Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Aliment Pharmacol Ther. 2019 Mar;49(6):744-758. doi: 10.1111/apt.15106. Epub 2019 Feb 10.
Biomarkers in irritable bowel syndrome (IBS) may guide targeted therapy in this multifactorial disease. It has been suggested that 75% accuracy and cost <$500 categorise biomarkers as cost-effective.
To identify differences in faecal bile acids, faecal fat and fasting serum C4 (7a-hydroxy-4-cholesten-3-one) and fibroblast growth factor 19 (FGF19) among patients with IBS-D, IBS-C and healthy controls and to determine accurate, cost-effective biomarkers for clinically relevant diarrhoea and constipation.
We assessed daily stool frequency and consistency (Bristol Stool Form Scale) from validated bowel diaries, 48 hours total and individual faecal bile acids, 48 hours faecal fat and weight, fasting serum C4 and FGF19, and colonic transit by scintigraphy from healthy volunteers (HV) and patients with IBS-D and IBS-C (Rome III criteria). We utilised multivariate logistic regression to determine biomarkers of clinically significant diarrhoea or constipation based on stool frequency, consistency and weight.
Among the 126 HV (44M/82F, 37.5 ± 10.9 years [SD]), 64 IBS-D (5M/59F, 41.9 ± 12.2 years), and 30 IBS-C (0M/30F, 44.6 ± 10 years) patients, there were significant differences between all groups in stool weight, frequency, and consistency; in addition, there were differences in colonic transit at 48 hours, faecal fat, and total and individual faecal bile acids between IBS-D and IBS-C. Reduced total and primary faecal bile acids and increased faecal lithocholic acid were significant predictors of decreased faecal weight, frequency and consistency with AUC > 0.82 (sensitivity >76%, specificity >72%). Total and primary faecal bile acids and faecal fat were significant predictors of increased stool weight, frequency and consistency with AUC > 0.71 (sensitivity >55%, specificity >74%).The faecal parameters had a 11.5 positive likelihood ratio in predicting elevated faecal weight.
Faecal bile acids and faecal fat are cost-effective and accurate biomarkers associated with significant bowel dysfunction among IBS-D and IBS-C patients.
在这种多因素疾病中，肠易激综合征（IBS）的生物标志物可能指导靶向治疗。有人提出，准确率达到 75%且成本低于 500 美元的生物标志物可被认为具有成本效益。
确定 IBS-D、IBS-C 患者与健康对照者粪便胆汁酸、粪便脂肪和空腹血清 C4（7a-羟基-4-胆甾烷-3-酮）和成纤维细胞生长因子 19（FGF19）的差异，并确定用于诊断临床相关腹泻和便秘的准确、具有成本效益的生物标志物。
我们评估了健康志愿者（HV）和 IBS-D 和 IBS-C 患者（罗马 III 标准）的每日粪便频率和稠度（布里斯托粪便形态量表）、48 小时总粪便和单个胆汁酸、48 小时粪便脂肪和重量、空腹血清 C4 和 FGF19，以及闪烁扫描法结肠转运。我们利用多变量逻辑回归，根据粪便频率、稠度和重量，确定临床显著腹泻或便秘的生物标志物。
在 126 名 HV（44M/82F，37.5±10.9 岁[SD]）、64 名 IBS-D（5M/59F，41.9±12.2 岁）和 30 名 IBS-C（0M/30F，44.6±10 岁）患者中，所有组之间在粪便重量、频率和稠度方面均存在显著差异；此外，IBS-D 和 IBS-C 之间在 48 小时结肠转运、粪便脂肪、总粪便和单个胆汁酸方面也存在差异。总胆汁酸和初级胆汁酸减少以及粪便胆酸增加是粪便重量、频率和稠度降低的显著预测因子，AUC>0.82（敏感性>76%，特异性>72%）。总粪便和初级胆汁酸和粪便脂肪是粪便重量、频率和稠度增加的显著预测因子，AUC>0.71（敏感性>55%，特异性>74%）。粪便参数在预测粪便重量升高方面具有 11.5 的阳性似然比。
粪便胆汁酸和粪便脂肪是具有成本效益的、与 IBS-D 和 IBS-C 患者显著肠道功能障碍相关的准确生物标志物。
