This study aims to characterize, the gut and oral microbiome in Asian subjects with Crohn’s disease (CD) using whole genome shotgun sequencing, thereby allowing for strain-level comparison. A case–control study with age, sex and ethnicity matched healthy controls was conducted. CD subjects were limited to well-controlled patients without oral manifestations. Fecal and saliva samples were collected for characterization of gut and oral microbiome respectively. Microbial DNA were extracted, libraries prepared and sequenced reads profiled. Taxonomic diversity, taxonomic association, strain typing and microbial gene pathway analyses were conducted. The study recruited 25 subjects with CD and 25 healthy controls. The oral microbe Streptococcus salivarius was found to be enriched and of concordant strains in the gut and oral microbiome of Crohn’s disease subjects. This was more likely in CD subjects with higher Crohn’s Disease Activity Index (184.3 ± 2.9 vs 67.1 ± 82.5, p = 0.012) and active disease status (Diarrhoea/abdominal pain/blood-in-stool/fever and fatigue) (p = 0.016). Gut species found to be significantly depleted in CD compared to control (Relative abundance: Median[Range]) include: Faecalibacterium prausnitzii (0.03[0.00–4.56] vs 13.69[5.32–18.71], p = 0.010), Roseburia inulinivorans (0.00[0.00–0.03] vs 0.21[0.01–0.53], p = 0.010) and Alistipes senegalensis (0.00[0.00–0.00] vs 0.00[0.00–0.02], p = 0.029). While Clostridium nexile (0.00[0.00–0.12] vs 0.00[0.00–0.00], p = 0.038) and Ruminococcus gnavus (0.43[0.02–0.33] vs 0.00[0.00–0.13], p = 0.043) were found to be enriched. C. nexile enrichment was not found in CD subjects of European descent. Microbial arginine (Linear-discriminant-analysis: 3.162, p = 0.001) and isoprene (Linear-discriminant-analysis: 3.058, p < 0.001) pathways were found at a higher relative abundance level in gut microbiome of Crohn’s disease. There was evidence of ectopic gut colonization by oral bacteria, especially during the active phase of CD. Previously studied gut microbial differences were detected, in addition to novel associations which could have resulted from geographical/ethnic differences to subjects of European descent. Differences in microbial pathways provide possible targets for microbiome modification.

中文翻译：

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异位肠道定植：克罗恩病口腔和肠道微生物组的宏基因组学研究

这项研究旨在使用全基因组shot弹枪测序来表征患有克罗恩病（CD）的亚洲受试者的肠道和口腔微生物组，从而进行菌株水平的比较。进行了一项年龄，性别和种族与健康对照相匹配的病例对照研究。CD受试者仅限于控制良好且无口腔表现的患者。收集粪便和唾液样品分别表征肠道和口腔微生物组。提取微生物DNA，制备文库并分析测序读数。进行了分类学多样性，分类学关联，菌株分型和微生物基因途径分析。该研究招募了25名患有CD的受试者和25名健康对照。发现在克罗恩病受试者的肠道和口腔微生物组中，唾液链球菌唾液链球菌富集，并且菌株一致。在CD受试者中，克罗恩病活动指数（184.3±2.9 vs 67.1±82.5，p = 0.012）和活动性疾病状态（腹泻/腹痛/血便/发烧和疲劳）更高（p = 0.016），这更有可能出现在CD受试者中）。发现与对照相比，CD中的肠道种类显着减少（相对丰度：中位数[范围]）包括：费氏杆状杆菌（0.03 [0.00-4.56]对13.69 [5.32-18.71]，p = 0.010），玫瑰花蔷薇（0.00 [0.00] 0.00–0.03]和0.21 [0.01–0.53]，p = 0.010）和塞内加尔群岛（0.00 [0.00–0.00] vs 0.00 [0.00–0.02]，p = 0.029）。而梭状芽胞杆菌（0.00 [0.00–0.12]与0.00 [0.00–0.00]，p = 0.038）和鲁米诺球菌（0.43 [0.02–0.33]与0.00 [0.00–0.13]，p = 0。043）被发现是丰富的。在欧洲血统的CD受试者中未发现C. nexile富集。在克罗恩病肠道微生物组中，微生物精氨酸（线性差异分析：3.162，p = 0.001）和异戊二烯（线性差异分析：3.058，p <0.001）途径被发现具有较高的相对丰度水平。有证据表明口腔细菌在异位肠中定植，特别是在CD的活跃期。除了可能由欧洲人后裔的地理/种族差异所导致的新型关联外，还检测了先前研究过的肠道微生物差异。微生物途径的差异为微生物组修饰提供了可能的靶标。在克罗恩病肠道微生物组中，微生物精氨酸（线性差异分析：3.162，p = 0.001）和异戊二烯（线性差异分析：3.058，p <0.001）途径被发现具有较高的相对丰度水平。有证据表明口腔细菌在异位肠中定植，特别是在CD的活跃期。除了可能由欧洲人后裔的地理/种族差异所导致的新型关联外，还检测了先前研究过的肠道微生物差异。微生物途径的差异为微生物组修饰提供了可能的靶标。在克罗恩病肠道微生物组中，微生物精氨酸（线性差异分析：3.162，p = 0.001）和异戊二烯（线性差异分析：3.058，p <0.001）途径被发现具有较高的相对丰度水平。有证据表明口腔细菌在异位肠中定植，特别是在CD的活跃期。除了可能由欧洲人后裔的地理/种族差异所导致的新型关联外，还检测了先前研究过的肠道微生物差异。微生物途径的差异为微生物组修饰提供了可能的靶标。有证据表明口腔细菌在异位肠中定植，特别是在CD的活跃期。除了可能由欧洲人后裔的地理/种族差异所导致的新型关联外，还检测了先前研究过的肠道微生物差异。微生物途径的差异为微生物组修饰提供了可能的靶标。有证据表明口腔细菌在异位肠中定植，特别是在CD的活跃期。除了可能由欧洲人后裔的地理/种族差异所导致的新型关联外，还检测了先前研究过的肠道微生物差异。微生物途径的差异为微生物组修饰提供了可能的靶标。