Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
Clin Gastroenterol Hepatol. 2024 Apr;22(4):821-830.e7. doi: 10.1016/j.cgh.2023.09.023. Epub 2023 Oct 5.
BACKGROUND & AIMS: Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC). However, it remains unclear if fungal composition is altered during active versus quiescent disease.
We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n = 52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity versus remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data.
During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (P-adj < 1 × 10) compared with during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (P < .05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii, and Bacteroides dorei relative abundance (P < .05) during remission; however, these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (area under the curve ∼0.80), with Candida relative abundance critical to the success of the model.
Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.
肠道真菌被认为与溃疡性结肠炎（UC）的发病机制有关。然而，在疾病活动期和缓解期，真菌组成是否发生改变尚不清楚。
我们分析了炎症性肠病前瞻性成人研究队列（SPARC IBD）的临床和宏基因组数据，这些数据可通过克罗恩病和结肠炎基金会的 IBD Plexus 计划获得。我们评估了 421 例 UC 患者在临床活动期和缓解期粪便样本中的真菌组成。在一个纵向亚队列（n=52）中，我们评估了随着时间推移临床活动的变化，分类学的动态变化。我们研究了在活动期与缓解期，真菌扩增子序列变异和真菌-细菌关系是否发生改变。最后，我们使用基于真菌丰度数据的监督机器学习随机森林模型对 UC 的活动进行分类。
与缓解期相比，在临床活动期，属 Candida 的相对丰度增加了 3.5 倍（P 调整值<1×10）。纵向临床活动减少的患者，Candida 的相对丰度也相应降低（P<0.05）。在缓解期，Candida 的相对丰度与 Parabacteroides diastonis、Faecalibacterium prausnitzii 和 Bacteroides dorei 的相对丰度呈正相关（P<0.05）；然而，在活动期，这些相关性被打破。真菌丰度数据成功地将活动期和缓解期的 UC 患者分类（曲线下面积约为 0.80），Candida 的相对丰度对模型的成功至关重要。
UC 的临床活动与 Candida 的相对丰度增加有关，无论是在横断面还是随时间动态变化。粪便 Candida 作为 UC 治疗靶点的作用应加以评估。
