Exercise modulation of gut microbiota in Alzheimer’s disease: pathophysiological mechanisms and therapeutic perspectives

Nov 24, 2025Frontiers in aging neuroscience

How Exercise Affects Gut Health in Alzheimer's Disease

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Abstract

Alzheimer's disease may be influenced by the gut microbiota, with exercise playing a significant role in modulating its diversity.

The gut microbiota is linked to the regulation of the central nervous system, impacting behavior and cognitive functions in Alzheimer's disease.
Physical exercise may slow Alzheimer's disease progression by positively affecting the gut microbiota's composition and diversity.
Exercise could enhance cognitive function by altering the synthesis and metabolism of neuroactive substances like glutamate and aspartate.
Modulation of gut microbiota through exercise may reduce neuroinflammation, amyloid-β deposition, and tau phosphorylation.
Exercise is associated with the regulation of metabolites such as short-chain fatty acids, which help maintain blood-brain barrier integrity.

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As global life expectancy increases, Alzheimer's disease (AD) has become a major public health concern. The gut microbiota plays a pivotal role in regulating the central nervous system, influencing both behavior and cognitive functions in AD through direct and indirect mechanisms. Physical exercise has been shown to positively modulate the diversity and composition of the gut microbiota, emerging as a significant factor in slowing AD progression. A growing body of research highlights the dynamic interactions between exercise, gut microbiota, and AD, revealing that exercise can alter the synthesis and metabolism of key neuroactive substances, such as glutamate and aspartate, thereby enhancing cognitive function. Moreover, exercise influences peripheral and central immune responses via microbiota modulation, reducing neuroinflammation, amyloid-β (Aβ) deposition, and tau phosphorylation. Exercise also regulates gut microbiota-derived metabolites, including short-chain fatty acids (SCFAs), which are crucial for alleviating neuroinflammation and maintaining the integrity of the blood-brain barrier (BBB). This review synthesizes recent advances in the molecular mechanisms underpinning the exercise-microbiota-AD axis, offering new therapeutic perspectives for AD.

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Exercise modulation of gut microbiota in Alzheimer’s disease: pathophysiological mechanisms and therapeutic perspectives

Abstract

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