TY - JOUR
T1 - Secondary Bile Acid Derivatives Are Contributors to the Fecal Bile Acid Pool and Associated With Bile Acid–Modulating Nutrients
AU - Wolf, Patricia G.
AU - Welsh, Caitlin
AU - Binion, Briawna
AU - Dai, Hanchu
AU - Oliveira, Manoela Lima
AU - Hamm, Alyshia
AU - Goldberg, Sarah
AU - Buobu, Pius Sarfo
AU - Schering, Teresa
AU - Vergis, Sevasti
AU - Kessee, Nicollette
AU - Gomez, Sandra L.
AU - Yazici, Cemal
AU - Maienschein-Cline, Mark
AU - Byrd, Doratha A.
AU - Gaskins, H. Rex
AU - Ridlon, Jason M.
AU - Mutlu, Ece
AU - Greening, Chris
AU - Tussing-Humphreys, Lisa
N1 - Although dietary fiber was negatively associated with high abundant derivatives of DCA, it was associated with the increased conversion of secondary BAs to protective secondary BA metabolites. The ratios for isodeoxycholic/DCA, isolithocholic acid/LCA, and 3-oxoallolithocholic acid/LCA were positively correlated with fiber intake. Isolithocholic acid, isodeoxycholic acid, and 3-oxoallolithocholic are secondary BA derivatives that are also supportive of T regulatory cell expansion and thus may protect from cancer development [38\u201341]. It has yet to be elucidated how fiber supports the production of secondary BA metabolites, but it is known that different fibers have diverse BA-binding capacities, which may reduce BA bioavailability and increase fecal excretion [44]. Further, fiber fermentation by gut bacteria produces short-chain fatty acids, which reduce luminal pH [45]. Because microbial enzymes for BA metabolism have varied pH optima, it is possible that reduced luminal pH selects for the production of protective secondary BA metabolites [46]. Given the consistent evidence that fiber intake reduces cancer risk, interventions using fermentable and nonfermentable fibers with varied BA-binding capacities are needed to understand their utility in promoting the production of protective BA metabolites [9,47].This work was supported by R01CA204808 (to HRG, EM, JR, LT-H), U54MD012523 (to LT-H, JR, HRG, EM), Hatch# ILLU-971-318 (to PGW, JR) T32CA057699 (to PGW, MLO), RSG-23-1154989-01-CSCT (to PGW), and NHMRC EL2 Fellowship APP1178715 (to CG). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or American Cancer Society.PGW reports financial support by the National Institutes of Health, the American Cancer Society, and the USDA. HRG, EM, LT-H, and MLO report financial support by the National Institutes of Health. JR reports financial support by the National Institutes of Health and the USDA. CG reports financial support by National Health and Medical Research Council.
This work was supported by R01CA204808 (H. Rex Gaskins, Ece Mutlu, Jason Ridlon, Lisa Tussing-Humphreys), U54MD012523 (Lisa Tussing-Humphreys, Jason Ridlon, H. Rex Gaskins, Ece Mutlu,), Hatch# ILLU-971-318 (Patricia G. Wolf, Jason Ridlon) T32CA057699 (Patricia G. Wolf, Manoela Lima Oliveira), RSG-23-1154989-01-CSCT (Patricia G. Wolf), and NHMRC EL2 Fellowship APP1178715 (Chris Greening). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or American Cancer Society.
PY - 2025/3
Y1 - 2025/3
N2 - 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 was assessed from stool metagenomes. Kendall τ correlation and regression-based modeling were 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. monounsaturated fatty acids (MUFA)s 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. Conclusion: 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.
AB - 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 was assessed from stool metagenomes. Kendall τ correlation and regression-based modeling were 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. monounsaturated fatty acids (MUFA)s 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. Conclusion: 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.
KW - bile acids
KW - colorectal cancer
KW - diet quality
KW - fecal bile acids
KW - metagenome
KW - secondary bile acids
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U2 - 10.1016/j.tjnut.2024.12.035
DO - 10.1016/j.tjnut.2024.12.035
M3 - Article
C2 - 39805403
AN - SCOPUS:85217644073
SN - 0022-3166
VL - 155
SP - 826
EP - 838
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 3
ER -