The Gut Microbiome and Metabolites Are Altered and Interrelated in Patients With Rheumatoid Arthritis

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.

Novel markers to evaluate the disease activity of rheumatoid arthritis based on some intestinal flora imbalance, abnormal immune cells and cytokines

“…However, Yang Sun et al found that the relative abundance of Bacteroides was increased in RA patients (35). Another study found that the relative abundance of Megammonas was increased in HCs (39), whereas our study found that the relative abundance of Megammonas was elevated in RA patients during the active and remission stage. Interestingly, we found that the relative abundance of Ruminococcaceae_Ruminococcus was also reduced in the active and remission stage of RA patients.…”

Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities

“…Dysbiosis of specific bacterial lineages and alterations in gut microbiota metabolism led to changes in the host immune profile that contribute to RA ( 8 ). It has been proposed that the mechanism by which gut microbiota imbalance leads to RA may be related to regulation of immune function by metabolites produced by gut microbes ( 9 , 10 ). Immune T and B cells have position-specific phenotypes and functions in the mucosa, influenced by the microbiota ( 11 ).…”

The bridge of the gut–joint axis: Gut microbial metabolites in rheumatoid arthritis

“…The study suggested that targeting the intestinal barrier is a potential strategy for treating autoimmune diseases such as RA (9). Some scholars have proposed that intestinal ecological disorders are related to the autoimmune mechanism involved in the development of RA (10). The gut microbiota produces metabolites that regulate host immunity and influence host resistance and susceptibility to disease.…”

“…Some scholars have proposed that intestinal ecological disorders are related to the autoimmune mechanism involved in the development of RA ( 10 ). The gut microbiota produces metabolites that regulate host immunity and influence host resistance and susceptibility to disease.…”