Abstract：
Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn\'s disease (CD) and the development of CD. Here, we utilize HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. When compared to non-relative controls, the use of HFDR controls identifies fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter are decreased in CD-R, independent of inflammation, and correlated with fecal short-chain fatty acids (SCFAs). Validation with a large multi-center cohort confirms decreased Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguish CD from healthy individuals and demonstrate superior diagnostic power than models constructed with markers identified using unrelated controls. Furthermore, these markers exhibited limited discriminatory capabilities for other diseases. Finally, our results are validated across multiple cohorts, underscoring their robustness and potential for diagnostic and therapeutic applications.
摘要：
先前的研究表明，克罗恩病（CD）患者的健康一级亲属（HFDRs）的肠道微生物与CD的发展之间没有相关性。这里,我们利用HFDRs作为对照来检查活跃（CD-A）和静止（CD-R）CD个体的微生物群和代谢组，从而最大限度地减少遗传和环境因素的影响。与非相对对照相比，使用HFDR对照可以识别出更少的差异分类单元。粪杆菌,Dorea,CD-R中镰刀菌减少，独立于炎症，并与粪便短链脂肪酸（SCFA）相关。使用大型多中心队列进行的验证证实了CD-R中粪杆菌和其他产生SCFA的属的减少。基于这些属的分类模型将CD与健康个体区分开，并显示出比使用无关对照鉴定的标记构建的模型更高的诊断能力。此外，这些标记对其他疾病的辨别能力有限.最后,我们的结果在多个队列中得到验证，强调它们的稳健性和诊断和治疗应用的潜力。
