The impact of nutritional and exercise interventions on Alzheimer’s disease pathophysiology via modulation of the microbiota-gut-brain-axis

Oct 21, 2025Nutritional neuroscience

How Diet and Exercise May Affect Alzheimer's Disease by Changing the Gut-Brain Connection

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Abstract

Interventions led to significantly improved measures of cognitive function and reduced beta-amyloid plaque aggregation in rodent models.

Nutrition, exercise, and combined lifestyle interventions were associated with beneficial changes in cognitive function and neuroinflammation.
Alterations in gut microbial composition and bacterial metabolites were observed as a result of these interventions.
These lifestyle changes may influence synaptic plasticity and blood-brain barrier integrity, potentially impacting Alzheimer's disease progression.
The findings suggest a link between the microbiota-gut-brain axis and neurodegenerative conditions like Alzheimer's disease.

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OBJECTIVES: The gut microbiota refers to a complex and essential ecosystem comprised of over 100 trillion microbial cells. The microbiota, the gut, and the brain together create an association which is vital to host health, 'the microbiota-gut-brain axis,' and coordinate the gut with the central nervous system to modify cognitive function and brain immune homeostasis. This bidirectional talk between the gut and brain operates via the immune system, the enteric nervous system, as well as various microbial metabolites, including short-chain fatty acids (SCFAs), and proteins. Recent studies have suggested an important role for the gut microbiota in many neurodegenerative diseases, including Alzheimer's disease (AD). The neuropathological hallmarks of Alzheimer's disease consist of beta-amyloid plaques, tau hyperphosphorylation, neurofibrillary tangles, glial activation, and neuronal and synaptic loss.

METHODS: In this narrative review, we summarize the major outcomes of recent studies investigating the impacts of nutrition interventions, exercise interventions, and combined lifestyle (exercise + nutrition) interventions on Alzheimer's pathophysiology in animal models.

RESULTS: Collectively, the interventions reviewed here all achieved significantly improved measures of cognitive function, beta-amyloid plaque aggregation and glial responses in the rodents, and led to the alterations in gut microbial composition, changes in bacterial metabolites, neuroinflammation, synaptic plasticity, and blood-brain barrier integrity.

DISCUSSION: Understanding the role of the microbiota-gut-brain axis pathways during lifestyle interventions discussed in this study may assist in providing novel targets to delay the onset and progression of AD or alleviate extant AD pathophysiology, and may promote a reduction in the prevalence of AD.

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The impact of nutritional and exercise interventions on Alzheimer’s disease pathophysiology via modulation of the microbiota-gut-brain-axis

Abstract

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