In commercial pig production systems, early weaning disrupts the coordinated maturation of the gastrointestinal tract, resulting in reduced feed intake, impaired digestive capacity, altered microbial ecology and increased susceptibility to post-weaning diarrhoea (PWD). Although enterotoxigenic Escherichia coli (ETEC) is frequently implicated, variation in disease expression is not explained by pathogen presence alone, but reflects interactions among host physiology, nutrient flow and microbial metabolism. This review examines the regulation of the gut microbiota in post-weaned pigs through the interaction between digestive capacity and dietary substrate supply. It proposes substrate flow as the organising principle linking digestive function, diet composition and microbial metabolism. Gut microbial function is regulated primarily by substrate availability, which is determined by the alignment between diet composition and host digestive capacity. When this alignment is disrupted, undigested nutrients are redistributed to the hindgut, driving a shift from saccharolytic to proteolytic fermentation. This transition generates metabolites that impair epithelial integrity, increase luminal pH and favour proliferation of opportunistic bacteria, thereby promoting intestinal dysfunction. Within this context, nutritional strategies, including optimisation of dietary protein, provision of fermentable carbohydrates and support of gastric function, act by regulating substrate flow rather than directly modifying microbial composition. Organic acids, functional ingredients and maternal influences operate through the same mechanisms, shaping nutrient digestion, microbial exposure and metabolic outcomes. The characteristic post-weaning increase in Enterobacteriaceae and reduction in microbial diversity are therefore best understood as consequences of altered substrate flow and luminal conditions, rather than primary initiating events. This interpretation provides a mechanistic basis for the design of integrated nutritional and management strategies to improve gut health and reduce antimicrobial reliance in pig production systems.