For the first time, researchers have demonstrated how the gut microbiome — the community of microorganisms living in the gut — can influence the immune system in humans. Their work could lead to new treatments for immune-related conditions.
The researchers at Memorial Sloan Kettering Cancer Center in New York, NY, tracked the recovery of patients’ gut microbiota and immune system after bone marrow transplants (BMTs) following treatment for blood cancers.
Healthcare professionals use chemotherapy and radiation therapy to destroy cancerous blood cells in conditions such as leukemia and lymphoma. After completion of the treatment, which also kills healthy immune cells, specialists inject patients with stem cells from a donor’s blood or bone marrow.
These donated cells slowly restore patients’ ability to make their own blood cells.
However, patients have to take antibiotics in the first few weeks after the transplant because they are still vulnerable to infections. These upset the balance of their gut microbiota, killing “friendly bacteria” and allowing dangerous strains to thrive.
Once patients’ immune systems are strong enough, they can stop taking the antibiotics, which allows their gut microbiota to recover.
The researchers at Sloan Kettering used this unique opportunity to study how the microbiota affects the immune system.
“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,” explains systems biologist Joao Xavier, who is co-senior author of the paper with his former postdoc Jonas Schluter.
“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,” says Dr. Schluter, who is now an assistant professor at NYU Langone Health in New York, NY.
Using blood and fecal samples from more than 2,000 patients treated at the cancer center between 2003–2019, the researchers were able to track daily changes in their gut microbiota and the number of immune cells in their blood.
“Our study shows that we can learn a lot from stool — biological samples that literally would be flushed down the toilet,” says Dr. Xavier. “The result of collecting them is that we have a unique dataset with thousands of data points that we can use to ask questions about the dynamics of this relationship.”
The researchers used a machine-learning algorithm to identify patterns in the data, which included information about patients’ medications and the side effects they experienced.
One of the findings was that the presence of three types of gut bacteria — called Faecalibacterium, Ruminococcus 2, and Akkermansia — was associated with increased blood concentrations of immune cells called neutrophils.
By contrast, two types called Rothia and Clostridium sensu stricto 1, were associated with reduced numbers of these immune cells.
Computer simulations by the researchers predicted that enriching microbiota with the three “friendly” genera would speed up the recovery of patients’ immune systems.
“This research could eventually suggest ways to make BMTs safer by more closely regulating the microbiota,” says co-author Marcel van den Brink.
The study appears in Nature.
Concluding their paper, the authors write:
“Our demonstration that the microbiota influences systemic immunity in humans opens the door toward an exploration of potential microbiota-targeted interventions to improve immunotherapy and treatments for immune-mediated and inflammatory diseases.”
A previous study found that having a greater diversity of bacterial species in the gut is associated with a better chance of survival after a stem cell transplant. This research also found that a low diversity of bacteria increased the likelihood of potentially fatal graft-versus-host disease, when the donor immune cells attack the recipient’s tissues.
In 2018, the Sloan Kettering researchers published results from a clinical trial in which they used fecal transplants to restore patients’ microbiota after treatment for blood cancer.
They used the patients’ own fecal matter, which had been collected and frozen before the bone marrow transplant and antibiotic treatment disrupted their gut microbiota.