The characteristic of microglia and gut-microglia-brain axis: Implications for cognitive impairment and therapeutic strategies

Aging-associated cognitive impairment (CI) is a core feature of neurodegenerative diseases, profoundly affecting the daily life of patients. Microglial dysfunction significantly contributes to the pathogenesis of CI. The gut-brain axis serves as a pivotal regulator of microglial functions, making it a promising target for halting the development and progression of CI. Deciphering the mechanisms of the gut-microglia-brain (GMB) axis may help devise potential therapeutic strategies to mitigate CI. This review first describes the recent progress in the development and functions of microglia, including the latest advancements in this field. Subsequently, the dynamic and complex communications between microglia and the gut microecosystem, including intestinal cells, gut microbiota, gut microbiota-derived metabolites, gut-derived exosomes, and intestinal bacteriophages, were discussed. Finally, current therapeutic strategies targeting the GMB axis to mitigate CI, such as lifestyle interventions, fecal microbiota transplantation, phages, exosomes, and pharmacological therapies, were summarized. The understanding of GMB axis-mediated cognitive function may pave the way for the identification of novel therapeutic strategies to mitigate aging-associated CI.