Jangi Sushrut, Zhao Naisi, Hsia Katie, Park Young Soo, Michaud Dominique S, Yoon Hyuk
Department of Medicine, Tufts Medical Center, Boston, MA, USA.
Tufts University School of Medicine, Public Health and Community Medicine, Boston, MA, USA.
J Crohns Colitis. 2025 Jan 11;19(1). doi: 10.1093/ecco-jcc/jjae125.
While there is increasing interest in microbiome-directed therapies for patients with ulcerative colitis (UC), the identification of microbial targets remains elusive, underlining the need for novel approaches.
Utilizing 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 used a tree-based dichotomous approach to assemble distinct clusters of species-level bacterial co-abundance groups (CAGs). We evaluated the abundance of bacterial CAGs and fungal taxa during remission (n = 166) and activity (n = 46). We examined if the bacterial CAGs identified in our cohorts were conserved in 2 healthy cohorts and a Korean UC cohort.
CAG3 and CAG8, dominated by bacteria from the family Lachnospiraceae, were associated with remission. Low abundance of CAG8 and elevated abundance of Candida genus were predictive of active UC. Constituents from CAG8 were influential hub species of the remission-associated microbial UC network, including Ruminococcus gnavus, Erysipelatoclostridium ramosum, Blautia, and Dorea species. These hub species interactions were preserved in 2 healthy cohorts and were partially recapitulated in a Korean UC cohort. CAG8 abundance correlated with the secondary bile acid production pathway. Bacterial CAGs did not correlate with Candida; however, Bifidobacterium adolescentis and Alistipes putredinis were negatively associated with Candida.
Lachnospiraceae-dominated bacterial CAGs were associated with remission in UC, with key bacterial interactions within the CAG also observed in 2 healthy cohorts and a Korean UC cohort. Bacterial CAG-based analyses may aid in designing candidate consortia for microbiome-based therapeutics.
尽管针对溃疡性结肠炎（UC）患者的微生物群导向疗法越来越受到关注，但微生物靶点的识别仍然难以捉摸，这凸显了采用新方法的必要性。
利用来自炎症性肠病前瞻性成人研究队列（SPARC IBD）的宏基因组数据（可通过克罗恩病和结肠炎基金会的IBD Plexus计划获取），我们采用基于树的二分法来组装不同的物种水平细菌共丰度组（CAG）簇。我们评估了缓解期（n = 166）和活动期（n = 46）期间细菌CAG和真菌类群的丰度。我们检查了在我们的队列中鉴定出的细菌CAG在2个健康队列和1个韩国UC队列中是否保守。
以毛螺菌科细菌为主的CAG3和CAG8与缓解相关。CAG8丰度低和念珠菌属丰度升高可预测UC活动期。CAG8的成分是缓解相关微生物UC网络的有影响力的枢纽物种，包括迟缓瘤胃球菌、多枝梭菌、布劳特氏菌和瘤胃球菌属物种。这些枢纽物种间的相互作用在2个健康队列中得以保留，并在一个韩国UC队列中部分重现。CAG8丰度与次级胆汁酸生成途径相关。细菌CAG与念珠菌无相关性；然而，青春双歧杆菌和腐败阿利斯杆菌与念珠菌呈负相关。
以毛螺菌科为主的细菌CAG与UC缓解相关，在2个健康队列和1个韩国UC队列中也观察到了CAG内关键的细菌相互作用。基于细菌CAG的分析可能有助于设计基于微生物群的治疗候选菌群。
