Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus
Open accessAbstract
Although the potential contribution of the human gastrointestinal (GI) tract microbiome to human health, aging and disease is becoming increasingly acknowledged, the molecular mechanics and signaling pathways of just how this is accomplished is not well understood. Major bacterial species of the GI tract, such as the abundant Gram-negative bacilli Bacteroides fragilis (B. fragilis) and Escherichia coli (E. coli), secrete a remarkably complex array of pro-inflammatory neurotoxins which, when released from the confines of the healthy GI tract, are pathogenic and highly detrimental to the homeostatic function of neurons in the central nervous system (CNS). For the first time here we report the presence of bacterial lipopolysaccharide (LPS) in brain lysates from the hippocampus and superior temporal lobe neocortex of Alzheimer’s disease (AD) brains. Mean LPS levels varied from 2-fold increases in the neocortex to 3-fold increases in the hippocampus, AD over age-matched controls, however some samples from advanced AD hippocampal cases exhibited up to a 26-fold increase in LPS over age-matched controls. This ‘Perspectives’ paper will further highlight some very recent research on GI tract microbiome signaling to the human CNS, and will update current findings that implicate GI tract microbiome-derived LPS as an important internal contributor to inflammatory degeneration in the CNS.
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Blood and brain endotoxin levels are elevated in Alzheimer's disease.
“Blood and brain endotoxin levels are elevated in Alzheimer’s disease”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [78]
Brain endotoxin levels are increased two- or threefold in Alzheimer's disease patients, and endotoxin is also found in AD amyloid plaques.
“Brain endotoxin levels are increased two- or threefold in AD patients [78, 79], and endotoxin is also found in AD amyloid plaques [79].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [78]
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- Authors
- Zhao, Y., Jaber, V., & Lukiw, W. J.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- Lukiw, Walter J.
- Venue
- Frontiers in Cellular and Infection Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2017-07-11
- Volume
- 7
- Pages
- 318-318
- ISSN
- 2235-2988 (ISSN-L)
- PMC
- PMC5504724
- OpenAlex
- W2735753950
- Cited by
- 379
- References
- 88
- Citations by year
- 2026: 23 · 2025: 35 · 2024: 45 · 2023: 42 · 2022: 61 · 2021: 69 · 2020: 42 · 2019: 36 · 2018: 20 · 2017: 6
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular and Infection Microbiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- NIH (NEI EY006311, NIA AG18031, NIA AG038834)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, gut microbiota, lipopolysaccharide, hippocampus, neocortex, Bacteroides fragilis, Escherichia coli, neuroinflammation, neurotoxins, gut-brain axis
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Bacteroides fragilis, Escherichia coli, Hippocampus, Humans, Lipopolysaccharides, Neocortex, Gastrointestinal Tract
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