Impact of gastrointestinal dysbiosis on tryptophan metabolism and neurological cancer progression.

Gastrointestinal dysbiosis, characterized as a pathological imbalance in gut microbial composition and function, has been increasingly implicated in the aetiology of various systemic diseases, including neurological malignancies. This review illustrates the mechanistic link between dysbiosis and aberrant tryptophan metabolism, highlighting their convergence in the pathogenesis of neuro-oncological disorders. Tryptophan, a critical precursor for bioactive metabolites such as serotonin and kynurenine, undergoes extensive microbial and host-mediated catabolism. Dysbiosis disrupts these metabolic pathways, leading to altered neurotransmitter biosynthesis, heightened oxidative stress, dysregulated neuroinflammation, and perturbations in immune surveillance-all of which contribute to tumour initiation and progression within the central nervous system (CNS). Furthermore, dysregulated kynurenine pathway activation fosters an immunosuppressive tumour microenvironment (TME) through aryl hydrocarbon receptor (AhR) signalling, facilitating immune evasion and malignancy. The review systematically explores the molecular and cellular mechanisms by which gut microbial imbalances modulate tryptophan catabolism and its downstream effects on neuroimmune dynamics, oncogenic signalling cascades, and blood-brain barrier integrity. Emphasis is placed on emerging therapeutic strategies targeting the microbiota-tryptophan axis, including microbiome modulation, enzymatic inhibitors, and metabolic reprogramming approaches. By elucidating the crosstalk between gastrointestinal dysbiosis and tryptophan metabolism, we identify molecular entry points for intervention in neuro-oncology. Progress will require coordinated work across microbiology, immunology, oncology, and neurobiology to develop microbiome-targeted strategies for neurological malignancies.