Systemic Metabolic & Microbiome Regulation

Systemic Metabolic & Microbiome Regulation refers to the complex, bidirectional communication network between the host's metabolic pathways and the gut microbiota. This axis is fundamental to maintaining energy homeostasis, glucose regulation, and lipid metabolism through the action of microbial-derived metabolites like short-chain fatty acids (SCFAs), bile acids, and indole derivatives (Fan & Pedersen, 2021, Nature Reviews Microbiology). These metabolites serve as ligands for host receptors, including G protein-coupled receptors (GPR41, GPR43) and nuclear receptors (FXR), thereby influencing systemic insulin sensitivity and inflammatory status (Cani, 2019, Nature Communications). Clinical evidence suggests that disruptions in this regulatory system, often termed dysbiosis, are central to the pathogenesis of obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) (Ley et al., 2006, Nature). While not a single druggable molecule, this system is the focus of diverse therapeutic strategies ranging from small-molecule agonists of metabolite receptors to live biotherapeutic products (LBPs) designed to restore ecological balance. Consequently, it represents a broad therapeutic framework or physiological axis rather than a discrete molecular target.

Other names

Gut-microbiome-metabolic axisMicrobiome-metabolism regulationHost-microbe metabolic crosstalk

Modulation of gut microbiota composition and the production of signaling metabolites, such as short-chain fatty acids and bile acids, which activate host receptors like GPR41, GPR43, and FXR to regulate energy balance and glucose metabolism (Fan & Pedersen, 2021, Nature Reviews Microbiology).