张婷、刘占举等:肠道菌群组成及代谢影响英夫利昔单抗对儿童克罗恩病的疗效
创作:吴芹 审核:aluba 01月20日
  • 纳入29名CD患儿及20名健康儿童,患儿的粪便菌群中,粪杆菌属等SCFA产生菌的丰度较低,且粪便SCFA水平降低,非结合胆汁酸水平降低;
  • IFX治疗使CD患儿粪便中的BSH产生菌富集,从而导致结合胆汁酸水平降低、非结合胆汁酸水平升高,非结合/结合胆汁酸的比例升高;
  • 对IFX治疗的持续应答与治疗前较高的甲基杆菌属、鞘氨醇单胞菌属、葡萄球菌属及链球菌属丰度,及较高的粪便L-天冬氨酸、亚油酸和L-乳酸浓度相关。
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上海市儿童医院的张婷团队、于广军团队及上海市第十人民医院的刘占举团队在Gut Microbes上发表的一项最新研究,发现克罗恩病(CD)患儿肠道菌群中的短链脂肪酸(SCFA)产生菌减少,且粪便中的SCFA及非结合胆汁酸的水平降低,而英夫利昔单抗(IFX)治疗可通过富集SCFA和胆盐水解酶(BSH)产生菌,从而抑制炎症,并恢复胆汁酸代谢。另外,该研究鉴定出了与对IFX治疗持续应答相关的特定菌属及粪便代谢产物。
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Gut Microbes [IF:7.74]

Microbial and metabolic features associated with outcome of infliximab therapy in pediatric Crohn’s disease

与英夫利昔单抗治疗儿童克罗恩病结局相关的菌群和代谢特征

10.1080/19490976.2020.1865708

01-11, Article

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Abstract:收起
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.

First Authors:
YiZhong Wang,Xuefeng Gao

Correspondence Authors:
YiZhong Wang,Zhanju Liu,Ting Zhang

All Authors:
YiZhong Wang,Xuefeng Gao,Xinyue Zhang,Fangfei Xiao,Hui Hu,Xiaolu Li,Fang Dong,Mingming Sun,Yongmei Xiao,Ting Ge,Dan Li,Guangjun Yu,Zhanju Liu,Ting Zhang

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