Heat-killed Mycobacterium aurum partially attenuates hyperglycemia in STZ-induced diabetic mice

Diabetes and other metabolic disorders are a global health crisis, often requiring lifelong management. Current therapies primarily focus on symptom control, leaving a gap for novel approaches that address underlying metabolic dysfunction. Postbiotics, particularly inactivated microorganisms, are gaining attention for their potential to improve glycemic control by modulating host metabolism and immune responses, offering a promising, less invasive strategy. This study explores the anti-hyperglycemic potential of heat-killed Mycobacterium aurum.

Male BALB/c mice were rendered diabetic with streptozotocin (STZ; 150 mg/kg) injection. Heat-killed M. aurum (1 mg) was administered via two regimens: orally (three prophylactic doses before STZ) or intradermally (six weekly therapeutic doses after STZ). Glycemic parameters, serum C-peptide/insulin levels (ELISA), and tissue protein expression (Western blot) for glucose transport (GLUT2, GLUT4, SGLT2), glycolysis (α-LDH), mitochondrial uncoupling (UCP2, UCP3), and antioxidant defense (CAT) were assessed.

Neither treatment route affected body weight or glucose homeostasis in non-diabetic mice. In STZ-diabetic mice, oral prophylactic treatment significantly attenuated hyperglycemia.

Oral prophylactic treatment in STZ-diabetic mice significantly attenuated hyperglycemia, achieving a 39-60% reduction in blood glucose levels between weeks 5-8 post-STZ. This prophylactic regimen also showed a trend toward improved serum C-peptide but did not significantly alter dysregulated expression of skeletal muscle (SM), hepatic, pancreatic, or renal proteins involved in glucose transport (GLUT2, GLUT4, SGLT2), glycolysis (α-LDH), mitochondrial uncoupling (UCP2, UCP3), or antioxidant defense (CAT). Therapeutic intradermal administration significantly decreased blood glucose by approximately 30% at week 5 and 40% at week 6, alongside a modest enhancement of insulin secretion. Hepatic UCP2 and α-LDH, and SM UCP3 protein levels were normalized towards non-diabetic levels, while hepatic GLUT2 and SM GLUT4 remained largely unchanged. These correlative findings suggest effects independent of insulin-dependent glucose transport, but functional validation of mitochondrial or redox status improvement is still needed.