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

Table 2 Dietary modulation of the gut microbiota and its impact on type 2 diabetes mellitus[106,108,113,114,118-122]

Method	Alterations in the gut microbiota	Strengths and weaknesses	Mechanism	Ref.
WD	Increased: Escherichia coli; Actinobacteria; Proteobacteria. Decreased: Firmicutes; Bacteroidetes	WD are associated with a higher risk of developing T2DM. WD induces gut microbiota dysbiosis, increases endotoxin levels, and disrupts the intestinal mucosal barrier, thereby exacerbating inflammation and obesity-related metabolic abnormalities	Reduce protective gut microbiota, downregulate the expression of the short-chain fatty acid receptor GPR43, suppress the activities of superoxide dismutase, catalase, and glutathione peroxidase, activate the NF-κB signaling pathway, upregulate TNF-α expression, and thereby exacerbate inflammatory responses	Agus et al[118]
KD	Increased: Verrucomicrobiae; Akkermansia; Verrucomicrobiales; Akkermansiaceae; Christensenellaceae; Parabacteroides distasonis; Anaerotruncus; Enterococcus; Rothia; Enterorhabdus; Bacteroidetes. Decreased: Firmicutes; Actinobacteria; Clostridia; Alistipes; Dialister; Lactobacillus; Lactococcus; Faecalitalea; Bifidobacterium	KD can improve T2DM but may potentially increase LDL-C levels, necessitating individualized monitoring of lipid profiles and cardiovascular risk. Issues related to adherence, long-term safety, and suitability for specific populations (such as patients with kidney disease or other special groups) still require clarification through more high-quality randomized controlled trials	Improve the structure and function of the gut microbiota, increase the levels of ketone bodies β-hydroxybutyrate and β-hydroxybutyrate salts, inhibit NF-κB signaling, reduce the expression of pro-inflammatory intestinal Th17 cells, caspase-1, IL-1β, and IL-18, and decrease HbA1c and triglyceride levels	Palmas et al[106]; Ang et al[108]; Song et al[119]; Lindefeldt et al[120]; Dowis and Banga[121]
MD	Increased: Clostridium leptum; Eubacterium rectale; Bifidobacteria; Bacteroides; Faecalibacterium prausnitzii. Decreased: Firmicutes; Blautia	MD is associated with a lower risk of T2DM, delays the initiation of glucose-lowering medications, and improves disease remission rates. MD is more oriented toward long-term, sustainable risk reduction; therefore, short-term glycemic control goals often require combination with pharmacotherapy or structured management programs	Promote the proliferation of short-chain fatty acid producing bacterial strains (particularly butyrate producers), reduce the levels of the pro-inflammatory cytokine IL-6 and the oxidative stress marker 8-hydroxy-2’-deoxyguanosine, and improve FBG and HbA1c	Barber et al[113]; Dimba et al[114]; Al-Aubaidy et al[122]

WD: Western diet; KD: Ketogenic diet; MD: Mediterranean diet; T2DM: Type 2 diabetes; LDL-C: Low-density lipoprotein cholesterol; NF-κB: Nuclear factor-kappa B; GPR: G protein-coupled receptor; IL: Interleukin; TNF: Tumor necrosis factor; Th17: T helper 17 cells; HbA1c: Glycated hemoglobin; FBG: Fasting blood glucose.