August 10, 2016
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Microbiome markers predict C. difficile treatment response, recurrence

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Markers of specific alterations in the gut microbiota appeared predictive of response to Clostridium difficile treatment and recurrent infection in a recent study.

“In this study funded by the Center for Individualized Medicine at Mayo Clinic, Rochester, Minn., we identified microbiome markers at the time of initial diagnosis that can predict response to therapy in patients with C. difficile infection,” Purna C. Kashyap, MBBS, of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn., told Healio Gastroenterology. “This will allow us to identify patients who are less likely to respond to conventional treatment and hence may be candidates for [alternative] therapies such as fecal microbiota transplant.”

Purna C. Kashyap, MBBS

Purna C. Kashyap

Sahil Khanna, MBBS

Sahil Khanna

To evaluate the role of gut microbiota alterations in determining outcomes of CDI treatment, Kashyap and colleagues, including Sahil Khanna, MBBS, prospectively collected stool samples from 88 patients with primary CDI (median age, 52.7 years; 60.2% women) before they were treated. Then they performed next generation 16s rRNA sequencing to identify differences in microbial community structure, and assessed for correlations with CDI outcomes, using a risk index to differentiate responders and nonresponders and those with and without recurrent infection.

Overall, 12.5% of patients failed treatment and 28.5% experienced recurrent infection after response to treatment, with a median time to recurrence of 23 days (range, 15-56 days).

Predicting treatment response

The researchers identified a panel of 36 operational taxonomic units (OTUs) that were significantly different between responders and nonresponders. Responders had an increased relative abundance of Ruminococcaceae, Rikenellaceae, Bacteroides and Faecalibacterium, while nonresponders had increased Clostridiaceae, Lachnospiraceae, Blautia, Coprococcus, Streptococcus, Bifidobacterium, Ruminococcus and Actinomyces.

A risk index of treatment response built from this panel of microbes showed significantly different risk index scores for responders (mean 0.07 ± 0.24) vs. nonresponders (0.52 ± 0.42; P < .0002). Moreover, receiver operating characteristic (ROC) curve analysis showed the risk-index strongly predicted response to treatment (area under the curve [AUC], 0.85).

“Thus, we found that our risk index ... accurately identified patients with CDI, likely to not respond to conventional treatment,” the researchers wrote.

Predicting recurrent infection

There were no significant differences in clinical variables between patients with and without recurrent infection, except for use of proton pump inhibitors, which were predictive of recurrent infection (OR = 3.75; 95% CI, 1.27-1.11; P = .01).

“However, PPI use was not associated with alterations in the gut microbiota,” the researchers wrote.

They identified a panel of 11 OTUs that were significantly different between patients with and without recurrent infection. Patients with recurrent CDI had significantly increased relative abundance of Veillonella, Enterobacteriaceae (Erwinia), Streptococcus, Parabacteroides and Lachnospiraceae. A risk index of recurrence built from this panel of microbes showed significantly different risk index scores between those with CDI recurrence (mean 0.09 ± 0.08) and those without CDI recurrence (mean 0.19 ± 0.12; P = .0001), and ROC curve analysis showed this risk-index strongly predicted CDI recurrence (AUC, 0.78).

“Thus, we found that our risk index can identify patients with CDI who are likely to have recurrence after initial response,” the researchers wrote.

“These findings need to be independently validated but provide an example of how microbiome based diagnostics are an important part of precision medicine tools needed to individualize treatment and improve patient care,” Kashyap said. – by Adam Leitenberger

Disclosures: Khanna reports he has received research grant support from Merck and has consulted for Rebiotix and Summit. Kashyap reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.