Microbial and metabolic features associated with outcome of infliximab therapy in pediatric Crohn's disease.
Microbial and metabolic features associated with outcome of infliximab therapy in pediatric Crohn's disease.
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与英夫利昔单抗治疗儿科克罗恩病结果相关的微生物和代谢特征
DOI：
10.1080/19490976.2020.1865708
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发表时间：
2021-01
期刊：
影响因子：
12.2
通讯作者：
Zhang T
中科院分区：
文献类型：
--
作者：
Wang Y;Gao X;Zhang X;Xiao F;Hu H;Li X;Dong F;Sun M;Xiao Y;Ge T;Li D;Yu G;Liu Z;Zhang T
肠道微生物生态失调和代谢组学改变与克罗恩病（CD）的发病机制有关。我们研究的目的是描述在英夫利西单抗（IFX）治疗后具有不同临床结局的儿童CD患者的肠道微生物组结构和代谢活性。收集了20名健康儿童和29名新诊断的儿童CD患者的粪便样本。16 S rRNA/ITS 2基因测序和靶向代谢组学分析分别用于分析肠道细菌微生物组、真菌组和代谢组。儿童CD患者表现出较低的相对丰度的短链脂肪酸（SCFAs）生产细菌，包括粪杆菌，梭菌簇IV和XIVb，罗斯拜瑞氏菌属，和瘤胃球菌，这与减少粪便中的SCFAs水平。减少未结合胆汁酸（BA）池的大小和较低的未结合/结合的BA的比例与减少相对丰度的双歧杆菌和梭菌簇IV和XIVb含有胆盐水解酶（BSH）基因。IFX治疗富集了CD受试者中的产生FSH的细菌，这可以解释结合型BA水平降低和未结合型BA以及未结合型/结合型BA比率增加。此外，IFX治疗的持续应答（SR）与基线时甲基杆菌、鞘氨醇单胞菌、葡萄球菌和链球菌的丰度较高以及粪便中氨基酸（包括L-天冬氨酸、亚油酸和L-乳酸）浓度较高相关。我们的研究表明，IFX的影响可能部分介导的富集细菌类群，产生SCFAs和BSH，从而抑制炎症和恢复BA代谢。某些粪便细菌和代谢产物可能预测儿童CD患者IFX治疗的结局。
Gut microbial dysbiosis and altered metabonomics have been implicated in the pathogenesis of Crohn’s disease (CD). The aim of our study was to characterize the gut microbiome structure and metabolic activities in pediatric CD patients with different clinical outcomes after infliximab (IFX) therapy. Fecal samples were collected from 20 healthy children and 29 newly diagnosed pediatric CD patients. 16S rRNA/ITS2 gene sequencing and targeted metabolomics analysis were applied to profile the gut bacterial microbiome, mycobiome, and metabolome, respectively. Pediatric CD patients exhibited lower relative abundances of short-chain fatty acids (SCFAs)-producing bacteria including Faecalibacterium, Clostridium clusters IV and XIVb, Roseburia, and Ruminococcus, which were correlated with reduced fecal levels of SCFAs. Decreased unconjugated bile acids (BAs) pool size and a lower unconjugated/conjugated BAs ratio were associated with reduced relative abundances of Bifidobacterium and Clostridium clusters IV and XIVb which contain bile salt hydrolases (BSH) genes. IFX treatment enriched the BSH-producing bacteria in CD subjects, which may explain a decreased level of conjugated BAs and an increase in unconjugated BAs as well as the unconjugated/conjugated BAs ratio. Furthermore, a sustained response (SR) of IFX therapy was associated with higher abundances of Methylobacterium, Sphingomonas, Staphylococcus, and Streptococcus, and higher fecal concentrations of amino acids, including L-aspartic acid, linoleic acid, and L-lactic acid at baseline. Our study suggests that the effects of IFX might be partially mediated by enriching bacteria taxa that producing SCFAs and BSH thereby inhibiting inflammation and restoring the BA metabolism. Some fecal bacteria and metabolites may be predictive of outcomes of IFX therapy for pediatric CD patients.
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