Targeting gut microbiota: Potential mechanisms in the pathogenesis of type 2 diabetes mellitus and emerging translational intervention strategies

Table 1 The relationship between gut microbiota dysbiosis and type 2 diabetes mellitus[59,60,64-66,69,79,80,81,85]

Microbe	Impact on T2DM	Mechanism	Ref.
Colidextribacter; Desulfovibrionaceae; Morganella	Promote	Promote LPS production, upregulate pro-inflammatory cytokines, exacerbate pancreatic β-cell dedifferentiation, reduce acetate, butyrate, and overall SCFA levels, ultimately leading to impaired islet function	Cao et al[59]
Acetatifactor; Clostridiales unclassified; Lacchnospiraceae unclassified; Oscillibacter; Murinomas; Tuzzerella		Inhibit GPR43/GPR109A signaling within the AMPK pathway, activate the Toll-like receptor 9-myeloid differentiation primary response protein 88-interferon-γ signaling pathway, increase the expression of TNF-α, IL-1β, and IL-6, and reduce the levels of ZO-1 and occludin	Zhang et al[60]
Anaerovorax; Bilophila; Blautia; Colidextribacter; Dubosiella; Lachnoclostridium; Roseburia		Upregulate the expression of pro-inflammatory cytokines, promote bacterial biosynthesis of BCAAs, and suppress the tissue-specific expression of BCAA catabolic enzymes	Zheng et al[64]
Bacteroides vulgatus		Reduce TLCA levels, inhibit TGR5 signaling, downregulate UCP-1 expression, and diminish thermogenic activity in white adipose tissue	Chen et al[65]
Bacteroides uniformis		Promote leukocyte production, reduce CA and CDCA levels, inhibit the TGR5/AMPK signaling pathway, and disrupt glucose and lipid metabolism	Zhu et al[66]
Akkermansia muciniphila	Alleviate	Strengthening the intestinal epithelial barrier to reduce the entry of microbial products such as LPS into the bloodstream, thereby preventing the activation of the innate immune system	Sabatino et al[69]
Eubacterium hallii		Increase energy expenditure, elevate butyrate levels, and regulate bile acid metabolism	Udayappan et al[79]
Parabacteroides distasonis		Alter the bile acid profile, with increased levels of LCA, UDCA, and succinate, thereby activating intestinal IGN and FXR signaling pathways	Wang et al[80]
Bacteroides uniformis CECT 7771		Increased Tregs, reduced B cells and total macrophages, decreased the M1/M2 ratio, upregulated the expression of IL-10, TSLP, and TLR5	Gauffin Cano et al[81]
Lactobacillus plantarum HAC01		Increase the area of insulin-positive pancreatic β cells, reduce the expression of gluconeogenesis-related enzymes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, promote phosphorylation of AMPK and Akt, and upregulate serum levels of SCFAs	Lee et al[85]

T2DM: Type 2 diabetes; LPS: Lipopolysaccharide; SCFA: Short-chain fatty acid; GPR: G protein-coupled receptor; IL: Interleukin; TNF: Tumor necrosis factor; AMPK: Adenosine 5’-monophosphate-activated protein kinase; ZO-1: Zonula occludens-1; BCAA: Branched-chain amino acid; TLCA: Taurolithocholic acid; TGR5: Takeda G protein-coupled receptor 5; UCP-1: Uncoupling protein 1; CA: Cholic acid; CDCA: Chenodeoxycholic acid; LCA: Lithocholic acid; UDCA: Ursodeoxycholic acid; IGN: Intestinal gluconeogenesis; FXR: Farnesoid X receptor; Treg: Regulatory T; TSLP: Thymic stromal lymphopoietin; TLR: Toll-like receptor; Akt: Protein kinase B.