The gut-brain axis is a bidirectional communication network that links the enteric and central nervous systems.
This network is not only anatomical, but it extends to include endocrine, humoral, metabolic, and immune routes of communication. Although bile acids may not be synthesized locally in the brain, the majority of brain bile acids are taken up from the systemic circulation. Since the composition of the brain bile acid pool may be regulated by the action of intestinal bacteria, it is possible that bile acids function as a communication bridge between the gut microbiome and the brain. This is an area where exciting new research may uncover the role of bile acids as neuroactive molecules.
There is growing evidence between the link in susceptibility of neurodegenerative conditions such as Alzheimer’s (AD) and Parkinson’s disease (PD) with Type 2 diabetes and obesity. BA regulation is disrupted in obese and Type 2 diabetic patients, altering bile acid NR and GCPR signalling pathways as well as causing changes to the gut microbiome that alter gut-liver-brain signalling. These disruptions may well be part of the complex pathways leading to neurodegenerative conditions and bile acids are now being considered as potential markers for prodromal diagnosis of both AD and PD.
Safety, Tolerability, and Cerebrospinal Fluid Penetration of Ursodeoxycholic Acid in Patients with Amyotrophic Lateral Sclerosis.
Parry, Gareth J. MD; Rodrigues, Cecilia M.P. PhD; Aranha, Marcia M. MSc; Hilbert, Sarah J. MS; Davey, Cynthia MS; Kelkar, Praful MD; Low, Walter C. PhD; Steer, Clifford J. MD. Clinical Neuropharmacology: January 2010 – Volume 33 – Issue 1 – p 17-21. doi: 10.1097/WNF.0b013e3181c47569
Bile acid receptors and signalling crosstalk in the liver, gut and brain
Jessica M. Ferrell, John Y.L. Chiang. Liver Research 5 (2021), 105-118.
Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.
A. E. Elia, S. Lalli, M. R. Monsurrò, A. Sagnelli, A. C. Taiello, B. Reggiori, V. La Bella, G. Tedeschi, and A. Albanese. Eur. J. Neurol 2016, 23(1): 45-52
Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson’s disease.
Heather Mortiboys, Jan Aasly and Oliver Bandmann. Brain 2013: 136; 3038–3050.
Altered bile acid profile in mild cognitive impairment and Alzheimer’s disease: Relationship to neuroimaging and CSF biomarkers
Kwangsik Nho et al, Alzheimer’s & Dementia,https://doi.org/10.1016/j.jalz.2018.08.012.
Altered Bile Acid Profile Associates with Cognitive Impairment in Alzheimer’s Disease – An Emerging Role for Gut Microbiome. Siamak Mahmoudian Dehkordi et al. Alzheimers Dement
2019 January ; 15(1): 76–92. doi:10.1016/j.jalz.2018.07.217.
Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease
Peopei Li et al. Metabolites 2021, 11, 29. https://doi.org/10.3390/metabo11010029.