Gut microbiota-host lipid crosstalk in Alzheimer’s disease: implications for disease progression and therapeutics

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Abstract

Trillions of intestinal bacteria in the human body undergo dynamic transformations in response to physiological and pathological changes. Alterations in their composition and metabolites collectively contribute to the progression of Alzheimer’s disease. The role of gut microbiota in Alzheimer’s disease is diverse and complex, evidence suggests lipid metabolism may be one of the potential pathways. However, the mechanisms that gut microbiota mediate lipid metabolism in Alzheimer’s disease pathology remain unclear, necessitating further investigation for clarification. This review highlights the current understanding of how gut microbiota disrupts lipid metabolism and discusses the implications of these discoveries in guiding strategies for the prevention or treatment of Alzheimer’s disease based on existing data.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13024-024-00720-0.

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Neuroinflammation in Alzheimer's disease.

Michael T Heneka, Monica Carson, Joseph El Khoury … (2015)

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

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The Microbiota-Gut-Brain Axis

John F. Cryan, Kenneth J. O'Riordan, Caitlin S M Cowan … (2019)

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.

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ROS function in redox signaling and oxidative stress.

Michael Schieber, Navdeep S. Chandel (2014)

Oxidative stress refers to elevated intracellular levels of reactive oxygen species (ROS) that cause damage to lipids, proteins and DNA. Oxidative stress has been linked to a myriad of pathologies. However, elevated ROS also act as signaling molecules in the maintenance of physiological functions--a process termed redox biology. In this review we discuss the two faces of ROS--redox biology and oxidative stress--and their contribution to both physiological and pathological conditions. Redox biology involves a small increase in ROS levels that activates signaling pathways to initiate biological processes, while oxidative stress denotes high levels of ROS that result in damage to DNA, protein or lipids. Thus, the response to ROS displays hormesis, given that the opposite effect is observed at low levels compared with that seen at high levels. Here, we argue that redox biology, rather than oxidative stress, underlies physiological and pathological conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Author and article information

Contributors

Xiu-Qing Yao:

ORCID: http://orcid.org/0000-0002-0292-2792

dryaoxq@cqmu.edu.cn

Journal

Journal ID (nlm-ta): Mol Neurodegener

Journal ID (iso-abbrev): Mol Neurodegener

Title: Molecular Neurodegeneration

Publisher: BioMed Central (London )

ISSN (Electronic): 1750-1326

Publication date (Electronic): 16 April 2024

Publication date PMC-release: 16 April 2024

Publication date Collection: 2024

Volume: 19

Electronic Location Identifier: 35

Affiliations

[1 ]Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, ( https://ror.org/00r67fz39) Chongqing, China

[2 ]GRID grid.453222.0, ISNI 0000 0004 1757 9784, Chongqing Municipality Clinical Research Center for Geriatric Medicine, ; Chongqing, China

[3 ]Department of Rehabilitation Therapy, Chongqing Medical University, ( https://ror.org/017z00e58) Chongqing, China

Author information

Xiu-Qing Yao http://orcid.org/0000-0002-0292-2792

Article

Publisher ID: 720

DOI: 10.1186/s13024-024-00720-0

PMC ID: 11020986

PubMed ID: 38627829

SO-VID: 5a98af82-c18c-4082-8295-6eaf6010b4bd

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 12 December 2023

Date accepted : 18 March 2024

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: No.82371427

Funded by: FundRef http://dx.doi.org/10.13039/501100012669, Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission;

Award ID: CSTB2023NSCQBHX0018

Award ID: CSTB2023NSCQ-MSX0323

Award Recipient : Ya-Xi Luo

Funded by: FundRef http://dx.doi.org/10.13039/501100004374, Chongqing Medical University;

Award ID: No. kryc-lj-2105

Custom metadata

ScienceOpen disciplines: Neurosciences

Keywords: gut microbiota,lipid metabolism,alzheimer’s disease,cholesterol,scfas,lps,apoe,neuroinflammation,probiotics,lifestyle,exercise

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ScienceOpen disciplines: Neurosciences

Keywords: gut microbiota, lipid metabolism, alzheimer’s disease, cholesterol, scfas, lps, apoe, neuroinflammation, probiotics, lifestyle, exercise

Gut microbiota-host lipid crosstalk in Alzheimer’s disease: implications for disease progression and therapeutics

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Abstract

Supplementary Information

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Alternative approaches to Alzheimer's Disease

Most cited references 259

Neuroinflammation in Alzheimer's disease.

The Microbiota-Gut-Brain Axis

ROS function in redox signaling and oxidative stress.

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