Association of dietary and gut microbiota-related metabolites with calcific aortic stenosis
Duygu Koçyiğit, Lâle Tokgözoğlu, Kadri Murat Gürses, Marcus Ståhlman, Jan Borén, Tolga Soyal, Hande Canpınar, Dicle Güç, Arzu Sağlam, Tuncay Hazırolan, Necla Özer
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.