首页|基于FXR-FGF19通路研究益生菌对胆总管结石患者胆汁酸代谢的影响

基于FXR-FGF19通路研究益生菌对胆总管结石患者胆汁酸代谢的影响

Effect of Probiotics on Bile Acid Metabolism via FXR-FGF19 Pathway in Patients With Choledocholithiasis

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背景:胆总管结石在取石术后有较高的复发率.近年研究表明肠道微生态失衡与胆固醇结石的形成有关.目的:探究益生菌干预对胆固醇结石高危人群血清脂多糖(LPS)以及胆汁酸代谢指标的影响.方法:选取2021年6月—2023年6月在石河子大学第一附属医院行ERCP取石术的胆总管结石患者60例,收集胆汁和粪便样本行细菌培养.将患者随机分为对照组和益生菌干预组,对照组取石术后予常规支持治疗,干预组在常规治疗的基础上服用双歧杆菌三联活菌肠溶胶囊420 mg,每日2次,连续6个月.检测治疗前后革兰阴性菌细胞壁成分LPS、胆汁酸代谢关键分子成纤维细胞生长因子19(FGF19)和胆汁酸合成限速酶胆固醇7α-羟化酶(CYP7A1)血清水平的变化.结果:胆总管结石患者胆汁、粪便细菌培养显示主要致病菌为大肠埃希菌和肺炎克雷伯菌.ERCP取石术后6个月,患者血清LPS、FGF19水平明显降低,CYP7A1水平明显升高(P均<0.05),益生菌干预组数据变化较对照组更为显著(P均<0.05).结论:口服益生菌制剂可降低胆固醇结石高危人群的血清LPS水平,同时调节胆汁酸经肠肝循环代谢的经典通路法尼酯X受体(FXR)-FGF19通路,从而减少胆汁中的胆固醇过饱和,降低胆固醇结石的形成概率.
Background:Recurrence after stone removal is common in patients with choledocholithiasis.Recent studies have indicated that dysbiosis in gut microbiota plays an important role in the formation of cholesterol gallstones.Aims:To explore the effect of probiotics supplementation on serum lipopolysaccharide(LPS)and the indicators of bile acid metabolism in patients with a high risk of cholesterol gallstone formation.Methods:Sixty choledocholithiasis patients undergoing ERCP lithotomy were recruited at the First Affiliated Hospital of Shihezi University from June 2021 to June 2023.Bile and stool samples were collected for bacterial culture.Then the patients were randomly allocated into two groups:patients in control group received conventional supportive therapy after calculus removal,while those in probiotics intervention group were given oral bifid triple viable enteric capsule 420 mg,twice a day for 6 months based on conventional therapy.Changes in serum levels of LPS,the cell wall component of Gram-negative bacteria,fibroblast growth factor 19(FGF19),the key molecule in bile acid metabolism,and cholesterol 7α-hydroxylase(CYP7A1),the rate-limiting enzyme of bile acid synthesis,were determined and compared between the two groups.Results:Escherichia coli and Klebsiella pneumoniae were the main pathogens in bile and stool of patients with choledocholithiasis.Six months after ERCP lithotomy,the serum levels of LPS and FGF19 were decreased,and the serum level of CYP7A1 was increased in both groups(all P<0.05),especially in probiotics intervention group(all P<0.05).Conclusions:Oral probiotics supplementation can reduce the serum LPS level and modulate the canonical pathway of enterohepatic circulation of bile acids--farnesoid X receptor(FXR)-FGF19 pathway in high-risk patients of cholesterol gallstone formation.These alterations reduce the cholesterol supersaturation in bile and inhibit the probability of cholesterol gallstone formation.

ProbioticsLipopolysaccharidesCholedocholithiasisBile Acid MetabolismFarnesoid X ReceptorCholesterol 7-alpha-Hydroxylase

叶绿望、王丛、范俊维、蒋婷、杜梦燕、陈卫刚、刘芳

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石河子大学医学院(832002)

石河子大学第一附属医院消化内科

益生菌 脂多糖类 胆总管结石 胆汁酸代谢 法尼酯X受体 胆固醇7-α-羟化酶

新疆生产建设兵团指导性科技计划项目新疆生产建设兵团指导性科技计划项目石河子大学自主资助支持校级科研项目石河子大学第一附属医院院级科研项目

2022ZD0862023ZD006ZZZC202197ZD201903

2024

10.3969/j.issn.1008-7125.2024.01.003

胃肠病学
上海交通大学医学院附属仁济医院

胃肠病学

CSTPCD
影响因子：1.217
ISSN：1008-7125
年,卷(期)：2024.29(1)