Fecal Metabolites Were Altered, Identified as Biomarkers and Correlated With Disease Activity in Patients With Systemic Lupus Erythematosus in a GC-MS-Based Metabolomics Study

一项基于气相色谱-质谱联用技术的代谢组学研究发现,系统性红斑狼疮患者的粪便代谢物发生改变,并被鉴定为生物标志物,且与疾病活动度相关。

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Abstract

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 (p = 3.40E-13) and aminoacyl-tRNA biosynthesis (p = 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 (p = 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.

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