Breaking the diabetes-depression cycle: Exploring shared mechanisms, neuroinflammation, and emerging interventions for metabolic-mood comorbidities

Table 2 Role of the gut-brain axis in type 2 diabetes mellitus and depression comorbidity

Component	Changes in T2DM	Impact on mental health	Potential intervention measures
Gut microbiota composition	Dysbiosis (microbial imbalance); reduction in beneficial bacteria; increase in pathogenic bacteria	Changes in neurotransmitter production; immune activation; vagus nerve signal dysregulation	Probiotics; prebiotics; dietary fiber
Intestinal barrier	“Leaky gut” syndrome; increased intestinal permeability; bacterial translocation	LPS-mediated endotoxemia; systemic inflammation; brain TLR4 activation	Intestinal barrier enhancers; anti-inflammatory drugs; restoration of symbiotic state
Bacterial metabolites	Reduction in SCFAs; increase in toxic metabolites; amino acid imbalance	Decreased GABA/serotonin production; neuroinflammation; vagus nerve afferent signaling	Prebiotic fiber; SCFA supplementation; dietary adjustment
Neuroendocrine signaling	HPA axis hyperactivation; elevated cortisol levels; adrenal-gut-brain axis dysregulation	Worsening of depression symptoms; further gut microbiota dysbiosis; malignant inflammatory cycle	Stress reduction measures; mindfulness therapy; HPA regulators
Vagus nerve	Autonomic neuropathy; altered gut-brain communication; gastrointestinal symptom signaling	Anxiety induction; emotional regulation disorder; altered stress response	Vagus nerve stimulation; management of gastrointestinal symptoms; autonomic nervous system regulation

T2DM: Type 2 diabetes mellitus; LPS: Lipopolysaccharide; TLR4: Toll-like receptor 4; SCFAs: Short-chain fatty acids; GABA: Gamma-aminobutyric acid; HPA: Hypothalamic-pituitary-adrenal.