肠道微生物群靶向治疗在非酒精性脂肪性肝病中的作用：一项系统评价和网状Meta分析
The effect of gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review and network meta-analysis.
作者信息
Song Yijia, Liu Sutong, Zhang Lihui, Zhao Wenxia, Qin Yuanmei, Liu Minghao
机构信息
Department of Spleen, Stomach, Hepatobiliary Disease, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
The First Clinical Medical School of Henan University of Chinese Medicine, Zhengzhou, China.
出版信息
Front Nutr. 2025 Jan 6;11:1470185. doi: 10.3389/fnut.2024.1470185. eCollection 2024.
BACKGROUND
The incidence of NAFLD is increasing. Preclinical evidences indicate that modulation of the gut microbiome could be a promising target in nonalcoholic fatty liver disease.
METHOD
A systematic review and network meta-analysis was conducted to compare the effect of probiotics, synbiotics, prebiotics, fecal microbiota transplant, and antibiotics on the liver-enzyme, metabolic effects and liver-specific in patients with NAFLD. The randomized controlled trails (RCTs), limited to English language were searched from database such as Pubmed, Embase, Web of science and Cochrane Library from inception to November 2024. Review Manager 5.3 was used to to draw a Cochrane bias risk. Inconsistency test and publication-bias were assessed by Stata 14.0. Random effect model was used to assemble direct and indirect evidences. The effects of the intervention were presented as mean differences with 95% confidence interval.
RESULTS
A total of 1921 patients from 37 RCTs were eventually included in our study. 23 RCTs evaluated probiotics, 10 RCTs evaluated synbiotics, 4 RCTs evaluated prebiotics, 3 RCTs evaluated FMT and one RCT evaluated antibiotics. Probiotics and synbiotics were associated with a significantly reduction in alanine aminotransferase [ALT, (MD: -5.09; 95%CI: -9.79, -0.39), (MD: -7.38, 95CI%: -11.94, -2.82)] and liver stiffness measurement by elastograph [LSM, (MD: -0.37;95%CI: -0.49, -0.25), (MD: -1.00;95%CI: -1.59, -0.41)]. In addition to, synbiotics was superior to probiotics in reducing LSM. Synbiotics was associated with a significant reduction of Controlled Attenuation Parameter [CAP, (MD: -39.34; 95%CI: -74.73, -3.95)]. Both probiotics and synbiotics were associated with a significant reduction of aspartate transaminase [AST, (MD: -7.81; 95%CI: -15.49, -0.12), (MD: -13.32; 95%CI: -23, -3.64)]. Probiotics and Allogenic FMT was associated with a significant reduction of Homeostatic Model Assessment for Insulin Resistance [HOMA-IR, (MD: -0.7, 95%CI: -1.26, -0.15), (MD: -1.8, 95%CI: -3.53, - 0.07)]. Probiotics was associated with a significant reduction of body mass index [BMI, MD: -1.84, 95%CI: -3.35, -0.33].
CONCLUSION
The supplement of synbiotics and probiotics maybe a promising way to improve liver-enzyme, LSM, and steatosis in patients with NAFLD. More randomized controlled trials are needed to determine the efficacy of FMT and antibiotics on NAFLD. And the incidence of adverse events of MTTs should be further explored.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, CRD42023450093.
背景
非酒精性脂肪性肝病（NAFLD）的发病率正在上升。临床前证据表明，调节肠道微生物群可能是治疗非酒精性脂肪性肝病的一个有前景的靶点。
方法
进行了一项系统评价和网络荟萃分析，以比较益生菌、合生元、益生元、粪便微生物群移植和抗生素对NAFLD患者肝酶、代谢效应和肝脏特异性指标的影响。从创刊至2024年11月，在PubMed、Embase、Web of science和Cochrane图书馆等数据库中检索仅限于英文的随机对照试验（RCT）。使用Review Manager 5.3绘制Cochrane偏倚风险图。通过Stata 14.0评估异质性检验和发表偏倚。采用随机效应模型汇总直接和间接证据。干预效果以平均差值和95%置信区间表示。
结果
本研究最终纳入了来自37项RCT的1921例患者。23项RCT评估了益生菌，10项RCT评估了合生元，4项RCT评估了益生元，3项RCT评估了粪便微生物群移植，1项RCT评估了抗生素。益生菌和合生元与丙氨酸氨基转移酶[ALT，（平均差值：-5.09；95%置信区间：-9.79，-0.39），（平均差值：-7.38，95%置信区间：-11.94，-2.82）]和通过弹性成像测量的肝脏硬度[LSM，（平均差值：-0.37；95%置信区间：-0.49，-0.25），（平均差值：-1.00；95%置信区间：-1.59，-0.41）]的显著降低相关。此外，合生元在降低LSM方面优于益生菌。合生元与受控衰减参数[CAP，（平均差值：-39.34；95%置信区间：-74.73，-3.95）]的显著降低相关。益生菌和合生元均与天冬氨酸转氨酶[AST，（平均差值：-7.81；95%置信区间：-15.49，-0.12），（平均差值：-13.32；95%置信区间：-23，-3.64）]的显著降低相关。益生菌和同种异体粪便微生物群移植与胰岛素抵抗稳态模型评估[HOMA-IR，（平均差值：-0.7，95%置信区间：-1.26，-0.15），（平均差值：-1.8，95%置信区间：-3.53，-0.07）]的显著降低相关。益生菌与体重指数[BMI，平均差值：-1.84，95%置信区间：-3.35，-0.33]的显著降低相关。
结论
补充合生元和益生菌可能是改善NAFLD患者肝酶、LSM和脂肪变性的一种有前景的方法。需要更多的随机对照试验来确定粪便微生物群移植和抗生素对NAFLD的疗效。并且应进一步探索MTTs不良事件的发生率。
系统评价注册
Zotero 插件