Regulating Gut Microbiota in Post-Weaned Pigs: The Role of Digestive Capacity and Substrate Flow

In commercial pig production systems, early weaning imposes abrupt nutritional, environmental and social challenges before full gastrointestinal maturation has occurred, increasing susceptibility to post-weaning diarrhoea (PWD) and impaired growth performance. Although enterotoxigenic Escherichia coli (ETEC) is frequently implicated in PWD, pathogen presence alone does not adequately explain variation in disease expression among pigs and production systems. Increasing evidence indicates that gastrointestinal stability following weaning is determined by interactions among digestive capacity, substrate flow, microbial metabolism, epithelial integrity and host immune responses. In this review, substrate flow refers to the quantity, composition and regional distribution of undigested dietary and endogenous substrates moving through the gastrointestinal tract (GIT) and becoming available for microbial fermentation. The review proposes substrate flow as the central mechanistic interface linking digestive physiology with microbial metabolic activity during the post-weaning transition. Commercial weaning frequently occurs before complete adaptation to cereal- and plant-based diets has developed. Reduced feed intake, elevated gastric pH, incomplete pancreatic adaptation and reduced brush-border enzyme activity impair nutrient digestion during this transition, increasing nutrient overflow to the distal intestine. Under these conditions, microbial metabolism shifts from predominantly saccharolytic fermentation towards proteolytic pathways associated with production of ammonia, phenols, indoles and branched-chain fatty acids. These metabolites impair epithelial integrity, alter luminal conditions and favour proliferation of opportunistic bacteria. Conversely, effective digestion supports saccharolytic fermentation, short-chain fatty acid production, epithelial integrity and microbial stability. Microbial dysbiosis is therefore more accurately interpreted as a metabolic consequence of altered substrate availability and fermentation dynamics rather than solely as a compositional imbalance of bacterial taxa. By integrating digestive physiology, microbial ecology and nutritional management, the substrate-flow concept provides a mechanistic framework for development of more biologically coherent nutritional strategies aimed at improving gastrointestinal resilience and reducing antimicrobial reliance in modern pig production systems.