4D pharma Cork Limited, Cavanagh Pharmacy Building, University College Cork, National University of Ireland, Cork, Ireland.
Department of Radiology, Cork University Hospital, Cork, Ireland.
Gastroenterology. 2020 Mar;158(4):1016-1028.e8. doi: 10.1053/j.gastro.2019.11.301. Epub 2019 Dec 14.
BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a heterogeneous disorder, but diagnoses and determination of subtypes are made based on symptoms. We profiled the fecal microbiomes of patients with and without IBS to identify biomarkers of this disorder.
We collected fecal and urine samples from 80 patients with IBS (Rome IV criteria; 16-70 years old) and 65 matched individuals without IBS (control individuals), along with anthropometric, medical, and dietary information. Shotgun and 16S ribosomal RNA amplicon sequencing were performed on feces, whereas urine and fecal metabolites were analyzed by gas chromatography and liquid chromatography-mass spectrometry. Co-occurrence networks were generated based on significant Spearman correlations between data. Bile acid malabsorption (BAM) was identified in patients with diarrhea by retention of radiolabeled selenium-75 homocholic acid taurine.
Patients with IBS had significant differences in network connections between diet and fecal microbiomes compared with control individuals; these were accompanied by differences in fecal metabolomes. We did not find significant differences in fecal microbiota composition among patients with different IBS symptom subtypes. Fecal metabolome profiles could discriminate patients with IBS from control individuals. Urine metabolomes also differed significantly between patients with IBS and control individuals, but most discriminatory metabolites were related to diet or medications. Fecal metabolomes, but not microbiomes, could distinguish patients with IBS with vs those without BAM.
Despite the heterogeneity of IBS, patients have significant differences in urine and fecal metabolomes and fecal microbiome vs control individuals, independent of symptom-based subtypes of IBS. Fecal metabolome analysis can be used to distinguish patients with IBS with vs those without BAM. These findings might be used for developing microbe-based treatments for these disorders.
肠易激综合征（IBS）是一种异质性疾病，但诊断和亚型的确定是基于症状。我们对 IBS 患者和非 IBS 患者的粪便微生物组进行了分析，以确定该疾病的生物标志物。
我们收集了 80 例 IBS 患者（罗马 IV 标准；16-70 岁）和 65 例匹配的非 IBS 患者（对照个体）的粪便和尿液样本，并收集了人体测量、医疗和饮食信息。对粪便进行了鸟枪法和 16S 核糖体 RNA 扩增子测序，而尿液和粪便代谢物则通过气相色谱和液相色谱-质谱分析。根据数据之间显著的 Spearman 相关性生成共现网络。通过放射性标记的硒-75 同型胆酸牛磺酸的保留来鉴定腹泻患者的胆汁酸吸收不良（BAM）。
与对照个体相比，IBS 患者的饮食与粪便微生物组之间的网络连接存在显著差异；这些差异伴随着粪便代谢组的差异。我们没有发现不同 IBS 症状亚型患者之间粪便微生物群组成的显著差异。粪便代谢组谱可以将 IBS 患者与对照个体区分开来。IBS 患者和对照个体的尿液代谢组也存在显著差异，但大多数有区别的代谢物与饮食或药物有关。粪便代谢组而不是微生物组可以区分 IBS 患者中是否存在 BAM。
尽管 IBS 存在异质性，但患者的尿液和粪便代谢组以及粪便微生物组与对照个体存在显著差异，与基于症状的 IBS 亚型无关。粪便代谢组分析可用于区分 IBS 患者是否存在 BAM。这些发现可用于开发针对这些疾病的基于微生物的治疗方法。
