Role of Gut Microbiota and Metabolite Remodeling on the Development and Management of Rheumatoid Arthritis: A Narrative Review
Simple Summary
Abstract
1. Introduction
2. The Compositional and Functional Imbalance of the Gut Microbiota in Patients and Animals with RA
3. The Role of Intestinal Flora Imbalance in the Pathogenesis of RA
3.1. Relationship Between RA and Gut Microbiota, Gut Microbiota Metabolites, and Gut Barrier
3.2. Interactions Among RA, Gut Microbiota, and Immune System
3.3. Relationship Between Specific Bacterial Species and RA
3.4. Molecular Simulation Is a Potential Mechanism for Connecting RA with Intestinal Flora
4. Application of Intestinal Flora Regulation in the Treatment of RA
4.1. Therapeutic Effects of Probiotics on RA
4.2. Intestinal Flora Transplantation and RA Treatment
4.3. Interaction Between Intestinal Flora and RA Therapeutics
4.4. Summary of Therapeutic Interventions Targeting Gut Microbiota in RA Management
4.5. Safety Considerations and Practical Suggestions for Microbial Therapy in Veterinary RA Treatment
5. Translational Strategies from Human/Rodent Research to Veterinary Medicine
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CIA | Collagen-induced arthritis |
DCs | Dendritic cells |
FMT | Fecal microbiota transplantation |
HIF | Hypoxia-inducible factor |
ILC3 | Type 3 innate lymphocytes |
LPS | Lipopolysaccharide |
MTX | Methotrexate |
NETs | Neutrophil extracellular traps |
NOX | NADPH oxidase |
PAD | Peptidylarginine deiminase |
RA | Rheumatoid arthritis |
RANKL | Nuclear factor-κB ligand |
SCFAs | Short-chain fatty acids |
5-HIAA | 5-hydroxyindole-3-acetic acid |
5-HT | 5-hydroxytryptamine |
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Animals Included | Types of Arthritis | Classification Levels | Changes in Microbiota in Animals with Inflammatory Arthritis |
---|---|---|---|
Rhesus monkeys [12] | Pro-inflammatory arthritis (CHIKV infected) | Genus | Prevotella and Sarcina ↑ Anaerostipes and Lactobacillus ↓ |
Species | Prevotella copri and Bacteroides fragilis ↑ Butyricicoccus intestinisimiae and Streptococcus lutetiensis ↓ | ||
Pigs [13] | Diet-induced exudative arthritis | Species | Clostridium perfringens ↑ |
Chicks [14] | Hypervirulent arthritis (Salmonella Pullorum infected) | Phylum | Proteobacteria ↑ Firmicutes ↓ |
Genus | Escherichia-Shigella and Klebsiell ↑ Lachnoclostridium and Blautia ↓ |
Patients Included | Classification Levels | Changes in Microbiota in RA Patients |
---|---|---|
RA patients [4] | Genus | Klebsiella and Escherichia ↑ Fusicatenibacter and Megamonas ↓ |
Female patients with early RA [5] | Phylum | Bacteroidetes ↑ Actinobacteria ↓ |
Genus | Collinsella ↓ | |
Female RA patients [15] | Genus | Bacteroides and Megamonas ↑ Prevotella and Gemmiger ↓ |
RA patients [16] | Phylum | Verrucomicrobia and Proteobacteria ↑ Bacteroidetes ↓ |
Genus | Lactobacillus and Streptococcus ↑ Bacteroides and Faecalibacterium ↓ | |
RA patients [17] | Species | Bifidobacterium longum and Dorea formicigenerans ↑ Faecalibacterium prausnitzii and Bacteroides spp. ↓ |
RA patients [18] | Genus | Eubacterium and Escherichia-Shigella ↑ |
RA patients grouped into stages I–IV [19] | Species | Escherichia coli ↑ Bacteroides uniformis and Bacteroides plebeius ↓ |
Metabolites of Intestinal Microorganisms | Associated Gut Microbes | Biological Functions |
---|---|---|
SCFAs [71,72] | Clostridium, Bacteroides, and Eubacterium | Decrease serum Zonulin concentration, increase the expression of tight junction protein, and restore the intestinal permeability |
