Expert insights: the potential role of the gut microbiome-bile acid-brain axis in the development and progression of alzheimer’s disease and hepatic encephalopathy
Abstract
Recent epidemiological and molecular studies have linked the disruption of cholesterol homeostasis to increased risk for developing Alzheimer's disease (AD). Emerging evidence also suggests that brain cholesterol accumulation contributes to the progression of hepatic encephalopathy (HE) via bile acid (BA)-mediated effects on the farnesoid X receptor. In this perspective paper, we reviewed several recently published studies that suggested a role for the gut microbiota transformation of BAs as a factor in AD and HE development/progression. We hypothesize that in addition to cholesterol elimination pathways, alteration of the gut microbiota and subsequent changes in both the serum and brain BA profiles are mechanistically involved in the development of both AD and HE, and thus, are a potential target for the prevention and treatment of the two diseases. Our understanding of the microbiome-BAs-brain axis in central nervous system disease is still evolving, and critical questions regarding the emerging links among central, peripheral, and intestinal metabolic failures contributing to brain health and disease during aging have yet to be addressed.
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Changes in the GM's composition correspond to changes in blood and brain BA profiles, and specific BA ligands' physicochemical properties determine the potency of BA receptor activation.
“Changes in the GM’s composition correspond to changes in blood and brain BA profiles, which are essential because specific BA ligands’ distinct physicochemical properties determine the potency of BA receptor activation (320–323).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [321]
Microbes create neurotoxic substances such as D-lactate, homocysteine, and ammonia that can pass through the BBB and affect cognition.
“Microbes also create neurotoxic substances such as D-lactate, homocysteine, and ammonia, which can pass through the BBB and affect cognition (321).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [321]
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- Authors
- Jia, W., Rajani, C., Kaddurah‐Daouk, R., & Li, H.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- Department of Psychiatry and Behavioral Sciences, Department of Medicine, Duke Institute of Brain Sciences Duke University Durham North Carolina
- Shanghai University of Traditional Chinese Medicine (CN)
- Corresponding author
- Jia, Wei
- Li, Houkai
- ORCID
- Venue
- Medicinal Research Reviews
- Publisher
- Wiley
- Published
- 2019-12-05
- Volume
- 40
- Issue
- 4
- Pages
- 1496-1507
- ISSN
- 0198-6325 (ISSN-L)
- 1098-1128
- OpenAlex
- W2992358021
- Cited by
- 88
- References
- 57
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 22 · 2023: 16 · 2022: 14 · 2021: 6 · 2020: 6
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medicinal Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81673662, 81873059)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- gut microbiota, bile acids, Alzheimer's disease, hepatic encephalopathy, cholesterol homeostasis, farnesoid X receptor, bile acid metabolism, aging, neurodegeneration
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Bile Acids and Salts, Brain, Hepatic Encephalopathy, Humans, Models, Biological, Disease Progression
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