Gut-derived metabolites function as critical signaling intermediaries that translate environmental cues into central nervous system (CNS) responses, playing an indispensable role in the pathogenesis and trajectory of neuroimmune inflammatory disorders. Key metabolites, including short-chain fatty acids (SCFAs) and bile acids, either traverse the blood-brain barrier directly or orchestrate immune modulation peripherally, thereby fine-tuning the dynamic crosstalk between systemic immunity and neural homeostasis.
SCFAs exert potent anti-inflammatory effects by promoting regulatory T-cell (Treg) differentiation through activation of G protein-coupled receptors (GPCRs) on immune cells and inhibition of histone deacetylases (HDACs). Within the CNS, they further confer neuroprotection by suppressing the pro-inflammatory activation of microglia and astrocytes.
In contrast, bile acids display a context-dependent, “double-edged sword” effect: while certain subtypes activate the anti-inflammatory TGR5 receptor, neurotoxic metabolites (e.g., taurolithocholic acid) can accumulate and directly provoke pro-inflammatory polarization of microglia, thereby fueling neuroinflammation.
Frontiers in Immunology published a clinical update in Infectious Disease on 02 Jun 2026.
The item focuses on Mechanisms and therapeutic advances of gut metabolites in the regulation of neuroimmune inflammatory diseases.
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