Dietary Fiber Modulates the Release of Gut Bacterial Products Preventing Cognitive Decline in an Alzheimer’s Mouse Model

Aug 11, 2022Cellular and molecular neurobiology

Dietary Fiber Changes Gut Bacterial Products That May Help Prevent Memory Loss in an Alzheimer's Mouse Model

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Abstract

Fiber intake is associated with a lower risk for Alzheimer’s disease in older adults.

Intake of soluble fiber leads to increased production of beneficial short-chain fatty acids, specifically butyrate, and decreased levels of propionate.
Restoration of healthy gut microbiota through fiber intake resulted in reduced activation of astrocytes and improved cognitive function in 6-month-old male mice with Alzheimer's disease.
Antibiotic treatment in mice eliminated the neuroprotective effects of fiber intake, highlighting the role of gut bacteria.
Higher levels of butyrate were linked to better cognitive performance, while propionate was associated with increased metabolic activity in astrocytes.
A fiber-rich diet may help prevent the onset of a dysbiotic microbiome and cognitive decline in individuals at risk for Alzheimer’s disease.

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Fiber intake is associated with a lower risk for Alzheimer´s disease (AD) in older adults. Intake of plant-based diets rich in soluble fiber promotes the production of short-chain fatty acids (SCFAs: butyrate, acetate, propionate) by gut bacteria. Butyrate administration has antiinflammatory actions, but propionate promotes neuroinflammation. In AD patients, gut microbiota dysbiosis is a common feature even in the prodromal stages of the disease. It is unclear whether the neuroprotective effects of fiber intake rely on gut microbiota modifications and specific actions of SCFAs in brain cells. Here, we show that restoration of the gut microbiota dysbiosis through the intake of soluble fiber resulted in lower propionate and higher butyrate production, reduced astrocyte activation and improved cognitive function in 6-month-old male APP/PS1 mice. The neuroprotective effects were lost in antibiotic-treated mice. Moreover, propionate promoted higher glycolysis and mitochondrial respiration in astrocytes, while butyrate induced a more quiescent metabolism. Therefore, fiber intake neuroprotective action depends on the modulation of butyrate/propionate production by gut bacteria. Our data further support and provide a mechanism to explain the beneficial effects of dietary interventions rich in soluble fiber to prevent dementia and AD. Fiber intake restored the concentration of propionate and butyrate by modulating the composition of gut microbiota in male transgenic (Tg) mice with Alzheimer´s disease. Gut dysbiosis was associated with intestinal damage and high propionate levels in control diet fed-Tg mice. Fiber-rich diet restored intestinal integrity and promoted the abundance of butyrate-producing bacteria. Butyrate concentration was associated with better cognitive performance in fiber-fed Tg mice. A fiber-rich diet may prevent the development of a dysbiotic microbiome and the related cognitive dysfunction in people at risk of developing Alzheimer´s disease.

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Dietary Fiber Modulates the Release of Gut Bacterial Products Preventing Cognitive Decline in an Alzheimer’s Mouse Model

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