Stec Albert, Maciejewska Magdalena, Paralusz-Stec Karolina, Michalska Milena, Giebułtowicz Joanna, Rudnicka Lidia, Sikora Mariusz
Department of Dermatology, Medical University of Warsaw, Warsaw, Poland.
Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland.
J Inflamm Res. 2023 May 1;16:1895-1904. doi: 10.2147/JIR.S409489. eCollection 2023.
Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease characterized by fibrosis of the skin and internal organs, whose pathogenesis is not fully understood. Recent studies have revealed dysbiosis in patients with systemic sclerosis and have indicated the possible role of the microbiota and its metabolites in the pathogenesis of the disease. Trimethylamine N-oxide (TMAO) is a compound produced by dysbiotic microbiota observed at higher concentrations in several autoimmune diseases.
To determine concentrations of the bacteria-derived metabolite TMAO in patients with systemic sclerosis and to assess possible correlation between TMAO and a specific manifestation of the disease.
The study included 63 patients with SSc and 47 matched control subjects. The concentration of TMAO was measured with high-performance liquid chromatography.
Plasma TMAO level was significantly increased in patients with SSc (283.0 [188.5-367.5] ng/mL versus 205.5 [101.0-318.0] ng/mL; p < 0.01). An increased concentration of TMAO was observed in patients with concomitant interstitial lung disease (ILD) (302.0 ng/mL [212.0-385.5] ng/mL versus 204.0 [135.5-292.0] ng/mL; p < 0.01) and esophageal dysmotility (289.75 [213.75-387.5] ng/mL versus 209.5 ng/mL [141.5-315.0] ng/mL; p < 0.05) compared to patients without these complications. Furthermore, TMAO concentration exhibited significant correlation with markers of heart involvement (left ventricle ejection fraction, NT-proBNP), marker of ILD severity and Scleroderma Clinical Trials Consortium Damage Index.
The concentration of TMAO, gut microbiota-associated metabolite, is increased in systemic sclerosis, particularly in patients with advanced organ involvement. This is the first study evaluating plasma TMAO in systemic sclerosis. Bacterial metabolites may be a link between dysbiosis and organ involvement in the course of the disease. Modulation of gut bacterial-derived metabolites may represent a new therapeutic approach in the management of systemic sclerosis.
系统性硬化症（SSc）是一种罕见的免疫介导的结缔组织疾病，其特征为皮肤和内脏器官纤维化，发病机制尚未完全明确。最近的研究揭示了系统性硬化症患者存在肠道菌群失调，并表明微生物群及其代谢产物在该疾病发病机制中可能发挥的作用。氧化三甲胺（TMAO）是一种由失调的微生物群产生的化合物，在几种自身免疫性疾病中浓度较高。
测定系统性硬化症患者中细菌衍生代谢产物TMAO的浓度，并评估TMAO与该疾病特定表现之间的可能相关性。
该研究纳入了63例系统性硬化症患者和47例匹配的对照受试者。采用高效液相色谱法测定TMAO的浓度。
系统性硬化症患者的血浆TMAO水平显著升高（283.0 [188.5 - 367.5] ng/mL vs 205.5 [101.0 - 318.0] ng/mL；p < 0.01）。与无这些并发症的患者相比，合并间质性肺病（ILD）的患者（302.0 ng/mL [212.0 - 385.5] ng/mL vs 204.0 [135.5 - 292.0] ng/mL；p < 0.01）和食管动力障碍患者（289.75 [213.75 - 387.5] ng/mL vs 209.5 ng/mL [141.5 - 315.0] ng/mL；p < 0.05）的TMAO浓度升高。此外，TMAO浓度与心脏受累标志物（左心室射血分数、NT - proBNP）、ILD严重程度标志物和硬皮病临床试验协会损伤指数显著相关。
肠道微生物群相关代谢产物TMAO的浓度在系统性硬化症中升高，尤其是在器官受累严重的患者中。这是第一项评估系统性硬化症患者血浆TMAO的研究。细菌代谢产物可能是疾病过程中肠道菌群失调与器官受累之间的联系。调节肠道细菌衍生的代谢产物可能代表系统性硬化症治疗的一种新方法。
