The clinical and mechanistic roles of bile acids in depression, Alzheimer's disease, and stroke

Abstract

The burden of neurological and neuropsychiatric disorders continues to grow with significant impacts on human health and social economy worldwide. Increasing clinical and preclinical evidences have implicated that bile acids (BAs) are involved in the onset and progression of neurological and neuropsychiatric diseases. Here, we summarized recent studies of BAs in three types of highly prevalent brain disorders, depression, Alzheimer's disease, and stroke. The shared and specific BA profiles were explored and potential markers associated with disease development and progression were summarized. The mechanistic roles of BAs were reviewed with focuses on inflammation, gut-brain-microbiota axis, cellular apoptosis. We also discussed future perspectives for the prevention and treatment of neurological and neuropsychiatric disorders by targeting BAs and related molecules and gut microbiota. Our understanding of BAs and their roles in brain disorders is still evolving. A large number of questions still need to be addressed on the emerging crosstalk among central, peripheral, intestine, and their contribution to brain and mental health.

Identifying Hair Biomarker Candidates for Alzheimer’s Disease Using Three High Resolution Mass Spectrometry-Based Untargeted Metabolomics Strategies

“…The 7alpha-dehydroxylation of cholic acids appears to be carried out by a pathway in gut microbiota, and they enter the brain through bile acid transporter from the peripheral circulation. 54,55 Recently, it was indicated that the serum elevated levels of a bacterially produced bile acid, deoxycholic acid, in patients with AD compared to cognitively healthy controls, suggesting that the secondary bile acid produced by gut microbiota might influence the pathogenesis of AD. 56 Our observations were that the levels of 7a,12adihydroxy-3-oxo-4-cholenoic acid, which was metabolized by gut microbiota, were significantly low in AD patients compared to controls.…”

Liver’s influence on the brain through the action of bile acids

“…Bile acids (BA) can independently modulate the function and effects of the brain ( Nunes et al, 2012 ; Bazzari et al, 2019 ), gut ( Zhou et al, 2020 ), and gut microbiome ( van Best et al, 2020 ), while each of these layers of the brain-gut-microbiome axis may contribute to the overall outcome in the brain ( Garcia et al, 2022 ; Lirong et al, 2022 ; MahmoudianDehkordi et al, 2022 ; Qu et al, 2022 ). Hence, there is a large spectrum and significant complexity in how BA and the intestinal flora affect brain function.…”

Determining the emotional regulation function of Bifidobacterium breve: the role of gut metabolite regulation over colonization capability

“…Increasing clinical and preclinical evidence supports the association between BAs and the development and progression of neuropsychiatric disorders. [44][45][46] The brain is abundant in cholesterol, which serves as a precursor for the synthesis of BAs. 47 BAs can enter the brain through BA transporter proteins present in the peripheral circulation.…”