Quantitative Analysis of Bile Acids

Bile Acid is a general term for a large class of cholanic acids and plays an important role in fat metabolism. The physiological function of bile acid can be summarized as: affecting bile secretion, promoting intestinal absorption of lipids and affecting intestinal function. Bile acids, one of the components of digestive juices, are synthesized by the liver and discharged into the intestine with bile to facilitate the digestion and absorption of lipids. It mainly includes cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, ursodeoxycholic acid acid and its glycine and taurine binding type.

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Sample Requirements

• Animal tissue ≥ 0.2g
• Liver ≥ 0.1g
• Bile≥ 10μl
• Serum, plasma ≥ 0.3ml
• Urine≥ 0.25ml
• Intestinal contents ≥ 0.3g
• Stool ≥ 0.3g
• Store in liquid nitrogen or -80°C
• Dry ice shipping

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Case Analysis

Altered Bile Acid Profile in Mild Cognitive Impairment and Alzheimer's Disease: Relationship to Neuroimaging and CSF Biomarkers

Journal: Alzheimers Dement       Impact factor: 17.127 Published date: April 2019       Published by: Indiana University School of Medicine, United States

Research Background

Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer’s disease (AD) including neuroinflammation and amyloid-b deposition.

Research Method

Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n=1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the “A/T/N” (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([18F]FDGPET).

A&B BAs and Imaging Association Results

Three bile acid ratios (TDCA:CA, GDCA:CA, GLCA:CDCA) were negatively correlated with CSF Aβ1-42(A)

Three bile acids (GCDCA, TLCA, GLCA) were positively correlated with CSF p-tau181 (T) and CSF t-tau (N) respectively

CA was positively correlated with FDG (brain glucose metabolism, N) and negatively correlated with 11 bile acids/ratio

CA was positively correlated with MRI (brain decline, N) and negatively correlated with 13 bile acids/ratio

Conclusion

The course of AD is highly correlated with the metabolism of bile acid.

Reference

Nho Kwangsik,Kueider-Paisley Alexandra,MahmoudianDehkordi Siamak et al. Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers.[J] .Alzheimers Dement, 2019, 15: 232-244

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Bile Acids and Alzheimer's Disease

Altered Bile Acid Profile Associates with Cognitive Impairment in Alzheimer's Disease—An Emerging Role for Gut Microbiome

Journal: Alzheimers Dementia       Impact factor: 17.127 Published date: 2019       Published by: Duke University, United States

Research Background

Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer’s disease (AD).

Research Method

370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases were enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD-related genetic variants.

Research Result

In AD compared to cognitively normal older adults, we observed significantly lower serum concentrations of a primary BA (cholic acid [CA]) and increased levels of the bacterially produced, secondary BA, deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio of deoxycholic acid:CA, which reflects 7a-dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response–related genes implicated in AD showed associations with BA profiles.

Conclusion

We report for the first time an association between altered BA profile, genetic variants implicated in AD, and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut-liver-brain axis in the pathogenesis of AD.

Reference

S. MahmoudianDehkordi et al., Altered bile acid profile associates with cognitive impairment in Alzheimer's disease—An emerging role for gut microbiome. Alzheimers Dement. 2019 Jan;15(1):76-92.