Ageing research reviewsSep 25, 2024

Microglia and gut bacteria: Their mixed roles in Alzheimer's disease

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

Gut microbiota dysbiosis is associated with neurological disorders including anxiety, depression, and Alzheimer's disease.

The gut-brain axis is a communication system where gut microbes influence brain functions such as mood and cognition.
Gut microbiota interacts with the brain through pathways including metabolites, the vagus nerve, and the immune system.
Dysbiosis, or imbalance in gut microbiota, may contribute to the progression of Alzheimer's disease through neuroinflammation.
Microglia, the brain's immune cells, are influenced by gut microbiota and may play a role in neurodegeneration.
Exploring how gut microbiota regulates microglia activation could lead to new therapeutic strategies for Alzheimer's disease.
Microbiota-targeted interventions like prebiotics and probiotics may provide novel approaches to mitigate neuroinflammation.

Simplified

The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration.

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Microglia and gut bacteria: Their mixed roles in Alzheimer's disease

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