Association of dietary and gut microbiota-related metabolites with calcific aortic stenosis. Issue 5 (16th July 2021) - Kocyigit, Duygu
Abstract: Background: Histopathological changes in calcific aortic stenosis (CAS) resemble changes in coronary atherosclerosis. Concerning recent evidence on dietary and gut microbiota-related metabolites representing players in atherosclerosis, we aimed to investigate the link between dietary and gut microbiota-derived metabolites and CAS. Methods: We consecutively recruited eligible subjects with moderate-severe CAS ( n = 60), aortic sclerosis (ASc) ( n = 49) and age and gender-matched control subjects ( n = 48) in May 2016-December 2016. Plasma dietary and gut microbiota-related metabolite levels, namely choline, betaine, and trimethylamine N-oxide (TMAO), were measured using ultra-performance liquid chromatography-tandem mass spectroscopy method. Histopathological examinations were performed in patients that underwent aortic valve surgery. Results: Prevalence of traditional cardiovascular risk factors or co-morbidities did not differ among groups (all p > 0.05). CAS patients had higher plasma choline levels compared to both control ( p < 0.001) and ASc ( p = 0.006). Plasma betaine and TMAO levels were similar (both p > 0.05). Compared to the lowest quartile choline levels (<11.15 μM), patients with the highest quartile choline levels (≥14.98 μM) had higher aortic valvular ( p < 0.001) and mitral annular ( p = 0.013) calcification scores. Plasma choline levels were independently associated with aortic peak flow velocity (B ± SE:0.165 ± 0.060, p = 0.009). Choline levels were elevated in subjects who had aortic valves with denser lymphocyte infiltration ( p < 0.001), neovascularization ( p = 0.011), osseous metaplasia ( p = 0.004), more severe tissue remodelling ( p = 0.002) and calcification ( p = 0.002). Conclusion: We found a significant association between choline levels and CAS presence and severity depicted on imaging modalities and histopathological examinations. Our study may open new horizons for prevention of CAS.