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Gut–Brain Axis and Bile Acid Signaling: Linking Microbial Metabolism to Brain Function and Metabolic Regulation

Bojan Stanimirov, Maja Đanić, Nebojša Pavlović, Dragana Zaklan, Slavica Lazarević, Momir Mikov, Karmen Stankov

2025International Journal of Molecular Sciences14 citationsDOIOpen Access PDF

Abstract

The gut-brain axis is a bidirectional communication network in which gut microbiota and their metabolites influence central nervous system (CNS) function. Among these metabolites, bile acids have emerged as key signaling molecules that modulate metabolic and neuroendocrine pathways. Microbiota-mediated modifications of bile acid composition affect receptors such as farnesoid X receptor (FXR)and Takeda G protein-coupled receptor 5 (TGR5), thereby influencing neuronal activity, appetite control, glucose metabolism, and energy balance. Emerging evidence indicates that bile acids act both directly on the CNS and indirectly via endocrine and immune mediators, linking microbial metabolism to brain function. By integrating microbiological, metabolic, and neuroendocrine perspectives, bile acids can be viewed as critical messengers in the communication between the gut microbiota and the CNS. The purpose of this review is thus to synthesize current mechanisms underlying these interactions and highlight their therapeutic potential in metabolic and neurodegenerative disorders.

Topics & Concepts

Farnesoid X receptorBile acidG protein-coupled bile acid receptorBiologyMetabolic pathwayGut floraBiochemistryMetabolismReceptorEndocrine systemGut–brain axisCentral nervous systemImmune systemMicrobial metabolismSignal transductionSecond messenger systemLipid metabolismEnteroendocrine cellFunction (biology)ChemistryCarbohydrate metabolismAppetiteCell signalingNuclear receptorNeuroscienceEndocrinologyCell biologyNeurotransmitter AgentsNervous systemInternal medicineGut microbiota and healthDrug Transport and Resistance MechanismsGastrointestinal motility and disorders
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