This study investigates the relationship between the gut microbiome and inflammatory cytokine responses in healthy individuals, aiming to understand how differences in gut microbial communities contribute to inter-individual variation in cytokine responses to microbial stimulations. The researchers analyzed multi-omic data, including microbial and cytokine profiles from approximately 500 healthy individuals, and found that the gut microbiome significantly influences cytokine responses, particularly TNFα and IFNγ. They identified specific bacterial species and genera that are associated with cytokine production and observed three types of interaction patterns: stimulus-specific, cytokine-specific, and cytokine- and stimulus-specific. The study also validated two predicted host-microbial interactions, showing that TNFα and IFNγ production are associated with specific microbial metabolic pathways, such as palmitoleic acid metabolism and tryptophan degradation to tryptophol. These findings provide insights into the complex interplay between the gut microbiome and immune responses, highlighting the importance of microbial metabolites in modulating cytokine production.This study investigates the relationship between the gut microbiome and inflammatory cytokine responses in healthy individuals, aiming to understand how differences in gut microbial communities contribute to inter-individual variation in cytokine responses to microbial stimulations. The researchers analyzed multi-omic data, including microbial and cytokine profiles from approximately 500 healthy individuals, and found that the gut microbiome significantly influences cytokine responses, particularly TNFα and IFNγ. They identified specific bacterial species and genera that are associated with cytokine production and observed three types of interaction patterns: stimulus-specific, cytokine-specific, and cytokine- and stimulus-specific. The study also validated two predicted host-microbial interactions, showing that TNFα and IFNγ production are associated with specific microbial metabolic pathways, such as palmitoleic acid metabolism and tryptophan degradation to tryptophol. These findings provide insights into the complex interplay between the gut microbiome and immune responses, highlighting the importance of microbial metabolites in modulating cytokine production.