Centre of Molecular Inflammation Research, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Inflamm Bowel Dis. 2024 Jul 3;30(7):1164-1177. doi: 10.1093/ibd/izad289.
There is growing evidence of the role of the mycobiome in inflammatory bowel disease (IBD). Variations within phenotypes and activity and with prognosis have been poorly studied.
A total of 111 individuals were prospectively enrolled: 89 IBD patients (52 ulcerative colitis and 37 Crohn's disease [CD]) and 22 healthy individuals. Disease characteristics were collected and a fecal calprotectin >100 μg/mg was considered indicative of activity. A subset of patients was followed for 6 ± 2 years. Disease course was designated as either complicated or uncomplicated based on the need of intensified medication and/or surgery. ITS sequencing was performed targeting the ITS1 region.
We found lower Ascomycota/Basidiomycota ratio in IBD. Patients showed a marked increase in Candida dublinensis and Ca albicans and were depleted of Aspergillus rubrobrunneus and Penicillium brevicompactum (P ≤ .001) Saccharomyces was predominant in total colitis and Penicillium in proctitis. Several Penicillium species were depleted in total colitis vs proctitis. Ileal CD patients were enriched in Debaromyces hansenii and depleted of Ca tropicalis (P ≤ .001). Ca albicans was overrepresented in inflammatory (B1) vs fibrostenosing (B2) CD. Ca dublinensis was more abundant in active patients and correlated positively with fecal calprotectin and neutrophil gelatinase-associated lipocalin, while S pastorianus correlated inversely with activity. Ca sake was associated with complicated disease and increased abundance of Cryptococcus carnescens with the need for surgery in CD.
This study shows important differences in the mycobiome in IBD and within phenotypes. Selected fungal species were associated with complicated disease and the need of surgery in CD. This work adds to our understanding of the role of fungi in IBD, with potential clinical implications.
越来越多的证据表明真菌群落与炎症性肠病(IBD)有关。表型和活动的变化及其预后尚未得到充分研究。
共前瞻性纳入 111 名个体:89 名 IBD 患者(52 例溃疡性结肠炎和 37 例克罗恩病[CD])和 22 名健康个体。收集疾病特征,粪便钙卫蛋白>100μg/mg 被认为是活动的指征。部分患者随访 6±2 年。根据是否需要强化药物治疗和/或手术,将疾病过程定义为复杂或不复杂。ITS 测序针对 ITS1 区域进行。
我们发现 IBD 患者的子囊菌/担子菌比值较低。患者的假丝酵母属(Candida dublinensis 和 C. albicans)明显增加,而深红被孢霉(A. rubrobrunneus)和短密青霉(P. brevicompactum)减少(P≤0.001)。在全结肠炎中以酿酒酵母(Saccharomyces)为主,在直肠炎中以青霉属(Penicillium)为主。全结肠炎中几种青霉属物种减少,而直肠炎中则增加。回肠 CD 患者富含德巴利酵母(Debaromyces hansenii),而热带假丝酵母(C. tropicalis)减少(P≤0.001)。白假丝酵母(C. albicans)在炎症性(B1)CD 中更为常见,而纤维化狭窄性(B2)CD 中则较少。在活动患者中,假丝酵母(C. dublinensis)较多,与粪便钙卫蛋白和中性粒细胞明胶酶相关脂质运载蛋白呈正相关,而 S. pastorianus 与活性呈负相关。假丝酵母(C. sake)与 CD 中复杂疾病有关,隐球菌(Cryptococcus carnescens)丰度增加与手术有关。
本研究表明 IBD 及表型内的真菌群落存在重要差异。一些真菌物种与 CD 中的复杂疾病和手术需求有关。这项工作增加了我们对真菌在 IBD 中作用的理解,具有潜在的临床意义。