Remodeling the gut microbiota: mechanistic insights into probiotic-mediated alleviation of weaning stress in piglets

Early weaning, characterized by the replacement of maternal milk with solid diets, is widely recognized as one of the most stressful developmental events affecting piglets in intensive production systems. During this stage, the digestive, immune, and metabolic systems remain immature, rendering piglets highly susceptible to environmental and nutritional stressors as well as opportunistic pathogens. These challenges frequently disrupt intestinal microbial homeostasis, impair gut barrier integrity, and trigger immune and metabolic disturbances, ultimately leading to post-weaning diarrhea, intestinal inflammation, growth retardation, and reduced production performance. For decades, dietary antibiotics have been extensively used to mitigate weaning-associated diseases. However, the emergence and dissemination of antimicrobial resistance, together with concerns regarding antibiotic residues and microbiota disruption, accelerated the search for safe, effective, and sustainable alternatives to maintain intestinal health in antibiotic-free swine production. As one of the most promising microbiota-targeted strategies, probiotics have demonstrated considerable potential for alleviating weaning stress by restoring the structure and function of the gut microbial ecosystem. This review systematically summarizes weaning-induced alterations in gut microbial composition, ecological succession, and microbial metabolic dysfunction, and discusses how these changes contribute to intestinal dysfunction in piglets. Emphasis is placed on the mechanisms by which probiotics remodel the intestinal microbiota, promote the establishment of health-associated microbial communities, and restore key microbial metabolic pathways, including short-chain fatty acid (SCFA), secondary bile acid, and tryptophan metabolism. Although probiotics may interact directly with host tissues, their effects are primarily mediated through restoration of the gut microbial ecosystem and re-establishing microbiota-derived metabolic signaling, thereby coordinating intestinal barrier repair, immune homeostasis, and redox balance while alleviating post-weaning diarrhea and growth impairment. Probiotic-mediated restoration of gut microbial structure and metabolic function represents the central mechanism underlying protection against weaning stress and can be conceptualized as a sequential process involving microbial ecosystem reconstruction, metabolic recovery, and host functional restoration. These insights provide a mechanistic framework for developing precision microbiome-based interventions and sustainable antibiotic-free strategies to improve intestinal health and production efficiency in modern swine production systems.