次级胆汁酸衍生物是粪便胆汁酸池的组成部分，并与胆汁酸调节营养素相关。
Secondary Bile Acid Derivatives Are Contributors to the Fecal Bile Acid Pool and Associated With Bile Acid-Modulating Nutrients.
作者信息
Wolf Patricia G, Welsh Caitlin, Binion Briawna, Dai Hanchu, Oliveira Manoela Lima, Hamm Alyshia, Goldberg Sarah, Buobu Pius Sarfo, Schering Teresa, Vergis Sevasti, Kessee Nicollette, Gomez Sandra L, Yazici Cemal, Maienschein-Cline Mark, Byrd Doratha A, Gaskins H Rex, Ridlon Jason M, Mutlu Ece, Greening Chris, Tussing-Humphreys Lisa
机构信息
Department of Nutrition Science, Purdue University, West Lafayette, IN, United States; Institute for Cancer Research, Purdue University, West Lafayette, IN, United States.
Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
出版信息
J Nutr. 2025 Mar;155(3):826-838. doi: 10.1016/j.tjnut.2024.12.035. Epub 2025 Jan 11.
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/m. 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.
背景
疏水性胆汁酸（BAs）的积累与癌症发展有关。然而，通过细菌代谢产生的脱氧胆酸（DCA）和石胆酸（LCA）衍生物可能会减轻疏水性BAs的促炎和细胞毒性作用。饮食对次级BA衍生物产生的影响尚未确定。
目的
本研究旨在探讨调节BA的营养素与次级BAs及其衍生物组成之间的关联。
方法
从138名年龄在45 - 75岁、自我认定为黑人或非西班牙裔白人的参与者中收集粪便和血液。从粪便和血清中提取BAs，并使用LC/ESI-MS/MS进行定量。通过两次24小时饮食回顾估计能量、宏量营养素、微量营养素和特定膳食营养素。从粪便宏基因组评估微生物BA代谢基因的丰度。进行肯德尔τ相关性分析和基于回归的建模，以确定BA类别、微生物基因与选定的能量调整膳食变量（酒精、钙、咖啡、纤维、脂肪和蛋白质）之间的关联。
结果
参与者的平均年龄为60岁，平均BMI为31 kg/m²。所有参与者的粪便中均存在BA衍生物，其中6 - 脱氧胆酸是定量分析中最丰富的衍生物。对粪便微生物宏基因组的分析显示，所有参与者中均存在次级BA衍生物产生的基因。蛋白质与次级BAs的积累呈正相关。在回归模型中，单不饱和脂肪酸（MUFA）与DCA的高丰度衍生物呈负相关。总纤维和咖啡摄入量与BAs向衍生物的转化率增加呈正相关。种族和吸烟状况是膳食变量与BA衍生物之间关联的重要预测因素。
结论
蛋白质、MUFA、总纤维和咖啡与次级BAs及其衍生物的浓度显著相关。未来的研究应考虑社会和结构因素对饮食摄入的影响及其与BA引发的癌症风险的关系。
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