Ho Karen J, Muhammad Lutfiyya N, Khanh Linh Ngo, Li Xinmin S, Carns Mary, Aren Kathleen, Kim Seok-Jo, Verma Priyanka, Hazen Stanley L, Varga John
Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
J Clin Med. 2024 Oct 8;13(19):5984. doi: 10.3390/jcm13195984.
Alterations in fecal microbial communities in patients with systemic sclerosis (SSc) are common, but the clinical significance of this observation is poorly understood. Gut microbial production of trimethylamine (TMA), and its conversion by the host to trimethylamine -oxide (TMAO), has clinical and mechanistic links to cardiovascular and renal diseases. Direct provision of TMAO has been shown to promote fibrosis and vascular injury, hallmarks of SSc. We sought to determine levels of TMAO and related metabolites in SSc patients and investigate associations between the metabolite levels with disease features. This is an observational case:control study. Adults with SSc ( = 200) and non-SSc controls ( = 400) were matched for age, sex, indices of renal function, diabetes mellitus, and cardiovascular disease. Serum TMAO, choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine were measured using stable isotope dilution liquid chromatography tandem mass spectrometry. Median TMAO concentration was higher ( = 0.020) in SSc patients (3.31 [interquartile range 2.18, 5.23] µM) relative to controls (2.85 [IQR 1.88, 4.54] µM). TMAO was highest among obese and male SSc participants compared to all other groups. Following adjustment for sex, BMI, age, race, and eGFR in a quantile regression model, elevated TMAO levels remained associated with SSc at each quantile of TMAO. Patients with SSc have increased circulating levels of TMAO independent of comorbidities including age, sex, renal function, diabetes mellitus, and cardiovascular disease. As a potentially modifiable factor, further studies examining the link between TMAO and SSc disease severity and course are warranted.
系统性硬化症（SSc）患者粪便微生物群落的改变很常见，但这一观察结果的临床意义却知之甚少。肠道微生物产生的三甲胺（TMA）及其被宿主转化为氧化三甲胺（TMAO），在心血管疾病和肾脏疾病中具有临床和机制联系。已证明直接给予TMAO可促进纤维化和血管损伤，这是SSc的特征。我们试图确定SSc患者中TMAO及相关代谢物的水平，并研究代谢物水平与疾病特征之间的关联。这是一项观察性病例对照研究。将200例成年SSc患者和400例非SSc对照者按年龄、性别、肾功能指标、糖尿病和心血管疾病进行匹配。使用稳定同位素稀释液相色谱串联质谱法测量血清TMAO、胆碱、甜菜碱、肉碱、γ-丁基甜菜碱和巴豆甜菜碱。相对于对照组（2.85[四分位间距1.88，4.54]µM），SSc患者的TMAO中位浓度更高（P = 0.020）（3.31[四分位间距2.18，5.23]µM）。与所有其他组相比，肥胖和男性SSc参与者中的TMAO最高。在分位数回归模型中对性别、BMI、年龄、种族和估算肾小球滤过率（eGFR）进行调整后，在TMAO的每个分位数处，升高的TMAO水平仍与SSc相关。SSc患者循环中TMAO水平升高，与包括年龄、性别、肾功能、糖尿病和心血管疾病在内的合并症无关。作为一个潜在的可调节因素，有必要进一步研究TMAO与SSc疾病严重程度和病程之间的联系。
