■即使没有炎症,克罗恩病(CD)的持续症状普遍存在,并恶化生活质量。在没有炎症(静止CD)的患者中,我们假设微生物群落结构和功能,包括色氨酸代谢,在有持续性症状(qCD+S)和无持续性症状(qCD-S)的患者之间会有所不同。
■我们在炎症性肠病前瞻性成人研究队列的研究中进行了一项多中心观察性研究。静态炎症定义为粪便钙卫蛋白水平<150mcg/g。持续症状由克罗恩病患者报告的结果2定义。活动CD,腹泻型肠易激综合征,健康对照者作为对照.粪便样品进行了全基因组鸟枪宏基因组测序。
■39名qCD+S患者,274qCD-S,21张活动CD,40腹泻型肠易激综合征,纳入50名健康对照进行分析.qCD+S患者的微生物组多样性较低。此外,qCD+S患者表现出口腔微生物组正常居民的细菌种类显著富集(例如,有核梭杆菌)和硫化物微生物(例如,嗜双菌属。).重要的丁酸盐和吲哚生产者的消耗(如Eubacteriumrectale,prausnitzii粪杆菌)在qCDS中也被注意到。半胱氨酸和蛋氨酸代谢中潜在的宏基因组相关功能变化,ATP转运,氧化还原反应在qCD+S中受到干扰,也提示硫代谢改变。最后,qCD+S显示细菌tnaA基因显著减少,介导色氨酸代谢为吲哚,与qCD-S相比,tnaA等位基因变异显著。
■qCD+S中的微生物组显示出显著的差异,丁酸生产者,与qCD-S和活性CD相比,通常是口腔微生物。这些结果表明,炎症可能导致持久的微生物组改变,这些改变可能通过可测试的机制介导持续的症状。
UNASSIGNED: Even in the absence of inflammation, persistent symptoms in Crohn\'s disease (CD) are prevalent and worsen quality of life. Amongst patients without inflammation (quiescent CD), we hypothesized that microbial community structure and function, including tryptophan metabolism, would differ between patients with persistent symptoms (qCD + S) and without persistent symptoms (qCD-S).
UNASSIGNED: We performed a multicenter observational study nested within the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease. Quiescent inflammation was defined by fecal calprotectin level <150 mcg/g. Persistent symptoms were defined by Crohn\'s Disease Patient-Reported Outcome-2. Active CD, diarrhea-predominant irritable bowel syndrome, and healthy controls were included as controls. Stool samples underwent whole-genome shotgun metagenomic sequencing.
UNASSIGNED: Thirty-nine patients with qCD + S, 274 qCD-S, 21 active CD, 40 diarrhea-predominant irritable bowel syndrome, and 50 healthy controls were included for analysis. Patients with qCD + S had a less-diverse microbiome. Furthermore, patients with qCD + S showed significant enrichment of bacterial species that are normal inhabitants of the oral microbiome (eg Rothia dentocariosa, Fusobacterium nucleatum) and sulfidogenic microbes (eg Prevotella copri, Bilophila spp.). Depletion of important butyrate and indole producers (eg Eubacterium rectale, Faecalibacterium prausnitzii) was also noted in qCD + S. Potential metagenome-related functional changes in cysteine and methionine metabolism, ATP transport, and redox reactions were disturbed in qCD + S, also suggestive of altered sulfur metabolism. Finally, qCD + S showed significant reductions in bacterial tnaA genes, which mediate tryptophan metabolism to indole, and significant tnaA allelic variation compared with qCD-S.
UNASSIGNED: The microbiome in qCD + S showed significant differences in sulfidogenesis, butyrate producers, and typically oral microbes compared to qCD-S and active CD. These results suggest that inflammation may lead to durable microbiome alterations which may mediate persistent symptoms through testable mechanisms.