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药物对克罗恩病肠道微生物群的影响。

The Effect of Drugs on the Intestinal Microbiota in Crohn's Disease.

作者信息

Yang Xue, Zhang Yinghui, Gao Caiping, Pan Yan, Du Shan, Xiao Shiyu, Zhou Zhou

机构信息

Department of Gastroenterology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.

出版信息

Biomedicines. 2024 Oct 1;12(10):2241. doi: 10.3390/biomedicines12102241.

DOI:10.3390/biomedicines12102241
PMID:39457554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11504731/
Abstract

OBJECTIVE

We took advantage of a single-center cross-sectional study to investigate the effect of different drugs on intestinal microbiota and function in Crohn's disease.

METHODS

We studied the difference in fecal microbiota of Crohn's disease patients treated with mesalazine, azathioprine, and infliximab, as well as untreated patients, by metagenome and screened for differential microbiota. Further, we investigated functional differences in intestinal microbiota among the four groups.

RESULTS

Through metagenomic sequencing, we found that there was no difference between the four groups in ACE and Chao1 indices, but IFX and mesalazine improved species diversity and homogeneity compared to the untreated group, as evidenced by statistically significant differences in the Shannon index, Simpson index, and pielou_evenness. In addition, beta diversity suggested a difference between groups, but the difference was not significant. Non-parametric tests revealed differences between the four groups at the phylum level, class level, and genus level. Further analysis by LEfSe analysis revealed that the level of short-chain fatty acid-producing microbiota was increased in the treated groups, while there was no difference between the treated groups when compared to each other. Finally, the KEGG database and EggNOG database revealed that there were functional differences in intestinal microbiota among the four groups, including microbial metabolism pathway, cysteine and methionine metabolism pathway, cytoskeleton, etc. Conclusions: Mesalazine, azathioprine, and infliximab can all affect the intestinal microbiota and function in patients with Crohn's disease, and the drugs may alleviate intestinal inflammation in patients with Crohn's disease by modulating the intestinal microbiota.

摘要

目的

我们利用一项单中心横断面研究来调查不同药物对克罗恩病肠道微生物群及其功能的影响。

方法

我们通过宏基因组学研究了接受美沙拉嗪、硫唑嘌呤和英夫利昔单抗治疗的克罗恩病患者以及未治疗患者粪便微生物群的差异,并筛选出差异微生物群。此外,我们还研究了这四组患者肠道微生物群的功能差异。

结果

通过宏基因组测序,我们发现四组患者的ACE和Chao1指数没有差异,但与未治疗组相比,英夫利昔单抗和美沙拉嗪改善了物种多样性和均匀度,香农指数、辛普森指数和pielou均匀度的统计学显著差异证明了这一点。此外,β多样性表明组间存在差异,但差异不显著。非参数检验显示四组在门水平、纲水平和属水平上存在差异。通过LEfSe分析进一步分析发现,治疗组中产生短链脂肪酸的微生物群水平有所增加,而治疗组之间相互比较时没有差异。最后,KEGG数据库和EggNOG数据库显示,四组患者肠道微生物群存在功能差异,包括微生物代谢途径、半胱氨酸和甲硫氨酸代谢途径、细胞骨架等。结论:美沙拉嗪、硫唑嘌呤和英夫利昔单抗均可影响克罗恩病患者的肠道微生物群及其功能,这些药物可能通过调节肠道微生物群来减轻克罗恩病患者的肠道炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/b9962a2cfe98/biomedicines-12-02241-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/6e04955aa7dc/biomedicines-12-02241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/d8049771a9c3/biomedicines-12-02241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/05fdf067a84e/biomedicines-12-02241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/2a9f581b3094/biomedicines-12-02241-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/fc266ec001ea/biomedicines-12-02241-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/b9962a2cfe98/biomedicines-12-02241-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/6e04955aa7dc/biomedicines-12-02241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/d8049771a9c3/biomedicines-12-02241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/05fdf067a84e/biomedicines-12-02241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/2a9f581b3094/biomedicines-12-02241-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/fc266ec001ea/biomedicines-12-02241-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/11504731/b9962a2cfe98/biomedicines-12-02241-g006.jpg

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本文引用的文献

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Roles of Short-Chain Fatty Acids in Inflammatory Bowel Disease.短链脂肪酸在炎症性肠病中的作用。
Nutrients. 2023 Oct 21;15(20):4466. doi: 10.3390/nu15204466.
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Comparison of the Strengths and Weaknesses of Machine Learning Algorithms and Feature Selection on KEGG Database Microbial Gene Pathway Annotation and Its Effects on Reconstructed Network Topology.比较机器学习算法和特征选择在 KEGG 数据库微生物基因途径注释中的优缺点及其对重建网络拓扑结构的影响。
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Gut Protective Effect from D-Methionine or Butyric Acid against DSS and Carrageenan-Induced Ulcerative Colitis.
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Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis.克罗恩病临床前期与免疫反应和屏障功能障碍相关的蛋白质组学特征凸显了发病机制的最早事件。
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Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation.细菌代谢产物对肠道屏障功能和宿主免疫的影响:关注细菌代谢及其与肠道炎症的相关性。
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