Guild-Level Response of the Gut Microbiome to Nutritional Signals: Advancing Precision Nutrition for Metabolic Health.

The gut microbiome functions as a hidden organ, providing essential ecosystem services to sustain human health. By identifying stably connected bacteria, we reveal two competing guilds (TCG) as the resilient core of the microbiome: the health-promoting foundation guild (FG) and the proinflammatory pathobiont guild (PG). FG members produce short-chain fatty acids (SCFAs), enhancing gut barrier integrity and systemic resilience, while PG members disrupt metabolism through endotoxins, indoles, and hydrogen sulfide. Together, the FG and PG mediate ∼85% of ecological interactions in a dynamic, seesaw-like relationship. As evolved nutrient sensors for coping with feast-famine cycles, these guilds align host metabolism with dietary patterns. Fiber-rich diets bolster FG activity, maintaining microbial balance and metabolic health, whereas fiber-deficient diets in modern-day society favor chronic PG dominance, driving inflammation and disease. Synthesizing clinical and experimental evidence, this review positions the TCG model as a transformative framework for precision nutrition, guiding strategies to restore microbial balance and address metabolic disorders.