Association of enhanced circulating trimethylamine N‐oxide with vascular endothelial dysfunction in periodontitis patients

Abstract

Background Accumulating evidences indicate that periodontitis is closely associated with endothelial dysfunction. Trimethylamine‐N‐oxide (TMAO), a harmful microbiota generated metabolite, has been implicated as a nontraditional risk factor for impaired endothelial function. However, whether increased circulating levels of TMAO in periodontitis patients induces endothelial dysfunction remains unknown. Methods Patients with periodontitis and periodontally healthy controls were enrolled. Periodontal inflamed surface area (PISA) was calculated to assess the inflammatory burden posed by periodontitis. The circulating TMAO was measured by high‐performance liquid chromatography with tandem mass spectrometry (HPLC‐MS/MS). Vascular endothelial function including peripheral endothelial progenitor cells (EPCs), brachial arterial flow‐mediated vasodilation (FMD), and brachial‐ankle pulse wave velocity (baPWV) were assessed. We also isolated and cultured EPCs from participants’ peripheral blood to investigate the effect of TMAO on EPC functions in vitro. Results One hundred and twenty two patients with Stage III‐IV periodontitis and 81 healthy controls were included. Patients with periodontitis presented elevated TMAO (P = 0.002), lower EPCs (P = 0.025), and declined FMD levels (P = 0.005). The TMAO concentrations were correlated with reduced circulating EPCs and FMD levels. Moreover, TMAO can injury EPCs function in vitro, and may induce cell pyroptosis via Bax/caspase‐3/GSDME pathway. Conclusions The present study demonstrates for the first time that circulating TMAO levels are increased in patients with Stage III‐IV periodontitis, and correlated with vascular endothelial dysfunction. These findings may provide a novel insight into the mechanism of vascular endothelial dysfunction in patient with periodontitis via TMAO‐downregulated EPC functions.

Gut microbiota may mediate the impact of chronic apical periodontitis on atherosclerosis in apolipoprotein E‐deficient mice

“…The sample distribution of the four groups was consistent with the beta diversity results. This is consistent with clinical studies showing that circulating TMAO levels are elevated in patients with stage III‐IV periodontitis and are associated with vascular endothelial dysfunction (Zhou et al, 2022). Interestingly, Lachnospiraceae was found to be positively correlated with the serum TMAO level and percentage of lesion area (Figure 6c; p < .05), and Ruminococcaceae and Prevotellaceae were negatively correlated with weight and positively correlated with the percentage of lesion area (Figure 6c; p < .05).…”

The impact of periodontitis on vascular endothelial dysfunction

“…It detected the trimethylamine-N-oxide (TMAO), a harmful intestinal microbiota-dependent metabolite in periodontitis (Jalandra et al, 2021). In this research, elevated TMAO was presented in patients with stage III-IV periodontitis, and its concentration has been correlated with reduced circulating endothelial progenitor cells (EPCs) and FMD levels (Zhou et al, 2022). These data provide a novel perspective on the possibility of periodontitis affecting endothelial function through the oral-intestinal axis, which deserves deep exploration.…”

Trimethylamine N-oxide promotes demyelination in spontaneous hypertension rats through enhancing pyroptosis of oligodendrocytes

“…A recent report has elucidated that TMAO participates in the regulation of neuroinflammation and cognitive dysfunction with aging ( Brunt et al, 2021 ). Furthermore, TMAO is implicated in vascular endothelial cell pyroptosis in atherosclerosis and periodontitis ( Wu et al, 2020 ; Zhou et al, 2021 ). Hereon, on basis of these previous studies, we speculated a functional role of TMAO-induced pyroptosis in oligodendrocytes for demyelination of white matter, verified by treating SHR in vivo and oligodendrocytes in vitro with TMAO.…”