AT DDW 2016

SAN DIEGO (FRONTLINE MEDICAL NEWS) – Bile acid salts in the stool may be a potential biomarker for recurrent episodes of Clostridium difficile infection, a preliminary study suggests.

Although the finding needs to be validated in a prospective study, it could have therapeutic implications, the study investigators said.

“If our results are validated, we could take bile salt profiles of patients who come in with their first episode of C. difficile infection and, using this biomarker, adjust therapy accordingly,” said study lead author Dr. Jessica Allegretti, who presented the findings at the annual Digestive Disease Week. “A patient at high risk of recurrence could get fecal transplant earlier. Right now, fecal transplant is used for recurrent infection.”

C. difficile represents a major public health threat, and recurrent disease complicates 20%-30% of cases.

The disease is communicated by spores that are resistant to heat and antibiotics, and they germinate in the gastrointestinal tract. Bile acids are part of that process. Bile acids assist in the digestion of fat, and a small proportion pass into the colon where primary bile acids undergo transformation into secondary bile acids such as deoxycholate and lithocholate.

In vitro, primary acids can stimulate C. difficile, explained Dr. Allegretti of Brigham and Women’s Hospital, Cambridge, Mass. “Antibiotic therapy may ablate critical members of the microbiota. We aimed to assess bile acid profiles in patients with C. difficile infection, compared with controls, to understand their role in pathogenesis and hopefully identify a biomarker for recurrence.”

The cross-sectional study collected serum and a single stool sample from three groups of 60 patients: patients with a first episode of C. difficile (fCDI) prior to antibiotics (20 patients), patients with a recurrent episode (rCDI) on treatment with chronic vancomycin at the time of sampling (19), and healthy controls who were fecal transplant donors (21).

The researchers sequenced stool microbial components and conducted bile salt metabolomic profiling. Significant differences were revealed in microbial analysis of the stool samples: Primary bile salts (which induce germination) were significantly elevated in rCDI, compared with fCDI and controls – while secondary bile salts in the stool (which are protective) such as deoxycholate and lithocholate were significantly elevated in controls, compared with fCDI and rCDI (P = .0002 and P = .0007, respectively).

“The same trends were seen in the plasma samples, but were less dramatic than in the stool,” Dr. Allegretti noted.

The median predicted bile salt hydrolase (BSH) gene abundance in rCDI was 20% of the median value in controls (P = .001), and it also was significantly lower than fCDI (P = .001). No significant difference was seen between predicted BSH gene abundance between controls and the fCDI groups.

“An association with reduced predicted bacterial bile salt hydrolase gene abundance may be associated with a diminished capacity to metabolize bile acids,” she said.

The difference in BSH gene abundance between controls and rCDI was largely due to changes in the abundance of 10 bacterial taxa, Dr. Allegretti said.

“This study reinforces the importance of bile salts in CDI and demonstrates for the first time in humans that this shift can be appreciated as early as the first episode of CDI in patients who are antibiotic naive,” Dr Allegretti said.

She noted that rCDI samples were collected in patients on chronic antibiotic therapy, and that may explain some of the decrease in biological microdiversity seen in the study.

In search of a biomarker, “secondary bile acids clearly seem to be the winner, and for now, stool seems to make more sense than blood for samples,” she stated.

Dr. Allegretti and her colleagues are conducting a prospective validation study.

The American College of Gastroenterology funded the study.