The human gut microbiota produces numerous metabolites that accumulate in the bloodstream, influencing host physiology and potentially disease. However, the metabolic pathways responsible for these metabolites are largely unknown. This study characterizes a metabolic pathway in the gut bacterium *Clostridium sporogenes* that generates aromatic amino acid metabolites. The pathway produces twelve compounds, nine of which are known to accumulate in host serum. The pathway involves reductive metabolism of tryptophan, phenylalanine, and tyrosine, with branching and alternative reductases for specific intermediates. Genetic manipulation of *C. sporogenes* using the ClosTron system modulates serum levels of these metabolites in gnotobiotic mice, affecting intestinal permeability and systemic immunity. The findings suggest that engineering gut bacteria could be a strategy to control the molecular output of the gut community, potentially impacting host health.The human gut microbiota produces numerous metabolites that accumulate in the bloodstream, influencing host physiology and potentially disease. However, the metabolic pathways responsible for these metabolites are largely unknown. This study characterizes a metabolic pathway in the gut bacterium *Clostridium sporogenes* that generates aromatic amino acid metabolites. The pathway produces twelve compounds, nine of which are known to accumulate in host serum. The pathway involves reductive metabolism of tryptophan, phenylalanine, and tyrosine, with branching and alternative reductases for specific intermediates. Genetic manipulation of *C. sporogenes* using the ClosTron system modulates serum levels of these metabolites in gnotobiotic mice, affecting intestinal permeability and systemic immunity. The findings suggest that engineering gut bacteria could be a strategy to control the molecular output of the gut community, potentially impacting host health.