The Gut Microbiota–Tryptophan–Brain Axis in Autism Spectrum Disorder: A New Frontier for Probiotic Intervention

Tryptophan (Trp) metabolism is involved in regulating various physiological and pathological processes, including neurological function, immune response, and gut homeostasis. This article focuses on autism spectrum disorder (ASD) and explores its relationship with abnormalities in the gut microbiota-Trp-brain axis. Studies have shown that ASD patients exhibit Trp metabolism disorders, with gut microbiota dysbiosis inducing systemic inflammation, activating indoleamine 2,3-dioxygenase 1 (IDO1), and promoting increased Trp entry into the kynurenine pathway (KP). This leads to a series of pathological changes, including the production of neurotoxic substances, serotonin system disorders, and impaired intestinal barrier function, which in turn exacerbate ASD symptoms through the gut-brain axis. Furthermore, based on preclinical and clinical studies, we have summarized that specific probiotic strains (such as <i>Lactobacillus</i> and <i>Bifidobacterium</i>) can alleviate the clinical manifestations of ASD by regulating the gut microbiota-Trp metabolic axis, improving immune responses, and enhancing intestinal barrier function. We emphasize that current probiotic interventions still face challenges such as insufficient long-term safety assessments and unclear molecular mechanisms. Future research should combine multi-omics technologies and multi-modal approaches to promote the development of personalized and precise intervention strategies. In summary, this review highlights the crucial role of tryptophan metabolism in ASD and the potential of probiotics as a novel adjunctive therapy targeting this metabolic pathway.