Evaluation of gut dysbiosis using serum and fecal bile acid profiles.

Dysbiosis in the intestinal microflora can affect the gut production of microbial metabolites, and toxic substances can disrupt the barrier function of the intestinal wall, leading to the development of various diseases. Decreased levels of Clostridium subcluster XIVa (XIVa) are associated with the intestinal dysbiosis found in inflammatory bowel disease (IBD) and Clostridium difficile infection (CDI). Since XIVa is a bacterial group responsible for the conversion of primary bile acids (BAs) to secondary BAs, the proportion of intestinal XIVa can be predicted by determining the ratio of deoxycholic acid (DCA)/[DCA + cholic acid (CA)] in feces orserum. For example, serum DCA/(DCA+CA) was significantly lower in IBD patients than in healthy controls, even in the remission period. These results suggest that a low proportion of intestinal XIVa in IBD patients might be a precondition for IBD onset but not a consequence of intestinal inflammation. Another report showed that a reduced serum DCA/(DCA + CA) ratio could predict susceptibility to CDI. Thus, the BA profile, particularly the ratio of secondary to primary BAs, can serve as a surrogate marker of the intestinal dysbiosis caused by decreased XIVa.

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

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, 3ß-hydroxy (3ßOH)-BAs/(3ßOH + 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.