Tryptophan-steroid interactions in the brain–gut–microbiome axis: Neuroactive metabolites as biomarkers and therapeutic targets

Abstract

Tryptophan metabolism plays a central role in connecting the brain, gut, and microbiome. Microbial and host-derived metabolites influence intestinal integrity, immune activity, and neural signaling, while steroid and neurosteroid hormones shape these pathways through receptor-mediated effects. Disturbance of this metabolic network contributes to neuropsychiatric, metabolic, and inflammatory disorders. This review integrates evidence from preclinical and clinical studies to explain how tryptophan catabolism interacts with microbial activity and steroid regulation. Key neuroactive metabolites involved in these interactions are discussed, along with their potential value as biomarkers and therapeutic targets. Current limitations of animal models and the need for human-focused, multi-omics approaches are also highlighted. Together, these insights outline how coordinated tryptophan–steroid–microbiome signalling influences health and disease and identify opportunities for more precise diagnostic and therapeutic strategies.