Abstract
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.
Graphical Abstract
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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Data Availability
All sequencing data generated in this study are deposited at NCBI sequence read archive repository as bioproject PRJNA718599 (https://www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA718599), and are publicly available as of the date of publications. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
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Acknowledgements
Thanks to Alberto Piña-Escobedo for assistance with semiconductor DNA sequencing, to Rodrigo García-Gutierrez with reagents, Viridana Rosas-Ocegueda administrative assistance, and Gustavo Bustillo Armendáriz (Bustar Foods) for fructans donation.
Funding
D.C.Z. and T.S. received a Ph.D. scholarship CONACyT-Mexico. CONACYT Grant No. A1S-42600 and CINVESTAV Grant No.128 for C.P.C, CONACYT Grant No. 163235 INFR-2011-01 for J.G.M. CECs is funded by the Chilean Government through the Centers of Excellence Basal Financing Program of ANID.
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Conceptualization, C.P.C. and J.G.M.; Methodology, D.C.Z., T.S., V.S.V, M.I.F., P.T.A., A.S.O., I.R.; Investigation, M.T.R., M.S.S., L.G.N., N.T., and A.R.T; Writing – Original Draft, C.P.C and D.C.Z; Writing – Review & Editing, C.P.C and J.G.M.; Funding Acquisition, C.P.C. and J.G.M.; Resources, C.P.C., J.G.M., N.T., A.T.; Supervision, C.P.C and J.G.M.
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Cuervo-Zanatta, D., Syeda, T., Sánchez-Valle, V. et al. Dietary Fiber Modulates the Release of Gut Bacterial Products Preventing Cognitive Decline in an Alzheimer’s Mouse Model. Cell Mol Neurobiol 43, 1595–1618 (2023). https://doi.org/10.1007/s10571-022-01268-7
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DOI: https://doi.org/10.1007/s10571-022-01268-7