Knoll Rebecca L, Forslund Kristoffer, Kultima Jens Roat, Meyer Claudius U, Kullmer Ulrike, Sunagawa Shinichi, Bork Peer, Gehring Stephan
Children's Hospital, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Am J Physiol Gastrointest Liver Physiol. 2017 Apr 1;312(4):G327-G339. doi: 10.1152/ajpgi.00293.2016. Epub 2016 Dec 30.
Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney -test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., and , were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like were enriched in UC patients (MWU FDR = 0.084). Moreover, abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD.
目前针对儿童炎症性肠病（IBD）患者的治疗往往无效，且伴有严重的副作用。通过粪便微生物群移植（FMT）来调控肠道微生物群是一种新兴的治疗方法，但仍存在争议。我们旨在通过比较儿童IBD患者与其健康同胞的粪便微生物组组成，评估在这种情况下FMT的风险和前景。开展了一项病例对照（同胞）研究，通过宏基因组测序分析6名克罗恩病（CD）患儿、6名溃疡性结肠炎（UC）患儿和12名健康同胞的粪便样本。此外，回顾性确定了终生抗生素摄入量。与对照组相比，UC患者的物种丰富度和多样性显著降低[曼-惠特尼检验错误发现率（MWU FDR）=0.011]。在UC中，对肠道稳态有积极影响的细菌，如[具体细菌名称1]和[具体细菌名称2]，其丰度显著降低（MWU FDR=0.05）。像[具体致病共生菌名称]这样的已知致病共生菌在UC患者中富集（MWU FDR=0.084）。此外，[具体细菌名称]的丰度与几种毒力基因的丰度呈正相关（斯皮尔曼相关系数>0.65，FDR<0.1）。两个IBD组均出现向抗生素耐药菌群的转变，这使其与对照组区分开来[UC中MWU本雅明尼-霍赫贝格-耶库蒂埃利程序（BY）FDR=0.062，CD中MWU BY FDR=0.019]。收集的结果证实了儿童UC中存在微生物失调，CD患者中程度较轻，重现了先前使用不同方法发现的关联。综上所述，这些观察结果表明，至少对于UC患儿而言，来自家族供体的微生物重塑疗法是一种可行的选择。在这项同胞研究中，先前关于IBD患者微生物失调的16S rRNA测序报告通过深度鸟枪法测序得到验证，并结合了对细菌毒力基因丰度和细菌抗生素耐药决定因素的深入了解，这些是在每个研究参与者特定抗生素摄入数据的背景下观察到的。观察到的将患者与同胞区分开来的失调现象，凸显了这些同胞作为IBD微生物重塑疗法潜在供体的可能性。
