Jim Kling

September 11, 2013

DENVER — Changes in intestinal microbiota, especially increases in populations of Bacteroides, predict which chemotherapy patients are likely to develop chemotherapy-induced diarrhea.

This finding comes from a study of patients with non-Hodgkin's lymphoma undergoing high-dose chemotherapy in preparation for hematopoietic stem cell transplantation. The work is the first to link chemotherapy-induced microbiota changes to diarrhea.

The changes occur a median of 6 days before the onset of symptoms, which could pave the way for probiotic or other targeted therapies, reported Emmanuel Montassier, MD, a PhD student at Université de Nantes in France, here at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.

Severe chemotherapy-induced diarrhea affects 20% to 30% of patients receiving chemotherapy, and can be life-threatening. "The pathophysiology of diarrhea is not clear, and the role of intestinal microbiota is not clear. Several studies have demonstrated that intestinal microbial growth is disrupted during chemotherapy, but they didn't connect this to diarrhea," Dr. Montassier explained.

The researchers studied 36 patients with non-Hodgkin's lymphoma who underwent chemotherapy in preparation for hematopoietic stem cell transplantation. On day 7 of the chemotherapy regimen, fecal samples were collected and analyzed with 454 high-throughput pyrosequencing of the V5–V6 hypervariable region of the 16S rRNA gene. The team used the Quantitative Insights Into Microbial Ecology (QIIME) pipeline to analyze sequences.

After a median delay of 13 days, 8 patients (22.2%) developed severe diarrhea. A metagenomic analysis identified 2 clusters of patients — those who went on to develop diarrhea and those who did not. In patients who developed diarrhea, the growth of Bacteroides bacteria was higher, whereas in patients who did not, the growth of Escherichia bacteria was higher.

The patients are on chemotherapy so they're vulnerable, and any kind of manipulation has to be done with the utmost care.

At-risk patients could potentially be treated with fecal transplantation, according to Dr. Montassier. Fecal material could be collected in advance of the chemotherapy regimen, and patients likely to develop diarrhea could undergo transplantation.

This study drew cautious praise. "It's not that big a sample, so it will have to be repeated in other people's hands," said Clifford McDonald, MD, a medical epidemiologist at the Centers for Disease Control and Prevention in Atlanta.

"The next question is, what can you do about it? A lot of people are interested in probiotics and fecal transplants. However, the patients are on chemotherapy so they're vulnerable, and any kind of manipulation has to be done with the utmost care," Dr. McDonald told Medscape Medical News.

The research caught the attention of at least one member of the pharmaceutical industry. Craig Volker, PhD, a computational biologist at GlaxoSmithKline who attended the session, said he sees potential.

If the results are confirmed, "rather than discontinuing the drug, physicians could attempt an intervention that would allow the effect of the drug to take place without the side effect. You could use selective antibiotics or, if you're using a global antibiotic, you can give the bacteria back with probiotics or a fecal transplant. More research is needed to figure out the best way," Dr. Volker said.

This study was funded by Nantes University Hospital (Grant BRD/10/04-Q) and BioFortis. Dr. McDonald and Dr. Volker have disclosed no relevant financial relationships.

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract B-030. Presented September 10, 2013.


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