Table 1.
The compositions or metabolites of microbiota affect ferroptosis.
| Microbiota | The function to the ferroptosis | Ref. |
|---|---|---|
| Lipopolysaccharides | Activation of ACSL4 by up-regulating special protein 1. Regulation of the secretion of serum ferritin. Aggravation of lipid metabolic disorders and ferroptosis in hepatocytes. |
52,53 |
| Glycochenodeoxycholate | Promotion of TFR-ACSL4-mediated ferroptosis | 38 |
| Short-chain fatty acid | Facilitation of mitochondrial Ca2+ and GPX4-dependent ferroptosis. Inhibition of cystine/glutamate transporter system by the upstream molecular RBM3 or FFAR2-AKT-NRF2 axis and FFAR2-mTORC1 axis and c-Fos. |
54–56 57–59 |
| Reduction of the production of ROS, enhancing oxidative phosphorylation and β-oxidation in physiological conditions. Activation of the PGC1α signaling axis to promote mitochondrial biogenesis; Protection of mitochondria. | ||
| Indigenous bacteria (metabolites, reuterin and 1,3, diaminopropane) |
Suppression of HIF-2α, the master transcription factor of intestinal iron absorption and transportation Increase in the iron storage protein ferritin. |
60 |
| Capsiate | Promotion of Gpx4 expression and restraint of ferroptosis via the overexpression of TRPV1 in intestinal I/R injury. | 61 |
| Urolithins | Increase in mitophagy and mitochondrial function by reducing excessive inflammation. | 62 |
| 5-HT and 3-HA | Elimination of radicals to resist ferroptosis | 63 |
| Histamine | Histamine deficiency accelerates myocardial ferroptosis by repressing the activation of STAT3, accompanied by decreased expression of SLC7A11, a major modulator of ferroptosis. | 64 |
| Lactobacillus rhamnosus GG | Regulation of lipid metabolism to inhibit ferroptosis | 24 |
| Aeromonas hydrophila | Increase in the levels of MDA and Fe2+ in brain tissues and decrease in GSH. | 65 |
| Pseudomonas aeruginosa | Elevation of levels of oxidized AA-phospholipids by expressing pLoxA (its mammalian orthologue is ALOX15). | 66 |
| Mycobacterium tuberculosis | Reduction in levels of GSH and Gpx4, along with increased levels of free iron, mitochondrial superoxide, and lipid peroxidation; alleviation of the disease is suppressed by Ferrostatin-1. | 67 |
| Porphyromonas gingivalis | Increase in ACSL4, Ptgs2, and Ncoa4 expression, while decreasing GPX4 and SLC7A11. | 68 |
| Lactiplantibacillus plantarum | Transformation of unsaturated fatty acids to resist ferroptosis and their derivatives promote antioxidative gene expression. | 69 |
| Escherichia coli | Increase in intracellular iron levels by inhibiting the expression of Ferroportin-1, followed by the induction of the Fenton reaction to release ROS. | 70 |
| Edwardsiella piscicida | Promotion of iron accumulation, mitochondrial dysfunction, and production of ROS | 71 |
HIF-2α, Hypoxia inducible factor 2α; ACSL4, Acyl-CoA synthetase long-chain family 4; GPX4, glutathione peroxidase 4; RBM3, RNA-binding motif protein 3; FFAR2, Free fatty acid receptor 2; NRF2, Nuclear factor erythroid 2-related factor 2; mTORC1, mTORC1, mammalian target of rapamycin complex 1; TRPV1, transient receptor potential vanilloid 1; I/R, Ischemia-reperfusion; TFR, transferrin receptor; 5-HT, serotonin; STAT3, Signal Transducer and Activator of Transcription 3; SLC7A11, solute carrier family 7 member 11; MDA, Malondialdehyde; GSH, glutathione; AA, arachidonic acid; ALOX15, arachidonate 15-lipoxygenase; Ptgs2, prostaglandin-endoperoxide synthase 2; Ncoa4, Nuclear Receptor Coactivator 4; RBCs, Red blood cells; ROS, reactive oxygen species.