The gut microbiome in Crohn's disease and modulation by exclusive enteral nutrition
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AbstractBackgroundInflammatory bowel diseases (IBD), with Crohn’s disease (CD) being one of the primary types, have been extensively studied for genetic and gut microbial factors leading to its epidemic in the modern world. However, limited information using metagenomic shotgun-sequencing to pinpoint the gut microbial species and functions involved. Exclusive enteral nutrition (EEN) is a nutritional therapy used for disease-modifying treatment of CD, but its impact on the gut microbiome remains unclear. ResultsWe collected 123 stool samples from 49 CD patients, 14 of whom were resampled after 2 weeks of EEN, and 56 subjects with no disease. Metagenomic shotgun sequencing and analyses confirmed a decreased diversity in the gut microbiota of CD patients, and identified microbial species and potential functions altered in CD, most notably an increased ratio of hexa- to penta-acylated lipopolysaccharide (LPS). Some co-abundance gene groups (CAGs) including Parabacteroides distasonis, Bacteroides intestinalis, Ruminococcus sp. showed strong correlation with clinical indicators such as hs.CRP, Prealbumin, platelets and BMI. The entire cohort could be divided into three types according to their species composition, with Type A largely consisting of healthy controls and Type C containing exclusively CD or after EEN samples. Although compositional changes were generally mild after 2 weeks of EEN, remodeling of the gut microbial network could be observed.ConclusionsOur metagenomic dataset unlock the gut microbiome in CD for functional investigations. Microbiome-based stratification of CD patients before EEN might help optimize the therapy for wider applications.
摘要 背景：炎症性肠病（Inflammatory Bowel Diseases, IBD）以克罗恩病（Crohn’s Disease, CD）为主要类型之一，学界已针对其在现代社会流行的遗传与肠道微生物组相关致病因素开展了大量研究，但目前利用宏基因组鸟枪测序（metagenomic shotgun-sequencing）技术精准定位参与疾病发生的肠道微生物物种与功能的相关报道仍较为有限。专属肠内营养（Exclusive Enteral Nutrition, EEN）是一种用于克罗恩病疾病修饰治疗的营养疗法，但其对肠道微生物组的影响尚不明确。 结果：本研究共收集49名克罗恩病患者的123份粪便样本，其中14名患者在接受2周专属肠内营养治疗后完成二次采样，同时纳入56名健康对照受试者。通过宏基因组鸟枪测序与分析，证实克罗恩病患者的肠道菌群多样性显著降低，并鉴定出克罗恩病患者中发生异常改变的微生物物种与潜在功能，其中最为突出的变化为六酰化与五酰化脂多糖（Lipopolysaccharide, LPS）的比值升高。部分共丰度基因簇（Co-abundance Gene Groups, CAGs），包括狄氏副拟杆菌（Parabacteroides distasonis）、肠道拟杆菌（Bacteroides intestinalis）、瘤胃球菌属（Ruminococcus sp.）物种，与超敏C反应蛋白（hs-CRP）、前白蛋白、血小板计数及体质量指数（BMI）等临床指标存在显著相关性。研究全部队列可根据物种组成划分为三种菌群类型：A型主要由健康对照受试者组成，C型则仅包含克罗恩病患者样本或专属肠内营养治疗后的样本。尽管接受2周专属肠内营养治疗后菌群组成的整体变化较为轻微，但仍可观察到肠道微生物网络的重塑。 结论：本研究产生的宏基因组数据集为克罗恩病肠道微生物组的功能研究提供了重要资源。基于肠道微生物组对专属肠内营养治疗前的克罗恩病患者进行分层，或有助于优化该疗法，拓展其临床应用范围。
