Article ; Online: Magnesium increases numbers of Foxp3+ Treg cells and reduces arthritis severity and joint damage in an IL-10-dependent manner mediated by the intestinal microbiome.
2023 Volume 92, Page(s) 104603
Abstract: Background: Rheumatoid arthritis (RA) is a common autoimmune disease with emerging environmental and microbiome risk factors. The western diet is typically deficient in magnesium (Mg), and there is some evidence suggesting that Mg may have anti- ... ...
| Abstract | Background: Rheumatoid arthritis (RA) is a common autoimmune disease with emerging environmental and microbiome risk factors. The western diet is typically deficient in magnesium (Mg), and there is some evidence suggesting that Mg may have anti-inflammatory properties. But the actual role of Mg supplementation in arthritis or in T cell subsets has not been explored. Methods: We investigated the role of a high Mg diet in two different mouse models of RA induced with the KRN serum, and collagen-induced arthritis. We also characterized the phenotypes of splenocytes, gene expression, and an extensive intestinal microbiome analyses including fecal material transplantation (FMT). Findings: The high Mg diet group was significantly protected with reduced arthritis severity and joint damage, and reduced expression of IL-1β, IL-6, and TNFα. The high Mg group also had increased numbers of Foxp3+ Treg cells and IL-10-producing T cells. The high Mg protective effect disappeared in IL-10 knockout mice. FMT from the high Mg diet mice recreated the phenotypes seen in the diet-treated mice, with reduced arthritis severity, increased Foxp3+ Treg, and increased IL-10-producing T cells. Intestinal microbiome analyses using 16S rDNA sequencing revealed diet-specific changes, including reduced levels of RA-associated Prevotella in the high Mg group, while increasing levels of Bacteroides and other bacteria associated with increased production of short-chain fatty acids. Metagenomic analyses implicated additional pathways including L-tryptophan biosynthesis and arginine deiminase. Interpretation: We describe a new role for Mg in suppressing arthritis, in expanding Foxp3+ T reg cells and in the production of IL-10, and show that these effects are mediated by the intestinal microbiome. Our discoveries suggest a novel strategy for modifying the intestinal microbiome to treat RA and other autoimmune and inflammatory diseases. Funding: None. |
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| MeSH term(s) | Mice ; Animals ; T-Lymphocytes, Regulatory ; Magnesium/metabolism ; Magnesium/pharmacology ; Interleukin-10/genetics ; Interleukin-10/metabolism ; Gastrointestinal Microbiome ; Cytokines/metabolism ; Arthritis, Rheumatoid/metabolism ; Mice, Knockout ; Th17 Cells ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism |
| Chemical Substances | Magnesium (I38ZP9992A) ; Interleukin-10 (130068-27-8) ; Cytokines ; Foxp3 protein, mouse ; Forkhead Transcription Factors |
| Language | English |
| Publishing date | 2023-05-16 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 2851331-9 |
| ISSN | 2352-3964 |
| ISSN (online) | 2352-3964 |
| DOI | 10.1016/j.ebiom.2023.104603 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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