Mortality Rate Higher After Stem Cell Transplant When Gut Bacteria Diversity Is Low

By Gene Emery

February 28, 2020

(Reuters Health) - There's new evidence that the diversity of bacteria, virus and other microbes in the gut affects a patient's odds of a successful stem cell transplant. It's the latest study in a growing body of research showing the microorganisms quietly thriving in our intestines affect our health in a variety of ways.

The new test of 1,362 volunteers at four centers on three continents found that in people with the widest variety of intestinal microbiota, the mortality rate was up to 54% lower than in patients with less diversity in their microbiome.

"The microbiome is really a factor that can impact outcomes," senior author Dr. Marcel van den Brink, head of the division of hematological malignancies at Memorial Sloan Kettering Cancer Center in New York, told Reuters Health in a telephone interview.

Researchers are gradually beginning to understand the degree to which gut bacteria affect things such as response to chemotherapy, inflammatory bowel disease, immunity and a variety of other health issues.

"If you crushed us up, we would be 99% microbial and only 1% human cells," said Dr. Stephen Hanauer, medical director of the Digestive Health Center at the Northwestern Feinberg School of Medicine in Chicago. "We have learned to live with this microbiome for hundreds of thousands of years. But in recent decades we have cleaned up our environment and changed the bacteria because we've introduced antibiotics, hygiene and been feeding our cattle and animals antibiotics."

That may help explain why some diseases such as asthma, psoriasis and multiple sclerosis have increased, said Dr. Hanauer, who was not involved in the new study.

As reported online in The New England Journal of Medicine, in one part of the study, conducted at Memorial Sloan Kettering Cancer Center in New York City, the risk of death among patients with the most diverse collection of gut organisms was 29.4%. In the group where the diversity was lowest, the death rate was 38.9%.

The other part was done with patients at Duke University Medical Center in North Carolina, University Hospital Regensburg in Germany, and Hokkaido University Hospital in Sapporo, Japan, where the collective death rate was 20.1% in the high diversity group compared with 38.0% in the low diversity group.

Most of the transplants were done to treat acute leukemia.

The van den Brink team found that patients were already suffering from a lack of diversity before the transplant was even attempted, because they had already been through a year or more of heavy chemotherapy and been exposed to other drugs that can wipe out many species of microorganisms in the gut, he said. That immediately puts them at risk.

The study did not involve trying to rebuild that diversity to see if treatment could improve the outcome.

That's going to be an even bigger challenge because researchers are only beginning to understand how it can be done, Dr. Hanauer told Reuters Health in a telephone interview.

"It's one layer of complexity on top of another," he said. "We're dealing with communities of organisms. It's not as simple as taking a probiotic before you get a bone marrow transplant. It's learning to restore a balance, and that's a lot of effort."

"We need to show with prospective studies that we can do something about that," said Dr. van den Brink. "Maybe patients who come in for transplant with a very damaged flora should get specific nutrients or a fecal transplant before you start."

Dr. Hanauer predicted that it could be another 5 or 10 years before doctors learn how to do it properly.

"I think eventually it will be a tailored approach," he said. "But at the start it's more likely to be a shotgun approach."

SOURCE: The New England Journal of Medicine, online February 26, 2020.