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

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.

Mechanism of the Immunomodulatory Effect of the Combination of Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus on Immunocompromised Rats

“…Additionally, several studies used various analytical methods to demonstrate that cyclophosphamide can reduce the fecal levels of short-chain fatty acids beneficial to health (e.g., acetic acid, propionic acid, butyric acid, and valeric acid), and these effects are reversed after treatment with various agents, e.g., exopolysaccharides ( 26 , 30 ). Detection of these compounds by different analytical methods may produce variable results ( 39 ); hence, these results in combination with the data of the present study more comprehensively describe the effects of cyclophosphamide and of the treatments by microbes or other substances on gut metabolism.…”

Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease

“…Previous metabolomic studies have shown an association between a disturbance of amino acid metabolism and autoimmune disease and a certain amino acid profile might have a diagnostic potential ( Fernández-Ochoa et al, 2019 ; Thoman and McKarns, 2020 ; Yan et al, 2020 ). Similarly, we found that amino acids were differentially expressed in urine from VKH patients and they were the most abundant differential metabolites in the present study.…”

Clinical and Immunological Biomarkers for Systemic Lupus Erythematosus

“…The metabolome is now considered to play a key role in SLE due to developments in mass-spectrometry-based metabolic flux analysis. The fecal metabolomes of 29 SLE patients and 30 healthy controls were analyzed by gas chromatography-mass spectrometry [117]. The results suggest that L-valine, pyrimidine, erucamide, and L-leucine are excellent potential diagnostic biomarkers for SLE, and alterations of fecal metabolites are closely correlated with SLE [117].…”

“…The fecal metabolomes of 29 SLE patients and 30 healthy controls were analyzed by gas chromatography-mass spectrometry [117]. The results suggest that L-valine, pyrimidine, erucamide, and L-leucine are excellent potential diagnostic biomarkers for SLE, and alterations of fecal metabolites are closely correlated with SLE [117]. Proteomic profiling of kidney tissues from SLE revealed that coronin-1A is a biomarker of LN, and the level of it in serum can distinguish LN patients from SLE patients without nephritis with 100% sensitivity and 100% specificity [118].…”