Gut-brain axis and neuroinflammation: mechanisms, interactions, and recent advances

In recent years, the gut-brain axis (GBA), an essential bidirectional communication network linking the gut microbiota and central nervous system (CNS) functions, has attracted increasing research interest at the intersection of microbiology and neuroscience. This pathway is involved in multiple physiological and pathological conditions including emotion regulation, cognitive function and neuroinflammation through neural, immune, endocrine and metabolic mechanisms. Based on human observational studies, animal models and in-vitro experiments, there is evidence that gut dysbiosis is also related to intestinal barrier dysfunction, altered microbial metabolites and neuroinflammatory response. Evidence is largely preclinical or mechanistic, whereas human data are currently more limited for causal relationships. Signal transfer involves three components: the vagus nerve, immune mediators and the blood-brain barrier (BBB). Microbiota-targeted interventions have been shown to yield proportionally consistent mechanistic benefits in preclinical models, whereas human intervention studies remain heterogeneous and show mixed positive and null outcomes—among these microbiota-targeted interventions there are probiotics, fecal microbiota transplantation (FMT), and dietary modulation. Hence, their clinical utility for neuroinflammatory disorders is only preliminary and needs to be validated in bigger, placebo-controlled trials. Although the present studies are confronted with difficulties, which include unclear causality and great individual variations among subjects, GBA research has been gradually moving into a novel stage from the perspective of mechanistic explanation and precision intervention along with advancements in multi-omics technologies and artificial intelligence, generating new theoretical hypotheses and translational significance for the prevention or treatment of neuroinflammatory diseases.