Table 4.
Regulatory mechanisms of keystone microorganisms and derived metabolites in radiation injury
| References | Keystone microorganism(s) | Functional constituents | Classification | Mechanism summary |
|---|---|---|---|---|
| Fan, China, [8] | NA | Butyrate | SCFA | Enhances barrier integrity and suppresses inflammation by activating GPR41/43 thereby ameliorating intestinal injury |
| Fan, China, [42] | NA | Valerate | SCFA | Enhances barrier integrity by re-elevating the post-radiation decline of cytoskeleton component KRT1, and constraints oxidative and inflammatory responses thereby ameliorating post-radiation hematopoietic and intestinal injury |
| Guo, US, [47] | Lachnospiraceae | Propionate, butyrate | SCFA | Ameliorates intestinal and hematopoietic injury by reducing release of reactive oxygen species and DNA damage |
| Fan, China, [43] | NA | IPA | Indole compound | Enhances barrier integrity by re-elevating the post-radiation decline of PXR/ACBP, and constraints oxidative and inflammatory responses thereby ameliorating post-radiation hematopoietic and intestinal injury |
| Fan, China, [11] | NA | 3,3'-diindolylmethane | Indole compound | Promotes post-radiation DNA damage repairment, intestinal stem cell survival and anti-oxidative reaction thereby ameliorating post-radiation intestinal injury |
| Crawford and Gordon, US, [4] | NA | NA | Lipid metabolism | Existence of gut microbiota increases apoptosis and aggravates post-radiation enteritis by suppressing the expression of fasting-induced adipose factor |
| Dar, US, [52] | Pseudomonas aeruginosa | 15-lipoxygenase | Lipid metabolism | Augments post-radiation intestinal barrier breach by inducing ferroptosis and promoting inflammation |
| Ciorba, US, [53], [54] | Lactobacillus | Lipoteichoic acid | Probiotics | Promotes intestinal mesenchymal stem cells to migrate to crypts to release PGE2 near intestinal stem cells by activating TLR2/MYD88 and CXCL12-CXCR4, so as to impart anti-apoptotic and pro-proliferative functions |
| Kweon, Korea, [55] | Lactobacillus, Bifidobacterium | Lactate | Probiotics | Promotes supply of Wnt ligands from Paneth cells and mesenchymal cells by activating GPR81 thereby activating β-catenin pathway and enhancing post-radiation intestinal epithelial regeneration |
| Kweon, Korea, [63] | Akkermansia | Acetate, propionate | Probiotics/SCFA | Produces SCFAs to activate Wnt/β-catenin-RAS-ERK pathway in intestinal stem cells thereby promoting proliferation and ameliorating post-radiation intestinal injury |
| Kaakoush, Australia, [67] | Sutterella | NA | NA | Degrades the immuno-protective secretory IgA thereby compromising host's anti-pathogenic capacity and possibly increasing susceptibility to injury insult like radiation, which still merits validation |
NA Not applicable, SCFA Short chain fatty acid, GPR G-protein-coupled receptor, KRT1 Keratin, type II cytoskeletal 1, IPA Indole 3-propionic acid, PXR Pregnane X receptor, ACBP Acyl-CoA-binding protein