Diet is a dominant ecological force shaping gut microbial metabolism and, in turn, host immunity and metabolic homeostasis. While short-chain fatty acids (SCFAs) are well-established mediators of host–microbiome interactions, recent studies have revealed a broader and more complex metabolic landscape involving bile acids, indoles, phenolic compounds, and host-modified microbial metabolites. Dietary interventions—particularly fiber supplementation—can unmask previously uncharacterized metabolic pathways, often referred to as microbial dark matter, with profound immunological and metabolic consequences. Notably, bile acid–driven immune activation, fiber-dependent exacerbation of intestinal inflammation, and host conjugation of microbial bile acids into bile acid–methylcysteamine (BA-MCY) highlight bidirectional host–microbe regulatory mechanisms. This review synthesizes emerging evidence on how dietary inputs restructure microbial metabolic networks, how these metabolites modulate immune and metabolic pathways, and the implications for precision nutrition and microbiome-based therapeutics.