Secondary Bile Acid Derivatives Are Contributors to the Fecal Bile Acid Pool and Associated With Bile Acid-Modulating Nutrients.

Abstract

Background: Accumulation of hydrophobic bile acids (BAs) is linked with cancer development. However, derivatives of deoxycholic acid (DCA) and lithocholic acid (LCA) produced via bacterial metabolism may mitigate the proinflammatory and cytotoxic effects of hydrophobic BAs. The impact of diet on secondary BA derivative production has not been determined.

Objectives: This study aimed to study the associations between BA-modulating nutrients and the composition of secondary BAs and their derivatives.

Methods: Stool and blood were collected from 138 participants aged 45-75 y that self-identified as Black or non-Hispanic White. BAs were extracted from stool and serum and quantified using LC/ESI-MS/MS. Energy, macronutrients, micronutrients, and specific dietary nutrients were estimated from two 24-h diet recalls. The abundance of genes for microbial BA metabolism were assessed from stool metagenomes. Kendall τ correlation and regression-based modeling was performed to determine associations between BA categories, microbial genes, and select energy adjusted dietary variables (alcohol, calcium, coffee, fiber, fat, and protein).

Results: Participants had a mean age of 60 y and a mean BMI of 31 kg/m². BA derivatives were present in all participant stools, with lagodeoxycholic acid being the most abundant derivative quantified. Analysis of stool microbial metagenomes revealed the presence of genes for secondary BA derivative production in all participants. Protein is positively associated with the accumulation of secondary BAs. MUFAs were negatively associated with high abundant derivatives of DCA in regression models. Total fiber and coffee intake were positively correlated with increased conversion of BAs to derivatives. Race and smoking status were significant predictors of associations between dietary variables and BA derivatives.

Conclusions: Protein, MUFAs, total fiber and coffee are significantly associated with concentrations of secondary BAs and their derivatives. Future work should account for social and structural influences on dietary intake and its relationship with BA-elicited cancer risk.