The gut-joint axis mediates the TNF-induced RA process and PBMT therapeutic effects through the metabolites of gut microbiota

ABSTRACT

The gut-joint axis, one of the mechanisms that mediates the onset and progression of joint and related diseases through gut microbiota, and shows the potential as therapeutic target. A variety of drugs exert therapeutic effects on rheumatoid arthritis (RA) through the gut-joint axis. However, the anti-inflammatory and immunomodulatory effect of novel photobiomodulatory therapy (PBMT) on RA need further validation and the involvement of gut-joint axis in this process remains unknown. The present study demonstrated the beneficial effects of PBMT on RA, where we found the restoration of gut microbiota homeostasis, and the related key pathways and metabolites after PBMT. We also discovered that the therapeutic effects of PBMT on RA mainly through the gut-joint axis, in which the amino acid metabolites (Alanine and N-acetyl aspartate) play the key role and rely on the activity of metabolic enzymes in the target organs. Together, the results prove that the metabolites of amino acid from gut microbiota mediate the regulation effect on the gut-joint axis and the therapeutic effect on rheumatoid arthritis of PBMT.

GRAPHICAL ABSTRACT

KEYWORDS:

• PBMT
• gut microbiota
• TNF-Tg mice
• rheumatoid arthritis
• gut-joint axis

Highlights

1. The gut-joint axis mediates the pathogenesis of TNF-α induced rheumatoid arthritis and the PBMT effects on RA.

2. The amino acid are main metabolites of gut microbiota for regulating of PBMT effects on RA.

3. The role of gut microbiota metabolites in the gut-joint axis was determined by the level of metabolic enzymes in the joint.

4. The effect of PBMT is mainly recovery of microbiota homeostasis, which characterized by the increase of Clostridium_IV, Lactobacillus and Odoribacter.

Disclosure statement

No potential conflict of interest was reported by the authors.

Authors’ contributions

Q.M., M.L., and W.S. contributed equally to this study. Q.M., M.L., and W.S. Conceptualization, Data curation, Formal analysis, Methodology, Visualization, writing – original draft. J.W., Y.Y., and W.G. Methodology, Resources, Writing – review & editing. P.H., G.C., and Z.S. performed the experiments; P.X., X.D. and H.L. analyzed the data; and all authors approved the final version to be published. F.Z. and H.L. Conceptualization, Funding acquisition, Investigation, Methodology, Resources, Writing – review & editing.

Data availability statement

All data generated or analyzed during the current study are included in this published article [and supplementary information files] or are available in the NCBI SRA repository, PRJNA1044260.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2281382

Additional information

Funding

This work was supported by the National Key Research and Development Program of China (2022YFB3604705, 2017YFB0403805.