Gut microbiota and its metabolites in Alzheimer’s disease: from pathogenesis to treatment

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Abstract

Introduction

An increasing number of studies have demonstrated that altered microbial diversity and function (such as metabolites), or ecological disorders, regulate bowel–brain axis involvement in the pathophysiologic processes in Alzheimer’s disease (AD). The dysregulation of microbes and their metabolites can be a double-edged sword in AD, presenting the possibility of microbiome-based treatment options. This review describes the link between ecological imbalances and AD, the interactions between AD treatment modalities and the microbiota, and the potential of interventions such as prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and dietary interventions as complementary therapeutic strategies targeting AD pathogenesis and progression.

Survey methodology

Articles from PubMed and china.com on intestinal flora and AD were summarized to analyze the data and conclusions carefully to ensure the comprehensiveness, completeness, and accuracy of this review.

Conclusions

Regulating the gut flora ecological balance upregulates neurotrophic factor expression, regulates the microbiota-gut-brain (MGB) axis, and suppresses the inflammatory responses. Based on emerging research, this review explored novel directions for future AD research and clinical interventions, injecting new vitality into microbiota research development.

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Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Valery L. Feigin, Emma Nichols, Tahiya Alam … (2020)

Summary Background Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding Bill & Melinda Gates Foundation.

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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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Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism

Douglas J. Morrison, Tom Preston (2016)

ABSTRACT The formation of SCFA is the result of a complex interplay between diet and the gut microbiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gut microbiota and the host. SCFA represent the major carbon flux from the diet through the gut microbiota to the host and evidence is emerging for a regulatory role of SCFA in local, intermediary and peripheral metabolism. However, a lack of well-designed and controlled human studies has hampered our understanding of the significance of SCFA in human metabolic health. This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role of SCFA on different metabolic systems.

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Author and article information

Contributors

Zetao Chen

Journal

Journal ID (nlm-ta): PeerJ

Journal ID (iso-abbrev): PeerJ

Journal ID (publisher-id): peerj

Title: PeerJ

Publisher: PeerJ Inc. (San Diego, USA )

ISSN (Electronic): 2167-8359

Publication date (Electronic): 13 March 2024

Publication date Collection: 2024

Volume: 12

Electronic Location Identifier: e17061

Affiliations

[1 ]Subject of Integrated Chinese and Western Medicine, Shandong University of Traditional Chinese Medicine , Jinan, Shandong, China

[2 ]Subject of Traditional Chinese Medicine, Shandong University Of Traditional Chinese Medicine , Jinan, Shandong, China

[3 ]College of Traditional Chinese Medicine, Hebei University , Baoding, Hebei, China

[4 ]Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine , Jinan, Shandong, China

Article

Publisher ID: 17061

DOI: 10.7717/peerj.17061

PMC ID: 10944166

PubMed ID: 38495755

SO-VID: cb5e639d-81cc-4642-ace4-801d3e645f3b

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

History

Date received : 22 December 2023

Date accepted : 15 February 2024

Funding

Funded by: The National Natural Science Foundation Youth Foundation of China

Award ID: No. 81303028

Funded by: Shandong Geriatrics Association Science and Technology Project

Award ID: No. LKJGG2021Y041

Funded by: Shandong Geriatrics Association Science and Technology Project

Award ID: No. LKJGG2021W116

This work was supported by the National Natural Science Foundation Youth Foundation of China (No. 81303028), the Shandong Geriatrics Association Science and Technology Project (No. LKJGG2021Y041), and the Shandong Geriatrics Association Science and Technology Project (No. LKJGG2021W116). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Gut microbiota and its metabolites in Alzheimer’s disease: from pathogenesis to treatment

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Abstract

Introduction

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Conclusions

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Karger: Neurology and Neuroscience

Most cited references 150

Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

The Microbiota-Gut-Brain Axis

Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism

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