Bile acids in Alzheimer’s disease: a double-edged sword in gut–liver–brain signaling and neurodegeneration
9 affiliations
- 1Department of Internal Medicine, College of Medicine, Jouf University, Sakaka, 72345, Aljouf, Saudi Arabia
- 2Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
- 3Department of Internal Medicine, College of Medicine, Jouf University, Sakaka, Saudi Arabia
- 4Department of Clinical Pharmacology and Medicine, Jabir Ibn Hayyan Medical University, Al-Ameer Qu./Najaf, P.O. Box (13), Kufa, Iraq
- 5European Academy of Sciences and Arts, Vienna, Austria
- 6University Centre for Research & Development, Chandigarh University, Chandigarh-Ludhiana Highway, Mohali, Punjab, India
- 7Faculty of Medicine, Health Sciences School, University of Ioannina, University Campus, 45110, Ioannina, Greece. [email protected]
- 8Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo-Suez Road, Badr City, 11829, Cairo, Egypt. [email protected]
- 9Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt. [email protected]
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau pathology, synaptic dysfunction, neuroinflammation, and metabolic impairment. Increasing evidence suggests that bile acids, traditionally recognized for their roles in lipid digestion and hepatic metabolism, act as endocrine signaling molecules that influence central nervous system (CNS) homeostasis. Through enterohepatic circulation and microbiota-dependent biotransformation, bile acid composition is dynamically regulated and can modulate peripheral metabolic and immune pathways with downstream effects on the brain. Notably, bile acid signaling via key receptors such as the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 and G-protein-coupled bile acid receptor 1 (TGR5/GPBAR1) has emerged as a mechanistic bridge linking liver-gut physiology to neuroinflammatory and neurodegenerative processes. Altered bile acid profiles have been reported in AD and mild cognitive impairment, with accumulating findings suggesting that hydrophobic secondary bile acids may contribute to blood-brain barrier (BBB) disruption and neurotoxicity. In contrast, hydrophilic bile acids may exert neuroprotective and anti-inflammatory effects. In addition, bile acids drive the release of gut hormones such as glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 19 (FGF19), highlighting indirect neurometabolic pathways relevant to cognition and neurodegeneration. This narrative review synthesizes current biochemical, experimental, and clinical evidence supporting a role for bile acid signaling in AD pathogenesis and progression. We discuss receptor-mediated pathways, microbiota-bile acid interactions, neuroimmune modulation, and translational perspectives, proposing that bile acid-based biomarkers and therapeutic strategies targeting FXR/TGR5 signaling may represent promising avenues for future AD intervention.
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BibTeX
@article{basri2026bile,
title = {{Bile acids in Alzheimer’s disease: a double-edged sword in gut–liver–brain signaling and neurodegeneration}},
author = {Rehana Basri and Hayder M. Al‐kuraishy and Mubarak Alruwaili and Ali Ismail Al-Gareeb and Ali K. Albuhadily and Athanasios T. Alexiou and Marios Papadakis and Safaa A. Faheem and Gaber El‐Saber Batiha},
journal = {Naunyn-Schmiedeberg s Archives of Pharmacology},
year = {2026},
month = jun,
doi = {10.1007/s00210-026-05516-1},
url = {https://doi.org/10.1007/s00210-026-05516-1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Bile acids in Alzheimer’s disease: a double-edged sword in gut–liver–brain signaling and neurodegeneration
AU - Rehana Basri
AU - Hayder M. Al‐kuraishy
AU - Mubarak Alruwaili
AU - Ali Ismail Al-Gareeb
AU - Ali K. Albuhadily
AU - Athanasios T. Alexiou
AU - Marios Papadakis
AU - Safaa A. Faheem
AU - Gaber El‐Saber Batiha
PY - 2026
DA - 2026/06/09
JO - Naunyn-Schmiedeberg s Archives of Pharmacology
DO - 10.1007/s00210-026-05516-1
UR - https://doi.org/10.1007/s00210-026-05516-1
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau pathology, synaptic dysfunction, neuroinflammation, and metabolic impairment. Increasing evidence suggests that bile acids, traditionally recognized for their roles in lipid digestion and hepatic metabolism, act as endocrine signaling molecules that influence central nervous system (CNS) homeostasis. Through enterohepatic circulation and microbiota-dependent biotransformation, bile acid composition is dynamically regulated and can modulate peripheral metabolic and immune pathways with downstream effects on the brain. Notably, bile acid signaling via key receptors such as the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 and G-protein-coupled bile acid receptor 1 (TGR5/GPBAR1) has emerged as a mechanistic bridge linking liver-gut physiology to neuroinflammatory and neurodegenerative processes. Altered bile acid profiles have been reported in AD and mild cognitive impairment, with accumulating findings suggesting that hydrophobic secondary bile acids may contribute to blood-brain barrier (BBB) disruption and neurotoxicity. In contrast, hydrophilic bile acids may exert neuroprotective and anti-inflammatory effects. In addition, bile acids drive the release of gut hormones such as glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 19 (FGF19), highlighting indirect neurometabolic pathways relevant to cognition and neurodegeneration. This narrative review synthesizes current biochemical, experimental, and clinical evidence supporting a role for bile acid signaling in AD pathogenesis and progression. We discuss receptor-mediated pathways, microbiota-bile acid interactions, neuroimmune modulation, and translational perspectives, proposing that bile acid-based biomarkers and therapeutic strategies targeting FXR/TGR5 signaling may represent promising avenues for future AD intervention.
SN - 0028-1298
SN - 0340-5249
SN - 1432-1912
ER -