Wang Ya, Deng Dazhang, Mai Meiqing, Song Wanhan, Yuan Qianhua, Xie Yutong, Mo Bingquan, Guo Honghui
Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
Department of Traditional Chinese Medicine, the First Affiliated Hospital of Dongguan, Guangdong Medical University, Dongguan 523710, China.
J Steroid Biochem Mol Biol. 2025 Oct;253:106812. doi: 10.1016/j.jsbmb.2025.106812. Epub 2025 Jun 9.
The incidence of gallstone disease (GSD) is often higher in female patients with nonalcoholic fatty liver disease (NAFLD) compared to their male counterparts; however, the underlying mechanisms remain unclear. This cross-sectional study aimed to investigate gender differences in susceptibility to GSD with a focus on the specificity of bile acid (BA) metabolism, while also considering the reciprocal influence between gut bacteria and BAs. A total of 16 female and 36 male NAFLD patients, identified as having a high risk of GSD, were included in the study. Serum and fecal BA profiles were analyzed, along with a correlation analysis of gut microbiota composition. Gender-specific divergence in hydrophobic BAs distribution was observed, with females exhibiting significantly higher serum retention. The concentrations of serum glycolithocholic acid, isolithocholic acid, and 12-ketolithocholic acid, as well as fecal lithocholic acid, were significantly higher in females than in males. Conversely, the levels of serum hyodeoxycholic acid, fecal 7-ketolithocholic acid (7-keto-LCA), chenodeoxycholic acid, glycocholic acid, and ursodeoxycholic acid were significantly lower in females. Additionally, the total abundance of Fusobacterium and Escherichia-Shigella in the gut microbiota was elevated in females. A statistically significant inverse correlation was observed in females between reduced fecal 7-keto-LCA levels and an increased abundance of butyrate-producing bacterial communities. Overall, BAs and gut microbiota exhibit gender dimorphism in NAFLD patients, which may be linked to the increased risk of secondary GSD in women.
与男性非酒精性脂肪性肝病（NAFLD）患者相比，女性患者胆结石病（GSD）的发病率通常更高；然而，其潜在机制仍不清楚。这项横断面研究旨在调查GSD易感性的性别差异，重点关注胆汁酸（BA）代谢的特异性，同时考虑肠道细菌与BA之间的相互影响。共有16名女性和36名男性NAFLD患者被纳入研究，这些患者被确定为具有较高的GSD风险。分析了血清和粪便中的BA谱，并对肠道微生物群组成进行了相关性分析。观察到疏水性BA分布存在性别特异性差异，女性血清潴留明显更高。女性血清中甘氨石胆酸、异石胆酸和12-酮石胆酸以及粪便中石胆酸的浓度显著高于男性。相反，女性血清猪去氧胆酸、粪便7-酮石胆酸（7-keto-LCA）、鹅去氧胆酸、甘胆酸和熊去氧胆酸的水平显著较低。此外，女性肠道微生物群中梭杆菌属和大肠埃希菌-志贺菌属的总丰度升高。在女性中，观察到粪便中7-keto-LCA水平降低与产丁酸细菌群落丰度增加之间存在统计学上的显著负相关。总体而言，NAFLD患者的BA和肠道微生物群存在性别二态性，这可能与女性继发性GSD风险增加有关。
