Role of gut microbiota metabolites in maintaining intestinal health and preventing weaning-associated diarrhea in piglets

Weaning is a critical challenge in swine production. Early weaning induces stress in piglets, which compromises intestinal barrier function, disrupts gut microbial homeostasis, and results in diarrhea. Enhancing intestinal microbial homeostasis by modulating the gut microbiota composition is considered an effective strategy to alleviate weaning-related diarrhea in piglets. However, due to the high degree of microbial crosstalk, directly investigating host-microbiota interactions remains challenging. Gut microbial metabolites, as functional outputs of host-microbiota co-metabolic networks, play pivotal roles in maintaining intestinal barrier integrity and homeostasis by regulating the intestinal epithelial barrier, immune equilibrium, and microbial community interactions. This review comprehensively examines the critical functions and recent advancements in understanding four major classes of microbial metabolites-short-chain fatty acids, amino acid derivatives, secondary bile acids, and vitamins-in safeguarding intestinal barrier integrity and preventing diarrhea during the weaning transition. By synthesizing current evidence, this review highlight how targeting gut microbial metabolites offers novel therapeutic avenues to overcome the limitations of direct microbiota modulation, thereby preserving intestinal homeostasis and preventing weaning-associated diarrhea in piglets.