Gut Microbiota–Mucosal Immune Interactions Underlying Intestinal Homeostasis in Weaned Piglets

The gut microbiota and mucosal immune system undergo extensive remodeling after weaning and jointly influence intestinal homeostasis, resistance to enteric pathogens, and growth performance in piglets. This developmental transition is particularly vulnerable to dietary changes, the loss of maternally derived factors, environmental stressors, and pathogen exposure, all of which can disrupt microbial ecology and mucosal immune regulation. This review examines the reciprocal interactions between the gut microbiota and mucosal immunity in weaned piglets. It describes how microbial communities and their metabolites regulate epithelial barrier integrity, innate and adaptive immune responses, B-cell differentiation, and secretory immunoglobulin A (sIgA) production, with particular emphasis on short-chain fatty acids, tryptophan-derived metabolites, and bile acids. Conversely, host-derived factors, including mucins, antimicrobial peptides, sIgA, cytokines, and inflammation-associated changes in the intestinal microenvironment, are discussed in relation to microbial colonization, spatial distribution, and functional activity. Disruption of these interactions can impair epithelial barrier function, promote excessive inflammation, weaken colonization resistance, and increase susceptibility to enteric infection and post-weaning diarrhea. Finally, this review evaluates nutritional and microbiota-targeted strategies for modulating microbiota–immune interactions and improving intestinal health in weaned piglets.