Department of Internal Medicine I, Gastroenterology, Hepatology, Metabolism & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria.
Christian Doppler Laboratory for Mucosal Immunology, Medical University of Innsbruck, Innsbruck, Austria.
J Crohns Colitis. 2021 Jan 13;15(1):88-98. doi: 10.1093/ecco-jcc/jjaa152.
The microbial ecosystem seems to be an important player for therapeutic intervenption in inflammatory bowel disease [IBD]. We assessed longitudinal microbiome changes in IBD patients undergoing therapy with either azathioprine [AZA] or anti-tumour necrosis factor [anti-TNF] antibodies. We predicted the metabolic microbial community exchange and linked it to clinical outcome.
Faecal and blood samples were collected from 65 IBD patients at baseline and after 12 and 30 weeks on therapy. Clinical remission was defined as Crohn's Disease Activity Index [CDAI] < 150 in Crohn´s disease [CD], partial Mayo score <2 in ulcerative colitis [UC], and faecal calprotectin values <150 µg/g and C-reactive protein <5 mg/dl. 16S rRNA amplicon sequencing was performed. To predict microbial community metabolic processes, we constructed multispecies genome-scale metabolic network models.
Paired Bray-Curtis distance between baseline and follow-up time points was significantly different for UC patients treated with anti-TNF antibodies. Longitudinal changes in taxa composition at phylum level showed a significant decrease of Proteobacteria and an increase of Bacteroidetes in CD patients responding to both therapies. At family level, Lactobacilli were associated with persistent disease and Bacteroides abundance with remission in CD. In-silico simulations of microbial metabolite exchange predicted a 1.7-fold higher butyrate production capacity of patients in remission compared with patients without remission [p = 0.041]. In this model, the difference in butyrate production between patients in remission and patients without remission was most pronounced in the CD group treated with AZA [p = 0.008].
In-silico simulation identifies microbial butyrate synthesis predictive of therapeutic efficacy in IBD.
微生物生态系统似乎是炎症性肠病（IBD）治疗干预的重要参与者。我们评估了接受硫唑嘌呤（AZA）或抗肿瘤坏死因子（抗-TNF）抗体治疗的 IBD 患者的纵向微生物组变化。我们预测了代谢微生物群落的交换，并将其与临床结果联系起来。
从 65 名 IBD 患者中收集粪便和血液样本，分别在基线时、治疗 12 周和 30 周时进行。克罗恩病（CD）的临床缓解定义为克罗恩病活动指数（CDAI）<150，溃疡性结肠炎（UC）的部分 Mayo 评分<2，粪便钙卫蛋白值<150μg/g 和 C 反应蛋白<5mg/dl。进行 16S rRNA 扩增子测序。为了预测微生物群落的代谢过程，我们构建了多物种基因组规模的代谢网络模型。
接受抗-TNF 抗体治疗的 UC 患者基线和随访时间点之间的配对 Bray-Curtis 距离有显著差异。在对两种治疗均有反应的 CD 患者中，门水平的分类群组成的纵向变化显示变形菌门的数量显著减少，拟杆菌门的数量增加。在科水平，乳杆菌与持续性疾病相关，而拟杆菌丰度与 CD 缓解相关。微生物代谢物交换的计算机模拟预测，缓解组患者的丁酸产量比未缓解组高 1.7 倍（p=0.041）。在该模型中，AZA 治疗的 CD 缓解组患者的丁酸产量差异最显著（p=0.008）。
计算机模拟鉴定出了微生物丁酸合成与 IBD 治疗疗效相关的预测因子。
