State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Department of Urology, Affiliated Wuxi No.2 People's Hospital, Nanjing Medical University, Wuxi, China.
Front Immunol. 2020 Sep 10;11:2138. doi: 10.3389/fimmu.2020.02138. eCollection 2020.
Gut metabolites are products of the crosstalk between microbes and their host and play an important role in the occurrence, development, diagnosis, and treatment of autoimmune diseases. This work profiled the fecal metabolome of patients with systemic lupus erythematosus (SLE) using gas chromatography-mass spectrometry (GC-MS) and analyzed the potential roles of metabolites in the diagnosis and development of SLE. Fecal sample from 29 SLE patients without any other diseases and 30 healthy controls (HCs) were analyzed by metabolomics profiling. All participants took no antibiotics in the month before sampling and clinical data collecting. The metabolome profiles of patients with SLE and HCs were significantly different. Thirty fecal metabolites, such as deoxycholic acid, erucamide, L-tryptophan and putrescine, were significantly enriched, while nine metabolites, such as glyceric acid, γ-tocopherol, (Z)-13-octadecenoic acid and 2,4-di-tert-butylphenol, were depleted in SLE patients vs. HCs. The areas under the curve (AUCs) of L-valine, pyrimidine, erucamide, and L-leucine during ROC analysis were 0.886, 0.833, 0.829, and 0.803, indicating their good diagnostic potential. Moreover, the combination of L-valine, erucamide and 2,4-di-tert-butylphenol gave an AUC of 0.959. SLE-altered metabolites were significantly located in 28 pathways, such as ABC transporters ( = 3.40E-13) and aminoacyl-tRNA biosynthesis ( = 2.11E-12). Furthermore, SLE-altered fecal metabolites were closely correlated with SLE indicators, e.g., L-tryptophan was positively correlated with the SLEDAI-2K ( = 0.007). Our results suggest that the SLE fecal metabolome is closely associated with the occurrence and development of SLE and is of great diagnostic value.
肠道代谢物是微生物与其宿主相互作用的产物,在自身免疫性疾病的发生、发展、诊断和治疗中发挥着重要作用。本研究采用气相色谱-质谱联用(GC-MS)技术对系统性红斑狼疮(SLE)患者的粪便代谢组进行了分析,并探讨了代谢物在 SLE 诊断和发病机制中的潜在作用。通过代谢组学分析,对 29 名无其他疾病的 SLE 患者和 30 名健康对照(HC)的粪便样本进行了分析。所有参与者在采样和临床数据收集前一个月内均未服用抗生素。SLE 患者和 HCs 的代谢组图谱有明显差异。与 HCs 相比,SLE 患者粪便中 30 种代谢物(如脱氧胆酸、芥酸、L-色氨酸和腐胺)明显富集,而 9 种代谢物(如甘油酸、γ-生育酚、(Z)-13-十八烯酸和 2,4-二叔丁基苯酚)明显减少。ROC 分析中 L-缬氨酸、嘧啶、芥酸和 L-亮氨酸的 AUC 分别为 0.886、0.833、0.829 和 0.803,表明其具有良好的诊断潜力。此外,L-缬氨酸、芥酸和 2,4-二叔丁基苯酚的组合 AUC 为 0.959。SLE 改变的代谢物在 28 条代谢途径中显著定位,如 ABC 转运体( = 3.40E-13)和氨基酸酰基-tRNA 生物合成( = 2.11E-12)。此外,SLE 改变的粪便代谢物与 SLE 指标密切相关,如 L-色氨酸与 SLEDAI-2K 呈正相关( = 0.007)。我们的研究结果表明,SLE 粪便代谢组与 SLE 的发生发展密切相关,具有重要的诊断价值。