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干酪乳杆菌减轻了结核病治疗期间胆汁淤积相关肝脏指标的异常升高:一项随机对照试验的事后分析

Lactobacillus casei Alleviated the Abnormal Increase of Cholestasis-Related Liver Indices During Tuberculosis Treatment: A Post Hoc Analysis of Randomized Controlled Trial.

作者信息

Xiong Ke, Cai Jing, Liu Peiying, Wang Jinyu, Zhao Shanliang, Xu Lei, Yang Yang, Liu Jiahong, Ma Aiguo

机构信息

School of Public Health, Institute of Nutrition and Health, Qingdao University, Qingdao, Shandong, 266021, China.

Linyi People's Hospital, Linyi, Shandong, 276000, China.

出版信息

Mol Nutr Food Res. 2021 Aug;65(16):e2100108. doi: 10.1002/mnfr.202100108. Epub 2021 Jul 19.

DOI:10.1002/mnfr.202100108
PMID:33864432
Abstract

SCOPE

Probiotics are promising in mitigating drug-induced liver injury in animal experiments. However, the clinical evidence is absent. The objective is to investigate the effect of adjunctive Lactobacillus casei on tuberculosis-drug-induced liver injury.

METHODS AND RESULTS

A post hoc analysis is conducted for a previous randomized controlled trial. The trial is registered at the Chinese Clinical Trial Registry (No. ChiCTR-IOR-17013210). Four hundred twenty nine patients are allocated to receive standard tuberculosis therapy alone (control group), or together with 1 × 10 colony-forming units (CFU) per day (low-dose group), or 2 × 10 CFU per day of L. casei (high-dose group) during tuberculosis treatment. The L. casei supplementation significantly reduced the incidence of the abnormal increase of cholestasis-related liver indices including alkaline phosphatase (p = 0.024) and bilirubin (p = 0.013). Plasma lipopolysaccharide (p = 0.02), intestinal permeability biomarkers including zonula occludens-1 (p = 0.001) and intestinal fatty acid binding protein (p = 0.002) are significantly reduced. The gut microbiota composition is dramatically altered with a reduction of Bacteroidetes (p < 0.001) and a corresponding increase of Actinobacteria (p < 0.001) and Firmicutes (p = 0.003).

CONCLUSIONS

L. casei supplementation is beneficial for suppressing abnormally elevated cholestasis-related liver indices during tuberculosis treatment, which may be related to its modification on blood lipopolysaccharide, intestinal barrier function, and gut microbiota.

摘要

范围

在动物实验中,益生菌有望减轻药物性肝损伤。然而,缺乏临床证据。目的是研究辅助干酪乳杆菌对结核药物性肝损伤的影响。

方法与结果

对先前的一项随机对照试验进行事后分析。该试验在中国临床试验注册中心注册(注册号:ChiCTR-IOR-17013210)。429例患者被分配接受单独的标准抗结核治疗(对照组),或在抗结核治疗期间每天联合1×10菌落形成单位(CFU)(低剂量组),或每天联合2×10 CFU的干酪乳杆菌(高剂量组)。补充干酪乳杆菌显著降低了胆汁淤积相关肝指标异常升高的发生率,包括碱性磷酸酶(p = 0.024)和胆红素(p = 0.013)。血浆脂多糖(p = 0.02)、肠道通透性生物标志物,包括闭合蛋白-1(p = 0.001)和肠脂肪酸结合蛋白(p = 0.002)显著降低。肠道微生物群组成发生显著改变,拟杆菌减少(p < 0.001),放线菌(p < 0.001)和厚壁菌门(p = 0.003)相应增加。

结论

补充干酪乳杆菌有利于抑制抗结核治疗期间胆汁淤积相关肝指标的异常升高,这可能与其对血脂多糖、肠道屏障功能和肠道微生物群的调节作用有关。

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