Evaluation of the Risk of Clostridium difficile Infection Using a Serum Bile Acid Profile

Abstract

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.

Evaluation of gut dysbiosis using serum and fecal bile acid profiles

“…G: Glycine; T: Taurine; DCA: Deoxycholic acid; CA: Cholic acid; CDCA: Chenodeoxycholic acid; LCA: Lithocholic acid; BA: Bile acid. This figure was adapted from a previous study[ 25 ].…”

“…Thus, by measuring the DCA/(DCA+CA) ratio in feces or serum, the abundance of XIVa and presumably the presence of dysbiosis can be estimated[ 24 ]. As shown in Table 2 , these product/(product+substrate) ratios of BAs are now being applied in several studies, including those involving IBD patients[ 24 ] and CDI patients[ 25 ], studies on the effects of a high-fat diet in mice[ 41 ], and studies on the effects of water-soluble dietary fiber in humans[ 42 ]. Furthermore, the product/(product+substrate) ratios of fecal BAs can be calculated from the fecal BA data shown in the previous studies[ 43 , 44 ].…”

“…However, GUDCA is not a substrate of DCA, and GUDCA concentration is influenced by a number of factors other than BA 7α-dehydroxylation activity, including glycine/taurine conjugation ratio, deconjugation activity, the conversion rate of CDCA to ursodeoxycholate (UDCA) by 7-epimerization, and the possibility of UDCA administration to patients with hepatobiliary diseases. On the other hand, we showed that the serum DCA/(DCA+CA) ratio at the time of admission (before the use of antibiotics and CDI onset), was significantly low in patients who developed CDI while in the hospital compared to those in patients who did not develop CDI or in healthy controls[ 25 ]. In this study, DCA/(DCA+CA) < 0.349 was the cut-off value for discriminating patients at high risk of CDI before treatment with antibiotics, and the sensitivity and specificity of this threshold were 91.67% and 66.10%, respectively (Figure 2 ).…”

“…Although many reports have shown the relationships between BAs and CDI, studies using BA composition as a predictive surrogate marker to CDI susceptibility are limited[ 25 , 75 ]. Allegretti et al [ 75 ] showed that the fecal DCA to glycoursodeoxycholate (GUDCA) ratio was the best predictor and a potential biomarker for the recurrence of CDI.…”

“…Therefore we have a new hypothesis that the fecal and serum BA profiles could be a useful biomarker for intestinal XIVa activity. We have demonstrated the new facts that fecal and serum ratios of DCA/(DCA+CA) are useful as surrogate indicators of the gut proportion of XIVa, including the inflammatory bowel diseases (IBD) and Clostridium difficile infection (CDI)[ 24 , 25 ]. The unique insight of this review is that this review focused on the studies using the BA calculated product/(product+substrate) ratio, which is not discussed enough in previous reviews.…”