Wu Richard Y, Tandon Parul, Oh Joyce S, Ambrosio Lindsy, Hotte Naomi, Shah-Gandhi Binal, Madsen Karen L, Dieleman Levinus A, Elahi Shokrollah, Kroeker Karen I, Huang Vivian
Department of Medicine, University of Toronto, Toronto, Canada.
Division of Gastroenterology, Mount Sinai Hospital, Toronto, Canada.
Gastro Hep Adv. 2022 Jul 19;1(6):993-1005. doi: 10.1016/j.gastha.2022.07.008. eCollection 2022.
Inflammatory bowel disease (IBD), inclusive of ulcerative colitis and Crohn's disease, are chronic inflammatory conditions that impact women of childbearing age. It has been previously shown that IBD is associated with altered metabolomic profiles, but whether metabolomic changes also affect pregnant patients with IBD is completely unknown.
This was a prospective cohort study comprised of 48 pregnant women with IBD who were followed throughout preconception and pregnancy. IBD disease activity was measured using biochemical markers C-reactive protein or fecal calprotectin using enzyme-linked immunosorbent assay and clinical disease activity using Harvey-Bradshaw Index or partial Mayo scores. Serum and urine samples were collected from preconception, trimester 1, and trimester 2 and analyzed using nuclear magnetic resonance spectroscopy combined with metabolomics set enrichment analysis.
We identified a total of 24 urine metabolites and 17 serum metabolites which were altered by active disease across pregnancy. First trimester (T1) active disease-associated metabolites were enriched in "amino acid metabolism" and "fatty-acid β-oxidation." The leading urine metabolites at T1 were trimethyl-N-oxide (TMAO), succinic acid, and 3-hydroxy-2-methylbutyric acid, and leading serum metabolites were TMAO, glucose, and acetic acid. Multivariate modeling using serum TMAO, glucose, and acetic acid predicts T1 disease activity and correlated with mode of delivery and infant weights at delivery. Moreover, cross-time point modeling using metabolomes predicted future disease flare-up during pregnancy.
These results suggest select host metabolites may be able to discriminate and predict disease activity and are correlated with pregnancy outcomes at delivery. This warrants further validation of metabolomics to monitor IBD in pregnancy.
炎症性肠病（IBD），包括溃疡性结肠炎和克罗恩病，是影响育龄女性的慢性炎症性疾病。此前已有研究表明，IBD与代谢组学特征改变有关，但代谢组学变化是否也会影响患有IBD的孕妇则完全未知。
这是一项前瞻性队列研究，纳入了48名患有IBD的孕妇，在孕前和孕期对她们进行随访。使用酶联免疫吸附测定法通过生化标志物C反应蛋白或粪便钙卫蛋白测量IBD疾病活动度，使用哈维-布拉德肖指数或部分梅奥评分评估临床疾病活动度。在孕前、孕1期和孕2期采集血清和尿液样本，采用核磁共振波谱结合代谢组学集富集分析进行分析。
我们共鉴定出24种尿液代谢物和17种血清代谢物，这些代谢物在整个孕期会因活动性疾病而发生改变。孕1期（T1）与活动性疾病相关的代谢物在“氨基酸代谢”和“脂肪酸β-氧化”中富集。T1期主要的尿液代谢物是氧化三甲胺（TMAO）、琥珀酸和3-羟基-2-甲基丁酸，主要的血清代谢物是TMAO、葡萄糖和乙酸。使用血清TMAO、葡萄糖和乙酸进行多变量建模可预测T1期疾病活动度，并与分娩方式和出生时婴儿体重相关。此外，使用代谢组进行跨时间点建模可预测孕期未来的疾病复发。
这些结果表明，特定的宿主代谢物可能能够区分和预测疾病活动度，并与分娩时的妊娠结局相关。这需要进一步验证代谢组学以监测孕期的IBD。
