Determination of Human Plasma Bile Acid Metabolic Profiles by Liquid Chromatography-tandem Mass Spectrometry

Chen, Yutao
Lu, Jun
Liu, Dong-Xu
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Master of Science
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Auckland University of Technology

Metabolic diseases, particularly type 2 diabetes mellitus (T2DM), are becoming serious health issues globally. Metabolic diseases are associated with changes in a number of biomarkers, such as glucose, insulin, and adiponectin. Many biomarkers have been used to predict or assess metabolic diseases, which are essential clinical tools for disease diagnosis and management. Recently, bile acids (BAs) have been shown to be linked with metabolic changes and diseases. Hence, this thesis focuses on applying a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to measure BAs in blood samples collected from a bariatric surgery study and a gestational probiotic intervention study. It intends to find out whether BAs are changing with those interventions and whether BAs are a good indicator of changes in metabolic diseases.

An LC-MS/MS method was successfully developed in the analytical laboratory of the Auckland University of Technology. The separation of BAs was achieved with a reverse-phase C18 column with the gradient elution of aqueous and methanol acetate mobile phases that contained formic acid. BAs were monitored and quantified based on their unique production of ions. Then the method was applied to measure plasma BA concentrations in blood samples collected from 19 patients at three days and three months after bariatric surgeries, including 8 gastric bypasses (GBP) and 11 sleeve gastrectomies (SG). The same method was used to measure BAs in plasma samples from 348 women at gestation, with 172 taking the probiotic supplement and 176 on placebo.

In the bariatric surgery trial, several BA species increased acutely after bariatric operations, along with fibroblast growth factor19 (FGF19). Significant correlations were observed between the post-operation changes of either BA compositions or FGF19 versus selected metabolic indices, such as the area under the curve (AUC) over 120 minutes (AUC0-120min) of glucose or insulin, insulin resistance, insulin sensitivity index (ISI), basal or total insulin secretion rate, and C-peptide at either three days or three months. In the probiotic gestational trial, a higher taurine-conjugated BA level was correlated with the higher concentration of one-hr glucose after an oral glucose test (r=0.10, P=0.05).

It is apparent from this study that plasma BAs are linked to metabolic diseases. Some BAs showed significant acute and short-term modifications induced by different types of bariatric surgery in obese individuals with T2DM. The alterations of BAs might contribute to improvements in glycemic control after surgery. In the probiotic intervention in women at gestation, changes in BAs indicate that taking probiotic supplements improves maternal glycemic control, particularly among obese women with gestational diabetes. The alteration of fasting plasma BAs by probiotic supplementation, which was notably recognised as a decrease in taurine-conjugated BAs, might play a role in the improvement of glucose metabolism. In conclusion, BAs are likely to link to metabolic diseases and have the potential to be developed into a biomarker for disease monitoring and management.

Bile acids , LC-MS/MS , Type 2 diabetes mellitus , FGF19 , Gastric bypass , Sleeve gastrectomy , Gestational diabetes mellitus , Lactobacillus rhamnosus HN001 , Glucose , Insulin , Lipid
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