Monma Tadakuni, Iwamoto Junichi, Honda Akira, Ueda Hajime, Kakizaki Fumio, Yara Shoichiro, Miyazaki Teruo, Ikegami Tadashi
Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Ibaraki 300-0395, Japan.
Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Ibaraki 300-0395, Japan.
Metabolites. 2022 Apr 6;12(4):331. doi: 10.3390/metabo12040331.
Since intestinal secondary bile acids (BAs) prevent Clostridium difficile infection (CDI), the serum BA profile may be a convenient biomarker for CDI susceptibility in human subjects. To verify this hypothesis, we investigated blood samples from 71 patients of the Division of Gastroenterology and Hepatology at the time of admission (prior to antibiotic use and CDI onset). Twelve patients developed CDI during hospitalization, and the other 59 patients did not. The serum unconjugated deoxycholic acid (DCA)/[DCA + unconjugated cholic acid (CA)] ratio on admission was significantly lower in patients who developed CDI than in patients who did not develop CDI (p < 0.01) and in 46 healthy controls (p < 0.0001). Another unconjugated secondary BA ratio, 3β-hydroxy (3βOH)-BAs/(3βOH + 3αOH-BAs), was also significantly lower in patients who developed CDI than in healthy controls (p < 0.05) but was not significantly different between patients who developed and patients who did not develop CDI. A receiver operating characteristic (ROC) curve determined a cut-off point of DCA/(DCA + CA) < 0.349 that optimally discriminated on admission the high-risk patients who would develop CDI (sensitivity 91.7% and specificity 64.4%). In conclusion, a decreased serum DCA/(DCA + CA) ratio on admission strongly correlated with CDI onset during hospitalization in patients with gastrointestinal and hepatobiliary diseases. Serum BA composition could be a helpful biomarker for predicting susceptibility to CDI.
由于肠道次级胆汁酸(BAs)可预防艰难梭菌感染(CDI),血清胆汁酸谱可能是人类受试者CDI易感性的便捷生物标志物。为验证这一假设,我们调查了胃肠病学和肝病科71例患者入院时(在使用抗生素和CDI发病之前)的血样。12例患者在住院期间发生了CDI,其他59例患者未发生。发生CDI的患者入院时血清未结合脱氧胆酸(DCA)/[DCA +未结合胆酸(CA)]比值显著低于未发生CDI的患者(p < 0.01)和46名健康对照者(p < 0.0001)。另一个未结合次级胆汁酸比值,即3β-羟基(3βOH)-BAs/(3βOH + 3αOH-BAs),在发生CDI的患者中也显著低于健康对照者(p < 0.05),但在发生CDI的患者与未发生CDI的患者之间无显著差异。受试者工作特征(ROC)曲线确定DCA/(DCA + CA)< 0.349为最佳切点,可在入院时最佳地区分将发生CDI的高危患者(敏感性91.7%,特异性64.4%)。总之,入院时血清DCA/(DCA + CA)比值降低与胃肠肝胆疾病患者住院期间CDI发病密切相关。血清胆汁酸组成可能是预测CDI易感性的有用生物标志物。