Microbiome and Metabolome Analyses Reveal the Disruption of Lipid Metabolism in Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects thousands of people worldwide. Recently, alterations in metabolism and gut microbiome have emerged as key regulators of SLE pathogenesis. However, it is not clear about the coordination of gut commensal bacteria and SLE metabolism. Here, by integrating 16S sequencing and metabolomics data, we characterized the gut microbiome and fecal and serum metabolome alterations in patients with SLE. Microbial diversity sequencing revealed gut microflora dysbiosis in SLE patients with significantly increased beta diversity. The metabolomics profiling identified 43 and 55 significantly changed metabolites in serum and feces samples in SLE patients. Notably, lipids accounted for about 65% altered metabolites in serum, highlighted the disruption of lipid metabolism. Integrated correlation analysis provided a link between the gut microbiome and lipid metabolism in patients with SLE, particularly according to regulate the conversion of primary bile acids to secondary bile acids. Overall, our results illustrate the perturbation of the gut microbiome and metabolome in SLE patients which may facilitate the development of new SLE interventions.

Microbiome and Metabolome Analyses Reveal Novel Interplay Between the Skin Microbiota and Plasma Metabolites in Psoriasis

“…Among them, we found several microbiome-generated metabolites that were also significantly changed. These included taurochenodeoxycholic acid (TCDCA), deoxycholic acid glycine conjugate (GDCA), chenodeoxycholic acid glycine conjugate, and L -kynurenine ( Chávez-Talavera et al, 2017 ; Agus et al, 2018 ; He et al, 2020 ). To uncover the metabolic pathway alterations, we conducted KEGG pathway analysis of the differentially expressed metabolites by using Metaboanalyst 6 ( Figure 4C ).…”

“…Many articles have reported the correlation of the gut microbiota and blood metabolism ( Liu et al, 2017 ; He et al, 2020 ), whereas little is known about the relationship of the skin microbiota and blood metabolism. In this study, we carried out Spearman correlation analysis of the annotated skin microbiota at the genus level and the identified plasma metabolites.…”

“…For liquid chromatography–mass spectrometry (LC-MS) metabolomic data collection, all plasma samples were analyzed by a 1290 UHPLC instrument (Agilent Technologies, CA, United States) coupled with a Thermo Q Exactive Focus (Thermo Fisher Scientific, MA, United States) by Biotree Ltd. (Shanghai, China), according to previously reported methods with minor modifications ( He et al, 2020 ). Briefly, mobile phase A in positive ion mode was 0.1% formic acid in water, and in negative ion mode, it was 5 mmol/L ammonium acetate in water.…”

“…The abundance and composition of the gut microbiome can vary under different conditions and are related to many human diseases ( Chávez-Talavera et al, 2017 ). Increasing evidence has suggested that the activity of the microbiota is critical, especially in modulating tissue metabolism ( Liu et al, 2017 ; He et al, 2020 ). In recent years, the role of the microbiome in maintaining healthy skin status and regulating skin-related diseases has been reported ( Zeeuwen et al, 2013 ; Dréno et al, 2016 ; Byrd et al, 2018 ).…”

Lactobacillus Acidophilus Supplementation Exerts A Synergistic Effect on Tacrolimus Efficacy by Restoring Th17/Treg Imbalance in Lupus-Prone Mice via the SIGNR3 Pathway

“…Furthermore, the dysbiosis is not only detected in the intestinal microbiota, but also in the oral mucosa and skin of lupus-affected subjects [20][21][22]. Therefore, bacterial dysbiosis may be related to the clinical status, or even the dietary metabolism, of lupus patients [23][24][25]. Whether changes in the caecal bacterial composition of lupus patients are merely coincidental, or are genuine etiological factors of the disease, are unknown; however, probiotic implantation as a novel therapeutic modality in SLE shows some promise [26].…”