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

Mar 16, 2026The Journal of nutritional biochemistry

Features of brain immune cells and their link to the gut-brain connection: implications for memory problems and treatments

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Abstract

Microglial dysfunction is significantly linked to cognitive impairment associated with aging.

The gut-brain axis may play a crucial role in regulating microglial functions.
Understanding the mechanisms of the gut-microglia-brain axis could lead to new therapeutic strategies for cognitive impairment.
Microglia communicate dynamically with the gut's ecosystem, which includes intestinal cells, microbiota, and metabolites.
Therapeutic strategies targeting the gut-brain-microglia axis may include lifestyle changes, fecal microbiota transplantation, and pharmacological treatments.

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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 (FMT), 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.

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

Abstract

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