Ng Ho Yu, Zhang Lina, Tan Jing Tong, Hui Rex Wan Hin, Yuen Man Fung, Seto Wai Kay, Leung Wai K, Cheung Ka Shing
Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Liver Int. 2025 Mar;45(3):e70023. doi: 10.1111/liv.70023.
We aimed to investigate whether gut microbiota could predict the treatment response to pharmacological agents among metabolic dysfunction-associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM), as data are lacking.
We prospectively followed up non-diabetic MASLD patients who used empagliflozin. Clinical, anthropometric, laboratory assessments and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) were performed from baseline to week 52 (EOT). Baseline stool samples were collected, and shotgun DNA metagenomic sequencing was performed to profile microbiome. The primary outcome was treatment response to empagliflozin at EOT, defined as MRI-PDFF decline ≥ 30% at EOT from baseline. Linear discriminant analysis [LDA] effect size was used to identify putative bacterial species. Multivariable logistic regression was used to derive adjusted odds ratio (aOR) of outcome with bacterial species by adjusting for clinical factors.
Twenty-two (48.9%) of 45 patients (median age: 56.9 years [IQR: 51.0-63.2]; male: 23 [51.1%]) achieved treatment response at EOT. There was difference in alpha diversity (Shannon index: p < 0.001; Simpson index: p = 0.001) and beta diversity (p = 0.048) in baseline microbiome between treatment response and non-response groups. Faecalibacterium prausnitzii (logLDAscore = 4.27), Lachnospira pectinoschiza (logLDAscore = 3.99), Anaerostipes hadrus (logLDAscore = 3.98), Roseburia faecis (logLDAscore = 3.97), Roseburia inulinivorans (logLDAscore = 3.58) and Agathobaculum butyriciproducens (logLDAscore = 2.77) were enriched in the treatment response group. L. pectinoschiza (aOR: 34.1; p = 0.015), A. hadrus (aOR:35.0; p = 0.032) and A. butyriciproducens (aOR:22.3; p = 0.023) independently predicted treatment response but not clinical factors. These three species collectively predicted treatment response with AUROC of 0.89 (95% CI: 0.80-0.99).
Certain gut bacterial species, particularly the combination of A. hadrus, L. pectinoschiza and A. butyriciproducens, may predict treatment response to empagliflozin in MAFLD patients without DM.
由于缺乏相关数据，我们旨在研究肠道微生物群是否能够预测无糖尿病（DM）的代谢功能障碍相关脂肪性肝病（MASLD）患者对药物治疗的反应。
我们对使用恩格列净的非糖尿病MASLD患者进行了前瞻性随访。从基线到第52周（治疗结束）进行临床、人体测量、实验室评估以及磁共振成像-质子密度脂肪分数（MRI-PDFF）检查。收集基线粪便样本，并进行鸟枪法DNA宏基因组测序以分析微生物组特征。主要结局是治疗结束时对恩格列净的治疗反应，定义为治疗结束时MRI-PDFF较基线下降≥30%。使用线性判别分析[LDA]效应大小来识别假定的细菌种类。通过对临床因素进行调整，使用多变量逻辑回归得出细菌种类与结局的调整优势比（aOR）。
45例患者（中位年龄：56.9岁[四分位间距：51.0 - 63.2]；男性：23例[51.1%]）中有22例（48.9%）在治疗结束时达到治疗反应。治疗反应组与无反应组的基线微生物组在α多样性（香农指数：p < 0.001；辛普森指数：p = 0.001）和β多样性（p = 0.048）方面存在差异。普拉梭菌（对数LDA分数 = 4.27）、果胶分解瘤胃球菌（对数LDA分数 = 3.99）、哈氏厌氧棒状菌（对数LDA分数 = 3.98）、粪便玫瑰杆菌（对数LDA分数 = 3.97）、嗜菊糖玫瑰杆菌（对数LDA分数 = 3.58）和丁酸阿加芽孢杆菌（对数LDA分数 = 2.77）在治疗反应组中富集。果胶分解瘤胃球菌（aOR：34.1；p = 0.015）、哈氏厌氧棒状菌（aOR：35.0；p = 0.032）和丁酸阿加芽孢杆菌（aOR：22.3；p = 0.023）独立预测治疗反应，而非临床因素。这三种细菌共同预测治疗反应的曲线下面积（AUROC）为0.89（95%置信区间：0.80 - 0.99）。
某些肠道细菌种类，特别是哈氏厌氧棒状菌、果胶分解瘤胃球菌和丁酸阿加芽孢杆菌的组合，可能预测无DM的MAFLD患者对恩格列净的治疗反应。
