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使用基线微生物组和代谢组学预测克罗恩病患者使用英夫利昔单抗后的早期缓解。

Prediction of early remission after infliximab in Crohn's disease using baseline microbiome and metabolomics.

机构信息

Department of general surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, PR China.

Jinling Clinical Medical College, Nanjing University of Chinese Medicine, PR China; Department of Anorectum, Shandong Second Provincial General Hospital, PR China.

出版信息

J Pharm Biomed Anal. 2024 Dec 15;251:116424. doi: 10.1016/j.jpba.2024.116424. Epub 2024 Aug 15.

DOI:10.1016/j.jpba.2024.116424
PMID:39180897
Abstract

To characterize the microbiome and metabolic profile in Crohn's disease (CD) patients with different outcome after infliximab (IFX) treatment. The clinical data of a cohort of 35 patients with moderate-to-severe CD admitted at Jinling hospital between Oct 2022 and Dec 2023 were collected. Stool samples at baseline were collected to perform 16SrRNA and ITS2 sequencing and LC-MS untargeted metabolomics. Of these, seven discontinued IFX and underwent surgery during the induction period, and 28 received IFX at weeks 0, 2, and 6, each administered intravenously. Clinical remission was assessed based on the clinical symptoms and HBI at baseline and week 14. Baseline microbial richness and evenness was not significantly different between remission and non-remission group. The taxonomic community analysis identified decrease of Ruminococcus, Lachnoclostridium, Akkermansia in bacterial community and decrease of Asterotremella and Wallemia in fungal community in the non-remission group. LC-MS analysis showed that histamine, creatinine and L-proline significantly increased in remission group, while androsterone, berberine and episterol significantly decreased. The combined prediction model of histamine, androsterone, and episterol demonstrated a high predictive value of remission in patients after IFX treatment (AUC=0.898, p<0.001). Together, these data might facilitate a priori determination of optimal therapeutics for CD patients.

摘要

为了描述克罗恩病(CD)患者在英夫利昔单抗(IFX)治疗后不同结局的微生物组和代谢特征。收集了 2022 年 10 月至 2023 年 12 月期间在金陵医院就诊的 35 名中重度 CD 患者的队列临床数据。在基线时收集粪便样本进行 16SrRNA 和 ITS2 测序和 LC-MS 非靶向代谢组学分析。其中,7 名患者在诱导期内停止使用 IFX 并接受了手术,28 名患者在第 0、2 和 6 周接受了 IFX 静脉注射治疗。根据基线和第 14 周的临床症状和 HBI 评估临床缓解。缓解组和未缓解组之间的基线微生物丰富度和均匀度没有显著差异。分类群社区分析发现,在细菌群落中,产努氏瘤胃球菌、lachnoclostridium 和阿克曼氏菌减少,真菌群落中 asterotremella 和 wallemia 减少。LC-MS 分析显示,在缓解组中组胺、肌酸和 L-脯氨酸显著增加,而雄甾酮、小檗碱和表甾醇显著降低。组胺、雄甾酮和表甾醇的联合预测模型显示,IFX 治疗后患者的缓解具有较高的预测价值(AUC=0.898,p<0.001)。总之,这些数据可能有助于预先确定 CD 患者的最佳治疗方法。

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