Gut microbiota-derived metabolite trimethylamine N-oxide and biomarkers of inflammation are linked to endothelial and coronary microvascular function in patients with inflammatory bowel disease

Background: Inflammatory bowel disease (IBD), which is an umbrella term used for ulcerative colitis (UC) and Crohn's disease (CD), is associated with an increased risk for atherosclerotic cardiovascular disease (CVD). We aimed to investigate the association of local and systemic biomarkers of inflammation and gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) with endothelial and coronary microvascular dysfunction in IBD.Methods: A total of 56 patients with IBD (20 with UC and 36 with CD) and 34 age and gender matched controls were included. For all participants, samples were collected to analyze faecal calprotectin, and TMAO concen-trations. Ultrasound-based examinations were done to measure flow-mediated vasodilatation (FMD) and coro-nary flow velocity reserve (CFVR).Results: Patients with IBD had lower CFVR (2.07 (1.82-2.40)) and FMD (8.7 +/- 3.7) as compared to controls (2.30 (2.07-2.74), p = 0.005 and 11.9 +/- 6.8, p = 0.03). In patients with IBD, TMAO concentration (r =-0.30, p = 0.03), C-reactive protein (r =-0.29, p = 0.03) and WBC count (r =-0.37, p = 0.006) had a significant negative correlation with CFVR, and TMAO (I3 =-0.27, 95 % CI:-0.23 to-0.02) and WBC count (I3 =-0.31, 95 % CI:-0.56 to-0.06) were significant predictors of CFVR after multivariate adjustment. None of the biomarkers of inflammation or TMAO showed significant correlations with FMD. In patients with UC, TMAO showed a sig-nificant correlation with both CFVR (r =-0.55, p = 0.01) and FMD (r =-0.60, p = 0.005) while only WBC count had a statistically significant correlation with CFVR (r =-0.49, p = 0.004) in patients with CD.Conclusions: Gut microbiota-derived metabolite TMAO and biomarkers of systemic inflammation are associated with measures of endothelial/coronary microvascular dysfunction in patients with IBD.