Background Alterations in gut microbiota composition and functions are involved in the pathogenesis of Inflammatory Bowel Disease (IBD) and the role of specific bacterial taxa has been particularly pointed out. The role of microbiota-derived metabolites, including those produced from tryptophan, are major actors in host-microbiota interactions in health and in IBD. Large studies analyzing both gut microbiota and metabolomics data are scarce. Methods In the current study, we analyzed a total of 764 individuals from Saint Antoine Hospital cohort, including 447 patients with Crohn's disease (CD), 262 patients with Ulcerative Colitis (UC) and 55 healthy subjects. We performed shotgun metagenomic sequencing on fecal samples and integrated the results with deep clinical phenotyping and targeted metabolomics data encompassing 294 different molecules. Results We observed strong changes in the taxonomic composition and functional capabilities of the microbiota in CD and UC patients compared to healthy subjects. Besides disease itself, the most important drivers of microbiota composition were the disease location (Montreal classification), recent antibiotic treatment, disease activity (flare vs remission) and history of ileocecal resection. Interestingly, IBD diagnosis explained much more the variations of microbiota functions than taxonomy. The decrease in microbiota diversity was stronger in CD than in UC. In parallel to a decreased amount of Faecalibacterium in IBD, we also observed a decrease in the diversity of Faecalibacterium strains, with a stronger decrease in CD. Our multifactorial analysis revealed specific microbial taxa and functions affected by disease-related factors. We particularly identified many correlations between tryptophan metabolites and microbial abundance. Targeted gene analysis of tryptophan-related enzymes in metagenomes further supported these findings. A network analysis considering bacterial taxa and metabolites revealed profound alterations in IBD with some specificities between CD and UC. Conclusion We pointed out new microbiome and metabolome alterations associated with IBD, with some phenotype specificities. Overall, our findings provide crucial information and a substantial resource for understanding the interactions between the host and microbiome in the context of IBD.

中文翻译：

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DOP26 IBD 宏基因组和代谢组学概况：从大型深度表型队列中了解微生物和代谢变化

背景肠道菌群组成和功能的改变与炎症性肠病（IBD）的发病机制有关，并且特别指出了特定细菌类群的作用。微生物群衍生的代谢物（包括由色氨酸产生的代谢物）的作用是健康和 IBD 中宿主-微生物群相互作用的主要参与者。分析肠道微生物群和代谢组学数据的大型研究很少。方法在本研究中，我们分析了来自圣安东尼医院队列的总共 764 名个体，其中包括 447 名克罗恩病 (CD) 患者、262 名溃疡性结肠炎 (UC) 患者和 55 名健康受试者。我们对粪便样本进行了鸟枪法宏基因组测序，并将结果与​​深入的临床表型分析和包含 294 种不同分子的靶向代谢组学数据相结合。结果我们观察到与健康受试者相比，CD 和 UC 患者微生物群的分类组成和功能能力发生了显着变化。除了疾病本身之外，微生物群组成最重要的驱动因素是疾病部位（蒙特利尔分类）、最近的抗生素治疗、疾病活动性（发作与缓解）和回盲部切除史。有趣的是，IBD 诊断比分类学更能解释微生物群功能的变化。CD 中微生物群多样性的下降比 UC 中更为严重。在 IBD 中粪杆菌数量减少的同时，我们还观察到粪杆菌菌株多样性下降，CD 下降幅度更大。我们的多因素分析揭示了受疾病相关因素影响的特定微生物类群和功能。我们特别发现了色氨酸代谢物与微生物丰度之间的许多相关性。宏基因组中色氨酸相关酶的靶向基因分析进一步支持了这些发现。一项考虑细菌分类群和代谢物的网络分析揭示了 IBD 的深刻变化，并且 CD 和 UC 之间存在一些特异性。结论 我们指出了与 IBD 相关的新的微生物组和代谢组改变，并具有一些表型特异性。总体而言，我们的研究结果为了解 IBD 背景下宿主与微生物组之间的相互作用提供了重要信息和大量资源。