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慢性炎症性肠病中病原菌和宿主基因多态性的差异流行:克罗恩病和肠结核。

Differential prevalence of pathobionts and host gene polymorphisms in chronic inflammatory intestinal diseases: Crohn's disease and intestinal tuberculosis.

机构信息

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.

出版信息

PLoS One. 2021 Aug 18;16(8):e0256098. doi: 10.1371/journal.pone.0256098. eCollection 2021.

Abstract

BACKGROUND AND OBJECTIVES

Crohn's disease (CD) and Intestinal tuberculosis (ITB) are chronic inflammatory ulcero-constrictive intestinal diseases with similar phenotype. Although both are disease models of chronic inflammation and their clinical presentations, imaging, histological and endoscopic findings are very similar, yet their etiologies are diverse. Hence, we aimed to look at differences in the prevalence of pathobionts like adherent-invasive Escherichia coli (AIEC), Listeria monocytogenes, Campylobacter jejuni and Yersinia enterocolitica in CD and ITB as well as their associations with host-associated genetic polymorphisms in genes majorly involved in pathways of microbial handling and immune responses.

METHODS

The study cohort included 142 subjects (69 patients with CD, 32 with ITB and 41 controls). RT- PCR amplification was used to detect the presence of AIEC, L. monocytogenes, C. jejuni, and Y. enterocolitica DNA in colonic mucosal biopsies. Additionally, we tested three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and one SNP in TNFRSF1A (rs4149570) by real-time PCR with SYBR green from peripheral blood samples in this cohort.

RESULTS

In patients with CD, AIEC was most frequently present (16/ 69, 23.19%) followed by L. monocytogenes (14/69, 20.29%), C. jejuni (9/69, 13.04%), and Y. enterocolitica (7/69, 10.14%). Among them, L. monocytogenes and Y. enterocolitica were significantly associated with CD (p = 0.02). In addition, we identified all the three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and TNFRSF1A (rs4149570) with a significant difference in frequency in patients with CD compared with ITB and controls (p<0.05).

CONCLUSION

Higher prevalence of host gene polymorphisms, as well as the presence of pathobionts, was seen in the colonic mucosa of patients with CD as compared to ITB, although both are disease models of chronic inflammation.

摘要

背景与目的

克罗恩病(CD)和肠结核(ITB)是两种具有相似表型的慢性炎症性、溃疡性、狭窄性肠道疾病。尽管两者都是慢性炎症性疾病模型,其临床表现、影像学、组织学和内镜表现非常相似,但病因却各不相同。因此,我们旨在研究黏附侵袭性大肠杆菌(AIEC)、李斯特菌、空肠弯曲菌和耶尔森菌等病原体在 CD 和 ITB 中的流行情况及其与宿主相关遗传多态性的差异,这些多态性主要涉及微生物处理和免疫反应途径。

方法

本研究队列包括 142 名受试者(69 名 CD 患者、32 名 ITB 患者和 41 名对照组)。使用 RT-PCR 扩增法检测结肠黏膜活检组织中 AIEC、李斯特菌、空肠弯曲菌和耶尔森菌 DNA 的存在情况。此外,我们还通过该队列中的外周血样本,用实时 PCR 与 SYBR 绿检测 IRGM 中的三个单核苷酸多态性(rs13361189、rs10065172 和 rs4958847)、ATG16L1 中的一个单核苷酸多态性(rs2241880)和 TNFRSF1A 中的一个单核苷酸多态性(rs4149570)。

结果

在 CD 患者中,AIEC 最为常见(69 例中的 16 例,23.19%),其次是李斯特菌(14/69,20.29%)、空肠弯曲菌(9/69,13.04%)和耶尔森菌(7/69,10.14%)。其中,李斯特菌和耶尔森菌与 CD 显著相关(p=0.02)。此外,我们发现 IRGM 中的三个单核苷酸多态性(rs13361189、rs10065172 和 rs4958847)、ATG16L1 中的一个单核苷酸多态性(rs2241880)和 TNFRSF1A 中的一个单核苷酸多态性(rs4149570)在 CD 患者中的频率与 ITB 和对照组有显著差异(p<0.05)。

结论

与 ITB 相比,CD 患者结肠黏膜中宿主基因多态性的存在以及病原体的存在更为普遍,尽管两者都是慢性炎症性疾病模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aad3/8372915/bec739b202fd/pone.0256098.g001.jpg

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