Ashton James J, Colquhoun Catherine M, Cleary David W, Coelho Tracy, Haggarty Rachel, Mulder Imke, Batra Akshay, Afzal Nadeem A, Beattie R Mark, Scott Karen P, Ennis Sarah
Department of Paediatric Gastroenterology, Southampton Children's Hospital Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton Gut Health Division, Rowett Institute, University of Aberdeen, Aberdeen Academic Unit of Clinical and Experimental Sciences, University of Southampton, Southampton 4D Pharma PLC, Aberdeen, UK.
Medicine (Baltimore). 2017 Jun;96(26):e7347. doi: 10.1097/MD.0000000000007347.
The human microbiome is of considerable interest to pediatric inflammatory bowel disease (PIBD) researchers with 1 potential mechanism for disease development being aberrant immune handling of the intestinal bacteria. This study analyses the fecal microbiome through treatment in newly diagnosed PIBD patients and compares to cohabiting siblings where possible. Patients were recruited on clinical suspicion of PIBD before diagnosis. Treatment-naïve fecal samples were collected, with further samples at 2 and 6 weeks into treatment. Samples underwent 16S ribosomal ribonucleic acid (RNA) gene sequencing and short-chain fatty acids (SCFAs) analysis, results were analyzed using quantitative-insights-into-microbial-ecology. Six PIBD patients were included in the cohort: 4 Crohn disease (CD), 1 ulcerative colitis (UC), 1 inflammatory bowel disease (IBD) unclassified, and median age 12.6 (range 10-15.1 years); 3 patients had an unaffected healthy sibling recruited. Microbial diversity (observed species/Chao1/Shannon diversity) was reduced in treatment-naïve patients compared to siblings and patients in remission. Principal coordinate analysis using Bray-Curtis dissimilarity and UniFrac revealed microbial shifts in CD over the treatment course. In treatment-naïve PIBD, there was reduction in functional ability for amino acid metabolism and carbohydrate handling compared to controls (P = .038) and patients in remission (P = .027). Metabolic function returned to normal after remission was achieved. SCFA revealed consistent detection of lactate in treatment-naïve samples. This study adds in-depth 16S rRNA sequencing analysis on a small longitudinal cohort to the literature and includes sibling controls and patients with UC/IBD unclassified. It highlights the initial dysbiosis, reduced diversity, altered functional potential, and subsequent shifts in bacteria from diagnosis over time to remission.
人类微生物群系是小儿炎症性肠病(PIBD)研究人员相当感兴趣的领域,疾病发展的一种潜在机制是肠道细菌的免疫处理异常。本研究通过对新诊断的PIBD患者进行治疗来分析粪便微生物群系,并尽可能与同居的兄弟姐妹进行比较。患者在诊断前因临床怀疑PIBD而被招募。收集未接受过治疗的粪便样本,并在治疗2周和6周时收集更多样本。样本进行了16S核糖体核糖核酸(RNA)基因测序和短链脂肪酸(SCFA)分析,结果使用微生物生态学定量洞察法进行分析。该队列纳入了6名PIBD患者:4例克罗恩病(CD)、1例溃疡性结肠炎(UC)、1例未分类的炎症性肠病(IBD),中位年龄12.6岁(范围10 - 15.1岁);招募了3名有未受影响的健康兄弟姐妹的患者。与兄弟姐妹和缓解期患者相比,未接受过治疗的患者的微生物多样性(观察到的物种/Chao1/香农多样性)降低。使用布雷 - 柯蒂斯差异和非加权组平均法的主坐标分析揭示了CD患者在治疗过程中的微生物变化。与对照组(P = 0.038)和缓解期患者(P = 0.027)相比,未接受过治疗的PIBD患者的氨基酸代谢和碳水化合物处理功能能力降低。缓解后代谢功能恢复正常。SCFA显示在未接受过治疗的样本中持续检测到乳酸。本研究在一个小型纵向队列中增加了深入的16S rRNA测序分析,并纳入了兄弟姐妹对照以及未分类的UC/IBD患者。它突出了从诊断到缓解随时间推移最初的生态失调、多样性降低、功能潜力改变以及随后的细菌变化。