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Host-microbiota interactions in collagen-induced arthritis rats treated with human umbilical cord mesenchymal stem
Zhongsheng Zhou1, Yang Li1, Shuhui Wu1
1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, China.
Abstract:
Mesenchymal stem cell exosome (MSCs-exo) is a class of products secreted by mesenchymal stem cells (MSCs) that contain various biologically active substances. MSCs-exo is a promising alternative to MSCs due to their lower immunogenicity and lack of ethical constraints. Ginsenoside Rh2 (Rh2) is a hydrolyzed component of the primary active substance of ginsenosides. Rh2 has a variety of pharmacological functions, including anti-inflammatory, anti-tumor, and antioxidant. Studies have demonstrated that gut microbiota and metabolites are critical in developing rheumatoid arthritis (RA). In this study, we constructed a collagen-induced arthritis (CIA) model in rats. We used MSCs-exo combined with Rh2 to treat CIA rats. To observe the effect of MSCs-exo combined with Rh2 on joint inflammation, rat feces were collected for 16 rRNA amplicon sequencing and untargeted metabolomics analysis. The results showed that the arthritis index score and joint swelling of CIA rats treated with MSCs-exo in combination with Rh2 were significantly lower than those of the model and MSCs-exo alone groups. MSCs-exo and Rh2 significantly ameliorated the disturbed gut microbiota in CIA rats. The regulation of Candidatus_Saccharibacteria and Clostridium_XlVb regulation may be the most critical. Rh2 enhanced the therapeutic effect of MSCs-exo compared with the MSCs-exo -alone group. Furthermore, significant changes in gut metabolites were observed in the CIA rat group, and these differentially altered metabolites may act as messengers for host-microbiota interactions. These differential metabolites were enriched into relevant critical metabolic pathways, revealing possible pathways for host-microbiota interactions.
Insights
Mesenchymal stem cell exosomes (MSCs-exo) combined with Ginsenoside Rh2 significantly reduced rheumatoid arthritis symptoms in rats. This therapy also restored gut microbiota balance and altered metabolites, enhancing treatment efficacy.
Area of Science:
- Immunology and Microbiology
- Pharmacology and Therapeutics
- Gastroenterology
Background:
- Rheumatoid arthritis (RA) pathogenesis is linked to gut microbiota and metabolites.
- Mesenchymal stem cell exosomes (MSCs-exo) offer a low-immunogenicity therapeutic alternative to mesenchymal stem cells (MSCs).
- Ginsenoside Rh2 (Rh2) exhibits anti-inflammatory, anti-tumor, and antioxidant properties.
Purpose of the Study:
- To investigate the therapeutic effects of combining MSCs-exo with Rh2 on a collagen-induced arthritis (CIA) rat model.
- To analyze the impact of this combination therapy on gut microbiota composition and host metabolites.
- To elucidate the role of host-microbiota interactions in the therapeutic mechanism.
Main Methods:
- A collagen-induced arthritis (CIA) rat model was established.
- Rats were treated with MSCs-exo, Rh2, a combination of MSCs-exo and Rh2, or served as controls.
- Fecal samples were analyzed using 16S rRNA amplicon sequencing and untargeted metabolomics.
Main Results:
- Combination therapy significantly reduced arthritis index scores and joint swelling compared to control and MSCs-exo alone groups.
- MSCs-exo and Rh2 treatment ameliorated gut dysbiosis, notably regulating Candidatus_Saccharibacteria and Clostridium_XlVb.
- Rh2 enhanced the therapeutic benefits of MSCs-exo, with significant alterations observed in gut metabolites involved in host-microbiota interactions.
Conclusions:
- Combined MSCs-exo and Rh2 therapy is a promising treatment for rheumatoid arthritis, superior to MSCs-exo alone.
- The therapeutic efficacy is associated with the modulation of gut microbiota and metabolic pathways.
- This study highlights the potential of targeting gut microbiota and metabolites for RA treatment.
