https://orcid.org/0000-0002-9537-6857
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ABSTRACT
Succinate is a circulating metabolite, and the relationship between abnormal changes in the physiological concentration of succinate and inflammatory diseases caused by the overreaction of certain immune cells has become a research focus. Recent investigations have shown that succinate produced by the gut microbiota has the potential to regulate host homeostasis and treat diseases such as inflammation. Gut microbes are important for maintaining intestinal homeostasis. Microbial metabolites serve as nutrients in energy metabolism, and act as signal molecules that stimulate host cell and organ function and affect the structural balance between symbiotic gut microorganisms. This review focuses on succinate as a metabolite of both host cells and gut microbes and its involvement in regulating the gut – immune tissue axis by activating intestinal mucosal cells, including macrophages, dendritic cells, and intestinal epithelial cells. We also examined its role as the mediator of microbiota – host crosstalk and its potential function in regulating intestinal microbiota homeostasis. This review explores feasible ways to moderate succinate levels and provides new insights into succinate as a potential target for microbial therapeutics for humans.
Abbreviations
| AAD | = | aortic aneurysm and dissection |
| AKG | = | α-ketoglutarate |
| APCs | = | antigen-presenting cells |
| ASCT | = | acetate:succinate CoA-transferase |
| BMDMs | = | bone-marrow-derived macrophages |
| CD | = | Crohn’s disease |
| CO2 | = | carbon dioxide |
| CoQ | = | coenzyme Q |
| DCs | = | dendritic cells |
| DSS | = | dextran sulfate sodium |
| ERK1/2 | = | extracellular signal-regulated kinases 1 and 2 |
| ETC | = | electron transport chain |
| FBPase | = | fructose-1,6-bisphosphatase |
| FMT | = | fecal microbiota transplantation |
| GABA | = | γ-aminobutyric acid |
| HIF-1α | = | hypoxia-inducible factor-1α |
| I/R | = | ischemia/reperfusion |
| IBD | = | inflammatory bowel disease |
| IDH | = | isocitrate dehydrogenase |
| IECs | = | intestinal epithelial cells |
| IgA | = | immunoglobulin A |
| ILC2s | = | type 2 innate lymphoid cells |
| iMoDCs | = | immature monocyte-derived DCs |
| IP3 | = | inositol trisphosphate |
| MCM | = | methylmalonyl-CoA mutase |
| MCT1 | = | monocarboxylate transporter 1 |
| MMA | = | methylmalonate |
| MSC | = | mesenchymal stem cell |
| NAFLD | = | nonalcoholic fatty liver disease. |
| NSCs | = | neural stem cells |
| OAA | = | oxaloacetate |
| OGDH | = | 2-oxoglutarate dehydrogenase |
| OXPHOS | = | oxidative phosphorylation |
| PEP | = | phosphoenolpyruvate |
| PEPCK | = | phosphoenolpyruvate carboxykinase |
| PGE2 | = | prostaglandin E2 |
| PHD | = | proline hydroxylase |
| PKA | = | protein kinase A |
| PLC | = | phospholipase C |
| Plcβ2 | = | phospholipase Cβ2 |
| RA | = | rheumatoid arthritis |
| RELMβ | = | resistin-like protein β |
| ROS | = | reactive oxygen species |
| SCFAs | = | short-chain fatty acid |
| SCS | = | succinyl-CoA synthetase |
| SDH | = | succinate dehydrogenase |
| SUCNR1 | = | succinate receptor 1 |
| Tas2rs | = | tuft cells express bitter taste receptors |
| TCA | = | tricarboxylic acid cycle |
| Th cells | = | T helper cells |
| TLRs | = | Toll-like receptors |
| Treg cells | = | regulatory T cells |
| TRPM5 | = | transient receptor potential cation channel subfamily M member 5 |
| UQ | = | ubiquinone |
| UQH2 | = | ubiquinol |
Acknowledgments
The authors’ profound admiration and respect are given to researchers in this field and their laboratories who are diligently working in this field of investigation. The authors would like to acknowledge and thank Robert Preston Story Jr. and Samantha Howe for their help editing this manuscript.
Disclosure statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Authors’ contributions
YHW wrote the first draft of the manuscript. XM and CQG helped to review the first draft of the manuscript. JCZ, XQW, and CQG reviewed and edited the final manuscript. All authors read and approved the final manuscript.
Data availability statement
The data that support the findings of this study are available from the corresponding author, [CQG], upon reasonable request. https://orcid.org/0000–0001–9119–1233.