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急性感染性腹泻患儿微生物群的时间序列分析及其治疗后的恢复情况

Time Series Analysis of the Microbiota of Children Suffering From Acute Infectious Diarrhea and Their Recovery After Treatment.

作者信息

Dinleyici Ener C, Martínez-Martínez Daniel, Kara Ates, Karbuz Adem, Dalgic Nazan, Metin Ozge, Yazar Ahmet S, Guven Sirin, Kurugol Zafer, Turel Ozden, Kucukkoc Mehmet, Yasa Olcay, Eren Makbule, Ozen Metehan, Martí Jose Manuel, P Garay Carlos, Vandenplas Yvan, Moya Andrés

机构信息

Department of Pediatrics, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.

Institute for Integrative Systems Biology, Catedrático José Beltrán, Valencia, Spain.

出版信息

Front Microbiol. 2018 Jun 12;9:1230. doi: 10.3389/fmicb.2018.01230. eCollection 2018.

Abstract

Gut microbiota is closely related to acute infectious diarrhea, one of the leading causes of mortality and morbidity in children worldwide. Understanding the dynamics of the recovery from this disease is of clinical interest. This work aims to correlate the dynamics of gut microbiota with the evolution of children who were suffering from acute infectious diarrhea caused by a rotavirus, and their recovery after the administration of a probiotic, CNCM I-745. The experiment involved 10 children with acute infectious diarrhea caused by a rotavirus, and six healthy children, all aged between 3 and 4 years. The children who suffered the rotavirus infection received CNCM I-745 twice daily for the first 5 days of the experiment. Fecal samples were collected from each participant at 0, 3, 5, 10, and 30 days after probiotic administration. Microbial composition was characterized by 16S rRNA gene sequencing. Alpha and beta diversity were calculated, along with dynamical analysis based on Taylor's law to assess the temporal stability of the microbiota. All children infected with the rotavirus stopped having diarrhea at day 3 after the intervention. We observed low alpha diversities in the first 5 days (-value < 0.05, Wilcoxon test), larger at 10 and 30 days after probiotic treatment. Canonical correspondence analysis (CCA) showed differences in the gut microbiota of healthy children and of those who suffered from acute diarrhea in the first days (-value < 0.05, ADONIS test), but not in the last days of the experiment. Temporal variability was larger in children infected with the rotavirus than in healthy ones. In particular, class was found to be abundant in children with acute diarrhea. We identified the microbiota transition from a diseased state to a healthy one with time, whose characterization may lead to relevant clinical data. This work highlights the importance of using time series for the study of dysbiosis related to diarrhea.

摘要

肠道微生物群与急性感染性腹泻密切相关,急性感染性腹泻是全球儿童死亡和发病的主要原因之一。了解这种疾病恢复过程中的动态变化具有临床意义。这项研究旨在将肠道微生物群的动态变化与感染轮状病毒导致急性感染性腹泻的儿童的病情发展以及服用益生菌CNCM I-745后的恢复情况相关联。该实验涉及10名感染轮状病毒导致急性感染性腹泻的儿童和6名健康儿童,所有儿童年龄均在3至4岁之间。感染轮状病毒的儿童在实验的前5天每天接受两次CNCM I-745治疗。在服用益生菌后的0、3、5、10和30天从每位参与者采集粪便样本。通过16S rRNA基因测序对微生物组成进行表征。计算了α和β多样性,并基于泰勒定律进行动态分析以评估微生物群的时间稳定性。所有感染轮状病毒的儿童在干预后第3天停止腹泻。我们观察到前5天的α多样性较低(P值<0.05,威尔科克森检验),在益生菌治疗后的10天和30天较大。典范对应分析(CCA)显示,健康儿童与急性腹泻儿童在实验开始几天的肠道微生物群存在差异(P值<0.05,ADONIS检验),但在实验后期没有差异。感染轮状病毒的儿童的时间变异性大于健康儿童。特别是,在急性腹泻儿童中发现拟杆菌属丰富。我们确定了微生物群随时间从患病状态向健康状态的转变,其特征可能会产生相关的临床数据。这项研究强调了使用时间序列研究与腹泻相关的生态失调的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee5/6005867/7d1c5a333be9/fmicb-09-01230-g0001.jpg

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