Engineering microbial therapeutics for metabolic disorders: synthetic biology strategies and future direction

Metabolic disorders, including type 2 diabetes mellitus, obesity, metabolic dysfunction-associated steatohepatitis, etc., are an escalating global health challenge with substantial clinical and socio-economic burdens. Conventional pharmacological therapies are constrained by short-term efficacy, instability, and energy-intensive production. This review aims to evaluate how synthetic biology enables engineered probiotics and microbial systems as self-regulating, living therapeutics that integrate precision treatment with sustainable, bio-based production. Such systems can secrete therapeutic molecules, degrade harmful metabolites, remodel host metabolic microenvironments, and respond to physiological signals to achieve adaptive, feedback-controlled interventions. By exploiting versatile microbial hosts and low-energy fermentation, they minimize chemical waste and carbon footprint. We also discussed preclinical studies demonstrating restored glucose and lipid homeostasis, modulation of appetite, and attenuation of inflammation. Collectively, our review highlights that synthetic biology exemplifies a transformative, sustainable paradigm for metabolic disease management.