Abstract
The relationship among the gut microbiome, global fecal metabolites and rheumatoid arthritis (RA) has not been systematically evaluated. In this study, we performed 16S rDNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based nontargeted metabolomic profiling on feces of 26 untreated RA patients and 26 healthy controls. Twenty-six genera and forty-one MS2-identified metabolites were significantly altered in the RA patients. Klebsiella, Escherichia, Eisenbergiella and Flavobacterium were more abundant in the RA patients, while Fusicatenibacter, Megamonas and Enterococcus were more abundant in the healthy controls. Function prediction analysis demonstrated that the biosynthesis pathways of amino acids, such as L-arginine and aromatic amino acids, were depleted in the RA group. In the metabolome results, fecal metabolites including glycerophospholipids (PC(18:3(9Z,12Z,15Z)/16:1(9Z)), lysoPE 19:1, lysoPE 18:0, lysoPC(18:0/0:0)), sphingolipids (Cer(d18:0/16:0), Cer(d18:0/12:0), Cer(d18:0/14:0)), kynurenic acid, xanthurenic acid and 3-hydroxyanthranilic acid were remarkably altered between the RA patients and healthy controls. Dysregulation of pathways, such as tryptophan metabolism, alpha-linolenic acid metabolism and glycerophospholipid metabolism, may contribute to the development of RA. Additionally, we revealed that the gut microbiome and metabolites were interrelated in the RA patients, while Escherichia was the core genus. By depicting the overall landscape of the intestinal microbiome and metabolome in RA patients, our study could provide possible novel research directions regarding RA pathogenesis and targeted therapy.
Highlights
Rheumatoid arthritis (RA) is a chronic, complex and systemic autoimmune disease
Body mass index (BMI) values were provided by 19 RA patients and 25 healthy controls (HCs)
We found that Proteobacteria and Verrucomicrobia were remarkably enriched in RA patients, while Firmicutes was depleted
Summary
Rheumatoid arthritis (RA) is a chronic, complex and systemic autoimmune disease. It is characterized by autoantibody production, synovitis, and long-standing inflammation (Scott et al, 2010). Prevotella copri was enriched and exhibited genomic rearrangement in new-onset untreated RA patients, and one of its 27-kDa proteins could stimulate the Th1 response in 42% of RA patients (Scher et al, 2013; Pianta et al, 2017). Some probiotics, such as Lactobacillus casei, significantly attenuate the expression of interferon gamma (IFN-g), tumor necrosis factor alpha (TNF-a) and interleukin (IL)-1b to prevent joint damage (Pan et al, 2019). A deficiency of beneficial bacteria and their metabolites may stimulate the inflammatory response (Velasquez-Manoff, 2015)
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