Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Inflamm Bowel Dis. 2024 Oct 3;30(10):1642-1653. doi: 10.1093/ibd/izae064.
Inflammatory bowel diseases (IBDs) pose a significant challenge due to their diverse, often debilitating, and unpredictable clinical manifestations. The absence of prognostic tools to anticipate the future complications that require therapy intensification presents a substantial burden to patient private life and health. We aimed to explore whether the gut microbiome is a potential biomarker for future therapy intensification in a cohort of 90 IBD patients.
We conducted whole-genome metagenomics sequencing on fecal samples from these patients, allowing us to profile the taxonomic and functional composition of their gut microbiomes. Additionally, we conducted a retrospective analysis of patients' electronic records over a period of 10 years following the sample collection and classified patients into (1) those requiring and (2) not requiring therapy intensification. Therapy intensification included medication escalation, intestinal resections, or a loss of response to a biological treatment. We applied gut microbiome diversity analysis, dissimilarity assessment, differential abundance analysis, and random forest modeling to establish associations between baseline microbiome profiles and future therapy intensification.
We identified 12 microbial species (eg, Roseburia hominis and Dialister invisus) and 16 functional pathways (eg, biosynthesis of L-citrulline and L-threonine) with significant correlations to future therapy intensifications. Random forest models using microbial species and pathways achieved areas under the curve of 0.75 and 0.72 for predicting therapy intensification.
The gut microbiome is a potential biomarker for therapy intensification in IBD patients and personalized management strategies. Further research should validate our findings in other cohorts to enhance the generalizability of these results.
炎症性肠病（IBD）具有多样化、常使人虚弱且不可预测的临床表现，这给治疗带来了极大的挑战。目前缺乏预测未来需要强化治疗的并发症的预后工具，这给患者的私人生活和健康带来了巨大负担。我们旨在探索肠道微生物组是否可以作为 90 例 IBD 患者队列中未来强化治疗的潜在生物标志物。
我们对这些患者的粪便样本进行了全基因组宏基因组测序，使我们能够分析其肠道微生物组的分类和功能组成。此外，我们对患者电子病历进行了回顾性分析，时间跨度为样本采集后的 10 年，并将患者分为（1）需要和（2）不需要强化治疗的两类。强化治疗包括药物升级、肠道切除术或对生物治疗的反应丧失。我们应用肠道微生物组多样性分析、差异评估、差异丰度分析和随机森林模型来建立基线微生物组特征与未来强化治疗之间的关联。
我们确定了 12 种微生物物种（如罗塞尔氏菌和隐匿真杆菌）和 16 种功能途径（如 L-瓜氨酸和 L-苏氨酸的生物合成）与未来强化治疗显著相关。使用微生物物种和途径的随机森林模型预测强化治疗的曲线下面积分别为 0.75 和 0.72。
肠道微生物组是 IBD 患者强化治疗和个性化管理策略的潜在生物标志物。应在其他队列中进一步验证我们的发现，以提高这些结果的普遍性。
