Role of gut microbiota in regulating host cell metabolism in digestive system diseases

The impact of gut microbiota on disease pathogenesis and progression is receiving increasing attention, particularly in the field of digestive system disorders. Previous reviews have predominantly focused on the composition and function of bacteria and their metabolites. However, host physiological activities rely on a series of interconnected hierarchical processes, including gene expression, signal transduction, and ultimately, physiological responses. Within this framework, cellular metabolic activities provide an essential foundation for cellular functions. In this study, we focused on to host intracellular metabolic reprogramming rather than extracellular metabolite profiles—specifically, how microbial signals rewire host cellular energy pathways, such as the balance between oxidative phosporylation and glycolysis. We systematically explain how dysregulation of the microbiota–host metabolism axis contributes to the pathophysiology of various digestive system disorders. We also outline current prevention and treatment strategies targeting this axis, including probiotics, dietary adjustments, fecal microbiota transplantation (FMT), traditional Chinese medicine, and emerging biotherapies. In addition, we explore future research directions and potential applications in this field. Standardizing interventions such as FMT and validating their efficacy through large‑scale cohort studies remain immediate priorities in clinical practice. The graphic abstract centers on the “gut microbiota–host metabolism axis” and summarizes four major regulatory mechanisms of microbial impact on host glucose, lipid, purine, and drug metabolism. Dysregulation of this axis drives various digestive system diseases, whereas therapeutic strategies targeting this axis (e.g., probiotics, dietary intervention, fecal microbiota transplantation [FMT]) offer potential avenues for restoring metabolic homeostasis.