Abstract

Primary bile acids (BAs) and their gut microbial metabolites have a role in regulating human health. Comprehensive characterization of BAs species in human biological samples will aid in understanding the interaction between diet, gut microbiota, and bile acid metabolism. Therefore, we developed a qualitative method using ultra-high performance liquid chromatography (UHPLC) coupled with a quadrupole time-of-flight (Q-TOF) to identify BAs in human plasma, feces, and urine samples. A quantitative method was developed using UHPLC coupled with triple quadrupole (QQQ) and applied to a previous clinical trial conducted by our group to understand the bile acid metabolism in overweight/obese middle-aged adults (n = 34) after four weeks strawberry vs. control intervention. The qualitative study tentatively identified a total of 81 BAs in human biological samples. Several BA glucuronide-conjugates were characterized for the first time in human plasma and/or urine samples. The four-week strawberry intervention significantly reduced plasma concentrations of individual secondary BAs, deoxycholic acid, lithocholic acid and their glycine conjugates, as well as glycoursodeoxycholic acid compared to control (p < 0.05); total glucuronide-, total oxidized-, total dehydroxyl-, total secondary, and total plasma BAs were also lowered compared to control (p < 0.05). The reduced secondary BAs concentrations suggest that regular strawberry intake modulates the microbial metabolism of BAs.

Highlights

  • Bile acids (BAs) are well known for their essential role in lipid digestion and absorption, stimulating the flow of bile and promoting the secretion of cholesterol from the liver [1]

  • Out of 81 tentatively identified BAs and their metabolites in the human biological samples, 37, 49, and 31 BA species were characterized in plasma, feces, and urine samples, respectively (Table 1)

  • Plasma samples contained a diverse array of BA species, including primary, secondary BAs, and their glycine, taurine, sulfate, and glucuronide-conjugates, whereas fecal samples mostly contained secondary BAs and sulfate-conjugates

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Summary

Introduction

Bile acids (BAs) are well known for their essential role in lipid digestion and absorption, stimulating the flow of bile and promoting the secretion of cholesterol from the liver [1]. In the last 10 years, BAs have been recognized as having a role in metabolic processes, such as glucose, lipid, and energy metabolism, gut microbiota structure and function, along with hepatic and colonic inflammation through activation of the farnesoid X receptor (FXR) and. Primary BAs, including chenodeoxycholic acid (CDCA) and cholic acid (CA), are synthesized from cholesterol in the liver and stored in the gallbladder as glycine or taurine conjugates. Around 95% of BAs are reabsorbed in the terminal ileum via enterohepatic circulation [6]. The remaining BAs undergo gut microbial biotransformation to form secondary BAs, mainly lithocholic acid (LCA) and deoxycholic acid (DCA) in the colon

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