Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Gastroenterology. 2021 May;160(6):1970-1985. doi: 10.1053/j.gastro.2021.01.030. Epub 2021 Jan 19.
BACKGROUND & AIMS: It is currently unclear whether reported changes in the gut microbiome are cause or consequence of inflammatory bowel disease (IBD). Therefore, we studied the gut microbiome of IBD-discordant and -concordant twin pairs, which offers the unique opportunity to assess individuals at increased risk of developing IBD, namely healthy cotwins from IBD-discordant twin pairs.
Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex-, and body mass index-matched controls, and 99 unrelated patients with IBD. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared among healthy cotwins, IBD-twins, unrelated patients with IBD, and healthy controls with multivariable (ie, adjusted for potential confounding) generalized linear models.
No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate <0.10). Compared with healthy controls, 13, 19, and 18 species, and 78, 105, and 153 pathways were found to be differentially abundant in healthy cotwins, IBD-twins, and unrelated patients with IBD, respectively (false discovery rate <0.10). Of these, 8 (42.1%) of 19 and 1 (5.6%) of 18 species, and 37 (35.2%) of 105 and 30 (19.6%) of 153 pathways overlapped between healthy cotwins and IBD-twins, and healthy cotwins and unrelated patients with IBD, respectively. Many of the shared species and pathways have previously been associated with IBD. The shared pathways include potentially inflammation-related pathways, for example, an increase in propionate degradation and L-arginine degradation pathways.
The gut microbiome of healthy cotwins from IBD-discordant twin pairs displays IBD-like signatures. These IBD-like microbiome signatures might precede the onset of IBD. However, longitudinal follow-up studies are needed to infer a causal relationship.
目前尚不清楚肠道微生物组的变化是炎症性肠病（IBD）的原因还是结果。因此，我们研究了 IBD 不一致和一致的双胞胎的肠道微生物组，这为评估有患 IBD 风险的个体提供了独特的机会，即来自 IBD 不一致的双胞胎的健康同卵双胞胎。
从 99 对双胞胎（属于 51 对双胞胎）、495 名年龄、性别和体重指数匹配的健康对照者和 99 名无关的 IBD 患者中获得粪便样本。进行全基因组宏基因组 shotgun 测序。使用多变量（即，调整潜在混杂因素）广义线性模型比较健康同卵双胞胎、IBD 双胞胎、无关的 IBD 患者和健康对照者之间的分类组成和功能（途径）组成。
健康同卵双胞胎与其 IBD 双胞胎之间的物种和途径相对丰度没有显着差异（错误发现率 <0.10）。与健康对照者相比，在健康同卵双胞胎、IBD 双胞胎和无关的 IBD 患者中分别发现了 13、19 和 18 种和 78、105 和 153 种差异丰富的物种和途径（错误发现率 <0.10）。其中，19 种中的 8 种（42.1%）和 18 种中的 1 种（5.6%）以及 105 种中的 37 种（35.2%）和 153 种中的 30 种（19.6%）在健康同卵双胞胎和 IBD 双胞胎以及健康同卵双胞胎和无关的 IBD 患者之间重叠。许多共享的物种和途径以前与 IBD 有关。共享途径包括潜在的与炎症相关的途径，例如丙酸盐降解和 L-精氨酸降解途径的增加。
来自 IBD 不一致的双胞胎的健康同卵双胞胎的肠道微生物组显示出 IBD 样特征。这些 IBD 样微生物组特征可能先于 IBD 的发生。然而，需要进行纵向随访研究来推断因果关系。
