Table 2.
Main microbial metabolites related to T2DM.
| Metabolite | Producing Bacteria (Genus or Species) |
Mechanism of T2DM Risk | Reference |
|---|---|---|---|
| SCFA (acetate, propionate, and butyrate) | Akkermansia, Ruminococcus, Faecalibacterium prausnitzii, Eubacterium, Roseburia, Blautia, Coprococcus, Anaerostipes, and others | - Increases epithelial barrier function by regulation of TJP; - Reduces the passage of LPS, improving inflammation; - Stimulates the secretion of PYY and GLP-1 from L-cells in a GPR41 and GPR43 dependent manner; - Reduces appetite, insulin secretion, plasma glucose levels, and slow gastric emptying through stimulation of GLP-1 and GLP-2 secretion. |
[39,40,41] |
| Imidazole propionate | Imidazole propionate: Eggerthella lenta, Streptococcus mutans, Aerococcus urinae, Brevibacillus laterosporus, and others |
- Impairs glucose tolerance and insulin signaling by activating the p38γ-p62-mTORC1 pathway. | [42] |
| TMAO/TMA | Desulfovibrio desulfuricans, Providencia, E. coli, Klebsiella pneumoniae, Sporosarcina, and others. | - Exacerbates blockage of the insulin signaling pathway and promotes inflammation in adipose tissue. | [43] |
| Branched-chain amino acids | former-Lactobacillus, Weissella, Leuconostoc, P. copri, and B. vulgatus | - Promotes insulin resistance through serine phosphorylation of IRS-1; by persistent activation of mTORC1/S6K1. |
[27,44,45] |
| Bile acids Secondary bile acids |
Secondary bile acids: Ruminococcus, Bifidobacterium, Bacteroides, Clostridium, former-Lactobacillus, Eubacterium, Listeria, and others. |
- Ligands of nuclear receptors, such as VDR, PXR, and FXR, induce TGR5 expression and regulate insulin and glucose sensitivity. | [46,47] |
| Tryptophan metabolites Tryptamine |
Clostridium bartlettii, Clostridium sporogenes, Ruminococcus gnavus, Bacteroides ovatus, Lactobaccilus acidophilus,Limosilactobacillus reuteri, Bifidobacterium fragilis, Bifidobacterium bifidum, and others. | - Improves intestinal epithelial barrier function by the activation of PXR; - Stimulates insulin secretion, supresses appetite, and slows gastric emptying by stimulating GLP-1 secretion; - Promotes gastrointestinal motility by stimulating serotonin release; - Anti-inflammatory and anti-oxidative effects in the systemic circulation. |
[48] |
Abbreviations: SCFA: short chain fatty acids; TJP: tight junction proteins; LPS: lipopolysaccharides; PYY: peptide YY; GLP-1: glucagon-like peptide; GPR: G-protein coupled receptor; mTORC1: mechanistic target of rapamycin complex 1; S6K1: ribosomal S6 kinase 1; TMAO: trimethylamine-N-oxide; TMA: trimethylamine; BCAA: branched-chain amino acids; IRS-1: insulin receptor substrate 1; VDR: vitamin D3 receptor; PXR: pregnane X receptor; FXR: farnesoid X receptor; TGR5: G-protein-coupled bile acid receptor.