites in the pulmonary embolism. MICTEP study.

<bold>Introduction:</bold> Functional analysis of microbiome with microbial-derived metabolites (MDM) has emerged with potential implications for cardiovascular diseases, but knowledge about its role in pulmonary embolism (PE) is still limited. <bold>Aims:</bold> To compare the levels of MDM in PE patients with a control group, as well as its association with risk factors (RF) for PE. <bold>Material and methods:</bold> Observational study of patients with acute PE prospectively enrolled in the RIETE registry and a prospective cohort of healthy subjects with no previous history of PE was included for control group. PE was defined as provoked in the presence of any of the following RF: recent immobilization, surgery, estrogen use, pregnancy, postpartum period, or long-haul travel. Cancer associated PE was considered when concomitant cancer. Alternatively, PE was considered unprovoked in the absence of all these RF. <bold>Results:</bold> 96 patients with acute PE were included (49% women, 63±16 yrs, 81±16 kg), along with 30 healthy controls (50% women, 49±5 yrs, 77±9 kg). 67 patients had unprovoked PE. Compared to control group, PE patients had higher levels of trimethylamine N-oxide (11.5 µM vs 6.7 µM;p=0.02) and acetate (48.3 µM vs 33.0 µM;p=0.04), and lower levels of propionate (3.8 µM vs 5.3 µM;p=0.007), isobutyrate (5.0 µM vs 7.32 µM;p=0.002), and valerate (0.4 µM vs 0.63 µM;p<0.001). Compared to provoked PE patients, unprovoked PE patients had higher levels of acetate (p=0.04). Acetate showed the ability to differentiate unprovoked PE and provoked PE by different factors from cancer (AUC 0.67;95%CI 0.52-0.86). <bold>Conclusions:</bold> PE patients exhibit a different metabolomic profile compared to controls, with relevant differences based on their triggering RF.