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The gut–brain axis is a central regulatory network linking dietary habits, metabolic homeostasis, and brain function through bidirectional communication among the intestine, microbiota, and central nervous system. Acting as a key mediator, the gut microbiota translates environmental and nutritional factors into systemic outcomes that influence both health and disease. Within this context, serine and glycine metabolism emerges as a critical yet underexplored hub connecting microbial activity with brain regulation. Changes in gut microbial composition can profoundly affect host one-carbon metabolism and amino acid availability, shaping systemic physiology and neural processes. In this review, we outline a biochemical framework in which gut microbiota alterations influence brain and liver serine/glycine (ser/gly) metabolism, driving the hepatic production of secondary metabolites, including taurine-conjugated bile acids. We delineate how gut–brain axis pathways orchestrate systemic and neural functions, and highlight glioblastoma (GBM) as a pathological context where hijacked serine–glycine metabolism fuels tumor growth, stemness, and therapy resistance. By focusing on the interplay between gut microbiota, ser/gly metabolism, and brain tumor biology, this review offers a cohesive perspective on translational interventions. Glycine-centered pathways emerge as promising targets to modulate the gut–brain–tumor axis, opening new avenues to influence GBM progression and enhance therapeutic strategies.
Mangano et al. (Mon,) studied this question.