肠道菌群失调及相关粪便特征可改善炎症性肠病生物治疗反应的预测。

Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease.

作者信息

Caenepeel Clara, Falony Gwen, Machiels Kathleen, Verstockt Bram, Goncalves Pedro J, Ferrante Marc, Sabino João, Raes Jeroen, Vieira-Silva Sara, Vermeire Séverine

机构信息

Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium; Center for Microbiology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

出版信息

Gastroenterology. 2024 Mar;166(3):483-495. doi: 10.1053/j.gastro.2023.11.304. Epub 2023 Dec 12.

DOI:10.1053/j.gastro.2023.11.304

PMID:38096956

Abstract

BACKGROUND & AIMS: Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies.

METHODS

The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation.

RESULTS

At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies.

CONCLUSION

Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.

摘要

背景与目的

肠道微生物群失调被认为是炎症性肠病（IBD）病因的关键因素。在此，我们研究了微生物群组成与生物治疗结果之间的潜在关联。

方法

该研究前瞻性招募了296例开始生物治疗的活动性IBD患者（203例克罗恩病患者，93例溃疡性结肠炎患者）。结合流式细胞术和16S扩增子测序获得治疗前和治疗后粪便样本的定量微生物组图谱。通过内镜检查、患者报告的结果以及粪便钙卫蛋白的变化评估治疗反应。使用受限排序方法评估治疗对微生物组变异的影响。使用逻辑回归和5折交叉验证对治疗结果进行预测。

结果

在基线时，65.9%的患者携带失调的拟杆菌2（Bact2）肠型，在回肠受累患者中的患病率显著更高（76.8%）。微生物组变异与生物治疗的选择有关，而不是与治疗结果有关。只有抗肿瘤坏死因子-α治疗导致微生物组从Bact2转变，同时微生物负荷和产丁酸菌丰度增加，潜在机会性韦荣球菌减少。基线时携带Bact2的患者接受抗肿瘤坏死因子-α治疗的缓解率显著高于维多珠单抗（65.1%对35.2%）。基于人体测量学和临床数据、粪便特征（微生物负荷、水分和钙卫蛋白）以及Bact2检测的预测模型对特定生物治疗的治疗结果预测准确率为73.9%。