GUT DYSBIOSIS-INDUCED MODULATION OF MICROGLIAL MORPHOLOGY AND FUNCTION

Microglia are the resident immune cells of the central nervous system (CNS). During both development and adulthood, they serve as essential regulators of neuronal activity, synaptic plasticity, and immune surveillance, thereby maintaining brain homeostasis. Microglia are highly sensitive to local and systemic inflammatory signals and coordinate immune responses through the production of cytokines and chemokines. Importantly, microglial functional states are closely linked to their morphology, reflecting their ability to adapt to diverse physiological and pathological conditions.
Through the gut-brain axis – a bidirectional communication network linking the gastrointestinal tract and the CNS via neural, endocrine, immunological, and metabolic pathways – disturbances of the gut microbiome can trigger neuroinflammatory signaling. This process is mediated by altered profiles of bacterial metabolites, including short-chain fatty acids, tryptophan derivatives, and secondary bile acids, which may cross a compromised intestinal epithelium and blood-brain barrier, thereby promoting excessive microglial activation, aberrant synaptic pruning, and potential neuronal loss.
To investigate the impact of gut dysbiosis during development and adulthood on microglial morphology and function, we employed mouse models subjected to broad-spectrum antibiotic treatment at distinct developmental stages. Our results demonstrate that antibiotic-induced dysbiosis increases hippocampal microglial and astrocyte reactivity, irrespective of the timing of microbiome disruption. Enhanced presynaptic pruning by activated microglial cells was observed following dysbiosis in adulthood and during pregnancy, whereas early-life dysbiosis selectively increased postsynaptic pruning in young mice.
Collectively, these findings indicate that dysbiosis-driven glial activation plays a significant role in promoting neuroinflammation and cognitive impairment.