The concentration of different kinds of immune cells in the blood alters in relation to the presence of different bacterial strains in the human gut, researchers at Memorial Sloan Kettering Cancer Center report.
The scientific community had already accepted the idea that the gut microbiota was important for the health of the human immune system, but the data they used to make that assumption came from animal studies,
A Unique Opportunity
The data used in the study came from people receiving allogeneic stem cell and bone marrow transplants (BMTs). After strong chemotherapy or radiation therapy is used to destroy cancerous blood cells, the patient’s blood-forming system is replaced with stem cells from a donor.
For the first few weeks until the donor’s blood cells — including the white blood cells that make up the immune system — have established themselves, the patients are extremely vulnerable to infections. To protect them during this time, patients are given antibiotics.
But many of these antibiotics have the unfortunate side effect of killing healthy microbiota that live in the gut, allowing dangerous strains to take over. When the patient’s immune system has reconstituted, the antibiotics are discontinued, and the gut microbiota slowly starts to grow back.
The parallel recoveries of the immune system and the microbiota, both of which are damaged and then restored, gives us a unique opportunity to analyze the associations between these two systems,
Dr. Schluter says.
For more than ten years, members of MSK’s BMT service have regularly collected and analyzed blood and fecal samples from patients throughout the bone marrow transplant process. The bacterial DNA were processed by the staff at MSK’s Lucille Castori Center for Microbes, Inflammation, and Cancer, which played a key role in creating the massive microbiota dataset.
Our study shows that we can learn a lot from stool — biological samples that literally would be flushed down the toilet. The result of collecting them is that we have a unique dataset with thousands of datapoints that we can use to ask questions about the dynamics of this relationship,
Dr. Xavier notes.
This wider effort has been led by Marcel van den Brink, Head of the Division of Hematologic Malignancies, and a team of infectious disease specialists, BMT doctors, and scientists.
For a fair number of patients, we collected daily samples so we could really see what was happening day to day. The changes in the microbiota are rapid and dramatic, and there is almost no other setting in which you would be able to see them,
Dr. van den Brink says.
Previous research using samples collected from this work has looked at how the gut microbiota affects patients' health during the bone marrow transplant process. A study published in February 20202 reported that having a greater diversity of species in the intestinal microbiota is associated with a lower risk of death after a BMT. It also found that having a lower diversity of microbiota before transplant resulted in a higher incidence of graft-versus-host disease, a potentially fatal complication in which the donor immune cells attack healthy tissue.
Complicated Relationship, New Clues
The databank that the Memorial Sloan Kettering team created contains details about the types of microbes that live in the patients' guts at various times. The computational team, including Drs. Schluter and Xavier, then used machine learning algorithms to mine electronic health records for meaningful data.
The data from the health records included the types of immune cells present in the blood, information about the medications that patients were given, and the side effects patients experienced.
This research could eventually suggest ways to make BMTs safer by more closely regulating the microbiota,
Dr. van den Brink says.
Analyzing this much data was a huge undertaking. Dr. Schluter, who at the time was a postdoctoral fellow in Dr. Xavier’s lab, developed new statistical techniques for this.
The purpose of this study was not to say whether certain kinds of microbes are ‘good’ or ‘bad’ for the immune system. It’s a complicated relationship. The subtypes of immune cells we would want to increase or decrease vary from day to day, depending on what else is going on in the body. What’s important is that now we have a way to study this complex ecosystem,
Dr. Xavier explains, adding that this will be a focus of future research. The researchers say they also plan to apply their data to studying the immune system in patients receiving other cancer treatments.
The research was supported by the National Institutes of Health, a grant from MSKCC Cancer Center Core, the Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center, the Sawiris Foundation, the Society of Memorial Sloan Kettering Cancer Center, a MSKCC Cancer Systems Immunology Pilot Grant and Empire Clinical Research Investigator Program.
Schluter, J., Peled, J.U., Taylor, B.P. et al. The gut microbiota is associated with immune cell dynamics in humans. Nature, 25 November 2020 ↩︎
Peled, J. U. et al. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. N. Engl. J. Med. 382, 822–834 (2020) ↩︎