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肾移植受者肠道微生物群的特征与失调

Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients.

作者信息

Swarte J Casper, Douwes Rianne M, Hu Shixian, Vich Vila Arnau, Eisenga Michele F, van Londen Marco, Gomes-Neto António W, Weersma Rinse K, Harmsen Hermie J M, Bakker Stephan J L

机构信息

Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands.

Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands.

出版信息

J Clin Med. 2020 Feb 1;9(2):386. doi: 10.3390/jcm9020386.

Abstract

Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5-12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome ( < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs ( < 0.05). Use of mycophenolate mofetil correlated to a lower diversity ( < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome.

摘要

肾移植在许多方面都能改变生活。这包括可能由于接触免疫抑制药物和抗生素而导致的肠道微生物群变化。因此,肾移植受者(RTRs)可能会出现肠道菌群失调。我们旨在研究RTRs的肠道微生物群,并将其与健康对照进行比较,以确定RTRs肠道微生物群的决定因素。因此,纳入了参与移植线生物样本库和队列研究(NCT03272841)的RTRs和健康对照。我们使用16S rRNA测序分析肠道微生物群,并使用线性模型多变量关联(MaAsLin)将RTRs的肠道微生物群组成与健康对照进行比较。收集了139名RTRs(50%为男性,平均年龄:58.3±12.8岁)和105名健康对照(57%为男性,平均年龄:59.2±10.6岁)的粪便样本。RTRs移植后的中位时间为6.0(1.5 - 12.5)年。RTRs的微生物群组成与健康对照有显著差异,且RTRs的肠道微生物群多样性较低(<0.01)。质子泵抑制剂、霉酚酸酯和估计肾小球滤过率(eGFR)是RTRs肠道微生物群的重要决定因素(<0.05)。霉酚酸酯的使用与较低的多样性相关(<0.01)。此外,在RTRs和健康对照之间的多个细菌类群中发现了显著变化。RTRs的肠道微生物群中变形菌门更多,放线菌门更少,并且RTRs的肠道微生物群中产生丁酸盐的细菌减少。通过将RTRs的肠道微生物群与健康对照进行比较,我们表明RTRs存在菌群失调,即肠道微生物群平衡的破坏。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5da3/7074359/55fb036d4344/jcm-09-00386-g001.jpg

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