Tryptophan [73,74] | Bifidobacterium, Clostridium, Escherichia coli, and Enterococcus | Activate the AHR pathway, inhibit the activation and inflammatory response of intestinal immune cells, regulate the proliferation and differentiation of intestinal mucosal cells, and promote the repair and stability of mucosal barrier |
Bile acid [75,76] | Clostridium, Bacteroides, and Alistipes | Promote the expression of tight junction proteins and blocking proteins and reduce the secretion of inflammatory cytokines (TNF-α and IL-6) to protect the intestinal barrier |
Indole-3-aldehyde, Indole-3-acetic acid [77,78] | Lactobacillus, Bifidobacterium, and Clostridium | Affect the activity of Tregs cells, thereby affecting the balance of immune responses |
Trimethylamine N-Oxide [79,80] | Anaerocccus hydrongenalis, Clostridium asparagiforme, and Clostridium hathewayi | Induce IL-1β, TNF-α, and IL-6, produce chemokines, and hinder bile acid synthesis and metabolism |
Intervention Type | Specific Approach | Animal Model/Study Cohort | Observed Effects | Mechanism of Action |
---|---|---|---|---|
Probiotics | Lactobacillus casei [64] | Adjuvant-induced arthritis rats | Inhibited joint swelling, lowered arthritis scores, and prevented bone destruction | Increases Lactobacillus abundance and reduces pro-inflammatory cytokines |
Lactiplantibacillus plantarum [67] | CIA mice | Reduced autoantibody levels and alleviated joint damage | Reduces intestinal permeability and corrects microbial imbalance | |
Bacillus coagulans [66] | Adult RA patients | Relieved pain, reduced total C-reactive protein, and improved patients’ self-assessment | Inhibits pathogenic bacteria and promotes SCFA production | |
FMT | Healthy donor fecal transfer [89] | A female RA patient | Decreased DAS28 score and dropped titer of RA | Restores the microbiota composition and inhibits Th17 cell activation |
Dietary Interventions | Anti-inflammatory diet [104] | RA patients | Alleviated swelling and pain of the joint | Reduces pro-inflammatory cytokines |
Pharmacological–Microbial Interactions | MTX [95] | RA patients | Altered Bacteroides and Faecalibacterium abundance and affected the metabolism of the microbial community | Modulates gut microbiota to reduce immune activation |
Traditional Chinese medicine (Jingfang Granules) [94] | RA rats | Restored intestinal tight junction proteins and mitigated tissue damage | Increases SCFA production and activates AMPK signaling |
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Yu, Y.; Jin, F.; Wang, L.; Cheng, J.; Pan, S. Role of Gut Microbiota and Metabolite Remodeling on the Development and Management of Rheumatoid Arthritis: A Narrative Review. Vet. Sci. 2025, 12, 642. https://doi.org/10.3390/vetsci12070642
Yu Y, Jin F, Wang L, Cheng J, Pan S. Role of Gut Microbiota and Metabolite Remodeling on the Development and Management of Rheumatoid Arthritis: A Narrative Review. Veterinary Sciences. 2025; 12(7):642. https://doi.org/10.3390/vetsci12070642
Chicago/Turabian StyleYu, Yichen, Fulin Jin, Lijun Wang, Ji Cheng, and Shifeng Pan. 2025. "Role of Gut Microbiota and Metabolite Remodeling on the Development and Management of Rheumatoid Arthritis: A Narrative Review" Veterinary Sciences 12, no. 7: 642. https://doi.org/10.3390/vetsci12070642
APA StyleYu, Y., Jin, F., Wang, L., Cheng, J., & Pan, S. (2025). Role of Gut Microbiota and Metabolite Remodeling on the Development and Management of Rheumatoid Arthritis: A Narrative Review. Veterinary Sciences, 12(7), 642. https://doi.org/10.3390/vetsci12070642